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Pastas dentales con flúor de diferentes concentraciones para prevenir las caries dentales en niños y adolescentes
Tanya Walsh, Helen V Worthington, Anne-Marie Glenny, Priscilla Appelbe, Valeria CC Marinho, Xin Shi
Esta revisión debería citarse como: Tanya Walsh, Helen V Worthington, Anne-Marie Glenny, Priscilla Appelbe, Valeria CC Marinho, Xin Shi. Pastas dentales con flúor de diferentes concentraciones para prevenir las caries dentales en niños y adolescentes (Revision Cochrane traducida). En: Biblioteca Cochrane Plus 2010 Número 1. Oxford: Update Software Ltd. Disponible en: http://www.bibliotecacochrane.com. (Traducida de The Cochrane Library, 2010 Issue 1 Art no. CD007868. Chichester, UK: John Wiley & Sons, Ltd.).

Resumen

Antecedentes

La caries dental es una enfermedad de los tejidos duros de los dientes causada por un desequilibrio, con el transcurso del tiempo, en las interacciones entre las bacterias cariogénicas de la placa dental y los carbohidratos fermentables (principalmente azúcares). El uso de pasta dental fluorada es la intervención primaria para la prevención de la caries.

Objetivos

Determinar la efectividad relativa de las pastas dentales fluoradas de diferentes concentraciones en la prevención de la caries dental en niños y adolescentes, y examinar los posibles efectos modificadores del nivel inicial de caries y el cepillado dental supervisado.

Estrategia de búsqueda

Se realizó una búsqueda en el Registro de Ensayos del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group), CENTRAL, MEDLINE y en otras bases de datos. También se hicieron búsquedas en las listas de referencias de artículos.
Fecha de las búsquedas más recientes: 8 de junio de 2009.

Criterios de selección

Ensayos controlados aleatorios y ensayos controlados aleatorios de diseño grupal que compararon pasta dental fluorada con placebo o con una pasta dental fluorada de diferente concentración, en niños de hasta 16 años de edad, con un período de seguimiento de al menos un año. El resultado primario fue el incremento de caries en la dentición permanente o temporal, medido por el cambio en las superficies dentales cariadas, (perdidas) u obturadas (C(P)OS) desde el inicio del ensayo.

Obtención y análisis de los datos

La inclusión de los estudios, la extracción de datos y la evaluación de la calidad fue realizada de forma independiente y por duplicado por dos miembros del equipo de revisión. Los desacuerdos se resolvieron mediante debate y consenso o con la participación de un tercero. La medida primaria del efecto fue la fracción de prevención (FP), que es el incremento de caries del grupo control menos el incremento de caries del grupo de tratamiento, expresado como porcentaje del incremento de caries del grupo control. Cuando fue apropiado agrupar los datos, se utilizaron modelos de metanálisis, metanálisis en red o metarregresión en red. Las fuentes potenciales de heterogeneidad se especificaron a priori y se examinaron mediante análisis de metarregresión de efectos aleatorios cuando fue apropiado.

Resultados principales

Se incluyeron 75 estudios, de los cuales 71 estudios que comprendían 79 ensayos proporcionaron datos para el metanálisis en red, la metarregresión en red o el metanálisis.

Según los 66 estudios (74 ensayos) que contribuyeron al metanálisis en red de C(P)OS en la dentición mixta o permanente, el efecto preventivo de caries de la pasta dental fluorada se incrementó de forma significativa con mayores concentraciones de flúor. La fracción de prevención de C(P)OS, en comparación con el placebo, fue del 23% (intervalo creíble [ICr] del 95%: 19% a 27%) para las concentraciones de 1000/1055/1100/1250 partes por millón (ppm) y alcanzó el 36% (ICr del 95%: 27% a 44%) para las pastas dentales con una concentración de 2400/2500/2800 ppm, pero las concentraciones de 440/500/550 ppm o menos no mostraron efectos estadísticamente significativos en comparación con el placebo. Hay algunas pruebas de una relación entre respuesta y dosis, ya que la FP aumentó cuando la concentración de flúor se incrementó desde el inicio del ensayo, aunque este aumento no siempre fue estadísticamente significativo. El efecto de la pasta dental fluorada también se incrementó con un nivel inicial de C(P)OS y cepillado supervisado, aunque no alcanzó la significación estadística. Seis estudios evaluaron los efectos de las concentraciones de flúor sobre la dentición temporal, con resultados equívocos según las concentraciones de flúor comparadas y la medida de resultado. Sólo unos pocos estudios evaluaron el cumplimiento del régimen de tratamiento y los efectos no deseados. En los casos que presentaron esta información, no se observaron diferencias en el cumplimiento y los efectos no deseados, tales como el daño de partes blandas y la pigmentación de los dientes, fueron mínimos.

Conclusiones de los autores

Esta revisión confirma los beneficios de la utilización de pasta dental fluorada para prevenir la caries en niños y adolescentes, cuando se comparó con placebo, pero estos beneficios sólo son significativos con las concentraciones de flúor de 1000 ppm y superiores. Los efectos relativos en la prevención de caries de las pastas dentales fluoradas de diferentes concentraciones se incrementan con una concentración mayor de flúor. La decisión sobre los niveles de flúor a utilizar para los niños menores de seis años debe tener en cuenta el riesgo de fluorosis.

Resumen en términos sencillos

Comparación entre pastas dentales fluoradas de diferentes concentraciones para prevenir la caries dental en niños y adolescentes

Muchos niños presentan caries dentales que causan dolor y pueden llevar a la extracción de uno o varios dientes. Aunque los dientes no se extraigan, la caries dental puede causar molestias, su tratamiento puede ser costoso y puede hacer que los niños y sus cuidadores tengan que restar tiempo a la escuela y el trabajo.

Otra revisión Cochrane demostró que las pastas dentales fluoradas reducen la caries dental, alrededor de un 24% en promedio, en comparación con una pasta dental no fluorada. Esta revisión compara pastas dentales con diferentes cantidades de flúor.

Esta revisión incluye 79 ensayos con un total de 73 000 niños. Tal como se espera, el uso de una pasta dental que contiene más flúor se asocia en general con menos caries. Las pastas dentales que contienen al menos 1000 partes por millón (ppm) de flúor son eficaces para prevenir la caries dental en los niños, lo que apoya el nivel estándar internacional recomendado en la actualidad.

Aunque ninguno de los ensayos incluidos en la revisión consideró la fluorosis o el moteado de los dientes de los niños, la fluorosis puede ser un resultado no deseado del uso de pasta dental fluorada en los niños pequeños y también se ha publicado una revisión Cochrane sobre este tema. El posible riesgo de fluorosis debe consultarse con el odontólogo, que puede recomendar el uso de una pasta dental que contenga menos de 1000 ppm de flúor.

Antecedentes

Descripción de la condición

Los dientes pierden y ganan minerales en un proceso continuo de des- y remineralización. La caries dental es una enfermedad de los tejidos duros de los dientes causada por un desequilibrio en este proceso, con el transcurso del tiempo, en las interacciones entre las bacterias cariogénicas de la placa dental y los carbohidratos fermentables (principalmente azúcares). Además del dolor que producen las lesiones cariosas en sí, también hay que considerar la tensión emocional a causa de la enfermedad y las posibles consecuencias de una intervención médica. Los dientes afectados no siempre pueden salvarse, en ocasiones deben extraerse. La extracción tiene consecuencias especiales en los niños pequeños, para quienes puede requerirse la anestesia general. Existe una repercusión social asociada con esta enfermedad que se refleja en la falta de asistencia a la escuela de los niños y al trabajo de sus cuidadores. Esta enfermedad también tiene implicaciones económicas importantes, ya que cada año un porcentaje significativo de los presupuestos de asistencia sanitaria se gasta en el tratamiento de la caries.

Aunque en algunas áreas del mundo desarrollado ha habido pruebas de una reducción de la prevalencia y la gravedad de la caries dental en los últimos años, existen desigualdades sociales en la salud dental y muchos individuos y comunidades tienen una carga clínicamente significativa de enfermedad dental prevenible. Si bien se ha tenido cierto éxito en la reducción de las caries en los adultos, sigue siendo un desafío la prevención de las caries en los niños pequeños, y la reducción de las desigualdades en esta población.

La conexión entre el flúor y la salud bucal se remonta a los años treinta. Casi 80 años después, el flúor continúa siendo una de las estrategias clave de la odontología para la prevención de la caries dental. En el VIII Congreso Internacional de Odontología Preventiva (Liverpool, 2005), los miembros de la International Association for Dental Research, la Organización Mundial de la Salud (OMS), la European Association of Dental Public Health y la British Association for the Study of Community Dentistry hicieron un llamado a la acción en la "Declaración de Liverpool" (IADR/WHO/BASCD 2005). En dicha declaración, se esbozaron nueve áreas de trabajo que deberían abordarse para el año 2020, una de ellas fue la necesidad de que los países garanticen la disponibilidad de programas de flúor asequible para la prevención de la caries dental. Ese tema se vio recientemente reforzado por los hallazgos de la Global Consultation on Oral Health through Fluoride (2006) que indica que la promoción de la salud dental mediante el uso de flúor "mejorará la calidad de vida y contribuirá al logro de los Objetivos de Desarrollo del Milenio al reducir la elevada carga de morbilidad dental de las poblaciones, especialmente los niños de poblaciones desfavorecidas" (FDI World Dental Federation 2006).

Descripción de la intervención

Existen muchos métodos de suministro de flúor, p.ej., el agua fluorada, la leche, la pasta dental, los geles, los barnices etc. Los efectos beneficiosos del flúor de uso tópico se han examinado en una serie de revisiones sistemáticas Cochrane de alta calidad (Marinho 2002; Marinho a 2002; Marinho 2003; Marinho a 2003; Marinho b 2003; Marinho 2004; Marinho a 2004). En particular, las pruebas sobre el uso de pastas dentales fluoradas son inequívocas (Marinho b 2003). Luego de resumir todas las pruebas disponibles provenientes de ensayos controlados aleatorios (ECA) que compararon pastas dentales fluoradas con placebo, la revisión concluyó que las mismas son eficaces para prevenir las caries en los niños y adolescentes, en comparación con las pastas dentales no fluoradas, y que el efecto de la pasta dental fluorada en la prevención de las caries aumenta según algunos factores, entre ellos, la mayor concentración de flúor. Sin embargo, no se evaluaron de manera explícita (directa) comparaciones de pastas dentales de diferentes concentraciones de flúor. Esta revisión se propone evaluar los efectos relativos para la prevención de las caries de pastas dentales de diferentes concentraciones de flúor, con miras al establecimiento de los beneficios de las diferentes concentraciones para los niños y adolescentes. Esta revisión se ha realizado conjuntamente con una revisión Cochrane que evalúa el efecto del flúor de uso tópico (incluido el de la pasta dental de diferentes concentraciones) sobre la fluorosis dental (Wong 2010). Para informarse de manera cabal sobre los posibles beneficios en la prevención de las caries de las pastas dentales fluoradas de diferentes concentraciones y los posibles riesgos de fluorosis que surgen del uso de pasta dental fluorada deben leerse ambas revisiones.

Por qué es importante realizar esta revisión

Los objetivos del WHO Global Oral Health Programme (programa mundial de salud bucodental de la OMS) se detallan en un informe de la OMS (Petersen 2003) y se resumen en un documento de política mundial (Petersen 2009) en el cual una de las áreas de acción prioritaria es el uso eficaz de flúor. La prevención y el uso eficaz de pasta dental fluorada es la estrategia recomendada para la salud oral de niños y adolescentes en un reciente artículo editorial de Lancet (Lancet 2009), aunque se reconoce que su costo impide el uso generalizado en muchos países de ingresos bajos y medios. Es importante que las recomendaciones en cuanto al uso de la pasta dental fluorada se basen en la evidencia. El documento recientemente publicado "'Delivering Better Oral Health: An Evidence-Based Toolkit" (Suministrar una mejor salud oral: Conjunto de herramientas basadas en la evidencia) del Departamento de Salud del Reino Unido (DoH 2007) , sobre la concentración de flúor en la pasta dental, cita pruebas de la revisión sistemática Cochrane (Marinho b 2003), un único ECA (Davies 2002) y tres revisiones publicadas de pastas dentales fluoradas para la prevención de caries en niños y adolescentes (Ammari 2003; Steiner 2004; Twetman 2003). Este documento recomienda que para prevenir las caries en los niños de hasta tres años se utilice "sólo una pizca de pasta dental que contenga no menos de 1000 ppm de flúor", y para todos los niños de tres a seis años "una cantidad del tamaño de un guisante de pasta dental que contenga 1350–1500 ppm de flúor". Para los niños mayores de seis años, se recomienda la pasta dental fluorada de 1350 ppm o más. La tabla de referencias claves citadas en el mencionado documento proporciona "referencias relevantes adicionales" relativas a la concentración de flúor:

  • "Las pastas dentales que contienen 1450 ppm de flúor poseen un efecto preventivo de caries mayor que las pastas dentales que contienen 440 ppm de flúor" y

  • "Las pastas dentales que contienen 1450 ppm de flúor poseen un efecto preventivo de caries mayor que las pastas dentales que contienen 1000 ppm de flúor".

Pueden encontrarse pruebas que apoyan la primera recomendación en la revisión sistemática Cochrane de ensayos controlados con placebo (Marinho b 2003) y en un único ECA a largo plazo realizado en áreas carenciadas del norte de Inglaterra (Davies 2002). Si bien la revisión sistemática Cochrane llegó a la conclusión de que el efecto de la pasta dental fluorada en la prevención de las caries aumentó según la mayor concentración de flúor, entre otros factores, esta cuestión no se evaluó explícitamente y no se proporcionó un nivel óptimo de concentración de flúor para la prevención de caries.

Pueden encontrarse pruebas que apoyan la segunda recomendación en los metanálisis de las revisiones realizadas en 2003 y 2004 (Ammari 2003; Steiner 2004; Twetman 2003). Las revisiones difieren en sus métodos, aunque ninguna de ellas se realizó como revisión sistemática Cochrane. No todas las revisiones incluyeron una evaluación de la calidad de los ensayos y algunos de los estudios incluidos son de diseño aleatorio grupal, sin indicios de que este hecho se haya tenido en cuenta en el análisis. Muchos detalles importantes del proceso de investigación de una revisión no fueron notificados en estas publicaciones. Por ejemplo, no está claro si se redactó un protocolo antes de realizar la revisión, y los criterios de búsqueda no están del todo documentados. Además, se omitió información importante sobre los métodos de análisis de la efectividad concentración-respuesta o, en ocasiones, se presentó de forma narrativa. Las comparaciones realizadas en las revisiones son:

  • 250 ppm en relación con 1000 ppm (n = 4 ensayos) (Steiner 2004);

  • 250 ppm en relación con 1000 ppm (n = 6 ensayos) y 500-550 ppm en relación con 1000-1055 ppm (n = 2 ensayos, sólo descripción narrativa) (Ammari 2003);

  • pasta dental fluorada en comparación con placebo, <1000 ppm en relación con 1000-1100 ppm (n = 4 ensayos), 1500 ppm en relación con 1000-1100 ppm (n = 9 ensayos) (Twetman 2003).

Otro metanálisis publicado examinó el efecto preventivo de caries de las pastas dentales con niveles más altos de flúor de 1700 ppm, 2200 ppm, 2800 ppm en comparación con 1100 ppm (Bartizek 2001). Este metanálisis se basó en un único ensayo controlado aleatorio multicéntrico. No se ha realizado ninguna revisión sistemática Cochrane que incluya ensayos de intervenciones activas, es decir, pastas dentales fluoradas de diferentes concentraciones, y ensayos controlados con placebo.

Las guías revisadas recientemente (EAPD 2009) de la European Academy of Paediatric Dentistry sobre el uso de flúor en los niños hacen recomendaciones acerca de la concentración de flúor, la frecuencia del cepillado dental y la cantidad diaria de pasta dental que debe utilizarse, para niños de seis meses a seis años y más. Si bien se han recomendado concentraciones de flúor para los diferentes grupos etarios, sobre la base de revisiones anteriores (Steiner 2004; Twetman 2003) los autores de las guías afirman que "puede indicarse una pasta dental para niños con una baja concentración de flúor, aunque las pruebas de un efecto preventivo anticaries de las fórmulas con menos de 500 ppm de flúor son insuficientes". Además, al considerar el posible beneficio preventivo de caries de la pasta dental fluorada en relación con los riesgos potenciales de fluorosis antes de los seis años de edad, los autores declaran que "debe tenerse cuidado para asegurar que se mantenga un equilibrio entre maximizar el efecto protector contra la caries dental y disminuir el riesgo de fluorosis dental".

Una revisión sistemática que analiza todas las pruebas disponibles sobre la concentración de flúor en las pastas dentales, mediante metodologías estadísticas apropiadas, identificará los efectos relativos de las pastas dentales de diferentes concentraciones de flúor en la prevención de las caries en niños y adolescentes. Los efectos sobre la dentición temporal y mixta/permanente se evaluarán por separado.

Los enfoques tradicionales de metanálisis se han centrado en las comparaciones por pares directas dentro de los ECA. Sin embargo, cuando existen muchas intervenciones diferentes, el número de comparaciones por pares se torna prohibitivo y la interpretación difícil. Por ejemplo, cuando hay seis intervenciones para comparar, las mismas darán lugar a 15 combinaciones por pares distintas. La combinación de los niveles de flúor similares puede ser una solución, pero conlleva el riesgo de oscurecer diferencias sutiles en el efecto relacionadas con la concentración. Pueden hacerse comparaciones indirectas corregidas entre los ensayos con un comparador común. A su vez, con los avances en las metodologías estadísticas, es posible combinar pruebas tanto directas como indirectas de ECA mediante lo que el Manual Cochrane para las revisiones sistemáticas de intervenciones denomina metanálisis de tratamientos múltiples (Higgins 2008). Esta metodología a veces se menciona en la bibliografía como metanálisis en red o comparaciones de tratamientos mixtos (MTC, por sus siglas en inglés). Dicha técnica se refiere a un metanálisis de múltiples intervenciones y puede incluir comparaciones de tratamientos tanto directas como indirectas. Se ha utilizado para evaluar muchas intervenciones diferentes que incluyen, por ejemplo, el autocontrol de la diabetes (Jansen 2006) y los tratamientos de prevención de accidentes cerebrovasculares (Cooper 2006), y es apropiado para las medidas de resultado binarias y continuas. Por consiguiente, la investigación incorporará un componente estadístico y metodológico significativo e impulsará el conocimiento en esta área. Una revisión sistemática que aborda todas las pruebas disponibles sobre la concentración de flúor en las pastas dentales ayudará a identificar los efectos relativos de las pastas dentales de diferentes concentraciones de flúor en la prevención de las caries. Este hecho es importante, ya que el flúor se ha identificado como un factor causal de la fluorosis antiestética del esmalte en niños.

También se evaluarán otros factores que pueden modificar la influencia de la concentración de flúor en la prevención de las caries, sobre la base de bibliografía publicada anteriormente. El nivel inicial de caries y si el cepillado dental es supervisado o no se han identificado como posibles modificadores del efecto en una revisión anterior (Marinho b 2003). El cumplimiento de la intervención también podría proponerse como factor que influye sobre los efectos del tratamiento. Los posibles efectos diferenciales sobre la dentición temporal y mixta o permanente se evaluarán mediante la realización de análisis separados.

El objetivo primario de esta revisión es proporcionar un resumen claro y consistente de las pruebas de investigación sobre los efectos relativos en la prevención de las caries de las pastas dentales fluoradas de diferentes concentraciones para la salud dental en niños y adolescentes.

Objetivos

Determinar la efectividad relativa del placebo y las pastas dentales fluoradas de diferentes concentraciones en la prevención de las caries dentales en niños y adolescentes, y examinar los posibles efectos modificadores del nivel inicial de caries y el cepillado dental supervisado.

Métodos

Criterios para la valoración de los estudios para esta revisión

Tipos de estudios

Ensayos controlados aleatorios (ECA) y ensayos aleatorios por grupos que compararon pasta dental fluorada con placebo o pasta dental fluorada de diferente concentración, con un período de seguimiento de al menos un año. Los estudios que no tuvieron asignación aleatoria o la misma no se indicó fueron excluidos, al igual que los estudios de boca dividida.

Tipos de participantes

Niños y adolescentes Se incluyeron los estudios en los cuales la mayoría de los participantes tenían 16 años o menos al comienzo del estudio (independientemente del nivel inicial de caries dentales, la exposición frecuente al flúor, el nivel de tratamiento odontológico, la nacionalidad, el ámbito en el que se recibió la intervención o cuándo se inició la misma). Se excluyeron los estudios en los cuales se seleccionaron los participantes sobre la base de condiciones especiales de salud (general u oral).

Tipos de intervenciones

Estudios que hicieron una comparación entre al menos dos pastas dentales fluoradas de diferentes concentraciones, o pasta dental fluorada y pasta dental de placebo. Agentes fluorados combinados o no en las siguiente formulaciones:

  • Fluoruro de sodio (NaF)

  • Monofluorofosfato de sodio (SMFP)

  • Fluoruro estañoso (SnF2)

  • Fluoruro fosfórico acidulado (APF)

  • Fluoruro de amina (AmF).

Estos agentes pueden estar preparados con cualquier sistema abrasivo compatible y se consideran en cualquier concentración de flúor (partes por millón [ppm]), frecuencia de uso, cantidad o duración de la aplicación y con cualquier técnica de cepillado o procedimiento posterior al cepillado. Se excluyeron los estudios en los cuales el grupo de intervención o tanto el grupo de intervención como el de control recibieron otro/s agente/s activo/s o medida/s para prevenir las caries (p.ej., clorhexidina, otros procedimientos con flúor, procedimientos de higiene oral, selladores, gomas de mascar con xilitol, ionómeros vítreos) además de la pasta dental fluorada o de placebo. Se excluyeron los estudios que incluyeron participantes que recibían medidas adicionales como parte de su cuidado bucal habitual, tales como asesoramiento de higiene oral, cepillado supervisado, selladores de fisuras, etc.

Se reconoció con antelación que las comparaciones de pastas dentales fluoradas de ciertas concentraciones podían ser escasas, y se realizaron comparaciones directas e indirectas cuando fue adecuado (Figura 1).

Tipos de medida de resultado

Resultados primarios

La medida de resultado primaria es el incremento de caries según las siguientes mediciones:

  • cambio desde el inicio del ensayo en el índice de superficies cariadas, (perdidas) y obturadas (C(P)OS), en todos los dientes permanentes erupcionados al comienzo y durante el curso del estudio (la caries dental se define aquí como diagnóstico clínica y radiológicamente registrado a nivel de la dentina);

  • cambio desde el inicio del ensayo en el índice de superficies cariadas, (perdidas/extracción indicada) y obturadas, en superficies de diente temporales;

  • cambio en el porcentaje que presentó nuevas caries.

Resultados secundarios

Los resultados secundarios son los efectos secundarios como la irritación, pigmentación/decoloración dental, etc.

Métodos de búsqueda para la identificación de los estudios

Las búsquedas intentaron identificar todos los estudios pertinentes, sin distinción de idioma, hasta junio de 2009. Se intentó traducir todos los documentos no publicados en inglés. No hubo restricciones con respecto al estado de la publicación y se buscaron tanto estudios publicados como no publicados.

Búsquedas electrónicas

Se hicieron búsquedas en las siguientes bases de datos:

  • Registro de Ensayos del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group) (8 junio 2009)

  • Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL) (The Cochrane Library 2009, número 2)

  • MEDLINE (OVID) (desde 1950 hasta 8 junio 2009)

  • EMBASE (OVID) (desde 1980 hasta el 8 junio 2009).

Se desarrollaron estrategias de búsqueda sensibles mediante una combinación de texto libre y vocabulario controlado. La estrategia para MEDLINE (OVID) se presenta en el Apéndice 1. Esta búsqueda se realizó mediante la Estrategia de Búsqueda Cochrane de Alta Sensibilidad (Cochrane Highly Sensitive Search Strategy [CHSSS]) para identificar ensayos aleatorios en MEDLINE: es una versión de alta sensibilidad (revisión 2008) como se menciona en el capítulo 6.4.11.1 y se detalla en el recuadro 6.4.c del Cochrane Handbook for Systematic Reviews of Interventions 5.0.1 (actualizado en septiembre de 2008) (Higgins 2008).

Búsqueda de otros recursos

Búsqueda de referencias

También se examinaron las revisiones sistemáticas de pastas dentales fluoradas publicadas anteriormente para identificar cualquier informe que cumpliera con los criterios de inclusión (Ammari 2003; Bartizek 2001; Clarkson 1993; Steiner 2004; Twetman 2003). La revisión sistemática Cochrane de pasta dental fluorada (Marinho b 2003)ha sido recientemente actualiza y los ensayos pertinentes localizados a través de la actualización fueron incorporados en esta revisión.

Búsqueda de ensayos en curso

Se hicieron búsquedas en las bases de datos de ensayos ClinicalTrials.gov (www.clinicaltrials.gov) , y en el metaRegister of Controlled Trials (www.controlled-trials.com) para identificar cualquier ensayo relevante en curso.

Obtención y análisis de los datos

Identificación de estudios

El conjunto de registros descargado de cada base de datos se importó al software bibliográfico EndNote. Los registros duplicados fueron identificados y eliminados. Dos revisores, de forma independiente, examinaron todos los registros para establecer su pertinencia sobre la base del título y el resumen (cuando estaba disponible). Los registros que no eran pertinentes se descartaron y se obtuvo el texto completo de los restantes para una evaluación adicional. La pertinencia se evaluó de acuerdo con las características de los participantes, la naturaleza de la intervención, la comparación y el resultado tal como se declaró en el título de la revisión.

Selección de los estudios

Luego de la revisión inicial, se obtuvo el informe completo de los estudios que parecían reunir los criterios de inclusión, o de los cuales no había datos suficientes en el título y el resumen para tomar una decisión clara. Estos informes fueron evaluados de forma independiente y por duplicado por dos revisores para establecer si los estudios reunían los criterios de inclusión. Los desacuerdos se resolvieron mediante discusión. Los estudios escritos en idiomas no conocidos por el equipo de revisión fueron traducidos por los miembros del Grupo Cochrane de Salud Oral e incluidos/excluidos según el caso. Los estudios en espera de traducción se presentan en la sección de la revisión de estudios en espera de clasificación.

En este estadio o en estadios posteriores, se registraron los estudios rechazados en la sección Características de los estudios excluidosjunto con la razón de la exclusión.

Extracción y manejo de los datos

La extracción de datos de todos los estudios que cumplieron los criterios de inclusión fue realizada, de forma independiente y por duplicado, por cuatro revisores (Helen Worthington [HW], Priscilla Appelbe [PA], Valeria Marinho [VM] y Tanya Walsh [TW]) mediante un formulario de extracción de datos previamente probado. Se extrajo la información sobre el diseño del estudio, los participantes, la intervención y el comparador y los resultados, específicamente:

  • Información del artículo: autor, revista, año de publicación

  • Información del estudio: ubicación, duración de la obtención de datos (meses), fecha de la obtención inicial[1], fechas de la obtención de datos, número de centros, ámbito en el cual se reclutaron los participantes (p.ej., escuela), otras fuentes de exposición al flúor[2], duración de la intervención, asignación al azar individual o grupal

  • Información del participante: edad al inicio del ensayo, número inicial, caries al inicio del ensayo[3], media de superficies/dientes cariados, perdidos y obturados (desviación estándar [DE]/error estándar [EE]) para la dentición temporal, permanente o ambas

  • Intervención: concentración y formulación de flúor, sistema abrasivo, frecuencia del cepillado, cepillado supervisado, duración de la intervención

  • Evaluación: dientes incluidos, criterios para el diagnóstico clínico, cálculo del cambio/incremento de caries, umbral de diagnóstico, incremento neto o bruto de caries

  • Información del resultado: caries finales y número, porcentaje de niños que presentaron nuevas caries, incremento medio de CPOS (DE/EE), incremento medio de CPOD (DE/EE), nivel de cumplimiento

  • Confiabilidad de la medida de resultado primaria: número de examinadores y detalles de calibración, método de evaluación clínica

  • Efectos secundarios: p.ej., daño de partes blandas, pigmentación dental, irritación.

[1]Cuando no se tenían datos del año de inicio del estudio, se calculó una "fecha probable" restando la duración del estudio (en años) más un año extra, desde la fecha de publicación del estudio.

[2]Los datos sobre la exposición frecuente a otras fuentes de flúor englobaron los datos sobre el uso (fuera del ensayo) de flúor tópico/enjuagues fluorados e incluso pastas dentales fluoradas (en los estudios en los cuales la intervención se evaluó bajo supervisión en la escuela y no se había entregado pasta dental para uso domiciliario), y el consumo de agua/sal/comprimidos fluorados. Se recomienda que el uso frecuente de otras fuentes de flúor (enjuagues, geles, comprimidos, etc.) se informe claramente como utilizado por la mayoría de los participantes del estudio para ser considerado como tal, y la exposición al agua/sal fluoradas sea superior a 0,3 ppm de flúor.

[3]De la muestra de estudio analizada (muestra final) y en relación con el incremento de caries según el índice elegido.

Se reconoce que el incremento de caries podría informarse de modo diferente en los distintos ensayos. A fin de contemplar este factor, la elección del resultado primario seguirá la jerarquía presentada en la revisión sistemática Cochrane de ensayos controlados con placebo (Marinho b 2003):

  • se preferirán los datos a nivel de la superficie a los datos a nivel de los dientes

  • se preferirán los datos de COS a los datos de CPOS y éstos a los de CS o de OS

  • se preferirán los datos de "todos los tipos de superficies combinados" a los datos de "tipos específicos" solamente;

  • se preferirán los datos sobre "todos los dientes erupcionados o en erupción combinados" a los datos sobre "dientes erupcionados" solamente y éstos a los datos sobre "dientes en erupción" solamente;

  • se preferirán los datos sobre "exámenes clínicos y radiológicos combinados" a los datos "clínicos" solamente y éstos a los "radiológicos" únicamente;

  • se preferirán los datos sobre las lesiones cariosas en la dentina/cavidades a los datos sobre las lesiones en el esmalte/sin cavidades

  • se preferirán los datos sobre el incremento neto de caries a los datos sobre el incremento bruto (observado)

  • se preferirá el seguimiento más cercano a los tres años (a menudo el del fin del período de estudio) a cualquier otro período de seguimiento, a menos que se especifique lo contrario.

Evaluación del riesgo de sesgo en los estudios incluidos

Se evaluó el riesgo de sesgo de todos los ensayos incluidos en la revisión, de forma independiente y por duplicado, como parte del proceso de extracción de datos, con referencia al Manual Cochrane para las revisiones sistemáticas de intervenciones 5.0.1 (Higgins 2008). A tal fin se utilizó un formulario especialmente diseñado y probado. Los ensayos incluidos se evaluaron según los siguientes criterios:

  • Generación de secuencia adecuada:Sí, No, Incierto

  • Ocultación de la asignación: Sí, No, Incierto

  • Cegamiento: Sí, No, Incierto

  • Datos de resultado incompletos: Sí, No, Incierto

  • Libre de informe selectivo de los resultados (p.ej., ¿CPOD o CPOS o ambos informados?): Sí, no, Incierto

  • Libre de desequilibrio inicial: Sí, No, Incierto

  • Libre de contaminación/cointervención: Sí, No, Incierto.

"Sí" indica bajo riesgo de sesgo, "No" indica alto riesgo de sesgo e "Incierto" indica la ausencia de información o la incertidumbre sobre la posibilidad de sesgo. Se completó una tabla del riesgo de sesgo para cada estudio incluido (ver Riesgo de sesgo en los estudios incluidos y Características de los estudios incluidos). Los resultados se presentan gráficamente por estudio (Figura 2) y por dominio sobre todos los estudios (Figura 3).

Medidas del efecto del tratamiento

La fracción de prevención (FP) fue la estimación primaria del efecto. La FP se expresa como el incremento medio en el grupo control menos el incremento medio en el grupo de intervención dividido por el incremento medio en el grupo control, es decir, el incremento de caries en el grupo de tratamiento expresado como un porcentaje del grupo control. La FP se considera más apropiada que la diferencia de medias absoluta o la diferencia de medias estandarizada, ya que permite la combinación de los diferentes modos de medir el incremento de caries empleados entre los estudios y es sencilla de interpretar. Las varianzas y los intervalos de confianza se calcularon mediante el programa Stata escrito por el usuario fielleri.ado (versión 1.0 2004-12-07, Joseph Coveney), según la fórmula de Fieller (Abrams 1972). La FP se calculó tanto a nivel de las superficies como de los dientes y las denticiones temporaria y permanente se analizaron completas.

Para un carácter integral y para comparar los resultados con las publicaciones anteriores, los valores brutos (media, desviación estándar [DE], n) se presentan junto con la diferencia de medias estandarizada (DME) (d de Cohen).

En cuanto al porcentaje de niños que presentó nuevas caries, los datos se analizaron mediante los cocientes de riesgos (CR). Se usó Review Manager (RevMan) 5 para la estimación de los efectos del tratamiento, mediante un modelo de efectos fijos para la estimación agrupada.

Manejo de los datos faltantes

En el caso de los principales datos de resultado, las desviaciones estándar faltantes para los incrementos de caries, que no pudieron obtenerse a través del contacto con los investigadores originales, se imputaron mediante la regresión lineal logarítmica (desviaciones estándar) sobre los incrementos logarítmicos (media de caries) de acuerdo con la revisión sistemática Cochrane de ensayos controlados con placebo (Marinho b 2003).

Síntesis de los datos

Se realizó una representación gráfica de la taxonomía de las intervenciones para determinar la naturaleza de la red. Las estimaciones de los efectos del tratamiento (FP y DME) se calcularon a través del paquete de software Stata. El metanálisis en red y la metarregresión se realizaron con el paquete WinBugs mediante un modelo de efectos aleatorios para el metanálisis de tratamientos múltiples para los datos de la fracción de prevención y la diferencia de medias estandarizada, teniendo en cuenta la correlación entre los ensayos con brazos múltiples cuando resultó apropiado. Lo anterior se realizó tanto a nivel de las superficies como de los dientes y las denticiones temporaria y permanente se analizaron completas por separado. Las estimaciones de la FP del efecto se calcularon y se introdujeron en el paquete WinBugs, mediante el enfoque de contraste para los datos a nivel del ensayo para estimar los efectos directos e indirectos. El método de metanálisis en red permite la comparación de los efectos indirectos, comparaciones de tratamientos no abordadas dentro de los ensayos primarios. Tal análisis en red sólo puede aplicarse a redes conectadas de ensayos (ver Figura 4; Figura 5). El metanálisis en red de efectos aleatorios en el cual se basó este análisis puede descargarse de www.bris.ac.uk/cobm/research/mpes/mixed-treatment-comparisons.html.

La adecuación de los modelos se evaluó mediante el cálculo de la desviación residual. Ésta se define como la diferencia entre la desviación del modelo ajustado y la diferencia entre el modelo saturado, donde la desviación mide el ajuste del modelo a los puntos de datos mediante la función de probabilidad. Bajo la hipótesis nula de que el modelo proporciona un ajuste adecuado a los datos, la desviación residual media equivaldrá aproximadamente al número de puntos de datos libres en el análisis.

En el caso del porcentaje de participantes que presentó nuevas caries, los datos se analizaron mediante el cálculo de los cocientes de riesgos. Se usó RevMan para la estimación de los efectos globales del tratamiento mediante un modelo de efectos fijos para la estimación agrupada. Se tomó nota de los estudios que informaban sobre el cumplimiento del régimen de tratamiento o cualquier efecto secundario del uso de la pasta dental.

Análisis de subgrupos e investigación de la heterogeneidad

La heterogeneidad se evaluó mediante la inspección de los diagramas de bosque de las estimaciones y los intervalos de confianza de los efectos del tratamiento.

Dos fuentes potenciales de heterogeneidad se especificaron a priori: el nivel inicial de caries y el cepillado dental (supervisado o no) y fueron un aspecto importante de la revisión. Con este fin, se propuso una metarregresión en red de efectos aleatorios cuando hubo ensayos suficientes para realizarla. Los datos del "nivel inicial de caries" se calcularon a partir de la muestra de estudio analizada y en conformidad con el índice de incremento de caries elegido.

Resultados

Descripción de los estudios

Ver: Características de los estudios incluidos; Características de los estudios excluidos.

Resultados de la búsqueda

Luego de la eliminación de los duplicados, se recuperaron 1563 registros de la búsqueda de bases de datos electrónicas. Después de aplicar el filtro Cochrane de ECA y eliminar los duplicados, este número se redujo a 535.

La búsqueda de ensayos en curso aportó informes adicionales, al igual que la búsqueda de fuentes no electrónicas.

Después de una primera revisión, 129 registros se consideraron potencialmente elegibles y se obtuvieron para una evaluación detallada adicional. Esta evaluación dio lugar a 75 estudios incluidos, 51 estudios excluidos y tres informes en espera de evaluación (ya sea en espera de traducción o con información insuficiente luego de su traducción como para realizar una evaluación de inclusión/exclusión).

Estudios incluidos

Ver Características de los estudios incluidospara los detalles de los estudios incluidos.

Hay 75 estudios incluidos en la revisión, de los cuales 35 tienen más de una publicación. Los siguientes estudios se han considerado como fuentes independientes porque contienen más de un ensayo, ya sea con grupos etarios diferentes (Marthaler 1965; Marthaler 1970; Zacherl 1970) o informe de los resultados por separado para diferentes locaciones (Forsman 1974; Held 1968) o ambos (Torell 1965). También hay estudios distintos publicados en el mismo año por el mismo autor (Slack 1967; Slack 1967a; Zacherl 1972; Zacherl 1972a). Este hecho dio lugar a 83 ensayos independientes.

Todos los informes se publicaron entre los años 1955 y 2008.

Los ensayos se realizaron principalmente en los Estados Unidos y en el Reino Unido, pero también en las siguientes localizaciones: Francia, Lituania, Alemania, Italia, Australia, Suecia, Suiza, Islandia, Dinamarca, China, Puerto Rico, Brasil y Canadá.

Diseño y métodos

La revisión incluye tanto ensayos controlados con placebo como ensayos que comparan una intervención activa con al menos una intervención activa alternativa. La revisión incluye ensayos con dos, tres, cuatro y cinco brazos.

La duración mínima del estudio para la inclusión en la revisión fue de 12 meses y el período de seguimiento más prolongado que se informó fue de siete años. El análisis se realizó sobre los resultados más cercanos a los tres años de seguimiento.

Un ensayo fue asignado al azar por grupos. (Sonju Clasen 1995) aunque se informó como un ensayo aleatorio individual.

Participantes

La edad mínima de los participantes de los estudios de los efectos sobre la dentición temporal fue de 12 meses; la edad mínima para los estudios de los efectos sobre la dentición mixta y permanente fue de cinco años. Los datos sobre el nivel inicial de caries en la dentición mixta y permanente se informaron en todos excepto cinco ensayos de (C(P)OS) y nueve ensayos de (C(P)OD) y el mismo varió de 1,4 a 23,5 CPOS. En los ensayos que incluyeron participantes con dientes temporales, el valor inicial máximo informado de COS fue de 3,6 COS.

Intervenciones

La revisión incluyó 58 estudios controlados con placebo y 17 estudios que hicieron una comparación entre intervenciones activas. A los fines del análisis, la concentración de flúor (F) se agrupó en las siguientes categorías y estos números se utilizan para designar las comparaciones específicas en las Tablas adicionales:

1. Placebo 0 ppm F
2. 250 ppm F
3. 440/500/550 ppm F
4. 1000/1055/1100/1250 ppm F
5. 1450/1500 ppm F
6. 1700/2000/2200 ppm F
7. 2400/2500/2800 ppm F.

Las intervenciones en la mayoría de los ensayos especificaron el cepillado no supervisado.

Medidas de resultado

La medida de resultado primaria fue el incremento de caries medido a nivel de la superficie, el cual fue incluido en todos los estudios. También se midió el incremento de caries a nivel del diente, el porcentaje libre de caries y el porcentaje que presentó nuevas caries. La mayoría de los estudios presentó resultados para la dentición permanente; sólo cinco ensayos informaron sobre los niveles de caries en la dentición temporal; dos ensayos que informaban sobre C(P)OS y C(P)OD, un estudio que informaba sólo sobre C(P)OD, un estudio que informaba sólo sobre COS y un estudio que informaba la progresión y control de las caries. Un ensayo que informó los efectos sobre la dentición permanente también evaluó los efectos sobre la dentición temporal. Los efectos adversos de la intervención no fueron notificados en la mayoría de los estudios, pero cuando se informaron incluyeron daño bucal (de partes blandas) y pigmentación de los dientes. Ningún ensayo informó sobre la fluorosis.

Estudios excluidos

Las razones de la exclusión de los ensayos de la revisión se presentan en la tabla Características de los estudios excluidos . Los 51 ensayos fueron excluidos por las siguientes razones: Asignación no aleatoria o sistemática, asignación al azar no declarada o indicada, asignación al azar inadecuada (asignación al azar de dos grupos, uno a cada uno de los grupos de comparación), otros agentes activos u otras intervenciones con flúor además de la pasta dental fluorada, o ensayos en los cuales los participantes eran niños o adolescentes institucionalizados con problemas de salud específicos. Un ensayo podía ser excluido por más de una razón.

Riesgo de sesgo en los estudios incluidos

Generación de secuencia adecuada

Se observó una generación de secuencias adecuada en 28 ensayos (34%), que informaron con claridad el método de asignación al azar. Los ensayos restantes recibieron la clasificación de "incierto" porque el informe carecía de descripción, con afirmaciones tales como "se asignaron al azar" o "se estratificaron" como las más frecuentes.

Asignación

Se observó una ocultación de la asignación adecuada en ocho ensayos (10%). Los restantes no indicaron si la generación de la secuencia de asignación al azar se ocultó a los individuos involucrados en la inclusión y asignación de los participantes.

Cegamiento

En 76 ensayos (92%), tanto los participantes como los examinadores clínicos estaban cegados a la intervención asignada. Existió alto riesgo de sesgo en este dominio solamente en un ensayo (1%), en el cual el placebo y las pastas dentales fluoradas tenían envases diferentes y en consecuencia, el cegamiento de los participantes no se logró.

Datos incompletos sobre los resultados de interés

En cuatro ensayos (5%), las tasas de desgaste fueron excesivamente altas dada la duración de seguimiento, p.ej., más del 50% en tres años, más del 40% en dos años, más del 30% en un año, lo que dio como resultado una calificación de alto riesgo de sesgo. En 68 ensayos (81%), no hubo información suficiente para establecer una calificación de alto o bajo riesgo de sesgo. Las razones principales para las calificaciones de "incierto" en este dominio fueron que no se presentó esta información o sí se presentó la información pero las pérdidas diferenciales no pudieron ser evaluadas. Los ensayos restantes presentaron información completa sobre las tasas de desgaste, por grupos, con los motivos del desgaste.

Descripción selectiva de los resultados de interés

Un total de 73 ensayos (88%) estuvieron libres de informe selectivo, dado que todos los índices preestablecidos para el resultado de caries fueron informados según las diferentes unidades medidas, los métodos de examen, los umbrales de diagnóstico para la caries y los enfoques para reversiones. En tanto que diez ensayos (12%) proporcionaron información insuficiente para establecer un juicio de alto o bajo riesgo de sesgo.

Otras fuentes potenciales de sesgo

Características iniciales

Se informaron las características iniciales, las cuales eran equivalentes entre los grupos en 71 ensayos (86%), con un alto riesgo de sesgo a raíz de un desequilibrio inicial de los niveles de caries en los diferentes grupos de flúor en cuatro (5%) ensayos. La semejanza inicial se logró mediante la estratificación según las variables pronósticas importantes. Ocho ensayos (9%) recibieron la calificación "incierto" cuando no informaron las características iniciales o no las informaron por grupo.

Libre de contaminación o cointervención

Se consideró que un estudio presentaba alto riesgo de sesgo de contaminación si los participantes del ensayo recibieron un programa de enjuague de flúor concomitante. Un total de 59 ensayos (71%) se consideraron libres de la posibilidad de cualquier aplicación inadvertida de la intervención evaluada a los pacientes del grupo control (contaminación) o cualquier tratamiento adicional administrado a uno de los grupos de forma diferencial (cointervención) y, en consecuencia, se calificaron como con bajo riesgo de sesgo. En 23 ensayos (28%), no había información suficiente para emitir un juicio.

Efectos de las intervenciones

Efecto de la pasta dental fluorada en el incremento de la caries dental

De acuerdo con los objetivos de la revisión, y de conformidad con la información suministrada en la sección de los métodos, los siguientes resultados se presentan por separado:

(1) Fracción de prevención de Superficies Cariadas, (Perdidas) y Obturadas (FP C(P)OS)

(2) Fracción de prevención de Dientes Cariados, (Perdidos) y Obturados (FP C(P)OD)

(3) C(P)OS y C(P)OD agrupados con el uso de una diferencia de medias estandarizada (DME).

(4) Fracción de prevención de Superficies/Dientes Cariados, (Perdidos) y Obturados (FP C(P)OD y FP C(P)OD). Estimaciones de los efectos sobre el incremento de caries en la dentición temporal

(5) Porcentaje que presentó nuevas caries en la dentición permanente o temporal

(6) Cumplimiento del cepillado dental y efectos secundarios de la pasta dental.

Cuatro estudios no informaron los datos necesarios para la inclusión en el análisis pero se mantienen en la revisión. Los datos del incremento de caries no fueron informados o no fue posible obtenerlos (Powell 1981 placebo versus 1000 ppm; Slack 1964placebo versus 1000 ppm), la concentración de flúor no se declaró (Kinkel 1972los estudios declararon sólo flúor versus placebo), o una combinación de ambos (Homan 1969pasta dental fluorada [tres grupos de SnF2y APF] versus placebo).

Las desviaciones estándar faltaban o no era posible obtenerlas y, por lo tanto, se imputaron para los siguiente estudios: Abrams 1980; Fogels 1979; Forsman 1974; Forsman 1974a; Held 1968; Held 1968a; Held 1968b; James 1977; Muhler 1955; Piccione 1979.

A partir de los datos disponibles de los ensayos que informaron las desviaciones estándar de los incrementos de caries, se derivó una ecuación de regresión para calcular las desviaciones estándar faltantes para los índices de incremento de caries C(P)OS y C(P)OD. Las ecuaciones fueron:

C(P)OS log(DE incremento de caries) = 0,7574 + 0,491 * log(incremento de caries medio)

C(P)OD log(DE incremento de caries) = 0,5264 + 0,3811 * log(incremento de caries medio).

(1) Efecto en las superficies dentales: FP C(P)OS

Las estimaciones del efecto y el error estándar para la/s diferencia/s por pares con respecto a la concentración de flúor se calcularon en Stata. El análisis agrupado incluyó 85 comparaciones por pares provenientes de 74 ensayos que aportaron datos sobre C(P)OS. A los fines del análisis, hubo 65 comparaciones de dos concentraciones de flúor, siete comparaciones de tres concentraciones de flúor y dos comparaciones de cuatro concentraciones de flúor. Las intervenciones se muestran como un diagrama de metanálisis en red Figura 4, donde las diferentes intervenciones están representadas como nodos en la red y las conexiones entre ellos representan las comparaciones de tratamientos por pares. Los ensayos formaron una red conectada. Hubo 67 ensayos controlados con placebo, dos ensayos con 250 ppm como valor inicial, dos ensayos con 440/500/550 ppm como valor inicial y 14 ensayos con 1000/1055/1100/1250 ppm como valor inicial. El modelo indicó un buen ajuste, con una desviación de resumen mediana de 80,00 (intervalo creíble del 95% [ICr]: 58,36 a 106,70). La tau fue de 68,52 (ICr del 95%: 46,15 a 100,30).

La FP C(P)OS y el IC del 95% para cada comparación directa, se encuentran disponibles en el Análisis 1.1Incremento de C(P)OS (fracción de prevención) de la sección Datos y análisis . La Tabla 1Adicional contiene los resultados tanto de la comparación directa como del metanálisis en red. Estos resultados se ilustran gráficamente por medio de una tabla de clasificación ( Figura 6) para todas las comparaciones por pares posibles. La FP agrupada aumenta a favor de una mayor cantidad de flúor a medida que se incrementa la diferencia en la concentración de flúor. Con respecto a las comparaciones con placebo, puede observarse en la tabla de clasificación que las concentraciones de 440/500/550 ppm e inferiores no muestran efectos estadísticamente significativos en comparación con el placebo; la significación estadística se alcanza con las concentraciones de 1000/1055/1100/1250 ppm, con una FP mediana del 23% en comparación con el placebo (ICr del 95%: 19% a 27%), que asciende al 36% (ICr del 95%: 27% a 44%) con la concentración más alta de flúor. Con respecto a las intervenciones activas, la FP para las comparaciones de 440/500/550 ppm con mayores concentraciones sólo alcanzó significación estadística (FP del 20%; ICr del 95%: 2% a 38%) cuando se compararon con 2400/2500/2800 ppm de flúor. Todas las comparaciones por pares se muestran en la Tabla 1Adicional. Los ICr del 95% son relativamente amplios, lo cual indica incertidumbre en muchas de las comparaciones y refleja el escaso número de ensayos para algunas de las comparaciones.Ver Tabla 1

Hay pruebas de un efecto dosis-respuesta, que se desprende de los resultados del metanálisis en red en la tabla de clasificación, en la que puede observarse que la magnitud de la fracción de prevención aumenta a medida que se incrementa la distancia entre la concentración inicial de flúor y las concentraciones mayores, aunque este aumento no siempre es estadísticamente significativo, en particular cuando las concentraciones de flúor son más bajas y similares a la concentración inicial.

En cuanto a la concentración de flúor óptima con la mayor fracción de prevención, la probabilidad más alta de beneficio en la prevención de caries se asoció con la mayor concentración de flúor: la probabilidad fue de 0,53 para las pastas dentales que contenían 2400/2500/2800 ppm de flúor, seguida de 0,40 para las pastas dentales que contenían 1700/2000/2200 ppm de flúor.

Metarregresión

Dos estudios no incluyeron datos sobre los niveles iniciales de caries (Chesters 2002; Segal 1967). El análisis agrupado incluyó 83 comparaciones por pares provenientes de 72 ensayos. Hubo una diferencia muy pequeña en el ajuste para este modelo: desviación de resumen mediana de 78,43 (ICr del 95%: 56,99 a 104,60). La tau fue de 78,43 (ICr del 95%: 44,6 a 99,33). La metarregresión de una variable indicó una asociación pequeña de las estimaciones de la FP C(P)OS con el nivel inicial de caries (coeficiente del 0,38%; ICr del 95%: -0,23% a 0,99%), aunque esta asociación no fue estadísticamente significativa.

Todos los estudios informaron sobre la supervisión del cepillado. El análisis agrupado incluyó 85 comparaciones por pares provenientes de 74 ensayos. El ajuste del modelo fue similar: desviación de resumen mediana de 80,38 (ICr del 95%: 58,31 a 107,00). La tau fue de 71,25 (ICr del 95%: 47,39 a 105,80). La metarregresión de una variable indicó una asociación de la FP C(P)OS con el cepillado supervisado (coeficiente del 5,98%; ICr del 95%: -0,59% a 12,55%), aunque la misma no fue estadísticamente significativa.

(2) Fracción de prevención de Dientes Cariados, (Perdidos) y Obturados (FP C(P)OD)

Las estimaciones del efecto y el error estándar para las diferencias por pares con respecto a la concentración de flúor se calcularon en Stata. El análisis agrupado incluyó 61 comparaciones por pares provenientes de 54 ensayos que aportaron datos sobre C(P)OD. A los fines del análisis, hubo 49 comparaciones de dos concentraciones de flúor, tres comparaciones de tres concentraciones de flúor y dos comparaciones de cuatro concentraciones de flúor. Las intervenciones se muestran como un diagrama de metanálisis en red Figura 5, donde las diferentes intervenciones están representadas como nodos en la red y las conexiones entre ellos representan las comparaciones de tratamientos por pares. Los ensayos formaron una red conectada. Hubo 51 ensayos controlados con placebo, dos ensayos con 250 ppm como valor inicial y ocho ensayos con 1000/1055/1100/1250 ppm como valor inicial. El modelo indicó un buen ajuste, con una desviación de resumen mediana de 57,08 (ICr del 95%: 39,06 a 79,81). La tau fue de 44,20 (ICr del 95%: 27,27 a 68,85).

La FP C(P)OD y el IC del 95% de cada comparación directa se encuentran disponibles en el Análisis 1.2Incremento de C(P)OS (fracción de prevención) de la sección Datos y análisis . La Tabla 2 Adicional contiene los resultados tanto de la comparación directa como del metanálisis en red. Estos resultados se ilustran gráficamente por medio de una tabla de clasificación ( Figura 7) para todas las comparaciones por pares posibles. La FP agrupada aumenta a medida que aumenta la diferencia en la concentración. Con respecto a las comparaciones con placebo, las concentraciones de 440/500/550 ppm de flúor e inferiores no muestran efectos estadísticamente significativos; la significación estadística se alcanza cuando el placebo se compara con 1000/1055/1100/1250 ppm de flúor, con una FP mediana del 25% (ICr del 95%: 19% a 30%), que asciende al 45% (ICr del 95%: 31% a 58%) cuando se compara con la concentración más alta de flúor. En el caso de las comparaciones activas, la magnitud de las diferencias en la concentración de flúor requerida para alcanzar la significación estadística es mayor que la de C(P)OS, el índice más sensible. En el caso de las intervenciones activas, sólo la FP para las comparaciones de 250 ppm con 2400/2500/2800 ppm (FP: 31%; ICr del 95%: 8% a 54%) y 1000/1055/1100/1250 ppm de flúor con 2400/2500/2800 ppm (FP: 20%; ICr del 95%: 6% a 34%) alcanzó la significación estadística. Los ICr del 95% son relativamente amplios, lo cual indica incertidumbre en muchas de las comparaciones y refleja el escaso número de ensayos para algunas de las comparaciones. Ver Tabla 2

Hay pruebas de un efecto dosis-respuesta, que indica que la magnitud de la fracción de prevención aumenta a medida que aumenta la distancia entre la concentración de flúor inicial y las concentraciones mayores, aunque este efecto rara vez es estadísticamente significativo, a diferencia de los ensayos controlados con placebo con concentraciones mayores o iguales a 1000 ppm.

En cuanto a la concentración de flúor óptima para la mayor fracción de prevención, la probabilidad más alta de beneficio en la prevención de caries se asoció con la mayor concentración de flúor: la probabilidad fue de 0,72 para las pastas dentales que contenían 2400/2500/2800 ppm de flúor, seguida de 0,17 para las pastas dentales que contenían 1700/2000/2200 ppm de flúor.

Metarregresión

Ocho estudios no incluyeron datos sobre los niveles iniciales de caries: Abrams 1980; Fogels 1979; Gish 1966; Hanachowicz 1984; Muhler 1955; Muhler 1962; Muhler 1970; Koch 1990. El análisis agrupado incluyó 53 comparaciones por pares provenientes de 46 ensayos. El ajuste del modelo fue bueno, con una desviación de resumen mediana de 49,31 (ICr del 95%: 32,75 a 70,86). La tau fue de 37,73 (ICr del 95%: 22,20 a 60,95). La metarregresión de una variable indicó una asociación pequeña de la FP C(P)OD con el nivel inicial de caries (coeficiente del - 0,93%; ICr del 95%: -3,21% a 1,36%), aunque esta asociación no fue estadísticamente significativa.

Todos los estudios informaron sobre la supervisión del cepillado. El análisis agrupado incluyó 61 comparaciones por pares provenientes de 54 ensayos. El ajuste del modelo fue bueno, con una desviación de resumen media de 56,66 (ICr del 95%: 38,66 a 79,56). La tau fue de 46,73 (ICr del 95%: 28,70 a 72,65). La metarregresión de una variable indicó una asociación de las estimaciones de la FP C(P)OS con el cepillado supervisado (coeficiente del 8,67%; ICr del 95%: -0,45% a 17,94%), aunque la misma no fue estadísticamente significativa.

(3) C(P)OS y C(P)OD fueron agrupados con el uso de una diferencia de medias estandarizada (DME).

Las estimaciones del efecto y el error estándar para las diferencias por pares relativas a la concentración de flúor para ambos índices se calcularon en Stata mediante la d de Cohen.

Las DME de los dos índices y el ICr del 95% de cada comparación directa están disponibles en el Análisis 1.3 Incremento de C(P)OS (DME) y Análisis 1.4Incremento C(P)OD (DME) de la sección Datos y análisis . Las tablas adicionales Tabla 3 y Tabla 4contienen los resultados de la comparación directa y del metanálisis en red para C(P)OS y C(P)OD con la DME. Los resultados de la DME agrupada fueron muy similares a los resultados obtenidos a partir del análisis de la FP, con la excepción del placebo versus la concentración más alta de flúor. El ajuste del modelo para estos datos fue relativamente deficiente (C(P)OS 128,7; ICr del 95%: 102,6 a 159,1; tau 90,27; ICr del 95%: 50,7 a 170,3; C(P)OD 108,60; ICr del 95%: 85,24 a 135,5; tau 107,4; ICr del 95%: 47,82 a 279,6).Ver Tabla 3 Ver Tabla 4

(4) Fracción de prevención de Superficies/Dientes Cariados, (Perdidos) y Obturados (FP C(P)OD y FP C(P)OD). Estimaciones de los efectos sobre el incremento de caries en la dentición temporal

Dos estudios proporcionaron datos para el incremento de caries tanto en C(P)OS como C(P)OD; dos estudios aportaron datos para el análisis de C(P)OD únicamente y un estudio proporcionó datos sólo para el análisis de COS. Un estudio que informó los C(P)OD como resultado primario también notificó la "tasa-CO" de los dientes temporales.

Comparación C(P)OS 1.5

(Análisis 1.5.)
Para evaluar los efectos en la prevención de la caries de las pastas dentales fluoradas de diferentes concentraciones en las superficies dentales de la dentición temporal, un ensayo comparó pasta dental fluorada con placebo y tres ensayos compararon pastas dentales de diferentes concentraciones. El ensayo controlado con placebo comparó una pasta dental no fluorada con una pasta dental que contenía 1500 ppm de flúor (Fan 2008). La FP fue del 39% (IC del 95%: 29% a 49%) a favor de la pasta dental fluorada. El primer ensayo comparó los efectos preventivos de caries del cepillado con pasta dental que contenía concentraciones de flúor de 250 ppm o 1450 ppm (Sonju Clasen 1995). Este ensayo era un ensayo con asignación aleatoria grupal que se analizó y se informó como un ensayo aleatorio individual. Mediante un coeficiente intragrupal de 0,05, con el tamaño promedio de los grupos de 17,2, se calculó un efecto del diseño de 1,81 (Higgins 2008) y el error estándar de la FP se corrigió en consecuencia. Estos cálculos dieron lugar a un incremento del error estándar; de 18,3 sin considerar la asignación grupal se pasó a 24,6. La FP fue del 41,4% (IC del 95%: -6,87%; -89,67%) a favor de la pasta dental fluorada de 1450 ppm. Un segundo ensayo comparó los efectos del cepillado con pasta dental que contenía concentraciones de flúor de 550 ppm versus 1055 ppm (Winter 1989). La FP fue del 9% (IC del 95%: -15% a 33%). Lima 2008evaluó la progresión/control de las caries según el estado inicial de caries e informó que no hubo diferencias estadísticamente significativas en el número medio de lesiones nuevas en el grupo inactivo de caries, en tanto que se registró una diferencia estadísticamente muy significativa en el incremento neto de caries en el grupo activo de caries a favor de la pasta dental fluorada de 1100 ppm en comparación con la pasta dental fluorada de 500 ppm.

No se llevó a cabo una metarregresión debido al escaso número de ensayos incluidos para este resultado.

Comparación C(P)OD 1.6

(Análisis 1.6.)
Estos ensayos informaron el incremento de caries al nivel de los C(P)OD. En el estudio de Sonju Clasen 1995 , la alta FP del 33,3% no alcanzó la significación estadística (IC del 95%: -21,77% a 88,37%) al igual que el estudio de Winter 1989con una FP del 16 % (IC del 95%: -2% a 34%). En contraste, el estudio de Davies 2002que comparó los efectos del cepillado con concentraciones de flúor de 440 ppm o 1450 ppm resultó en una FP estadísticamente significativa del 11% (IC del 95%: 3% a 19%) a favor de la pasta dental con mayor concentración de flúor.

En un ensayo controlado con placebo de pasta dental fluorada de 1500 ppm, Cahen 1982calculó la "tasa-CO", definida como el número de dientes cariados u obturados cada 100 dientes primarios observados. En el grupo de placebo, esta "tasa-CO" fue de 18,25, en tanto que en los grupos de flúor combinados se registró una "tasa-CO" inferior de 11,45.

No se llevó a cabo una metarregresión debido al escaso número de ensayos incluidos para este resultado.

(5) Porcentaje que presentó nuevas caries en la dentición permanente o temporal

Siete estudios (ocho ensayos) aportaron datos para el análisis del porcentaje de niños que presentó nuevas caries en la dentición permanente; tres estudios proporcionaron datos para el efecto sobre la dentición temporal. Para evaluar los efectos preventivos de caries sobre la dentición permanente, siete ensayos utilizaron una pasta dental de placebo. La representación gráfica de las comparaciones de tratamientos por pares relativas a la concentración de flúor reveló un modelo radial, en lugar de una red conectada, de modo que para este resultado los efectos directos sólo se compararon mediante el cociente de riesgos. Se utilizó un modelo de efectos fijos para calcular las estimaciones agrupadas del efecto para cada comparación por pares. Las estimaciones del efecto (CR) y el IC del 95% pueden observarse en las comparaciones 1.7 y 1.8 de la sección Datos y análisis . Los resultados de los ensayos fueron equívocos; dos de las comparaciones por pares alcanzaron la significación estadística a favor de la pasta dental fluorada: placebo versus 1000/1055/1100/1250 ppm (CR [efectos fijos] 0,88; IC del 95%: 0,82 a 0,95) y placebo versus 1450/1500 ppm (CR [efectos fijos] 0,95; IC del 95%: 0,91 a 0,98). La comparación directa de 1000/1055/1100/1250 ppm con 1450/1500 ppm no alcanzó la significación estadística (CR [efectos fijos] 1,07; IC del 95%: 1,00 a 1,14) y, en términos generales , el efecto agrupado no fue estadísticamente significativo (CR 0,98; IC del 95%: 0,94 a 1,02).

Tres estudios de pastas dentales fluoradas de diferentes concentraciones presentaron datos sobre el porcentaje de niños que presentó nuevas caries en la dentición primaria (Davies 2002; Sonju Clasen 1995; Winter 1989). Para este resultado, los efectos directos sólo se compararon mediante el cociente de riesgos. Mediante un modelo de efectos fijos se calcularon las estimaciones agrupadas del efecto para las tres comparaciones por pares directas. Las estimaciones del efecto (CR) y el IC del 95% se presentan en la comparación 1.8 de la sección Datos y análisis . En el caso de la comparación de 250 ppm versus 1450 ppm (Sonju Clasen 1995), no hubo una diferencia estadísticamente significativa en el número de niños que presentó nuevas caries (CR 1,01; IC del 95%: 0,63 a 1,62). Las comparaciones restantes fueron estadísticamente significativas, a favor de las concentraciones de flúor más elevadas (550 ppm en comparación con 1055 ppm: CR [efectos fijos] 0,89; IC del 95%: 0,80 a 0,99; y 440 ppm en comparación con 1450 ppm: CR [efectos fijos] 0,85; IC del 95%: 0,78 a 0,93). En términos generales, la estimación agrupada fue estadísticamente significativa a favor de una concentración mayor de flúor (CR 0,87; IC del 95%: 0,81 a 0,93).

(6) Cumplimiento del cepillado dental y efectos secundarios de la pasta dental

Dieciséis ensayos evaluaron los posibles efectos secundarios del uso de pasta dental, principalmente en cuanto a las enfermedades bucales (partes blandas) y la pigmentación de los dientes. Con respecto a los resultados de partes blandas, seis ensayos informaron que no hubo eventos adversos o no hubo eventos adversos que pudieran atribuirse al uso de la pasta dental (Conti 1988; Fogels 1979; Fogels 1988; Koch 1990; Rule 1984; Stephen 1994). En el caso de la pigmentación, seis ensayos informaron una mayor incidencia de pigmentación en el grupo de fluoruro estañoso (Fanning 1968; James 1967; Naylor 1967; Slack 1964; Slack 1967; Slack 1967a). Un ensayo (Jackson 1967) informó que no hubo diferencias en la pigmentación entre los grupos (grupo de flúor 2,5% versus grupo placebo 1%) y en otro ensayo no se encontró pigmentación (Fogels 1979).

No se observaron o informaron efectos secundarios en tres ensayos (Fan 2008; Glass 1983; Kleber 1996).

El cumplimiento del cepillado dental se consideró en 21 ensayos y se evaluó ya sea como frecuencia del cepillado (< 1 por día, 1 por día o > 1 por día; número promedio de sesiones de cepillado [supervisadas], asistencia a >75% de las sesiones de cepillado por semana), evaluación del consumo de pasta dental, o cumplimiento general o cooperación con el régimen de tratamiento.

Cuando los resultados fueron presentados por grupo, dos ensayos no encontraron diferencias en el cumplimiento con respeto a la frecuencia del cepillado dental (Conti 1988) (374,1 sesiones de cepillado en el grupo de 1000 ppm de flúor y 370,4 en el grupo de 1500 ppm de flúor, de un máximo de 450 sesiones de cepillado durante un período de tres años); Marks 1994(varió de 352 a 354 sesiones de cepillado, sin significación estadística en el número medio de sesiones de cepillado). El porcentaje de niños que tuvo una actitud de cooperación se reportó en un ensayo (James 1967)sin diferencias entre los grupos (8% versus 6% control).

Algunos ensayos afirmaron que no hubo problemas con el cumplimiento ni cumplimiento diferencial, pero los resultados no se presentaron o no se presentaron por grupo. Con respecto a la frecuencia del cepillado, Ashley 1977informó que la media de asistencias a las sesiones escolares de cepillado no difirió por grupo; Hanachowicz 1984informó que en un 11% de los niños, la frecuencia del cepillado fue menor de cinco veces por semana, sin diferencias entre los grupos. Hodge 1980informó que el 85% de los sujetos asistió a >75% de las sesiones de cepillado y que los asistentes menos regulares se distribuyeron por igual entre los grupos, al igual que Howat 1978donde el 58% de los sujetos asistió a >75% de las sesiones de cepillado. Koch 1990informó que el 65% de los niños participantes se cepillaron los dientes más de dos veces por día, cuando se evaluó la frecuencia autonotificada de cepillado. Marthaler 1970notificó 680 sesiones de cepillado por año en promedio y Marthaler 1970a, Muhler 1962informaron que el participante promedio se cepilló los dientes 0,9 veces por día. O'Mullane 1997reportó una frecuencia similar de cepillado entre los grupos de 1000 y 1500 y Stephen 1994halló que el 51% se cepilló los dientes más de una vez por día. Tres ensayos informaron que el uso de pasta dental fue muy similar en cada grupo (Jackson 1967; Marthaler 1965; Marthaler 1965a). Ripa 1988)evaluaron el cumplimiento del régimen del ensayo por medio de una llamada telefónica a una muestra de 150 hogares de niños participantes y encontraron un patrón de cumplimiento "similar para todos los grupos". Asimismo, Kleber 1996 reportó "ningún problema de cumplimiento". Piccione 1979informó que no hubo resultados diferenciales.

Los resultados del cumplimiento de los participantes "se informaron en otro sitio" en un ensayo (Winter 1989) y en otro directamente no se informaron (Fan 2008).

Discusión

Resumen de los resultados principales

El interés principal de esta revisión fue evaluar el efecto relativo de las pastas dentales que contienen flúor en diferentes concentraciones para la prevención de las caries en niños y adolescentes. Después de una búsqueda bibliográfica exhaustiva, el número de estudios incluidos en la revisión fue de 75 (83 ensayos).

Resultados de los estudios: Las pastas dentales fluoradas poseen un efecto beneficioso para la prevención de las caries cuando son utilizadas por niños y adolescentes, pero no en todas las concentraciones. Cuando se usó la fracción de prevención (FP) como la medida primaria del efecto, en los ensayos controlados con placebo, se halló una diferencia estadísticamente significativa en cuanto al beneficio de aumentar la concentración de flúor para prevenir las caries sólo en el caso de las concentraciones de 1000/1055/1100/1250 ppm y superiores (FP (C(P)OS del 23%; intervalo creíble [ICr] del 95%: 19% a 27%; FP C(P)OD del 25%; ICr del 95%: 19% a 30%), con un aumento de la FP a partir de esos valores. En términos subjetivos, este porcentaje puede considerarse de magnitud relativamente pequeña pero de importancia clínica. En el caso de las comparaciones activas, con 250 ppm como valor inicial, las comparaciones con las concentraciones de flúor de 1000/1055/1100/1250 ppm y superiores son estadísticamente significativas, con una variación de la FP C(P)OS del 14% (ICr del 95%: 1% a 27%); al 26% (ICr del 95%: 11% a 41%) en las concentraciones de 2400/2500/2800 ppm. El cepillado con una pasta dental que tiene una concentración de flúor de 1000 ppm y superior presenta un beneficio mayor para la prevención de las caries, en comparación con el cepillado con una pasta dental que contiene 250 ppm de flúor. Las comparaciones por pares que emplearon concentraciones de flúor de 440/500/550 ppm y 1000/1055/1100/1250 ppm como valor inicial sólo fueron estadísticamente significativas al nivel más alto de 2400/2500/2800 ppm. Cuando se utilizaron concentraciones de flúor de 1450/1500 ppm o 1700/2000/2200 ppm como valor inicial, no hubo beneficios estadísticamente significativos de las concentraciones mayores. Hay algunas pruebas de la relación dosis-respuesta, ya que la fracción de prevención aumenta a medida que se incrementa la concentración de flúor a partir del valor inicial. Sin embargo, el aumento de la fracción prevenida no siempre es estadísticamente significativo. Aunque los niveles de caries al inicio del ensayo y el cepillado supervisado se han citado anteriormente como modificadores importantes del efecto, no se halló que fueran estadísticamente significativos en esta revisión.

Con respecto a la dentición temporal, se incluyeron en la revisión dos ensayos controlados con placebo y cuatro ensayos que comparaban los efectos de diferentes concentraciones de flúor. Tanto para la FP C(P)OS como para la FP C(P)OD los resultados de los ensayos fueron equívocos. Este hecho no es sorprendente dadas las diferentes concentraciones comparadas.

En cuanto al porcentaje de niños y adolescentes que presentó nuevas caries durante el ensayo, siete estudios (ocho ensayos) informaron sobre nuevas caries en la dentición permanente y tres ensayos notificaron nuevas caries en la dentición temporal. En el caso de la dentición permanente, los resultados de los ensayos fueron equívocos y dos de las tres comparaciones por pares alcanzaron la significación estadística a favor de la pasta dental fluorada. La comparación directa de 1000/1055/1100/1250 ppm con 1450/1500 ppm no alcanzó la significación estadística y en general, el efecto agrupado no fue estadísticamente significativo (CR 0,98; IC del 95%: 0,94 a 1,02). En el caso de la dentición temporal, los resultados de los ensayos que compararon diferentes concentraciones de flúor fueron también equívocos y dependieron de las concentraciones comparadas. Las comparaciones por pares directas de flúor de concentraciones similares arrojaron una diferencia en el beneficio preventivo de caries entre las diferentes concentraciones, aunque en términos generales, la estimación agrupada fue estadísticamente significativa a favor de una concentración mayor de flúor (CR 0,87; IC del 95%: 0,81 a 0,93).

Compleción y aplicabilidad general de las pruebas

La revisión procuró identificar todos los ensayos controlados aleatorios (ECA) que evaluaban el uso de pastas dentales fluoradas en la prevención de las caries. La presente revisión ha evaluado explícitamente el efecto preventivo del flúor en diferentes niveles. Sin embargo, en la revisión predominan los estudios que compararon concentraciones de flúor de 1000/1055/1100/1250 ppm con placebo. Si bien se incluyeron en la revisión ensayos que compararon otras concentraciones de flúor, de 250 ppm a 2500 ppm y que son de importancia para la práctica y la política clínicas, estos ensayos se realizan con menos frecuencia. Aunque las comparaciones por pares explícitas de diferentes concentraciones de flúor abordan temas importantes para la práctica y la política clínicas, la falta de ensayos de diferentes concentraciones de flúor y en diferentes denticiones puede citarse como una limitación de la revisión. Es preocupante la falta de ensayos sobre la dentición temporal, que evalúen la posibilidad de daño como resultado de la caries o la exposición al flúor, en comparación con la dentición mixta o permanente.

Esta revisión estuvo destinada a evaluar el efecto relativo en la prevención de las caries de las pastas dentales fluoradas de diferentes concentraciones. Cuando se declararon en los informes de los ensayos, los efectos adversos como el daño bucal (partes blandas) y la pigmentación fueron documentados en la tabla "Características de los estudios incluidos". Una consideración importante cuando se recomienda el flúor de uso tópico en niños y adolescentes, en diferentes modalidades de tratamiento como las pastas dentales, los geles, los barnices, etc. y en diferentes concentraciones, es la posibilidad de fluorosis que surge de la aplicación de flúor. Una revisión Cochrane publicada recientemente, (Wong 2010) concluyó que no había una asociación significativa entre la frecuencia del cepillado dental y la cantidad de pasta dental utilizada (sustitutos imperfectos para las cantidades de flúor ingeridas) y la fluorosis. Con respecto a la concentración de pasta dental fluorada en la dentición temporal, un metanálisis de dos estudios no encontró una asociación estadísticamente significativa entre la concentración de flúor y la fluorosis (RE OR = 0,79; IC del 95%: 0,61 a 1,02). Este resultado debe interpretarse con cautela, ya que el metanálisis incluyó sólo dos estudios y difirió en cuanto a las concentraciones de flúor comparadas (440 ppm con 1450 ppm y 550 ppm con 1000 ppm), la duración de la exposición y la edad de inicio del cepillado dental con flúor. Para informarse de manera cabal sobre los posibles beneficios en la prevención de las caries de las pastas dentales fluoradas de diferentes concentraciones y los posibles riesgos de fluorosis que surgen del uso de del flúor deben leerse ambas revisiones.

Se eligió la fracción de prevención (FP) como la estimación primaria del efecto. La FP se consideró más apropiada que la diferencia de medias absoluta o la diferencia de medias estandarizada porque permite la combinación de los diferentes modos de medir el incremento de caries empleados entre los estudios, tiene relevancia clínica para los investigadores como lo demuestra su uso en los ensayos sobre caries y es sencilla de interpretar para los odontólogos. La revisión no aborda la relación entre costo y efectividad en términos de la reducción potencial del costo económico asociado con la prevención diagnóstica y el tratamiento de las caries. Sin embargo, cabe destacar que para los valores constantes de la FP entre diferentes poblaciones la carga de morbilidad (número medio de lesiones cariosas) "evitada" mediante un nivel más alto de flúor en la pasta dental se incrementará a medida que se incremente la enfermedad causante en la población.

En diez estudios, los grupos de tratamiento que recibieron como parte de la intervención agentes no fluorados adicionales, con posibles beneficios anticaries, fueron excluidos del análisis si el posible efecto anticaries del agente adicional se evaluó en grupos aislados en comparación con los grupos de flúor o placebo. Los agentes secundarios identificados en los ensayos de esta revisión fueron el pirofosfato de calcio (un ensayo), ortofosfato de calcio tratado térmicamente (un ensayo), N-lauroil sarcosinato sódico (cinco ensayos), fosfato de calcio/glicerofosfato (dos ensayos) y agentes antisarro adicionales (un ensayo). Estos grupos fueron excluidos porque los efectos anticaries de dichos agentes aún no se han establecido y es posible que su agregado a la pasta dental ejerza un beneficio preventivo adicional en comparación con las formulaciones que no tuvieron tales beneficios adicionales. Sin embargo, la influencia de tales agentes adicionales podría haberse establecido mediante un análisis de sensibilidad. Esto se considerará en la actualización de la revisión.

Si bien en la tabla de las características de los estudios incluidos se presenta una indicación de la exposición frecuente al flúor de cada uno de los estudios, es evidente que la información relativa a la exposición frecuente no se informó en muchos de ellos. Tal modificador potencial del efecto podría haberse incluido en el análisis, pero debido a que la información fue insuficiente en muchos de los informes de los ensayos este factor no se incluyó y podría identificarse como una limitación de la revisión. No obstante, una clasificación errónea potencial, especialmente como consecuencia del informe incompleto de los datos sobre exposición a flúor por otras fuentes además del agua (Marinho b 2003) requeriría una interpretación cautelosa de los resultados de tal análisis.

Calidad de las pruebas

Los estudios incluidos fueron publicados entre 1955 y 2008. La calidad de la realización y el informe de ECA han mejorado enormemente durante ese período, lo cual se refleja en los estudios incluidos en la revisión. Muchos de los primeros estudios carecían de información sobre los métodos de asignación al azar y el proceso de asignación de los tratamientos, de allí el gran número de estudios clasificados como "incierto" en estos dominios. Muchos estudios emplearon la asignación al azar estratificada para asegurar, en la medida de lo posible, valores de comparación iniciales equivalentes en relación con los indicadores pronósticos conocidos y desconocidos, aunque no declararon de forma explícita el método de asignación al azar. En cuanto a la ocultación de la asignación, los participantes fueron asignados a pastas dentales diferentes sin la participación de los evaluadores, con un mínimo riesgo de sesgo. De los otros dominios de calidad clave evaluados, el riesgo de sesgo es relativamente bajo en los ensayos de pastas dentales como estos. El cegamiento de los participantes a la pasta dental asignada se realizó en todos los ensayos menos uno, mediante envases que garantizaban que los productos tuvieran un sabor y apariencia similares, y la evaluación fue realizada por examinadores cegados a la asignación de tratamientos. Excepto por una posible objeción al sabor, o la pigmentación de los dientes como resultado del uso de la pasta dental, la ausencia de cegamiento habría tenido consecuencias mínimas para el cumplimiento o la evaluación de resultados. Todos los estudios informaron el incremento de caries a nivel de las superficies como medida de resultado, la medida de resultado primaria que se espera que se informe en los ensayos de pasta dental, y la mayoría de los estudios informó además sobre el incremento de caries a nivel del diente. El riesgo de sesgo que surge del desequilibrio inicial en los niveles de caries entre los grupos fue bajo. La mayoría de los ensayos empleó e informó al menos la estratificación según el nivel inicial de caries.

La duración mínima del seguimiento aceptada para los ensayos en los cuales el resultado es el incremento de caries es de 12 meses. Esta duración mínima fue un criterio de inclusión para la revisión. Se prefiere un período de seguimiento más cercano a los tres años, y el incremento de caries informado más cercano a este período se eligió como la medida de resultado para esta revisión. Con tal duración, algún grado de desgaste es esperable y en gran parte no está relacionado con la pasta dental asignada. Las razones informadas para el desgaste fueron principalmente que los participantes cambiaron de escuela, o faltaron a la escuela el día del examen. Cuando se informó que los participantes fueron excluidos explícitamente de la participación este hecho se hizo constar, pero reflejó sólo un porcentaje muy pequeño de los participantes estudiados. El riesgo de sesgo de este dominio fue incierto para la mayoría de los estudios, ya que el motivo de los abandonos y las pérdidas diferenciales no se informaron. Sólo cuatro ensayos presentaron alto riesgo de sesgo en este dominio como resultado de los altos niveles de desgaste.

Una posible fuente de sesgo en la revisión es la contaminación de otras fuentes de flúor (pasta dental u otros productos) o la cointervención. Si la intervención tuvo lugar dentro del ámbito escolar, es improbable que haya habido contaminación y es muy improbable que haya ocurrido si la sesión de cepillado dental fue supervisada con cuidado o la pasta dental tenía el nombre del niño en el tubo. Una fuente posible de contaminación fue el uso de la pasta dental familiar, pero esta posibilidad se redujo en los estudios que proporcionaron pasta dental suficiente para toda la familia. El riesgo de sesgo en este dominio fue bajo.

En general, los estudios pueden considerarse en gran medida exentos de sesgo en los dominios clave identificados, con la excepción de la asignación al azar, la ocultación de la asignación y los datos de resultado incompletos tal como se analizó anteriormente, donde la mayoría de los estudios recibieron la calificación de "incierto".

Sesgos potenciales en el proceso de revisión

Hubo una sola desviación del protocolo: se consideró que el porcentaje de niños que presentó nuevas caries constituía una medida más apropiada de la prevención que el porcentaje que se mantuvo libre de caries. La última medida habría excluido a todos los participantes con caries al comienzo del ensayo. Por consiguiente, el porcentaje de niños que se mantuvo libre de caries se eliminó de la lista de resultados.

Los revisores no identificaron deficiencias en la estrategia de búsqueda.

Sólo resta obtener o traducir tres estudios (que en consecuencia se hallan en espera de clasificación).

Una limitación de la revisión en términos de ausencia de datos resulta de las características incompletas de los estudios, el nivel inicial de las covariables y las estimaciones de resumen y en la mayoría de los casos se debe a la cantidad de años desde la publicación. La revisión incluyó documentos publicados a partir de 1955, mucho antes de la publicación de la declaración CONSORT y, por lo tanto, en algunos casos se omitieron datos importantes. Los gran cantidad de años transcurridos desde la publicación excluyeron la posibilidad de establecer contacto con los autores para solicitarles mayor información. En cuanto a la evaluación de la calidad de los estudios, la ausencia de información importante en algunos de los informes de ensayos ha dado lugar a clasificaciones de "incierto".

La validez externa de la revisión es buena, ya que el nivel inicial de caries en los estudios incluidos es muy variado, así como la edad de los participantes al comienzo de los estudios, y el sexo a menudo se utiliza como un factor de estratificación en el método de asignación al azar. La revisión incluye estudios de intervenciones realizadas en el domicilio y bajo condiciones supervisadas, generalmente en un ámbito escolar. La metarregresión evaluó si tales diferencias en las intervenciones tuvieron un efecto. Se consideró la FP como medida de resultado primaria para asegurar que las mediciones con diferentes índices puedan combinarse de forma adecuada, en una medida del efecto que sea fácil de comprender e interpretar clínicamente.

Para la medida de resultado primaria FP C(P)OS, hubo pocas pruebas de heterogeneidad entre los ensayos que compararon niveles similares de concentración de flúor. Se realizó formalmente una metarregresión con el nivel inicial de caries y el cepillado supervisado como posibles modificadores del efecto. Hubo un efecto del nivel inicial de caries y el cepillado supervisado sobre la FP C(P)OS (coeficiente del 0,38%; ICr del 95%: -0,23% a 0,99% y coeficiente del 5,98%; ICr del 95%: -0,59% a 12,55% respectivamente), aunque el mismo no fue estadísticamente significativo, lo cual indica un efecto anticaries de la pasta dental fluorada independientemente del nivel inicial de caries y la supervisión del cepillado.

Acuerdos y desacuerdos con otros estudios o revisiones

Si bien los ensayos controlados con placebo fueron considerados en una revisión anterior (Marinho b 2003), el efecto de las pastas dentales fluoradas de diferentes concentraciones sólo se evaluó indirectamente, mediante un análisis de metarregresión. La revisión mostró un efecto inequívoco del flúor en comparación con el placebo, y los resultados del análisis de metarregresión indicaron un mayor efecto del tratamiento con el incremento de la concentración de flúor, pero no estableció conclusiones firmes en cuanto a la efectividad relativa de las pastas dentales fluoradas de diferentes concentraciones en la prevención de las caries dentales en niños y adolescentes.

Para un carácter integral, se harán comparaciones con las revisiones publicadas, pero debe tenerse en cuenta que las diferencias en el proceso de revisión probablemente repercutan sobre los resultados. La presente revisión halló pruebas de un beneficio estadísticamente significativo de la pasta dental fluorada de 250 ppm en relación con la pasta dental fluorada de 1000 ppm para la prevención de caries en la dentición mixta/permanente ( FP C(P)OS 14%; ICr del 95%: 1% a 26%). Este resultado también se encontró en las dos revisiones que compararon pastas dentales fluoradas de estas concentraciones (Ammari 2003; Steiner 2004).

En una revisión que comparó los efectos de la pasta dental fluorada con placebo y pastas dentales de diferentes concentraciones, se realizó una evaluación de la calidad y los resultados se presentaron de forma narrativa (Twetman 2003). En la revisión, que comprendió 26 ensayos, se informó un efecto global de la pasta dental fluorada cuando se comparó con placebo (promedio simple) (Twetman 2003). En la comparación de las pastas dentales con una concentración de flúor menor de 1000 ppm en relación con 1000-1100 ppm, los resultados de cuatro ensayos se presentaron de forma narrativa e indicaron ya sea un beneficio o ningún efecto de los niveles superiores de flúor. El análisis realizado en esta revisión indica que, en comparación con placebo, las pastas dentales fluoradas de 1000 ppm y más reportan un beneficio (FP C(P)OS 23%; ICr: 19% a 27%) y que existe un beneficio significativo de las pastas dentales fluoradas de 1000 ppm en comparación con las pastas dentales fluoradas de 250 ppm (FP C(P)OS 14%; ICr: 1% a 26%). No existe un beneficio adicional, estadísticamente significativo, de las pastas dentales fluoradas de 500 ppm en comparación con las pastas dentales fluoradas de 250 ppm (FP C(P)OS 6%; ICr: -14% a 26%) o de las pastas dentales fluoradas de 1000 ppm en comparación con las pastas dentales fluoradas de 500 ppm (FP C(P)OS 8% ; ICr: -10% a 25%). Se informó que el efecto preventivo de caries de la pasta dental fluorada de 1500 ppm de flúor en comparación con 1000-1100 ppm de flúor también favoreció las concentraciones mayores de flúor (promedio simple, n = 9 ensayos). Si bien la magnitud del efecto fue similar en esta revisión y también favoreció la concentración mayor de flúor, la misma no fue estadísticamente significativa (FP C(P)OS 6%; ICr del 95%: -2% a 14%). Finalmente, un metanálisis de pastas dentales estándar y experimentales con concentraciones de flúor de 1700 ppm, 2200 ppm y 2800 ppm de flúor en relación con 1000 ppm de flúor informó un efecto preventivo de caries de la concentración mayor de flúor, aunque este efecto sólo alcanzó la significación estadística al nivel de flúor de 2800 ppm (Bartizek 2001). En esta revisión se observó este patrón de resultados con concentraciones similares de flúor (1000/1055/1100/1250 ppm en relación con 1700/2000/2200 ppm: FP C(P)OS 11%; ICr: -6% a 28%; 1000/1055/1100/1250 ppm en relación con 2400/2500/2800 ppm: FP C(P)OS 13%; ICr: 5% a 20%).

Conclusiones de los autores

Implicaciones para la práctica

Cuando se usó la fracción de prevención (FP) como la medida primaria del efecto, en los ensayos controlados con placebo, se halló una diferencia estadísticamente significativa en cuanto al beneficio de aumentar la concentración de flúor para prevenir las caries sólo en el caso de las concentraciones de 1000/1055/1100/1250 ppm y superiores (FP (C(P)OS 23%; FP C(P)OD 25%; con un aumento de la FP a partir de esos valores; pero las concentraciones de 440/500/550 ppm e inferiores no mostraron efectos estadísticamente significativos en comparación con el placebo). Sobre la base de estos resultados, puede no ser apropiado recomendar el uso de pasta dental fluorada de 440/500/550 ppm para la prevención de las caries en la dentición temporal, aunque se reconoce que existe bastante incertidumbre con respecto a las estimaciones en estos niveles. El uso de 1000 ppm o más en los niños menores de seis años debe hacerse teniendo en cuenta el riesgo de fluorosis. Los resultados apoyan el nivel estándar internacional de 1000 ppm de flúor para los niños más pequeños y hasta 1500 ppm para los niños mayores.


Implicaciones para la investigación

Se necesita más investigación sobre los efectos de las pastas dentales fluoradas con niveles inferiores de concentración de flúor. Dado que el nivel de concentración de flúor recomendado en la actualidad es de alrededor de 1500 ppm en el Reino Unido y de alrededor de 1000 ppm a nivel internacional, los estudios para evaluar los potenciales efectos anticaries de las pastas dentales con concentraciones de flúor inferiores pueden enfrentar dificultades éticas. La mayoría de los estudios incluidos en esta revisión son estudios antiguos, controlados con placebo, realizados antes de que el flúor se utilizara comúnmente. Dado que el flúor se ha convertido en una medida de prevención de la caries aceptada, los estudios que realicen comparaciones directas de diferentes concentraciones de flúor serían un buen aporte a la bibliografía. En particular, es escaso el número de estudios que evalúa los efectos sobre la dentición temporal (seis estudios) y los posibles efectos adversos del uso de pasta dental.


Agradecimientos

Los autores de la revisión desean agradecer el apoyo de: el Grupo Cochrane de Salud Oral, los revisores externos por sus extensas y útiles observaciones sobre las versiones anteriores de esta revisión y de Brian Bonner y Obinna Onwoods por su ayuda con la extracción de datos.

Datos y análisis

Comparación 1. Pasta dental fluorada versus placebo u otra pasta dental fluorada

Título del subgrupo o resultado

Nº de estudios

Nº de participantes

Método estadístico

Tamaño del efecto

1 Incremento de C(P)OS (fracción de prevención) - más cercano a los 3 años (74 ensayos)

74

Fracción prevenida (efectos aleatorios, IC del 95%)

19.79 [16.72, 22.87]

1.1 Placebo versus 250 ppm

3

Fracción prevenida (efectos aleatorios, IC del 95%)

8.90 [-1.62, 19.42]

1.2 Placebo versus 440/500/550 ppm

2

Fracción prevenida (efectos aleatorios, IC del 95%)

7.91 [-6.11, 21.94]

1.3 Placebo versus 1000/1055/1100/1250 ppm

54

Fracción prevenida (efectos aleatorios, IC del 95%)

22.20 [18.68, 25.72]

1.4 Placebo versus 1450/1500 ppm

4

Fracción prevenida (efectos aleatorios, IC del 95%)

22.07 [15.26, 28.88]

1.5 Placebo versus 2400/2500/2800 ppm

4

Fracción prevenida (efectos aleatorios, IC del 95%)

36.55 [17.46, 55.64]

1.6 250 ppm versus 1000/1055/1100/1250 ppm

2

Fracción prevenida (efectos aleatorios, IC del 95%)

16.80 [8.47, 25.12]

1.7 440/500/550 ppm versus 1000/1055/1100/1250 ppm

1

Fracción prevenida (efectos aleatorios, IC del 95%)

0.48 [-14.98, 15.94]

1.8 440/500/550 ppm versus 2400/2500/2800 ppm

1

Fracción prevenida (efectos aleatorios, IC del 95%)

12.66 [-1.65, 26.97]

1.9 1000/1055/1100/1250 ppm versus 1450/1500 ppm

6

Fracción prevenida (efectos aleatorios, IC del 95%)

9.58 [2.52, 16.64]

1.10 1000/1055/1100/1250 ppm versus 1700/2000/2200 ppm

2

Fracción prevenida (efectos aleatorios, IC del 95%)

9.44 [2.12, 16.76]

1.11 1000/1055/1100/1250 ppm versus 2400/2500/2800 ppm

6

Fracción prevenida (efectos aleatorios, IC del 95%)

12.15 [5.95, 18.35]

2 Incremento de C(P)OD (fracción de prevención) - más cercano a los 3 años (54 ensayos)

54

Fracción prevenida (efectos aleatorios, IC del 95%)

21.16 [16.86, 25.47]

2.1 Placebo versus 250 ppm

1

Fracción prevenida (efectos aleatorios, IC del 95%)

15.75 [2.78, 28.72]

2.2 Placebo versus 440/500/550 ppm

2

Fracción prevenida (efectos aleatorios, IC del 95%)

31.66 [-11.63, 74.95]

2.3 Placebo versus 1000/1055/1100/1250 ppm

41

Fracción prevenida (efectos aleatorios, IC del 95%)

22.39 [16.85, 27.93]

2.4 Placebo versus 1450/1500 ppm

4

Fracción prevenida (efectos aleatorios, IC del 95%)

22.27 [16.46, 28.09]

2.5 Placebo versus 2400/2500/2800 ppm

3

Fracción prevenida (efectos aleatorios, IC del 95%)

37.38 [18.96, 55.81]

2.6 250 ppm versus 1000/1055/1100/1250 ppm

2

Fracción prevenida (efectos aleatorios, IC del 95%)

14.66 [7.70, 21.62]

2.7 1000/1055/1100/1250 ppm versus 1450/1500 ppm

3

Fracción prevenida (efectos aleatorios, IC del 95%)

11.88 [-2.37, 26.14]

2.8 1000/1055/1100/1250 ppm versus 1700/2000/2200 ppm

2

Fracción prevenida (efectos aleatorios, IC del 95%)

6.57 [0.26, 12.89]

2.9 1000/1055/1100/1250 ppm versus 2400/2500/2800 ppm

3

Fracción prevenida (efectos aleatorios, IC del 95%)

12.40 [7.64, 17.16]

3 Incremento C(P)OS (DME) - más cercano a los 3 años (74 ensayos)

74

73684

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.24 [-0.27, -0.20]

3.1 Placebo versus 250 ppm

3

1460

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.09 [-0.19, 0.02]

3.2 Placebo versus 440/500/550 ppm

2

816

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.07 [-0.21, 0.06]

3.3 Placebo versus 1000/1055/1100/1250 ppm

54

31727

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.28 [-0.32, -0.24]

3.4 Placebo versus 1450/1500 ppm

4

4406

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.34 [-0.51, -0.18]

3.5 Placebo versus 2400/2500/2800 ppm

4

2041

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.72 [-1.11, -0.33]

3.6 250 ppm versus 1000/1055/1100/1250 ppm

2

1346

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.20 [-0.31, -0.09]

3.7 440/500/550 ppm versus 1000/1055/1100/1250 ppm

1

342

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

0.01 [-0.21, 0.22]

3.8 440/500/550 ppm versus 2400/2500/2800 ppm

1

348

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.18 [-0.39, 0.04]

3.9 1000/1055/1100/1250 ppm versus 1450/1500 ppm

6

12200

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.08 [-0.14, -0.03]

3.10 1000/1055/1100/1250 ppm versus 1700/2000/2200 ppm

2

5534

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.08 [-0.13, -0.02]

3.11 1000/1055/1100/1250 ppm versus 2400/2500/2800 ppm

6

13464

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.11 [-0.18, -0.05]

4 Incremento C(P)OD (DME) - más cercano a los 3 años (54 ensayos)

54

53095

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.24 [-0.28, -0.20]

4.1 Placebo versus 250 ppm

1

776

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.16 [-0.30, -0.02]

4.2 Placebo versus 440/500/550 ppm

2

816

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.28 [-0.72, 0.15]

4.3 Placebo versus 1000/1055/1100/1250 ppm

41

24837

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.26 [-0.31, -0.21]

4.4 Placebo versus 1450/1500 ppm

4

4406

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.37 [-0.50, -0.24]

4.5 Placebo versus 2400/2500/2800 ppm

3

1259

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-1.05 [-2.14, 0.04]

4.6 250 ppm versus 1000/1055/1100/1250 ppm

2

1346

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.20 [-0.32, -0.08]

4.7 1000/1055/1100/1250 ppm versus 1450/1500 ppm

3

6564

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.08 [-0.17, 0.01]

4.8 1000/1055/1100/1250 ppm versus 1700/2000/2200 ppm

2

5534

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.06 [-0.11, -0.00]

4.9 1000/1055/1100/1250 ppm versus 2400/2500/2800 ppm

3

7557

Diferencia de medias estandarizada (IV, efectos aleatorios, IC del 95%)

-0.11 [-0.16, -0.07]

5 Incremento de C(P)OS (fracción de prevención) - más cercano a los 3 años (3 ensayos)

3

Fracción prevenida (efectos fijos, IC del 95%)

34.82 [25.68, 43.96]

5.1 Placebo versus 1450/1500 ppm

1

Fracción prevenida (efectos fijos, IC del 95%)

39.32 [29.19, 49.45]

5.2 250 ppm versus 1450/1500 ppm

1

Fracción prevenida (efectos fijos, IC del 95%)

41.4 [-6.87, 89.67]

5.3 440/500/550 ppm versus 1000/1055/1100/1250 ppm

1

Fracción prevenida (efectos fijos, IC del 95%)

9.0 [-14.52, 32.52]

6 Incremento de C(P)OD (fracción de prevención) - más cercano a los 3 años (3 ensayos)

3

Fracción prevenida (efectos fijos, IC del 95%)

12.18 [5.08, 19.29]

6.1 250 ppm versus 1450/1500 ppm

1

Fracción prevenida (efectos fijos, IC del 95%)

33.3 [-21.77, 88.37]

6.2 440/500/550 ppm versus 1000/1055/1100/1250 ppm

1

Fracción prevenida (efectos fijos, IC del 95%)

16.0 [-1.64, 33.64]

6.3 440/500/550 ppm versus 1450/1500 ppm

1

Fracción prevenida (efectos fijos, IC del 95%)

11.0 [3.16, 18.84]

7 Porcentaje que presentó nuevas caries (dentición permanente) (8 ensayos)

8

5348

Cociente de riesgos (M-H, efectos fijos, IC del 95%)

0.98 [0.94, 1.02]

7.1 Placebo versus 250 ppm

2

684

Cociente de riesgos (M-H, efectos fijos, IC del 95%)

1.06 [0.90, 1.26]

7.2 Placebo versus 1000/1055/1100/1250 ppm

6

1806

Cociente de riesgos (M-H, efectos fijos, IC del 95%)

0.88 [0.82, 0.95]

7.3 Placebo versus 1450/1500 ppm

1

945

Cociente de riesgos (M-H, efectos fijos, IC del 95%)

0.95 [0.91, 0.98]

7.4 1000/1055/1100/1250 ppm versus 1450/1500 ppm

1

1913

Cociente de riesgos (M-H, efectos fijos, IC del 95%)

1.07 [1.00, 1.14]

8 Porcentaje que presentó caries nuevas (dentición temporal) (3 ensayos)

3

Cociente de riesgos (efectos fijos, IC del 95%)

0.87 [0.81, 0.93]

8.1 250 ppm versus 1450/1500 ppm

1

Cociente de riesgos (efectos fijos, IC del 95%)

1.01 [0.63, 1.62]

8.2 440/500/550 ppm versus 1000/1055/1100/1250 ppm

1

Cociente de riesgos (efectos fijos, IC del 95%)

0.89 [0.80, 0.99]

8.3 440/500/550 ppm versus 1450/1500 ppm

1

Cociente de riesgos (efectos fijos, IC del 95%)

0.85 [0.78, 0.93]



Apéndices

Appendix 1. MEDLINE (OVID) search strategy

1. Dental Caries.mp. or exp Dental Caries/
2. Dental Caries Activity Tests/
3. Dental Caries Susceptibility/
4. carie$.mp.
5. DMF$.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
6. exp Fluorides/
7. exp Fluorides, Topical/
8. FLUOR$.mp.
9. AMF.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
10. AMINE F.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
11. SNF2.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
12. STANNOUS F.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
13. NAF.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
14. SODIUM F.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
15. APF.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
16. SMFP.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
17. MFP.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
18. monofluor$.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
19. exp Cariostatic Agents/
20. exp Dentifrices/
21. toothpaste$.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
22. paste$.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
23. dentrifice$.mp. [mp=title, original title, abstract, name of substance word, subject heading word]
24. 4 or 1 or 3 or 2 or 5
25. 6 or 11 or 7 or 9 or 17 or 12 or 15 or 14 or 8 or 18 or 19 or 16 or 10 or 13
26. 22 or 21 or 23 or 20
27. 25 and 24 and 26

Antecedentes

Primera publicación del protocolo: Número 3, 2009
Primera publicación de la revisión: Número 1, 2010

Contribuciones de los autores

Redacción del protocolo

Anne-Marie Glenny (AMG), Tanya Walsh (TW), Helen Worthington (HW), Valeria Marinho (VM)

Desarrollo de una estrategia de búsqueda:

AMG, VM

Búsqueda de ensayos

AMG, Priscilla Appelbe (PA)

Obtención de copias de ensayos

PA

Selección de los ensayos a incluir:

TW, HW, VM

Extracción de datos de los ensayos

TW, HW, VM, PA

Introducción de los datos en RevMan

PA

Realización del análisis:

AMG, TW, HW, VM, Xin Shi (XS)

Interpretación del análisis:

AMG, TW, HW, VM

Redacción de la revisión final

AMG, TW, HW, VM

Actualización de la revisión:

AMG, TW, HW, VM



Declaraciones de interés

Helen Worthington tiene un consultorio ubicado en la Unidad de Salud Dental la Universidad de Manchester, que es financiado conjuntamente por la Universidad de Manchester y Colgate Palmolive. Helen Worthington no recibe financiamiento de Colgate Palmolive y no considera este hecho como un conflicto de interés. Helen Worthington participó en el diseño y análisis de tres ensayos incluidos. No realizó la evaluación del riesgo de sesgo o la extracción de datos para estos ensayos. No se sabe de otros conflictos de interés potenciales.

Fuentes de financiación

Recursos internos

  • School of Dentistry, The University of Manchester, UK.

    The University of Manchester pays the salaries of Tanya Walsh, Helen Worthington and Anne-Marie Glenny. The Cochrane Oral Health Group is supported by the Department of Health and the Manchester Academic Health Sciences Centre (MAHSC) and the NIHR Manchester Biomedical Research Centre.

Recursos externos

  • Department of Health Cochrane Review Incentive Scheme 2008, UK.

    Provided GBP 5000 to support this review.

  • National Institute for Health Research (NIHR), UK.

    Funds the editorial base of the Cochrane Oral Health Group.

Información de contacto

Authors: Tanya Walsh1, Helen V Worthington2, Anne-Marie Glenny2, Priscilla Appelbe1, Valeria CC Marinho3, Xin Shi4


1The University of Manchester, School of Dentistry, Higher Cambridge Street, Manchester, UK

2MANDEC, School of Dentistry, The University of Manchester, Cochrane Oral Health Group, Higher Cambridge Street, Manchester, UK

3Queen Mary University of London, Clinical and Diagnostic Oral Sciences, Barts and The London School of Medicine and Dentistry, Turner Street, Whitechapel, London, UK

4CMMC NHS Trust, Biostatistics Group, Manchester Biostatistics Research Centre, Manchester Royal Infirmary, Off Grafton Street, Manchester, UK

Contact: Tanya Walsh1 tanya.walsh@manchester.ac.uk. Editorial group: Cochrane Oral Health Group (HM-ORAL)

Referencias

( * indica la publicación principal del estudio)

Referencias de los estudios incluidos en esta revisión

Abrams 1980 {published data only}

Abrams RG, Chambers DW. Caries-inhibiting effect of a stannous fluoride silica gel dentifrice: a three-year clinical study. Clinical Preventive Dentistry 1980; 2: 22-7.

Andlaw 1975 {published data only}

* Andlaw RJ, Tucker GJ. A dentifrice containing 0.8 per cent sodium monofluorophosphate in an aluminium oxide trihydrate base. A 3-year clinical trial. British Dental Journal 1975; 138: 426-32.

Tucker GJ, Andlaw RJ, Burchell CK. The relationship between oral hygiene and dental caries incidence in 11-year-old children. A 3-year study. British Dental Journal 1976; 141: 75-9.

Ashley 1977 {published data only}

Ashley FP, Mainwaring PJ, Emslie RD, Naylor MN. Clinical testing of a mouthrinse and a dentifrice containing fluoride. A two-year supervised study in school children. British Dental Journal 1977; 143: 333-8.

Biesbrock 2001 {published data only}

Biesbrock AR, Gerlach RW, Bollmer BW, Faller RV, Jacobs SA, Bartizek RD. Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year. Community Dentistry and Oral Epidemiology 2001; 29: 382-9.

Blinkhorn 1983 {published data only}

Blinkhorn AS, Holloway PJ, Davies TG. Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries. Community Dentistry and Oral Epidemiology 1983; 11: 7-11.

Brudevold 1966 {published data only}

Brudevold F, Chilton NW. Comparative study of a fluoride dentifrice containing soluble phosphate and a calcium-free abrasive: second-year report. Journal of the American Dental Association 1966; 72: 889-94.

Brudevold F, Chilton NW, Wellock WD. A preliminary comparison of a dentifrice containing fluoride and soluble phosphate and employing a calcium-free abrasive with other types of fluoride dentifrices. First year report of a clinical study. Journal of Oral Therapeutics and Pharmacology 1964; 56: 1-6.

Buhe 1984 {published data only (unpublished sought but not used)}

Barlage B, Buhe H, Buttner W. A 3-year clinical dentifrice trial using different fluoride levels: 0.8 and 1.2% sodium monofluorophosphate. Caries Research 1981; 15: 185.

* Buhe H, Buttner W, Barlage B. 3-year clinical tooth cream test with toothpastes of varying fluoride content: 0.8% and 1.2% sodium monofluorophosphate [Uber einen dreijahrigen klinischen Zahncremetest mit Zahnpasten unterschiedlicher Fluoridkonzentration: 0,8% und 1,2% Natriummonofluorphosphat]. Quintessenza 1984; 35: 103-11.

Cahen 1982 {published data only}

Cahen PM, Frank RM, Turlot JC, Jung MT. Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France. Community Dentistry and Oral Epidemiology 1982; 10: 238-41.

Chesters 2002 {published data only}

Chesters RK, Pitts NB, Matuliene G, Kvedariene A, Huntington E, Bendinskaite R, et al. An abbreviated caries clinical trial design validated over 24 months. Journal of Dental Research 2002; 81(9): 637-40.

Conti 1988 {published data only}

Conti AJ. The anticaries benefit of a higher fluoride content dentifrice in a Florida community. Compendium Supplement 1988; (11): s379-83.

* Conti AJ, Lotzkar S, Daley R, Cancro L, Marks RG, McNeal DR. A 3-year clinical trial to compare efficacy of dentifrices containing 1.14% and 0.76% sodium monofluorophosphate. Community Dentistry and Oral Epidemiology 1988; 16: 135-8.

Moorhead JE, Conti AJ, Marks RG, Cancro LP. The effect of supervised brushing on caries inhibition in school age children. Journal of Clinical Dentistry 1991; 2(4): 97-102.

Davies 2002 {published data only}

* Davies GM, Worthington HV, Ellwood RP, Bentley EM, Blinkhorn AS, Taylor G, et al. A randomised controlled trial of the effectiveness of providing free fluoride toothpaste from the age of 12 months on reducing caries in 5-6 year old children. Community Dental Health 2002; 19: 131-6.

Davies GM, Worthington HV, Ellwood RP, Blinkhorn AS, Taylor GO, Davies RM, et al. An assessment of the cost effectiveness of a postal toothpaste programme to prevent caries among 5 year old children in the North West of England. Community Dental Health 2003; 20: 207-10.

Ellwood RP, Davies GM, Worthington HV, Blinkhorn AS, Taylor GO, Davies RM. Relationship between area deprivation and the anticaries benefit of an oral health program providing free fluoride toothpaste to young children. Community Dentistry and Oral Epidemiology 2004; 32: 159-65.

Tavener JA, Davies GM, Davies RM, Ellwood RP. The prevalence and severity of fluorosis and other developmental defects of enamel in children who received free fluoride toothpaste containing either 440 or 1450 ppm F from the age of 12 months. Community Dental Health 2004; 21: 217-23.

Di Maggio 1980 {published data only}

Di Maggio M, Zuccarino L. Cariostatic effect of Fluocaril; controlled clinical research [Effetto cariostatico del Fluocaril; ricerca clinica controllata]. Minerva Stomatologica 1980; 29: 45-50.

Fan 2008 {published data only}

Fan X, Li X, Wan H, Hu D, Zhang YP, Volpe AR, et al. Clinical investigation of the anticaries efficacy of a 1.14% sodium monofluorophosphate (SMFP) calcium carbonate based dentifrice: a two-year caries clinical trial on children in China. Journal of Clinical Dentistry 2008; 19(4): 134-7.

Fanning 1968 {published data only}

Cellier KM, Fanning EA, Gotjamanos T, Vowles NJ. Some statistical aspects of a clinical study on dental caries in children. Archives of Oral Biology 1968; 13: 483-508.

Fanning EA, Cellier KM, Gotjamanos T, Vowles NJ. The effect of fluoride dentifrices on the caries incidence of individual tooth surfaces. Australian Dental Journal 1971; 16: 287-90.

Fanning EA, Gotjamanos T, Vowles NH, Wielen I. The effects of fluoride dentifrices on the incidence and distribution of stained tooth surfaces in children. Archives of Oral Biology 1968; 13: 467-9.

Fanning EA, Gotjamanos T, Vowles NJ. The use of fluoride dentifrices in the control of dental caries: methodology and results of a clinical trial. Australian Dental Journal 1968; 13: 201-6.

Fanning EA, Gotjamanos T, Vowles NJ, Cellier KM, Simmons DW. The use of fluoride dentifrices in the control of dental caries: a preliminary report of a clinical trial. Medical Journal of Australia 1967; 1: 383-5.

Fogels 1979 {published data only}

Fogels HR, Alman JE, Meade JJ, O'Donnell JP. The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base. Journal of the American Dental Association 1979; 99: 456-9.

Fogels 1988 {published data only}

Fogels HR, Meads JJ, Griffith J, Miragliuolo R, Cancro LP. A clinical investigation of a high-level fluoride dentifrice. Journal of Dentistry for Children 1988; 55(3): 210-5.

Forsman 1974 {published data only}

Forsman B. Studies on the effect of dentifrices with low fluoride content. Community Dentistry and Oral Epidemiology 1974; 2: 166-75.

Forsman 1974a {published data only}

Forsman B. Studies on the effect of dentifrices with low fluoride content. Community Dentistry and Oral Epidemiology 1974; 2: 166-75.

Gish 1966 {published data only}

Gish CW, Muhler JC. Effectiveness of a stannous fluoride-calcium pyrophosphate (SnF2-Ca2P2O7) dentifrice on dental caries in children whose teeth calcified in a natural fluoride area. II. Results at the end of 24 months. Journal of the American Dental Association 1966; 73: 853-5.

Gish CW, Muhler JC. Effectiveness of a stannous fluoride dentifrice on dental caries. ASDC Journal of Dentistry for Children 1971; 38: 211-4.

Gish CW, Muhler JC, Stookey GK. Effectiveness of a stannous fluoride-calcium pyrophosphate (SnF2-Ca2P2O7) dentifrice on dental caries in children whose teeth calcified in a natural fluoride area. I. Results at the end of 12 months. Journal of the American Dental Association 1965; 71: 60-5.

Glass 1978 {published data only}

Glass RL. Caries reduction by a dentifrice containing sodium monofluorophosphate in a calcium carbonate base. Partial explanation for diminishing caries prevalence. Clinical Preventive Dentistry 1981; 3: 6-8.

Glass RL, Shiere FR. A clinical trial of a calcium carbonate base dentifrice containing 0.76% sodium monofluorophosphate. Caries Research 1978; 12: 284-9.

Glass 1983 {published data only}

Glass RL, Peterson JK, Bixler D. The effects of changing caries prevalence and diagnostic criteria on clinical caries trials. Caries Research 1983; 17: 145-51.

Hanachowicz 1984 {published data only}

Hanachowicz L. Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base. Community Dentistry and Oral Epidemiology 1984; 12: 10-6.

Hanachowicz L. Prevention of caries with a dentifrice containing a 1.2% concentration of sodium monofluorophosphate in an alumina base (a 3-year clinical trial) [Prevention des caries par un dentrifrice contenant du monofluorophosphate de sodium a la concentration de 1.2% dans une base alumine (Test clinique de 3 ans)]. Chirurgien Dentiste de France 1984; 54: 59-67.

Held 1968 {published data only}

Held AJ, Spirgi M. Clinical experimentation with a fluoridated dentifrice [Experimentation clinique d'une pate dentifrice fluoree]. Revue Francaise d'Odontostomatologie 1966; 13: 1109-20.

Held AJ, Spirgi M. Clinical experimentation with a fluoridated toothpaste. SSO Schweiz Monatsschrift Fuer Zahnheilkund 1965; 75: 883-905.

Held AJ, Spirgi M. Clinical experiments with a fluoridated toothpaste [Klinische versuche mit einer mit fluor versetzten zahnpasta]. DDZ (Das Deutsche Zahnarzteblatt) 1966; 20: 288-93.

Held AJ, Spirgi M. Three years of clinical observations with fluoridated toothpastes [Trois ans d'observations cliniques avec des pates dentifrices fluorees]. Bulletin du Groupement International pour la Recherche Scientifique en Stomatologie 1968; 11: 539-70.

Held 1968a {published data only}

Held AJ, Spirgi M. Clinical experimentation with a fluoridated dentifrice [Experimentation clinique d'une pate dentifrice fluoree]. Revue Francaise d'Odontostomatologie 1966; 13: 1109-20.

Held AJ, Spirgi M. Clinical experimentation with a fluoridated toothpaste. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1965; 75: 883-905.

Held AJ, Spirgi M. Clinical experiments with a fluoridated toothpaste [Klinische versuche mit einer mit fluor versetzten zahnpasta]. DDZ (Das Deutsche Zahnarzteblatt) 1966; 20: 288-93.

Held AJ, Spirgi M. Three years of clinical observations with fluoridated toothpastes [Trois ans d'observations cliniques avec des pates dentifrices fluorees]. Bulletin du Groupement International pour la Recherche Scientifique en Stomatologie 1968; 11: 539-70.

Held 1968b {published data only}

Held AJ, Spirgi M. Clinical experimentation with a fluoridated dentifrice [Experimentation clinique d'une pate dentifrice fluoree]. Revue Francaise d'Odontostomatologie 1966; 13: 1109-20.

Held AJ, Spirgi M. Clinical experimentation with a fluoridated toothpaste. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1965; 75: 883-905.

Held AJ, Spirgi M. Clinical experiments with a fluoridated toothpaste [Klinische versuche mit einer mit fluor versetzten zahnpasta]. DDZ (Das Deutsche Zahnarzteblatt) 1966; 20: 288-93.

Held AJ, Spirgi M. Three years of clinical observations with fluoridated toothpastes [Trois ans d'observations cliniques avec des pates dentifrices fluorees]. Bulletin du Groupement International pour la Recherche Scientifique en Stomatologie 1968; 11: 539-70.

Hodge 1980 {published data only}

Hodge HC, Holloway PJ, Davies TG, Worthington HV. Caries prevention by dentifrices containing a combination of sodium monofluorophosphate and sodium fluoride. Report of a 3-year clinical trial. British Dental Journal 1980; 149: 201-4.

Homan 1969 {published and unpublished data}

Homan BT, Messer HH. The comparative effect of three fluoride dentifrices on clinical dental caries in Brisbane schoolchildren. Preliminary report. Journal of Dental Research 1969; 48: 1094.

Howat 1978 {published data only}

Howat AP, Hollaway PJ, Davies TG. Caries prevention by daily supervised use of a MFP gel dentifrice. Report of a 3-year clinical trial. British Dental Journal 1978; 145: 233-5.

Jackson 1967 {published data only}

Jackson D. Allocation to control and experimental groups in short-term clinical trials designed to test a caries preventive. In: Hardwick JL, Dustin JP, Held HR editor(s). Advances in Fluorine Research and Dental Caries Prevention. Oxford: Pergamon Press, 1964: 17-9.

Jackson D, Sutcliffe P. Clinical testing of a stannous fluoride-calcium pyrophosphate children in Yorkshire school children. British Dental Journal 1967; 123: 40-8.

James 1967 {published data only}

James PM, Anderson RJ. Clinical testing of stannous fluoride-calcium pyrophosphate dentifrices in Buckinghamshire school children. British Dental Journal 1967; 123: 33-9.

James PMC. Organization of a clinical trial. In: James PMC, Konig KG, Held HR editor(s). Advances in Fluorine Research and Dental Caries Prevention. Oxford: Pergamon Press, 1966: 33-9.

James 1977 {published data only}

James PM, Anderson RJ, Beal JF, Bradnock G. A 3-year clinical trial of the effect on dental caries of a dentifrice containing 2% sodium monoflurophosphate. Community Dentistry and Oral Epidemiology 1977; 5: 67-72.

Kinkel 1972 {published data only}

Kinkel HJ, Raich R. Caries-inhibiting properties of Na2FPO3 toothpaste after 5-year evaluation studies [Die Karieshe-mung einer Na2FPO3-Zahnpasta nach 5 Jahren Applikation]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1974; 84: 1245-7.

Kinkel HJ, Raich R. Caries prevention by means of a Na2FPO 3 toothpaste after 3 years of application [Die Karieshemmung einer Na2FPO3 -Zahnpasta nach 3 Jahren Applikation]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1972; 82: 1240-4.

Kinkel HJ, Raich R. Effectiveness of a Na2FP03 toothpaste on caries in children [Zur Wirkung einer Na2FPO3-Zahnpasta auf die Karies bei Kindern]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1972; 82: 169-75.

Kinkel HJ, Raich R. The caries-inhibiting property of a Na2FPO3 toothpaste after 4-year use [Die Karieshemmung einer Na2FPO3-Zahnpasta nach 4 Jahren Applikation]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1974; 84: 226-9.

Kinkel HJ, Raich R, Muller M. Caries prevention by means of a Na2FPO3-toothpaste after 7 year's application [Die Karieshemmung durch eine Na2FPO3-Zahnpasta nach 7 Jahren Applikation]. Deutsche Zahnarztliche Zeitschrift 1977; 32: 859-60.

Kinkel HJ, Raich R, Muller M. Caries prevention by the use of a Na2FPO3 containing toothpaste, after 7 years [Die Karieshemmung einer Na2FPO3-Zahnpasta nach 7 Jahren Applikation]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1977; 87: 1218-20.

Kleber 1996 {published data only}

Kleber CJ, Putt MS, Smith CE, Gish CW. Effect of supervised use of an alum mouthrinse on dental caries incidence in caries-susceptible children: a pilot study. ASDC Journal of Dentistry for Children 1996; 63: 393-402.

Koch 1990 {published data only}

Bjarnason S. On dental health in Icelandic children. Swedish Dental Journal Supplement 1989; 57: 1-40.

* Koch G, Bergmann-Arnadottir I, Bjarnason S, Finnbogason S, Hoskuldsson O, Karlsson R. Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: A 3-year controlled clinical trial. Caries Research 1990; 24: 72-9.

Lima 2008 {published data only}

Lima TJ, Ribeiro CC, Tenuta LM, Cury JA. Low-fluoride dentifrice and caries lesion control in children with different caries experience: a randomized clinical trial. Caries Research 2008; 42(1): 46-50.

Lind 1974 {published data only}

Lind OP, Larsen MJ, Moller IJ, von der Fehr FR. A 2% sodium monofluorophosphate toothpaste's caries preventive effect in a Danish fluoride area [En 2% natrium monofluorfosfattandpasta's cariesforebyggende effekt i et dansk fluoromrade]. Tandlaegebladet 1975; 79: 793-9.

Lind OP, Moller IJ, von der Fehr FR, Larsen MJ. Caries-preventive effect of a dentifrice containing 2 percent sodium monofluorophosphate in a natural fluoride area. Results after 3 years. Helvetica Odontologica Acta 1974; 18: 53.

Lind OP, Moller IJ, von der Fehr FR, Larsen MJ. Caries-preventive effect of dentifrice containing 2 percent sodium monofluorophosphate in a natural fluoride area in Denmark. Community Dentistry and Oral Epidemiology 1974; 2: 104-13.

Lind OP, von der Fehr FR, Larsen MJ, Moller IJ. Anti-caries effect of a 2% Na2PO3F-dentifrice in a Danish fluoride area. Community Dentistry and Oral Epidemiology 1976; 4: 7-14.

Lu 1987 {published data only}

Lu KH, Ruhlman CD, Chung KL, Sturzenberger OP, Lehnhoff RW. A three-year clinical comparison of a sodium monofluorophosphate dentifrice with sodium fluoride dentifrices on dental caries in children. Journal of Dentistry for Children 1987; 54(4): 241-4.

Mainwaring 1978 {published data only}

Mainwaring PJ, Naylor MN. A three-year clinical study to determine the separate and combined caries-inhibiting effects of sodium monofluorophosphate toothpaste and an acidulated phosphate-fluoride gel. Caries Research 1978; 12: 202-12.

Mainwaring 1983 {published data only}

* Mainwaring PJ, Naylor MN. A four-year clinical study to determine the caries-inhibiting effect of calcium glycerophosphate and sodium fluoride in calcium carbonate base dentifrices containing sodium monofluorophosphate. Caries Research 1983; 17: 267-76.

Mainwaring PJ, Naylor MN. Anti-caries effects of NaMFP/CaCO3 toothpastes containing calcium glycerohosphate (CaGP) or sodium fluoride (NaF) - A 4 year clinical study. Journal of Dental Research 1981; 60: 1091.

Marks 1994 {published data only}

Marks RG, Conti AJ, Moorhead JE, Cancro L, D'Agostino RB. Results from a three year caries clinical trial comparing NaF and SMFP fluoride formulations. International Dental Journal 1994; 44: 275-85.

Marks RG, D'Agostino R, Moorhead JE, Conti AJ, Cancro L. A fluoride dose response evaluation in an anticaries clinical trial. Journal of Dental Research 1992; 71(6): 1286-91.

Marthaler 1965 {published data only}

Konig KG, Muhlemann HR. Caries inhibiting effect of aminfluoride containing dentifrices tested in an animal experiment and in a clinical study. In: Muhlemann HR, Konig KG editor(s). The Present Status of Caries Prevention by Fluorine-Containing Dentifrices. Caries Symposium Zurich. Berne and Stuttgart: Hans Huber, 1961: 30.

Marthaler T. The caries inhibiting effect of amine fluoride dentifrices in children during three years of unsupervised use. British Dental Journal 1965; 119: 153-63.

Marthaler TM. Caries control with the use of an amine fluoride dentifrice for 5 years. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1965; 75: 509-15.

Marthaler TM. Caries-inhibition after seven years of unsupervised use of an amine fluoride dentifrice. British Dental Journal 1968; 124: 510-5.

Marthaler TM. Caries inhibition with amino fluoride toothpastes following a 7-year-long study [Karieshemmung durch Aminfluoridzahnpasten nach 7 jahriger Studiendauer]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1968; 78: 134-47.

Marthaler TM. The cariostatic effect of amine fluoride containing dentifrices in an unsupervised clinical study. In: Muhlemann HR, Konig KG editor(s). The Present Status of Caries Prevention by Fluorine-Containing Dentifrices. Caries Symposium Zurich. Berne and Stuttgart: Hans Huber, 1961: 14-25.

Marthaler 1965a {published data only}

Konig KG, Muhlemann HR. Caries inhibiting effect of aminfluoride containing dentifrices tested in an animal experiment and in a clinical study. In: Muhlemann HR, Konig KG editor(s). The Present Status of Caries Prevention by Fluorine-Containing Dentifrices. Caries Symposium Zurich. Berne and Stuttgart: Hans Huber, 1961: 30.

Marthaler T. The caries inhibiting effect of amine fluoride dentifrices in children during three years of unsupervised use. British Dental Journal 1965; 119: 153-63.

Marthaler TM. Caries control with the use of an amine fluoride dentifrice for 5 years. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1965; 75: 509-15.

Marthaler TM. Caries-inhibition after seven years of unsupervised use of an amine fluoride dentifrice. British Dental Journal 1968; 124: 510-5.

Marthaler TM. Caries inhibition with amino fluoride toothpastes following a 7-year-long study [Karieshemmung durch Aminfluoridzahnpasten nach 7 jahriger Studiendauer]. SSO Schweizerische Monatsschrift Fuer Zahnheilkund 1968; 78: 134-47.

Marthaler TM. The cariostatic effect of amine fluoride containing dentifrices in an unsupervised clinical study. In: Muhlemann HR, Konig KG editor(s). The Present Status of Caries Prevention by Fluorine-Containing Dentifrices. Caries Symposium Zurich. Berne and Stuttgart: Hans Huber, 1961: 14-25.

Marthaler 1970 {published data only}

Marthaler TM, Konig KG, Muhlemann HR. The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year. Helvetica Odontologica Acta 1970; 14: 67-77.

Marthaler 1970a {published data only}

Marthaler TM, Konig KG, Muhlemann HR. The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year. Helvetica Odontologica Acta 1970; 14: 67-77.

Marthaler 1974 {published data only}

Marthaler TM. Caries-inhibition by an amine fluoride dentifrice. Results after 6 years in children with low caries activity. Helvetica Odontologica Acta 1974; 18(Suppl VIII): 35-44.

Mergele 1968 {published data only}

Mergele M. Report II. An unsupervised brushing study on subjects residing in a community with fluoride in the water. Bulletin of the New York Academy of Medicine 1968; 14: 251-5.

Mitropolous 1984 {published data only}

Mitropoulos CM, Holloway PJ, Davies TGH, Worthington HV. Relative efficacy of dentifrices containing 250 or 1000 ppm F- in preventing dental caries - report of a 32-month clinical trial. Community Dental Health 1984; 1: 193-200.

Muhler 1955 {published data only}

Muhler JC, Radike AW, Nebergall WH, Day HG. A comparison between the anticariogenic effects of dentifrices containing stannous fluoride and sodium fluoride. Journal of the American Dental Association 1955; 51: 556-9.

Muhler 1962 {published data only}

Muhler JC. Effect of a stannous fluoride dentifrice on caries reduction in children during a three year study period. Journal of the Americal Dental Association 1962; 64: 216-24.

Muhler JC. The effect of a stannous fluoride dentifrice on caries reduction in children during a three-year study period (Summary). In: Muhlemann HR, Konig KG editor(s). Caries Symposium Zurich. Berne and Stuttgart: Hans Huber, 1961: 9-13.

Muhler 1970 {published data only}

* Muhler JC. A clinical comparison of fluoride and antienzyme dentifrices. ASDC Journal of Dentistry for Children 1970; 37: 501.

Muhler JC. A clinical comparison of fluoride and antienzyme dentifrices. Journal of Dental Research 1967; IADR Abstr. No 273: 105.

Naylor 1967 {published data only}

Ashley FP, Naylor MN, Emslie RD. Stannous fluoride and sodium monofluorophosphate dentifrices. Clinical testing in London school children--radiological findings. British Dental Journal 1969; 127: 125-8.

Naylor MN, Emslie RD. Clinical testing of stannous fluoride and sodium monofluorophosphate dentifrices in London school children. British Dental Journal 1967; 123: 17-23.

Naylor 1979 {published data only}

Naylor MN, Glass RL. A 3-year clinical trial of calcium carbonate dentifrice containing calcium glycerophosphate and sodium monofluorophosphate. Caries Research 1979; 13: 39-46.

O'Mullane 1997 {published data only}

O'Mullane DM, Kavanagh D, Ellwood RP, Chesters RK, Schafer F, Huntington E, et al. A three-year clinical trial of a combination of trimetaphosphate and sodium fluoride in silica toothpastes. Journal of Dental Research 1997; 76(11): 1776-81.

Peterson 1967 {published data only}

Peterson JK, Williamson L. Comparative effectiveness of a sodium fluoride-acid orthophosphate-insoluble metaphosphate dentifrice on caries reduction in children. Journal of Dental Research 1966; IADR Abstr. No 249: 100.

Peterson JK, Williamson L. Field test of a sodium fluoride dentifrice containing acid orthophosphate and an insoluble metaphosphate abrasive--second year report. Journal of Oral Therapeutics and Pharmacology 1967; 4: 1-4.

Peterson JK, Williamson L. Three-years caries inhibition of a sodium fluoride acid orthophosphate dentifrice compared with a stannous fluoride dentifrice and a non-fluoride dentifrice. Journal of Dental Research 1968; IADR Abstr. No 255: 101.

Peterson 1979 {published data only}

* Peterson JK. A supervised brushing trial of sodium monofluorophosphate dentifrices in a fluoridated area. Caries Research 1979; 13: 68-72.

Peterson JK, Williamson L, Casad R. Caries inhibition with MFP-calcium carbonate dentifrice in fluoridated area. Journal of Dental Research 1975; 54: L85.

Piccione 1979 {published data only (unpublished sought but not used)}

Piccione N. Controlled clinical study of the caries prophylactic activity of a new bifluoride toothpaste (sodium monofluorophosphate + sodium fluoride) [Studio clinico controllato sull'attivita carioprofilattica di una nuova pasta dentifricia bifluorurata (monofluorofosfato di sodio + fluoruro di sodio)]. Minerva Stomatologica 1979; 28: 325-7.

Powell 1981 {published data only}

Powell KR, Barnard PD, Craig GG. Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth. Journal of Dental Research 1981; 60: 1648-54.

Reed 1973 {published data only}

Reed MW. Clinical evaluation of three concentrations of sodium fluoride in dentifrices. Journal of the American Dental Association 1973; 87: 1401-3.

Reed 1975 {published data only}

Reed MW, King JD. A clinical evaluation of a sodium fluoride dentifrice. Journal of Dental Research 1970; IADR Abstr. No 340: 133.

* Reed MW, King JD. A clinical evaluation of a sodium fluoride dentifrice. Pharmacology and Therapeutics in Dentistry 1975; 2: 77-82.

Ringelberg 1979 {published data only}

Ringelberg ML, Webster DB. Effects of an amine fluoride mouthrinse and dentifrice on the gingival health and the extent of plaque of school children. Journal of Periodontology 1977; 48: 350-3.

Ringelberg ML, Webster DB, Dixon DO. Effects of an amine fluoride dentifrice and mouthrinse on the dental caries of school children after 18 months. Journal of Preventive Dentistry 1978; 5: 26-30.

Ringelberg ML, Webster DB, Dixon DO, Fairchild S, Driscoll WS. Results of gingival, plaque, and stain assessments after 30 months use of amine fluorides and their inorganic counterparts. Pharmacology and Therapeutics in Dentistry 1979; 4: 27-31.

Ringelberg ML, Webster DB, Dixon DO, LeZotte DC. The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use. Journal of the American Dental Association 1979; 98: 202-8.

Ripa 1988 {published data only}

Ripa LW, Leske , GS , Sposato A, Varma A. Clinical comparisom of the caries inhibition of two mixed NaF-Na2PO3F dentifrices containing 1,000 and 2,500 ppm F compared to a conventional Na2PO3F dentifrice containing 1,000 ppm F: 3-year results. Journal of the American Dental Association 1988; 116: 69-73.

Ripa LW, Leske GS, Sposato A, Varma A. Clinical comparisom of the caries inhibition of two mixed NaF-Na2PO3F dentifrices containing 1,000 and 2,500 ppm F compared to a conventional Na2PO3F dentifrice containing 1,000 ppm F: results after two years. Caries Research 1987; 21: 149-57.

Rule 1984 {published data only}

Rule J, Smith M, Truelove R, Macko D, Castaldi C. Anticaries properties of a 0.78% sodium monofluorophosphate-silica base dentifrice. Journal of Dental Research 1982; 61: 281.

* Rule JT, Smith MR, Truelove RB, Macko DJ, Castaldi CR. Caries inhibition of a dentifrice containing 0.78% sodium monofluorophosphate in a silica base. Community Dentistry and Oral Epidemiology 1984; 12: 213-7.

Segal 1967 {published data only}

Segal AH, Stiff RH, George WA. Caries inhibiting effectiveness of a stannous fluoride-insoluble sodium metaphosphate (IMP) dentifrice in children. Two year results. Journal of Dental Research 1966; IADR Abstr. No 250: 101.

* Segal AH, Stiff RH, George WA, Picozzi A. Cariostatic effect of a stannous fluoride-containing dentifrice on children: two-year report of a supervised toothbrushing study. Journal of Oral Therapeutics and Pharmacology 1967; 4: 175-80.

Slack 1964 {published data only}

Slack GL, Martin WJ. The use of a dentifrice containing stannous fluoride in the control of dental caries. Report of an unsupervised clinical trial. British Dental Journal 1964; 117: 275-80.

Slack 1967 {published data only}

Slack GL, Berman DS, Martin WJ, Young J. Clinical testing of stannous fluoride-insoluble metaphosphate dentifrice in Kent girls. British Dental Journal 1967; 123: 9-16.

Slack 1967a {published data only}

Slack GL, Berman DS, Martin WJ, Hardie JM. Clinical testing of a stannous fluoride-calcium pyrophosphate dentifrice in Essex school girls. British Dental Journal 1967; 123: 26-33.

Slack 1971 {published data only}

Slack GL, Bulman JS, Osborn JF. Clinical testing of fluoride and non-fluoride containing dentifrices in Hounslow school children. British Dental Journal 1971; 130: 154-8.

Sonju Clasen 1995 {published data only}

Sonju Clasen AB, Ogaard B, Sonju T. A comparison of the anticaries effect on the primary dentition of two dentifrices containing 250 pppm and 1450 ppm fluoride. International Journal of Paediatric Dentistry 1995; 5: 3-8.

Stephen 1988 {published data only}

Stephen KW, Creanor SL, Russell JI, Burchell CK, Huntington E, Downie CF. A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results. Community Dentistry and Oral Epidemiology 1988; 16(6): 321-5.

Stephen 1994 {published data only}

Chestnutt IG, Schaefer F, Jacobson APM, Stephen KW. The influence of toothbrushing frequency and post-brushing rinsing on caries experience in a clinical trial. Community Dentistry and Oral Epidemiology 1998; 26: 406-11.

* Stephen KW, Chestnutt IG, Jacobson AP, McCall DR, Chesters RK, Huntington E, et al. The effect of NaF and SMFP toothpastes on three-year caries increments in adolescents. Indian Dental Journal 1994; 33(3 Suppl 1): 287-95.

Stookey 2004 {published data only}

Stookey GK, Mau MS, Isaacs RL, Gonzalez-Gierbolini C, Bartizek RD, Biesbrock AR. The relative anticaries effectiveness of three fluoride-containing dentifrices in Puerto Rico. Caries Research 2004; 38(6): 542-50.

Thomas 1966 {published data only}

Thomas AE, Jamison HC. Effect of SnF2 dentrifices on caries in children: two-year clinical study of supervised brushing in children's homes. Journal of the American Dental Association 1966; 73: 844-52.

Torell 1965 {published data only}

Torell P. The Goteborg studies of methods of applying fluorides topically. In: Hardwick JL, Held HR, Konig KG editor(s). Advances in Fluorine Research and Dental Caries Prevention. Vol. 3, Oxford: Pergamon Press, 1965: 255-8.

Torell P, Ericsson Y. Two-year clinical tests with different methods of local caries-preventive fluorine application in Swedish school-children (Part I: The Goteborg study). Acta Odontologica Scandinavica 1965; 23: 287-312.

Torell 1965a {published data only}

Torell P, Ericsson Y. Two-year clinical tests with different methods of local caries-preventive fluorine application in Swedish school-children (Part II: The Sodertalje study). Acta Odontologica Scandinavica 1965; 23: 313-22.

Torell 1965b {published data only}

Torell P, Ericsson Y. Two-year clinical tests with different methods of local caries-preventive fluorine application in Swedish school-children (Part II: The Sodertalje study). Acta Odontologica Scandinavica 1965; 23: 313-22.

Weisenstein 1972 {published data only}

Weisenstein PR, Zacherl WA. A multiple-examiner clinical evaluation of a sodium fluoride dentifrice. Journal of the American Dental Association 1972; 84: 621-3.

Winter 1989 {published data only}

Holt RD, Morris CE, Winter GB, Downer MC. Enamel opacities and dental caries in children who used a low fluoride toothpaste between 2 and 5 years of age. International Dental Journal 1994; 44: 331-41.

* Winter GB, Holt RD, Williams BF. Clinical trial of a low fluoride toothpaste for young children. International Dental Journal 1989; 39: 227-35.

Zacherl 1970 {published data only}

Zacherl WA, McPhail CW. Evaluation of a stannous fluoride-calcium pyrophosphate dentifrice. Journal of the Canadian Dental Association 1965; 31: 174-80.

Zacherl WA, McPhail CW. Final report on the efficacy of a stannous fluoride-calcium pyrophosphate dentifrice. Journal of the Canadian Dental Association 1970; 36: 262-4.

Zacherl 1970a {published data only}

Zacherl WA, McPhail CW. Evaluation of a stannous fluoride-calcium pyrophosphate dentifrice. Journal of the Canadian Dental Association 1965; 31: 174-80.

Zacherl WA, McPhail CW. Final report on the efficacy of a stannous fluoride-calcium pyrophosphate dentifrice. Journal of the Canadian Dental Association 1970; 36: 262-4.

Zacherl 1972 {published data only}

Zacherl WA. Clinical evaluation of an aged stannous fluoride-calcium pyrophosphate dentifrice. Journal of the Canadian Dental Association 1972; 38: 155-7.

Zacherl 1972a {published data only}

Zacherl WA. A clinical evaluation of a sodium fluoride and stannous fluoride dentifrices. Journal of Dental Research 1968; IADR Abstr. No 253: 101.

* Zacherl WA. Clinical evaluation of neutral sodium fluoride, stannous fluoride, sodium monofluorophosphate and acidulated fluoride-phosphate denifrices. Journal of the Canadian Dental Association 1972; 38: 35-8.

Zacherl 1973 {published data only}

* Zacherl WA. A clinical evaluation of a stannous fluoride and a sarcosinate dentifrice. ASDC Journal of Dentistry for Children 1973; 40: 451-3.

Zacherl WA. Clinical evaluation of a sarcosinate dentifrice. Journal of Dental Research 1970; IADR Abstr. No 339: 133.

Zacherl 1981 {published data only}

Biesbrock AR, Faller RV, Bartizek RD, Court LK, McClanahan SF. Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial. Journal of Clinical Dentistry 1998; 9: 5-10.

Caplan DJ, Slade GD, Biesbrock AR, Bartizek RD, McClanahan SF, Beck JD. A comparison of increment and incidence density analyses in evaluating the anticaries effects of two dentifrices. Caries Research 1999; 33: 16-22.

Zacherl WA. A three-year clinical caries evaluation of the effect of a sodium fluoride-silica abrasive dentifrice. Pharmacology and Therapeutics in Dentistry 1981; 6: 1-7.

Zacherl WA. Clinical evaluation of a sodium fluoride-silica abrasive dentifrice. Journal of Dental Research 1981; 60: 577.

Referencias de los estudios excluidos de esta revisión

Andlaw 1983 {published data only}

Andlaw RJ, Palmer JD, King J, Kneebone SB. Caries preventive effects of toothpastes containing monofluorophosphate and trimetaphosphate: a 3-year clinical trial. Community Dentistry and Oral Epidemiology 1983; 11: 143-7.

Baysan 2001 {published data only}

Baysan A, Lynch E, Ellwood R, Davies R, Petersson L, Borsboom P. Reversal of primary root caries using dentifrices containing 5,000 ppm and 1,100 ppm fluoride. Caries Research 2001; 35: 41-6.

Beiswanger 1981 {published data only}

Beiswanger BB, Gish CW, Mallatt ME. A three-year study of the effect of a sodium fluoride-silica abrasive dentifrice on dental caries. Pharmacology and Therapeutics in Dentistry 1981; 6(1-2): 9-16.

Beiswanger 1989 {published data only}

Beiswanger BB, Lehnhoff RW, Mallatt ME, Mau MS, Stookey GK. A clinical evaluation of the relative cariostatic effect of dentifrices containing sodium fluoride or sodium monofluorophosphate. Journal of Dentistry for Children 1989; 56(4): 270-6.

Bibby 1945 {published data only}

Bibby BG. A test of the effect of fluoride containing-dentifrices on dental caries. Journal of Dental Research 1945; 24: 297-303.

Biesbrock 2003 {published data only}

Biesbrock AR, Bartizek RD, Gerlach RW, Jacobs SA, Archila L. Effect of three concentrations of sodium fluoride dentifrices on clinical caries. American Journal of Dentistry 2003; 16(2): 99-104.

Bixler 1966 {published data only}

Bixler D, Muhler JC. Effectiveness of a stannous fluoride-containing dentifrice in reducing dental caries in children in a boarding school environment. Journal of the American Dental Association 1966; 72: 653-8.

Blinkhorn 1988 {published data only}

Blinkhorn AS, Kay EJ. A clinical study in children: comparing the anticaries effect of three fluoride dentifrices. Clinical Preventive Dentistry 1988; 10(3): 14-6.

Curnow 2002 {published data only}

* Curnrow MMT, Pine CM, Burnside G, Nicholson JA, Chesters RK, Huntington E. A randomised trial of the efficacy of supervised toothbrushing in high caries risk children. Caries Research 2002; 36: 294-300.

Pine CM, Curnrow MMT, Burnside G, Nicholson JA, Roberts AJ. Caries prevalence four years after the end of a randomised controlled trial. Caries Research 2007; 41: 431-6.

Cutress 1992 {published data only}

Cutress T, Tahiati Howell P, Finidori C, Abdullah F. Caries preventive effect of high fluoride and xylitol containing dentifrices. Journal of Dentistry for Children 1992; 59(4): 313-8.

De Paola 1993 {published data only}

DePaola PF, Soparkar PM, Triol C, Volpe AR, Garcia L, Duffy J, et al. The relative anticaries effectiveness of sodium monofluorophosphate and sodium fluoride as contained in currently available dentifrice formulations. American Journal of Dentistry 1993; 6: S7-S12.

Dolles 1980 {published and unpublished data}

Dolles OK, Eriksen HM, Gjermo P. Tooth stain during 2 years' use of chlorhexidine - and fluoride-containing dentifrices. Scandinavian Journal of Dental Research 1979; 87: 268-74.

Dolles OK, Gjermo P. Caries increment and gingival status during 2 years' use of chlorhexidine- and fluoride-containing dentifrices. Scandinavian Journal of Dental Research 1980; 88: 22-7.

Downer 1976 {published data only}

* Downer MC, Holloway PJ, Davies TG. Clinical testing of a topical fluoride caries preventive programme. British Dental Journal 1976; 141: 242-7.

Downer MC, Spencer SJ. Evaluating a dental caries preventive programme. Royal Society Health Journal 1973; 93: 129-32.

Edlund 1977 {published data only}

Edlund K, Koch G. Effect on caries of daily supervised toothbrushing with sodium monofluorophosphate and sodium fluoride dentifrices after 3 years. Scandinavian Journal of Dental Research 1977; 85: 41-5.

Ennever 1980 {published data only (unpublished sought but not used)}

Ennever J, Peterson JK, Hester WR, Segreto VA, Radike AW. Influence of alkaline pH on the effectiveness of sodium fluoride dentifrices. Journal of Dental Research 1980; 59: 658-61.

Feng 2007 {published data only}

Feng Y, Yin W, Hu D, Zhang YP, Ellwood RP, Pretty IA. Assessment of autofluoressence to detect the remineralization capabilities of sodium fluoride monofluorophosphate and non-fluoride dentifrices. Caries Research 2007; 41: 358-64.

Finn 1963 {published data only}

Finn SB, Jamison HC. A comparative clinical study of three dentifrices. ASDC Journal of Dentistry for Children 1963; 30: 17-25.

Frankl 1968 {published data only}

Frankl SN, Alman JE. Report of a three-year clinical trial comparing a toothpaste containing sodium monofluorophosphate with two marketed products. Journal of Oral Therapeutics and Pharmacology 1968; 4(6): 443-50.

Gerdin 1972 {published data only}

Gerdin P. Studies in dentifrices VI: The inhibitory effect of some grinding and non-grinding fluoride dentifrices on dental caries. Swedish Dental Journal 1972; 65: 521-32.

Gish 1965 {published data only}

Gish CW, Muhler JC. Effect on dental caries in children in a natural fluoride area of combined use of three agents containing stannous fluoride: a prophylactic paste, a solution and a dentifrice. Journal of the American Dental Association 1965; 70: 914-20.

Hargreaves 1973 {published data only}

Hargreaves JA, Chester CG. Clinical trial among Scottish children of an anti-caries dentifrice containing 2 percent sodium monofluorophosphate. Community Dentistry and Oral Epidemiology 1973; 1: 47-57.

Heidmann 1997 {published data only}

Heidmann J, Poulsen S. Comparative three-year caries protection from an aluminium-containing and a fluoride-containing toothpaste. Caries Research 1997; 31: 85-90.

Hill 1959 {published data only}

Hill TJ. Fluoride dentifrices. Journal of the American Dental Association 1959; 59: 1121-7.

Horowitz 1966 {published data only}

Horowitz HS, Chamberlin SR. Evaluation of a stannous fluoride dentifrice for use in dental public health programs. II. Operational procedures. Journal of the American Dental Association 1966; 73: 1090-4.

Horowitz HS, Law FE, Thompson MB, Chamberlain SR, Shirley R. Evaluation of a stannous fluoride dentifrice for use in dental public health programs. I. Basic findings. Journal of the American Dental Association 1966; 72: 408-21.

Horowitz HS, Thompson MB, Mary B. Evaluation of a stannous fluoride dentifrice for use in dental public health programs. III. Supplementary findings. Journal of the American Dental Association 1967; 74: 979-86.

Horowitz 1966a {published data only}

Horowitz HS, Lucye HS. A clinical study of stannous fluoride in a prophylaxis paste and as a solution. Journal of Oral Therapeutics and Pharmacology 1966; 3(1): 17-25.

Jordan 1959 {published data only}

* Jordan WA, Peterson JK. Caries-inhibiting value of a dentifrice containing stannous fluoride: final report of a two year study. Journal of the American Dental Association 1959; 58: 42-4.

Jordan WA, Peterson JK. Caries-inhibiting value of a dentifrice containing stannous fluoride: first year report of a supervised toothbrushing study. Journal of the American Dental Association 1957; 54: 589-94.

Koch 1967 {published data only}

Hollender L, Koch G. Influence of topical application of fluoride on rate of progress of carious lesions in children. A long-term roentgenographic follow-up. Odontologisk Revy 1969; 20: 37-41.

Koch G. Effect of sodium fluoride in dentifrice and mouthwash on dental caries in school children. 8. Effect of daily supervised toothbrushing with a sodium fluoride dentifrice. A 3-year double-blind clinical test. Odontologisk Revy 1967; 18: 48-66.

Koch G. Effect of sodium fluoride in dentifrice and mouthwash on incidence of dental caries in school children. 9. Effect of unsupervised toothbrushing at home with sodium fluoride dentifrice. A 2-year double-blind clinical test. Odontologisk Revy 1967; 18: 67-71.

Koch G. Long-term study of effect of supervised toothbrushing with a sodium fluoride dentifrice. Caries Research 1970; 4: 149-57.

Koch G, Lindhe J. The effect of supervised oral hygiene on the gingiva of children. The effect of sodium fluoride. Journal of Periodontal Research 1967; 2: 64-9.

Koch G, Lindhe J. The state of the gingivae and the caries-increment in school-children during and after withdrawal of various prophylactic measures. In: McHugh WD editor(s). Dental Plaque. A Symposium Held at the University of Dundee, 22 to 24 September, 1969. Edinburgh and London: E & S Livingstone, 1970: 271-81.

Koch 1972 {published data only}

Koch G. Comparison and estimation of effect on caries of daily supervised toothbrushing with a dentifrice containing sodium fluoride and a dentifrice containing potassium fluoride and manganese chloride. Odontologisk Revy 1972; 23: 341-54.

Koch 1982 {published data only}

Koch G, Petersson LG, Kling E, Kling L. Efffect of 250 ppm and 1000 ppm fluoride dentifrice on caries. Swedish Dental Journal 1982; 6: 233-8.

Kunzel 1977 {published data only}

Franke W, Kunzel W, Treide A, Bluthner K. Caries prevention by means of aminofluoride after 7 years of collectively conducted oral hygiene [Karieshemmung durch Aminfluorid nach 7 Jahren kollektiv angeleiteter Mundhygiene]. Stomatologie der DDR 1977; 27: 13-6.

Franke W, Kunzel W, Treide A, Bluthner K. Longitudinal studies on the inhibition of caries by amine fluoride within the framework of guided and supervised oral hygiene actions [Langsschnittstudien zur Karieshemmung durch Aminfluorid im Rahmen angeleiteter und uberwachter Mundhygiene-Aktionen]. Stomatologie der DDR 1976; 26: 532-7.

Franke W, Kunzel W, Treide A, Bluthner K. Wirkungsweise und effwktivitat lokal applizierter aminofluoride zur kariespravention. Medicamentum 1975; 16: 362.

Geiger L, Kunzel W, Treide A. Comparative clinical-radiological studies on the increase of caries after controlled mouth hygiene with aminofluoride [Vergleichende klinisch-rontgenologische Untersuchungen uber den Karieszuwachs nach kontrollierter Mundhygiene mit Aminfluorid]. Deutsch Stomatologie 1971; 21: 132-5.

Kunzel W. Comparative clinical and x-ray study of the cariostatic effectiveness of aminofluorides [Sravnitel'noe kliniko-rentgenologicheskoe issledovanie protivokarioznoi effektivnosti aminoftoridov]. Stomatologiia Mosk 1980; 59: 67-70.

Kunzel W, Franke W, Treide A. Clinical-radiological parallel control of a longitudinal study of the anti-caries effect of aminofluoride applied locally for 7 years in a double-blind test [Klinisch-rontgenologische Paralleluberwachung einer Langsschnittstudie zum Nachweis der Karieshemmenden Effektivitat 7 Jahre lokal angewandten Aminfluorids im Doppelblindtest]. Zahn Mund und Kieferheilkund mit Zentralblatt 1977; 65: 626-37.

Kyes 1961 {published data only}

Kyes FM, Overton NJ, McKean TW. Clinical trials of caries inhibitory dentifrices. Journal of the American Dental Association 1961; 63: 189-93.

Lu 1985 {published data only}

Lu KH, Yen DJ, Zacherl WA, Ruhlman CD, Sturzenberger OP, Lehnhoff RW. The effect of a fluoride dentifrice containing an anticalculus agent on dental caries in children. ASDC Journal of Dentistry for Children 1985; 52: 449-51.

Mergele 1968a {published data only}

Mergele M. A supervised brushing study in state institution schools. Bulletin of the New York Academy of Medicine 1968; 14: 247-50.

Moller 1968 {published data only}

Bay I, Moller IJ. The effect of a sodium monofluorophosphate dentifrice on the gingiva. Journal of Periodontal Research 1969; 4: 103-8.

Moller IJ, Holst JJ, Sorensen E. Caries reducing effect of a sodium monofluorophosphate dentifrice. British Dental Journal 1968; 124: 209-13.

Moller IJ, Holst JJ, Sorensen E. Effect of a toothpaste containing sodium monofluorophosphate with controlled toothbrushing [Effekten af en natriummonofluorfosfatholdig tandpasta ved kontrolleret tandborstning]. Tandlaegebladet 1968; 72: 705-17.

Muhler 1958 {published data only}

Muhler JC. The effect of a modified stannous fluoride-calcium pyrophosphate dentifrice on dental caries in children. Journal of Dental Research 1958; 37: 448-50.

Muhler 1960 {published data only}

* Muhler JC. Combined anticariogenic effect of a single stannous fluoride solution and the unsupervised use of a stannous fluoride-containing dentifrice II. Results at the end of three years. Journal of Dental Research 1960; 39: 955-8.

Muhler JC. The combined anticariogenic effect of a single stannous fluoride treatment and the unsupervised use of a stannous fluoride-containing dentifrice. Journal of Dental Research 1959; 38: 994-7.

Murray 1980 {published data only}

Murray JJ, Shaw L. A 3-year clinical trial into the effect of fluoride content and toothpaste abrasivity on the caries inhibitory properties of a dentifrice. Community Dentistry and Oral Epidemiology 1980; 8: 46-51.

Onisi 1970 {published data only}

Onisi M, Tani H. Clinical trial on the reduction of caries incidence by use of two different fluoride dentifrices. Koku Eisei Gakkai Zasshi 1970; 20: 105-11.

Patz 1970 {published data only}

Patz J, Naujoks R. The caries prophylactic effect of an aminofluoride containing toothpaste in adolescents after 3 years of controlled use [Die kariesprophylaktische Wirkung einer aminfluoridhaltigen Zahnpaste bei Jugendlichen nach dreijahrigem unuberwachten Gebrauch]. Deutsche Zahnarztliche Zeitschrift 1970; 25: 617-25.

Peffley 1960 {published data only}

Peffley GE, Muhler JC. Effect of a commercial stannous fluoride dentifrice under controlled bruhing habits on dental caries incidence in children: preliminary report. Journal of Dental Research 1960; 39: 871-4.

Petersson 1991 {published data only}

Petersson LG, Borkhed D, Gleerup A, Johansson M, Jonsson G. Caries-preventive effect of dentifrices containing various types and concentrations of fluorides and sugar alcohols. Caries Research 1991; 25: 74-9.

Ran 1991 {published data only (unpublished sought but not used)}

Ran F, Gedalia I, Fried M, Hadani P, Tved A. Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects. Journal of Oral Rehabilitation 1991; 18: 311-6.

Riethe 1975 {published data only (unpublished sought but not used)}

Riethe P, Schubring G. Clinical studies on a sodium monofluorophosphate toothpaste in school children [Klinische Prufung einer Natriummonofluorphosphat-Zahnpaste an Schulkindern]. Deutsche Zahnarztliche Zeitschrift 1975; 30: 513-7.

Ripa 1990 {published data only}

* Ripa LW, Leske GS, Triol CW, Volpe AR. Clinical study of the anticaries efficacy of three fluoride dentifrices containing anticalculus ingredients: Three year (final) results. Journal of Clinical Dentistry 1990; 2(2): 29-33.

Triol CW, Ripa LW, Leske GS, Volpe AR. A clinical study of the anticaries efficacy of three fluoride dentifrices containing anticalculus ingredients: one and two-year results. Journal of Clinical Dentistry 1988; 1: 48-50.

Saporito 2000 {published data only}

Saporito RA, Boneta ARE, Feldman CA, Cinotti W, Sintes JL, Stewart B, et al. Comparative anticaries efficacy of sodium fluoride and sodium monofluorophosphate dentifrices. A two-year clinical trial on children in New Jersey and Puerto Rico. American Journal of Dentistry 2000; 13(4): 221-6.

Sjorgren 1995 {published data only}

Sjorgen K, Birkhed D, Rangmar B. Effect of a modified toothpaste technique on approximal caries in preschool children. Caries Research 1995; 29: 435-41.

Stookey 1975 {published data only (unpublished sought but not used)}

Stookey GK, Beiswanger BB. Influence of an experimental sodium fluoride dentifrice on dental caries incidence in children. Journal of Dental Research 1975; 54: 53-8.

Tavener 2006 {published data only}

Tavener JA, Davies GM, Davies RM, Ellwood RP. The prevalence and severity of fluorosis in children who received toothpaste containing either 440 or 1450 ppm F from the age of 12 months in deprived and less deprived communities. Caries Research 2006; 40: 66-72.

Thomas 1970 {published data only}

Thomas AE, Jamison HC. Effect of a combination of two cariostatic agents in children: two-year clinical study of supervised brushing in children's homes. Journal of the American Dental Association 1970; 81(1): 118-24.

Triol 1987 {published data only}

Triol CW, Mandanas BY, Juliano GF, Yraolo B, Cano-Arevalo M, Volpe AR. A clinical study of children comparing anticaries effect of two fluoride dentifrices. A 31-month study. Clinical Preventive Dentistry 1987; 9(2): 22-4.

You 2002 {published data only}

You BJ, Jian WW, Sheng RW, Jun Q, Wa WC, Bartizek RD, et al. Caries prevention in Chinese children with a sodium fluoride dentifrice delivered through a kindergarten-based oral health program in China. Journal of Clinical Dentistry 2002; 13: 179-84.

Referencias de los estudios en espera de evaluación

Horowitz 1976 {published data only}

Kinkel 1968 {published data only}

Kinkel HJ, Stolte G. On the effect of a sodium monofluorophosphate-bromochlorophenol containing toothpaste in a chronic animal experiment and on caries in children during a 2-year long unsupervised use [Xur Wirkung einer natriummonofluorophosphat- und bromchlorophenhaltigen Zahnpasta im chronischen Tierexperiment und auf die Karies bei Kindern wahrend eines zqei Jahre langen, unuberwachten Gebrauches]. Deutsche Zahnarzteblatt 1968; 22: 455-60.

Takeuchi 1968 {published data only}

Takeuchi M, Shimizu T, Kawasaki T, Kizu T. A field study effect of a dentifrice containing sodium monofluorophosphate in caries prevention. Koku Eisei Gakkai Zasshi 1968; 18: 26-38.

Referencias adicionales

Abrams 1972

Abrams AM, McClendon BJ, Horowitz HS. Confidence intervals for percentage reductions. Journal of Dental Research 1972; 51(2): 492-7.

Ammari 2003

Ammari AB, Bloch-Zupan A, Ashley PF. Systematic review of studies comparing the anti-caries efficacy of children's toothpaste containing 600 ppm of fluoride or less with high fluoride toothpastes of 1,000 ppm or above. Caries Research 2003; 37(2): 85-92.

Bartizek 2001

Bartizek RD, Gerlach RW, Faller RV, Jacobs SA, Bollmer BW, Biesbrock AR. Reduction in dental caries with four concentrations of sodium fluoride in a dentifrice: a meta-analysis evaluation. Journal of Clinical Dentistry 2001; 12(3): 57-62.

Clarkson 1993

Clarkson JE, Ellwood RP, Chandler RE. A comprehensive summary of fluoride dentifrice caries clinical trials. American Journal of Dentistry 1993; 6 Spec No: S59-106.

Cooper 2006

Cooper NJ, Sutton AJ, Lu G, Khunti K. Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation. Archives of Internal Medicine 2006; 166(12): 1269-75.

Davies 2002

Davies GM, Worthington HV, Ellwood RP, Bentley EM, Blinkhorn AS, Taylor GO, et al. A randomised controlled trial of the effectiveness of providing free fluoride toothpaste from the age of 12 months on reducing caries in 5-6 year old children. Community Dental Health 2002; 19(3): 131-6.

DoH 2007

Department of Health/British Association for the Study of Community Dentistry. Delivering better oral health: An evidence-based toolkit for prevention. Department of Health 2007.

EAPD 2009

European Academy of Paediatric Dentistry. EAPD guidelines on early childhood caries (ECC). www.eapd.gr 2009.

FDI World Dental Federation 2006

FDI World Dental Federation. Oral health through fluoride. www.fdiworldental.org/public_health/3_2fluoride.html. 2006.

Higgins 2008

Higgins J, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions 5.0.1 (updated September 2008). The Cochrane Collaboration, 2008. Available from: www.cochrane-handbook.org.

IADR/WHO/BASCD 2005

IADR/WHO/BASCD . The Liverpool declaration: promoting oral health in the 21st century. www.who.int/oral_health/events/liverpool_declaration/en/index.html 2005.

Jansen 2006

Jansen JP. Self-monitoring of glucose in type 2 diabetes mellitus: a Bayesian meta-analysis of direct and indirect comparisons. Current Medical Research and Opinion 2006; 22(4): 671-81.

Lancet 2009

Editorial . Oral health: prevention is key. Lancet 2009; 373(9657): 1.

Marinho 2002

Marinho VCC, Higgins JPT, Logan S, Sheiham A. Fluoride varnishes for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2002, Issue 1. [DOI: 10.1002/14651858.CD002279]

Marinho 2003

Marinho VCC, Higgins JPT, Logan S, Sheiham A. Topical fluoride (toothpastes, mouthrinses, gels or varnishes) for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2003, Issue 4. [DOI: 10.1002/14651858.CD002782]

Marinho 2004

Marinho VCC, Higgins JPT, Sheiham A, Logan S. Combinations of topical fluoride (toothpastes, mouthrinses, gels, varnishes) versus single topical fluoride for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD002781.pub2]

Marinho a 2002

Marinho VCC, Higgins JPT, Logan S, Sheiham A. Fluoride gels for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2002, Issue 1. [DOI: 10.1002/14651858.CD002280]

Marinho a 2003

Marinho VCC, Higgins JPT, Logan S, Sheiham A. Fluoride mouthrinses for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD002284]

Marinho a 2004

Marinho VCC, Higgins JPT, Sheiham A, Logan S. One topical fluoride (toothpastes, or mouthrinses, or gels, or varnishes) versus another for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD002780.pub2]

Marinho b 2003

Marinho VCC, Higgins JPT, Sheiham A, Logan S. Fluoride toothpastes for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2003, Issue 1. [DOI: 10.1002/14651858.CD002278]

Petersen 2003

Petersen PE. The World Oral Health Report 2003: continuous improvement of oral health in the 21st century - the approach of the WHO Global Oral Health Programme. Community Dentistry and Oral Epidemiology 2003; 31 Suppl 1: 3-23.

Petersen 2009

Petersen PE. Global policy for improvement of oral health in the 21st century - implications to oral health research of World Health Assembly 2007, World Health Organization. Community Dentistry and Oral Epidemiology 2009; 37(1): 1-8.

Steiner 2004

Steiner M, Helfenstein U, Menghini G. Effect of 1000 ppm relative to 250 ppm fluoride toothpaste. A meta-analysis. American Journal of Dentistry 2004; 17(2): 85-8.

Twetman 2003

Twetman S, Axelsson S, Dahlgren H, Holm AK, Kallestal C, Lagerlof F, et al. Caries-preventive effect of fluoride toothpaste: a systematic review. Acta Odontologica Scandinavica 2003; 61(6): 347-55.

Wong 2010

Wong MCM, Glenny AM, Tsang BWK, Lo ECM, Worthington HV, Marinho VCC. Topical fluoride as a cause of dental fluorosis in children. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD007693.pub2]

Tablas

Características de los estudios

Características de los estudios incluidos [ordenados por ID del estudio]

Abrams 1980

Methods

Stratified random allocation; double-blind; placebo-controlled; 48% drop out after 3 years (study duration = 3 years). Reasons for high drop out described: change of residence, absenteeism, non-adherence to study protocol; no differential group losses.

Participants

1141 children analysed at 3 years (available at final examination).
Age range at start: 5-12 years.
Surfaces affected at start: 3.2 DFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1976.
Location: USA.

Interventions

FT (2 groups) versus PL
(both SnF2 groups = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: silica gel in one SnF2 and placebo toothpaste, Ca pyrophosphate in the other SnF2 toothpaste.

Outcomes

3yNetDFS increment - (E+U) (CA)cl+(ER)xr.
Reported at 1, 2 and 3 years follow-ups.

DMFT.
DMFS.
DFT.
MD-DFS.
DFT rate.
DFS rate.

Notes

Participants randomised (n = 2210).
Baseline characteristics (DFS) 'balanced' .
Clinical (VT) caries assessment by 2 examiners, diagnostic threshold = CA. Radiographic assessment (postBW) by 2 examiners; diagnostic threshold = ER. State of tooth eruption included = E/U. Intra- and inter-examiner reproducibility of clinical caries diagnosis (DFS) assessed annually by duplicate examination of 10% random sample (percentage of times diagnosis replicated in all 3 examinations ranged 42% to 97% and 77% to 92% for both examiners and for each respectively).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Children were randomly assigned to one of 3 treatment groups. A stratified sequential sampling technique was used within each school to balance the sample size with respect to sex and grade level for each dentifrice."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "A 3 year double-blind study of a dentifrice containing 0.4% stannous fluoride and a placebo..."

"The examiners at all times were unaware of the children's dentifrice assignment."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 48% in 3 years. Drop out by group: 357/740 FD1, 343/721 FD2, 369/749 PL. Reasons for losses: Change of residence, absenteeism, exclusion due to non-adherence to study requirements.

Comment: Numbers lost were high for the length of follow-up. No differential loss between groups. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (E+U) (CA)cl+(ER)xr, reported at 1, 2 and 3 years follow-ups.
DMFT.
DMFS.
DFT.
MD-DFS.
DFT rate.
DFS rate.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported: DFS: 2.90 FD1, 3.28 FD2, 2.94 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quotes: "Provisions were made ensuring the randomization process to assure that only one dentifrice code would be available in each household....A letter to parents was attached, giving brushing instructions and urging use of only the assigned dentifrice."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Andlaw 1975

Methods

Stratified random allocation; double-blind; placebo-controlled; 13% drop out after 3 years (study duration = 3 years). Main reasons for attrition described: moved away, absent at final examination; no differential group losses.

Participants

740 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years. Surfaces affected at start: 6.9 DFS.
Background exposure to fluoride: none reported.
Year study began: 1970.
Location: UK.

Interventions

FT versus PL
(SMFP group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Al oxide trihydrate.

Outcomes

3yNetDFS increment - (E+U)(CA)cl+(ER)xr.
Reported at 3 years follow-up.

DMFS.
DFT.
DMFT.
PF-DMFS.
MD-BL-DMFS.
MD-DMFS.
O-DMFS.
ECSI.

Notes

Participants randomised (n = 846).
Baseline characteristics (age, dental age, TAR, DFS, DMFS, DFT, DMFT, ECSI) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA. Radiographic assessment (2 postBW) by 2 examiners; diagnostic threshold = ER. State of tooth eruption included = E/U. Reproducibility ratio was less than 0.22 for intra-examiner reproducibility of clinical and radiographic caries diagnosis; "significant differences between examiners could not have affected caries increment figures since each examined same children annually."

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Following baseline examinations, the children were grouped on the basis of age, sex, previous caries experience and the number of erupted 2nd permanent molars; they were then randomly assigned to either the test or control group."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "Radiographs were examined ......without reference to the clinical examination data."

"The test dentifrice contained MFP....The toothpastes were packed in similar but distinguishable tubes. The investigators did not know which of the tubes contained the test paste nor which of the pastes any child was using."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 13% in 3 years. Drop out by group: 54/418 FD, 52/428 PL. Reasons for losses: Did not like taste of paste (1 from control group), changed school or moved away (63), exclusion due to absence at last examination.

Comment: Numbers lost were not unduly high for the length of follow-up, with no differential loss between groups. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (E+U) (CA)cl+(ER)xr, reported at 3 years follow-up.
DMFS.
DFT.
DMFT.
PF-DMFS.
MD-BL-DMFS.
MD-DMFS.
O-DMFS.
ECSI.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 6.30 (4.04) FD, 6.43 (4.31) PL.

Age (years): 11.73 (0.33) FD, 11.69 (0.32) PL.

TAR: 17.25 (4.35) FD, 17.35 (4.40) PL.

Dental age: 21.75 (4.51) FD, 21.77 (4.47) PL.

DFT: 4.52 (2.56) FD, 4.42 (2.66) PL.

DMFT: 5.04 (2.68) FD, 4.96 (2.99) PL.

DMFS: 8.80 (6.55) FD, 9.10 (7.25) PL.

ECSI: 12.03 (8.34) FD, 12.41 (8.66) PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "The distribution of toothpastes and toothbrushes was the responsibility of two ladies called 'home visitors', whose duties were to visit each home every 5 weeks to supply enough of the appropriate toothpaste for the needs of the whole family....and maintaining the interest and co-operation of participants throughout the trial."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Ashley 1977

Methods

Stratified random allocation; double-blind; placebo-controlled; 12% drop out (for all study groups combined) after 2 years (study duration = 2 years). Natural losses; any differential group losses not assessable.

Participants

489 children analysed at 2 years (available at final examination).
Average age at start: 12 years.
Surfaces affected at start: 9.1 DFS.
Background exposure to fluoride: none.
Year study began: 1973.
Location: UK.

Interventions

FT versus PL
(SMFP group = 1000 ppm F).

School use/supervised, daily, 1 g applied for 1 min, post-brushing water rinse done (non-fluoride toothpaste provided to all for home use).
Abrasive system: IMP (main abrasive).

Outcomes

2yNetDFS increment - (E+U) (NCA)cl+(ER)xr.
Reported at 2 years follow-up.

PF-DFS.
MD-BL-DFS.
MD-DFS.
DFS (U).
Compliance.

Notes

Participants randomised (numbers for relevant groups not reported).
Baseline characteristics (age, DFS, DMFS, DMFT) 'balanced'.
Clinical (V) caries assessment by 1 examiner (FOTI used); diagnostic threshold = NCA. Radiographic assessment (postBW) by 1 examiner; diagnostic threshold = ER. State of tooth eruption included = E/U. Intra-examiner reproducibility checks for incremental caries data (ICC for clinical 0.95, for radiographic 0.8); reversal rate between 12% and 7% of observed DFS increment in study groups.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "Using a table of random numbers, subjects were allocated within each school to one of four study groups."

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The control dentifrice was identical, except that it did not contain sodium MFP."

"The study was organised on a double-blind basis..."

"Records of earlier examinations were not available at the subsequent examination sessions."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 12% in 2 years (133/1135, all 4 groups combined). Drop out by group: Not reported. Reasons for losses: Mainly due to moving from the area.

Comment: Numbers lost were not unduly high given length of follow-up; it is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants present at baseline and final exams.                 

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (E+U) (NCA)cl+(ER)xr, reported at 2 years follow-up.
PF-DFS.
MD-BL-DFS.
MD-DFS.
DFS (U).

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 8.44 (5.58) FD, 9.79 (7.28) PL.

DMFT: 5.35 (3.03) FD, 6.06 (3.66) PL.

DMFS: 9.89 (6.94) FD, 11.05 (7.98) PL.

Age: 12.33 FD, 12.28 PL.

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quote: "...all subjects received ample supplies of the non-fluoride control toothpaste and toothbrushes. This ensured that the exposure of the subjects to fluoride dentifrice or rinse was restricted to the experimental regime."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Biesbrock 2001

Methods

Stratified random allocation; double-blind; 18.5% drop out (for all groups combined) after 1 year (study duration = 3 years). Reasons for attrition not reported.

Participants

4431 children analysed at 1 year (available at examination).
Age range at start: 6-15 years (average = 9).
Surfaces affected at start: 5.3 DMFS.
Background exposure to fluoride: water <0.3 ppm F in community.
Year study began: in/before 2001.
Location: USA.

Interventions

FT (4 groups) (all groups NaF: 1100 ppm F, 1700 ppm F, 2200 ppm F, 2800 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: silica abrasive.

Outcomes

1yNet DMFS increment cl+xr, reported at 1 year follow-up.

DMFS increment.
DMFS increment by surface.
DMFT increment.
Reported at 1 year follow-up.

DMFS increment at years 1, 2 and 3 from baseline exam.

Notes

Participants randomised (n = 5439).
Baseline characteristics (age, DMFS, DMFT) 'balanced'.
Clinical (VT) caries assessment and radiographic assessment carried out by a single examiner established as "repeatably sensitive" based on prior trial experience.

Results at years 2 and 3 confounded by a concurrent fluoride rinse programme, which involved half of the study population.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "randomly assigned to one of the four dentifrice groups."

 

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quote: "...double-blind study."

Quote: "They [dentifrices] were supplied in plain white 2.7 oz tubes."

Quote: "Subject and examiner blindness to treatment were maintained throughout the study."

Incomplete outcome data addressed?
All outcomes

Unclear

Comment: 38% drop out at 3 years. No reasons are given for those not examined but similar attrition rate in each of the 4 groups. Not stated but assumed that ITT analysis carried out for those present at exam. No imputation carried out.

Free of selective reporting?

Unclear

Comment: Unclear but DMFS data not presented by surface for years 2 and 3, unlike year 1.

Baseline characteristics balanced?

Yes

Quote: "..well balanced with respect to ....mean caries experience as measured by DMFS and DMFT at baseline."

Free of contamination/co-intervention?

No

Quote "Results at years 2 and 3 confounded by a concurrent fluoride rinse programme."
Comment: After 1 year schools participated to varying degrees in a fluoride rinse programme. Only results for 1 year follow-up analysed in review.



Blinkhorn 1983

Methods

Stratified random allocation; double-blind; placebo-controlled; 10% drop out after 3 years (study duration = 3 years). Reasons for attrition described with respective total numbers: 57 left school, 12 withdrawn by parents, 6 absent at final examination; no differential group losses.

Participants

368 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years.
Surfaces affected at start: 8.2 DMFS.
Background exposure to fluoride: none reported.
Year study began: 1972.
Location: UK.

Interventions

FT versus PL
(SMFP group = 1000 ppm F).

School use/supervised, daily, for 1 min, post-brushing water rinse done (appropriate toothpastes also provided for home use).
Abrasive system: IMP (main abrasive).

Outcomes

3yNetDFS increment - (E+U) (CA)cl+(DR)xr.
Reported at 3 years follow-up.

PF-DFS.
MD-BL-DFS.
MD-DFS.
postMD-DFS.
DFS (U).
DMFT.
anterior DMFT.
posterior DMFT.
DMFT (U).

Notes

Participants randomised (n = 410).
Baseline characteristics (DMFS, DMFT, SAR) 'balanced' (DFS baseline data not reported).
Clinical (V) caries assessment by 1 examiner, diagnostic threshold = CA. Radiographic assessment (1 postBW) by 1 examiner; diagnostic threshold = DR. State of tooth eruption included = E/U. Intra-examiner reproducibility checks for incremental clinical and radiographic caries data in 10% sample (ICC score 0.9).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "The children were allocated to four groups by stratified random sampling at two levels: school and dental age."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The trial was organized on a double-blind basis, neither the children nor the examiner being aware of who was receiving test or control products."

"...another group used the fluoride dentifrice..... and a fourth group....a placebo dentifrice."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 10% in 3 years. Drop out by group: 21/ 205 FD, 21/205 PL. Reasons for losses: Left school (57), withdrawn by parents (12), absent at final examination (6) (not reported by group).

Comment: Numbers lost were not unduly high for the length of follow-up with no differential loss between groups. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.                           

Free of selective reporting?

Yes

Outcomes reported:
DFS increment (E+U) (CA)cl+(DR)xr, reported at 3 years follow-up.
PF-DFS.
MD-BL-DFS.
MD-DFS.   

postMD-DFS.
DFS (U).
DMFT.
Anterior DMFT.
Posterior DMFT. DMFT (U).

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFT: 4.94 (2.86) FD, 5.26 (3.47) PL.

DMFS: 7.83 (5.17) FD, 8.48 (6.29) PL.

SAR: 93.41 (21.30) FD, 93.61 (20.43) PL.

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quote: "..both dentifrice tubes and rinse bottles were colour coded so that the children received the correct products. Independent laboratory checks of the dispensed rinse and dentifrice were made at regular intervals to assess the reliabilty of the supervisors who dispensed agents. The coded dentifrice and rinse was dispensed in the school..."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Brudevold 1966

Methods

Stratified random allocation; double-blind; placebo-controlled; 25% drop out (for all study groups combined) after 2 years (study duration = 2 years). Reasons for attrition not reported; any differential group losses not assessable.

Participants

1278 children analysed at 2 years (present for the entire trial period).
Average age at start: 7-16 years (average = 12).
Surfaces affected at start: 15.7 DFS.
Background exposure to fluoride: data not available for fluoridation status of site.
Year study began: 1961.
Location: USA.

Interventions

FT (3 groups)** versus 'PL'
(both SnF2 groups = 1000 ppm F, APF group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Ca pyrophosphate in one SnF2 toothpaste, IMP in the other SnF2 and in the APF toothpaste, control toothpaste abrasive not reported.

Outcomes

2yDFS increment - cl+xr.
Reported at 2 years follow-up.

DMFS.
DMFT.
DFT.

Notes

Participants randomised (numbers for relevant groups not reported).
Baseline characteristics (dental age, DFS, DFT, DMFS, DMFT, gender) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA. Radiographic assessment (10 BW) by 1 examiner; diagnostic threshold not reported. State of tooth eruption included not reported. Diagnostic errors not reported.
**NaF-secondary Ca pyrophosphate toothpaste group not considered (abrasive system known to be incompatible with NaF).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "At the initial exam, the record cards of these youngest, or master, siblings were stratified (ordered) simultaneously according to 12 characteristics....The ordered cards of the 'master' siblings were then divided into 5 dentifrice groups by superimposing the numbers 1 through 5 in random sequence. The same dentifrice was assigned automatically to the other, or "trailing", siblings in his household."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "Each (of 2 ) examiner assessed about half of the subjects in each group, and each subject had the same dentist-examiner throughout the study. Separate records were used for each examination, and previous records were never available to the examiner. All observations were recorded in code for subsequent transfer to machine data processing. The radiographs were read and recorded independently by a third dentist. At no time was it possible for the examiners to identify a subject with a dentifrice group."

"An independent laboratory was assigned the responsibility of coding, packaging, and shipping all dentifrices in this study...

NaF dentifrice was compared to.....and a fluoride free dentifrice."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 24.7% in 2 years (534/2156, all 5 groups combined). Drop out by group: Not reported. Reasons for losses: Not reported.

Comment: Numbers lost were not unduly high given length of follow-up; It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants examined after 2 years.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - cl+xr, reported at 2 years follow-up.
DMFS.
DMFT.
DFT.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 16.88 (12.81) FD1, 14.03 (10.16) FD2, 14.89 (10.19) FD3, 15.70 (10.96) PL.

DFT: 8.53 (5.49) FD1, 7.61 (4.80) FD2, 6.04 PL; 7.59 (5.01) FD3, 8.07 (5.02) PL.

DMFT: 8.84 (5.86) FD1, 7.87 (4.80) FD2, 2.94 PL; 7.91 (5.34) FD3, 8.35 (5.21) PL.

DMFS: 18.43 (13.91) FD1, 15.33 (11.08) FD2, 16.48 (12.86) FD3, 17.09 (11.68) PL.

Dental age: 21.12 (6.59) FD1, 22.28 (6.47) FD2, 20.49 (6.51) FD3, 21.70 (6.29) PL.

Comment: Initial caries appears balanced although adjustment for baseline imbalance was made in the analysis.

Free of contamination/co-intervention?

Yes

Quotes: "As the study group was assembled, all siblings were noted to permit limitiation of one dentifrice code to a family."

"New shipments supplied every 8 to 10 weeks, and new toothbrushes supplied every 6 months."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Buhe 1984

Methods

Stratified random allocation; double-blind; placebo-controlled; 18% drop out after 3 years (study duration = 3 years). No differential group losses.

Participants

1286 children analysed at 3 years (available at final examination).
Age range at start: 11-13 years (average = 12).
Surfaces affected at start: 17.4 DMFS.
Background exposure to fluoride: data not obtained for fluoridation status of site.
Year study began: 1976.
Location: FRG.

Interventions

FT (2 groups) versus PL
(SMFP groups = 1000 ppm F and 1500 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: IMP.

Outcomes

3yNetDFS increment - cl+xr.
Reported at 3 years follow-up.

DMFS.
DMFS (U).
DMFT.

Notes

Participants randomised (n = 1562).
Baseline characteristics (age, TAR, DMFS) 'balanced' (DFS baseline data not reported).
Clinical (VT) caries assessment; diagnostic threshold not reported; state of tooth eruption included E/U. Radiographic caries assessment; diagnostic threshold not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...stratified randomisation..."

Comment: Translation of report not detailed enough to make a categorical decision regarding sequence generation.

Allocation concealment?

Unclear

Translation of report not detailed enough to make a categorical decision regarding allocation concealment.

Blinding?
All outcomes

Yes

Quotes: "Double blind study."

"...as compared to the placebo group.."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 17.7% in 3 years. Drop out by group: FD1 99/520, FD2 82/520, PL 95/522. Reasons for losses not reported.

Comment: Numbers lost were not unduly high given length of follow-up and showed no differential loss between groups. It is unclear if reasons for the missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants present at final examination.

Free of selective reporting?

Unclear

Outcomes reported:
DFS increment - cl+xr, reported at 3 years follow-up.
DMFS.
DMFS (U).
DMFT.

Comment: Trial protocol unavailable. Translation of methods section not detailed enough to make a categorical decision regarding selective outcome reporting.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
Mean age 12.3 years (for all groups).

DMFS: 17.1 FD1, 17.4 FD2, 17.8 PL.

TAR: 15.4 FD1, 15.5 FD2, 15.3 PL.

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Unclear

Translation of report not detailed enough to make a categorical decision regarding any contamination and/or co-intervention.



Cahen 1982

Methods

Stratified random allocation; double-blind; placebo-controlled; 20% drop out after 3 years (study duration = 3 years). Natural losses and exclusions based on presence in all follow-up examinations; any differential group losses not assessable.

Participants

2008 children analysed at 3 years (present for all examinations).
Age range at start: 6-8 years (average = 7).
Surfaces affected at start: 1.4 DMFS (control group only).
Background exposure to fluoride: data not obtained for fluoridation status of site.
Year study began: 1977.
Location: France.

Interventions

FT (2 groups) versus PL
(SMFP group = 1500 ppm F, AmF group = 1500 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: IMP in the SMFP and placebo toothpaste, Ca carbonate/Na and Al silicates in the AmF toothpaste.

Outcomes

3yDMFS increment - cl+xr.
Reported at 3 years follow-up.

DMFT.
df-rate.

Notes

Participants randomised (n = 2500); numbers by group not reported.
Baseline characteristics (age, gender) 'balanced'.
Clinical (V) caries assessment by 6 examiners; diagnostic threshold not reported; state of tooth eruption included not reported. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold not reported; partial recording. Inter- and intra-examiner reproducibility of clinical and radiographic caries diagnosis assessed in 10% sample ("good reproducibility, no significant difference between or within examiners").

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...children were stratified by age, sex...were then randomly distributed into 3 groups. Additional modifications were made by placing brothers and sisters in the same groups in order to ensure that only one type of dentifrice entered the household during the trial period."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The dentifrices were packed in neutral white tubes with no other inscription than 'Pate Dentifrice'...allocation code was known only by the manufacturer until the final results were obtained."

"The whole study was conducted double-blind. The yellow toothpaste was not fluoridated and ..."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 19.7% in 3 years (492/2500). Drop out by group: Not reported. Reasons for losses: Sickness, change of address, exclusion based on presence at all examinations (not reported by group).

"The balance between boys and girls, and between age groups was preserved in each treatment group...allowing unbiased comparisons."

Comment: Overall drop out not unduly high for length of follow-up; it is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced, and how balance between groups was maintained. Caries data used in the analysis pertain to participants present at all examinations.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - cl+xr, reported at 3 years follow-up.
DMFT.
df rate.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Unclear

Prognostic factors reported: Age and gender reported as balanced; DMFS: 1.42 (PL); DMFT: 0.98 (PL).

Comment: Initial caries derived for the control group only.

Free of contamination/co-intervention?

Yes

Quote: "...by placing brothers and sisters in the same groups in order to ensure that only one type of dentifrice entered the household during the trial period."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Chesters 2002

Methods

Stratified random allocation; double-blind. 15.8% drop out (for all study groups combined) after 2 years (study duration = 2 years). Reasons for attrition not reported.

Participants

2011 children analysed at 2 years (available at final examination).
Age range at start: 11-14 years (average = 13).
Surfaces affected at start: not reported.
Background exposure to fluoride: none reported.
Year study began: 1999.
Location: Lithuania.

Interventions

FT (2 groups) 1000 ppm F SMFP versus 2500 ppm F SMFP.

Home use twice daily/unsupervised; daily brushing at school.
Abrasive system: silica (both groups).

Outcomes

2yNet DMFS Increment cl(DSTM) FOTI at D3 all radiographic lesions.
D1MFS Increment (DSTM only).
D3MFS Increment (DSTM only).
D1MFS Events (DSTM).
D3MFS Events (DSTM).

Reported at 1 and 2 year follow-up.

Notes

Participants randomised (n = 2387).
Baseline characteristics (sex, baseline caries) 'well balanced'.

No significant D1MFS or D3MFS or baseline differences (values not stated). Examinations carried out by a single examiner. Intra-examiner reliability: repeat DSTM and FOTI examinations held throughout the baseline, 12 and 24 month examinations on 5% to 10% of subjects. For radiography, baseline and 12 and 24 month radiographs re-assessed for 5% to 10% of subjects. Reproducibility "excellent", Kappa values >0.8.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: " . .randomized to one of two silica-based dentifrices."

Quote: "...stratified into 12 strata ...allocated to a product group according to a pre-prepared list of randomized blocks?"

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quote: "... double-blind study."

Quote: "Neither the subjects, clinical examiners, nor those distributing the test products were aware of the product identities at any time during the trial. The investigators were supplied with sealed code-break envelopes that could be opened in an emergency. This was not required and the integrity of the product code was confirmed with regular GPC monitoring and independent audit."

Quote: "The products were identical except for the fluoride level and different coloured packaging for each product code?"

Incomplete outcome data addressed?
All outcomes

Yes

2387 randomised (994/1193 included in final main analysis in low fluoride group; 1017/1194 in high fluoride group).

Comment: Not unreasonable drop-out rate; similar in both groups.  Reasons unlikely to be due to intervention.

Comment: Numbers absent and withdrawn are given for each group. Well balanced between groups. No further information about drop outs given.

Free of selective reporting?

Unclear

Comment: Results reported traditional increment and DSTM increment at different levels of diagnosis. DMFT and proportion developing new caries missing. DSTM, FOTI and radiographic assessments.

Baseline characteristics balanced?

Yes

Comment: Balance of gender and baseline DMFS.

Free of contamination/co-intervention?

Unclear

Comment: Unlikely as used different colours for toothpaste tubes/cartons, but possibility of contamination during school brushing sessions.



Conti 1988

Methods

Stratified random allocation; double-blind. 39% drop out (for all study groups combined) after 3 years (study duration = 3 years). Reasons for high attrition described: moved, withdrew, absent or not available for examination; no differential group losses.

Participants

2415 children analysed at 3 years (available at final examination).
Age range at start: 7-11 years (average = 10).
Surfaces affected at start: 2.8 DMFS.
Background exposure to fluoride: water <0.3 ppm F in community.
Year study began: in/before 1984.
Location: USA.

Interventions

FT (2 groups) 1000 ppm SMFP, 1500 ppm SMFP.

Home use/supervised brushing at school, daily frequency assumed.
Abrasive system: silica (both groups).

Outcomes

3yNetDFS increment - cl+xr.
Reported at 3 years follow-up.

DMFS.
DMFT.
DFT.
DFS Prox.
Oral (soft tissue) findings.
Compliance.

Notes

Participants randomised (n = 3957).
Baseline characteristics (age, gender, sound surfaces, DMFT, DMFS) 'balanced'.
Clinical examinations carried out by 1 primary examiner and 2 back-up examiners.10% of children randomly selected each year to be re-examined.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: " . .stratified according to age and sex and then randomly assigned to one of two treatment groups by a computer program."

Allocation concealment?

Yes

Quote: "assigned by computer program designed for this purpose."

Blinding?
All outcomes

Yes

Quote: "The study was double blind, multiple codes were used for each product, the dentrifices used were identical in appearance and flavour and the packaging were similar for both products."

Incomplete outcome data addressed?
All outcomes

Unclear

2415/3957 children received clinical and radiographic assessment (39% attrition rate; similar across both groups).
Quote: "Moved, withdrew, absent or not available."

Comment: Attrition rate was high after 3 years, 38% and 40% in the groups. Although reasons for drop outs unlikely to be due to intervention, high rates could influence results.

Free of selective reporting?

Yes

Comment: Results reported DMFT, DMFS, per cent caries free at 3 years. Clinical and radiography assessments.

Baseline characteristics balanced?

Yes

Comment: Comparable age, gender, baseline DMFT DMFS.

Free of contamination/co-intervention?

Yes

Comment: School co-ordinators hired and trained to supervise daily toothbrushing. Contamination possible in school brushing sessions but unlikely under supervision.



Davies 2002

Methods

Random allocation; single-blind (clinical assessors). 32% drop out after 5 years (study duration 5 years). Reasons for attrition: refused to participate (9%), change of residence (19%); product related and dental recommended withdrawals in high fluoride group only (0.07%).

Participants

3731 children analysed at 5 years (remained in the study and available at final examination); 5028 children analysed at 5 years (initially allocated to study groups and available at final examination).
Age range at start: 12 months.
Surfaces affected at start: 0 dmfs.
Background exposure to fluoride: none reported.
Year study began: 1993 (5 health districts) 1994 (4 health districts).
Location: UK.

Interventions

FT (440 ppm NaF, 1450 ppm NaF). Control group receiving no intervention also reported.**

Home use/unsupervised, daily frequency assumed.
Abrasive system: not reported.

Outcomes

5ydmft increment - cl.
Reported at 5 years follow-up.

mt.
Prevalence of caries experience (dmft >0).

Notes

Participants initially randomised (n = 7422).
Baseline characteristics: not reported.
Clinical (VT) caries assessments by trained, standardised, calibrated examiners. Clinical data only. Reliability values not reported.

**Control group (n = 2462) not considered.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "..randomised controlled parallel group clinical trial."

Quote: "..centrally allocated to either one of the two test groups or a control group using random number tables."

Allocation concealment?

Yes

Quote: "..centrally allocated to either one of the two test groups or a control group."

Comment: Centralised allocation.

Blinding?
All outcomes

Unclear

Quote: "Dental examinations were conducted under blind conditions but as "off the shelf" toothpaste was delivered to the participants, subjects and their families were aware of which toothpaste they were using."

Comment: Clinical assessors blinded, but participants and their families were not. Participants very young children so knowledge of intervention unlikely to influence outcome.

Incomplete outcome data addressed?
All outcomes

Yes

1677/2472 available for examination in low fluoride group; 1696/2488 available in the high fluoride group. Total drop-out rate of 32%.

Comment: Drop-out rate mainly due to refusal to participate, change of residence; product related and dental recommended withdrawals in high fluoride group only but this number is very small. Reasons for drop outs primarily unlikely to be due to intervention.

Free of selective reporting?

Yes

Comment: Routine caries diagnosis. No radiographs taken; clinical examination only. Caries indices reported: mt, dmft, caries free.

Baseline characteristics balanced?

Unclear

Comment: No baseline data presented. Study undertaken in deprived areas of North West of England with comparable caries prevalence in 5 year olds.

Free of contamination/co-intervention?

Unclear

Comment: Contamination possible. Toothpaste supplied for use by children participating in the trial only and not to other family members.



Di Maggio 1980

Methods

Random allocation; double-blind; placebo-controlled; 16% drop out (for both study groups combined) after 2 years (study duration = 2 years). Main reason for attrition described: left institution; any differential group losses not assessable.

Participants

42 children analysed at 2 years (available at final examination).
Age range at start: 11-12 years. Surfaces affected at start: 11.7 DMFS.
Background exposure to fluoride: data not obtained for fluoridation status of site.
Year study began: in/before 1977.
Location: Italy.

Interventions

FT versus PL
(SMFP-NaF group = 2500 ppm F).

Institution use/supervised, 3 times a day.
Abrasive system: not clearly specified.

Outcomes

2yDMFS increment - cl.
Reported at 1 and 2 years follow-ups.

DMFT.

Notes

Participants randomised (n = 50).
Baseline characteristics (DMFS, DMFT) 'balanced'.
Clinical caries assessment by 2 examiners; diagnostic threshold not reported; state of tooth eruption included not reported. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "... following a randomisation list the children were allocated to 2 groups..."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "...to 2 treatment groups that differed only by the presence or absence of fluoride. ...the dentifrices were indistinguishable by colour or flavour."

"...using the most strict double-blind condition."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 16% (8/50) in 2 years. Drop out by group: Not reported. Reasons for losses: Essentially due to leaving the orphanage.

Comment: Numbers lost were not unduly high for the length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examinations.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - cl, reported at 1 and 2 years follow-ups.
DMFT.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFT: 5.68 FD, 5.90 PL.

DMFS: 11.50 FD, 11.85 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "The institute personnel actively collaborated in controlling the regular dentifrice use, as prescribed."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Fan 2008

Methods

Stratified random allocation; double-blind; placebo-controlled; drop outs not obtainable. Reasons for attrition not reported; differential losses not assessable.

Participants

998 children analysed after 2 years (present for the entire trial period).
Age range at start: 4 years.
Surfaces affected at start: 3.6 dfs.
Background exposure to fluoride: public drinking water <0.3 ppm F.
Year study began: in or before 2005.
Location: China.

Interventions

FT (2 groups) versus PL (both SMFP groups = 1500 ppm F).

Home use/unsupervised, twice daily frequency assumed.
Abrasive system: not reported.

Outcomes

2ydfs increment - cl.
Reported at 2 years follow-up.

Compliance.
Side effects.

Notes

Participants randomised (numbers not reported).
Baseline characteristics (age, gender, dfs) 'well balanced'.
Clinical (VT) assessment by 1 examiner. A subsample of 40 children were re-assessed Kappa >0.9.

Analysis of covariance adjusted for baseline dfs.
Children with orthodontic appliances or participating in any other clinical study during the 3 months prior to baseline examination were excluded.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Subjects were randomly assigned..."

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quote: "...employed a double-blind..." "Dentifrices were packaged in white tubes or overwrapped with white tape so as to mask their identity."

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: "A total of 1200 qualifying children...entered the study."
Quote: "Subjects who did not complete the study dropped out for reasons unrelated to the use of the treatments."
Comment: Number randomised/excluded/withdrawn not reported.

Free of selective reporting?

Yes

Mean dfs increment. Clinical (VT) assessment only.

Baseline characteristics balanced?

Unclear

Comment: Analysis adjusted for baseline dfs. Baseline data reported for participants completing the trial only. However groups analysed are similar with respect to gender and mean dfs score at baseline.

Free of contamination/co-intervention?

Unclear

Comment: Insufficient information. Possibility of contamination during brushing sessions.



Fanning 1968

Methods

Stratified random allocation; double-blind; placebo-controlled; 22% natural drop out after 2 years (study duration = 2 years); no differential group losses (46% drop out based on analysis performed for randomised block design).

Participants

844 children analysed at 2 years (422 complete replicates of each group available).
Age range at start: 12-14 years (average = 13).
Surfaces affected at start: 17.7 DMFS (from sample randomised).
Background exposure to fluoride: none.
Year study began: 1964.
Location: Australia.

Interventions

FT** versus PL
(SnF2 group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: IMP.

Outcomes

2yDMFS increment - (CA)cl+(ER)xr.
Reported at 2 years follow-up.

Stain score.

Notes

Participants randomised (n = 1576).
Baseline characteristics (DMFS, DMFT, SAR) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA. Radiographic assessment (5 BW) by 2 examiners; diagnostic threshold = ER. State of tooth eruption included = E/U. Intra- and inter-examiner reproducibility of clinical caries diagnosis (DFS) assessed annually by duplicate examination of 10% random sample ("error relatively small, NS difference between or within examiners").

**Na N-lauroyl sarcosinate/SMFP toothpaste group not considered (additional non-F active agent used in this group only).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "Within each school students were separated into groups according to sex and examiner; within each group they were listed in order of increasing DMFS, and then allotted at random to the treatments by the method of taking successive groups of three subjects from the ordered lists...in a randomised block design."

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "At no time was it possible for the examiners or recorders to identify a subject with a dentifrice group....subjects did not know what dentifrice they were using."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 46.4% in 2 years. Drop out by group: 139/788 FD, 163/788 PL. Reasons for losses: Children leaving school.

Comment: Numbers lost were unduly high for the length of follow-up. No differential losses between groups. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants in complete randomised blocks at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (CA)cl+(ER)xr, reported at 2 years follow-up.
Stain score.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 19.84 FD, 19.89 PL; SAR: 112.42 FD, 112.58 PL; DMFT: 10.39 FD, 10.39 PL.

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quotes: "At the beginning of each month, enough dentifrice was sent for the entire family."

"All siblings were placed in the same treatment group to ensure that only one dentifrice formula was sent to a home."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Fogels 1979

Methods

Random allocation; double-blind; placebo-controlled; 40% drop out after 3 years (study duration = 3 years). Reasons for attrition described: graduations, change of residence/school, parental requests, and ortho treatment; no differential group losses.

Participants

1339 children analysed at 3 years (available at final examination).
Age range at start: 6-11 years (average = 9).
Surfaces affected at start: 4.9 DFS. Background exposure to fluoride: none reported.
Year study began: 1972.
Location: USA.

Interventions

FT (2 groups) versus PL
(both SnF2 groups = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: silica gel in one SnF2 and placebo toothpaste, Ca pyrophosphate in the other.

Outcomes

3yNetDFS increment - (CA)cl+(ER)xr.
Reported at 3 years follow-up.

MD-DFS.
DFS (U).
DMFT.

Oral soft tissues lesions (data not reported).
Proportion of children with tooth staining (data not reported).

Notes

Participants randomised (n = 2218).
Baseline characteristics (DFS) 'balanced'.
Clinical (VT) caries assessment by 2 examiners, diagnostic threshold = CA. Radiographic assessment (postBW) by 2 examiners; diagnostic threshold = ER. State of tooth eruption included E/U. Results shown for each examiner and for the pooled data from both (F-ratios less than unit for examiner by treatment interactions); combined results considered.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Children were stratified according to age and sex, and randomly assigned one of the 3 dentifrices."

Comment: Insufficient information.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "Throughout the duration of the study, the double-blind design was maintained; neither the examiners nor the hygienists had access to the identity of the dentifrice codes or to the findings of the previous examination."

"Parents were informed that the dentifrices would be assigned randomly and that their children had 1:3 chance to be assigned a non-fluoride dentifrice."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 40% in 3 years. Drop out by group: 280/731 FD1, 296/735 FD2, 303/752 PL. Reasons for losses: Graduations, change of residence/school, parental requests, and ortho treatment.

Comment: Numbers lost are not unduly high for length of follow-up, with no differential loss between groups. It is unclear if reasons for the missing data are acceptable and balanced. Caries data used in the analysis pertain to participants present at final examinations.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (CA)cl+(ER)xr, reported at 3 years follow-up.
MD-DFS.
DFS (U).
DMFT.

Oral soft tissues lesions (data not reported).
Proportion of children with tooth staining (data not reported).

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 5.69 FD1, 6.04 FD2, 6.04 PL.

FS: 2.69 FD, 2,30 FD2, 2.94 PL.

Age (months): 114.0 FD, 114.6 FD2, 115.0 PL.

Dental age: 14.93 FD, 15.23 FD2, 15.09 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quotes: "To avoid assigning two different dentifrices to children in the same household, only one child per family, usually the oldest child, was used in the randomisation."

"No evidence of switching dentifrices among children was found."

"Care was taken to ensure each child got the correct product."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Fogels 1988

Methods

Stratified random allocation; double-blind; 20.7% drop out (for all study groups combined) after 3 years (study duration = 3 years). Reasons for attrition: withdrawal from the study or absent from final examination; no differential group losses.

Participants

1913 children analysed at 3 years (available at final examination).
Age range at start: 6-11 years (average = 9).
Surfaces affected at start: 3.7 DMFS.
Background exposure to fluoride: drinking water fluoride adjusted to 1 ppm.
Year study began: 1981.
Location: USA.

Interventions

FT (2 groups) 1000 ppm F SMFP and 1500 ppm SMFP.

Home use/supervised brushing at school, daily frequency assumed.
Abrasive system: silica (both groups).

Outcomes

3yNet DMFS increment cl+xr.
Reported at 3 years follow-up.

DMFT increment.
DF Prox. increment.
Proportion developing caries.
Adverse effects.

Notes

Participants randomised (n = 2411).
Baseline characteristics (age, gender, DMFS, DMFT, sound surfaces) 'balanced'.
1 trained and calibrated examiner used. 10% of children randomly re-examined to assess consistency of scoring: decayed surfaces 84.7% to 88.9% consistent, filled surfaces 95.1% to 98.8% consistent.

18.8% of children had orthodontic treatment with banded teeth excluded from the analysis and 8.4% were given sealants.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: " . .subjects were stratified according to age and sex and were randomly assigned to one of two fluoride dentifrices."

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quote: "...double-blind study."

Incomplete outcome data addressed?
All outcomes

Unclear

Comment: Attrition rate was moderate after 3 years, 21% and 21% in 1000, 1500 groups.

Quote: "The drop-outs either withdrew from the study during the course of the trial or were absent at the third year clinical or radiographic examination."

Comment: Not given for each group separately.

Free of selective reporting?

Yes

Comment: Results reported DMFT, DMFS, per cent caries free at 3 years.

Baseline characteristics balanced?

Yes

Comment: Balance of gender, age and caries disease at baseline comparable.

Free of contamination/co-intervention?

Unclear

Comment: Possible in school brushing sessions.

A proportion of the subjects were fitted with sealants during the course of the study and this proportion was higher (9.6% as opposed to 7.2%) in the higher fluoride group which showed a lower caries increment.



Forsman 1974

Methods

Random allocation; double-blind; placebo-controlled; 18% drop out after 2 years (study duration = 2 years). Reasons for attrition described with respective total numbers: change of residence/school, ortho treatment, did not wish to continue; no differential group losses reported (but not assessable).

Participants

559 children analysed at 2 years (available at final examination).
Age range at start: 10-11 years. Surfaces affected at start: 5.1 DMFS.
Background exposure to fluoride: mouthrinse.
Year study began: in/before 1970.
Location: Sweden.

Interventions

FT (3 groups) versus PL
(250 ppm NaF, 250 ppm SMFP, 1000 ppm SMFP).

Home use/unsupervised, daily frequency assumed.
Abrasive system: silica in all toothpastes.

Outcomes

2yDMFS increment - (NCA)cl.
Reported at 2 years follow-up.

BLMD-DFS (clin).
MD-DFS (x-ray).

Proportion of children with new smooth surface caries.

Notes

Participants randomised (n = 681); numbers by group not reported.
Baseline characteristics (dental age, DMFS) 'balanced'.
Clinical (VT) caries assessment by 1 examiner, diagnostic threshold = NCA. Radiographic assessment (postBW) by 1 examiner; diagnostic threshold = ER. State of tooth eruption included not reported. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "From lists for girls resp. boys in all classes each fourth child on the Vaxjo lists and each third child on the Ljungby lists was randomly selected for the respective groups."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The toothpaste was delivered in tubes with the word ‘Toothpaste’ printed in different colours. During the period of investigation, only the manufacturer knew the code."

"...study was designed as a double-blind experiment."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 17.9% (122/681) in 2 years. Drop out by group: Not reported. Reasons for losses: Orthodontic treatment (6), moved away (39), did not wish to continue (77) (not reported by group).

Comment: Numbers lost are not unduly high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants continuing the study up to year 2 (children completing tests).

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (NCA)cl, reported at 2 years follow-up.
BLMD-DFS (clin).
MD-DFS (x-ray).
Proportion of children with new smooth surface caries.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 5.57 FD1, 4.87 FD2, 4.53 FD3, 5.16 PL.

Dental age: 18.89 FD1, 19.08 FD2, 18.66 FD3, 19.03 PL.

Comment: Initial caries appears balanced.           

Free of contamination/co-intervention?

Yes

Quote: "The dentifrice was distributed every second month in amounts calculated to meet the needs of the whole family, to ensure as far as possible that the participants did not have access to other toothpastes."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Forsman 1974a

Methods

Random allocation; double-blind; placebo-controlled; 16% drop out after 2 years (study duration = 2 years). Reasons for attrition described with respective total numbers: change of residence/school, ortho treatment, did not wish to continue; no differential group losses reported (but not assessable).

Participants

394 children analysed at 2 years (available at final examination).
Age range at start: 10-12 years.
Surfaces affected at start: 12.9 DMFS.
Background exposure to fluoride: mouthrinse.
Year study began: in/before 1970.
Location: Sweden.

Interventions

FT (2 groups) versus PL
(one SMFP group = 250 ppm F, another SMFP group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Ca carbonate in all toothpastes.

Outcomes

2yDMFS increment - (NCA)cl.
Reported at 2 years follow-up.

BLMD-DFS (clin).
MD-DFS (x-ray).

Proportion of children with new smooth surface caries.

Notes

Participants randomised (n = 469); numbers by group not reported.
Baseline characteristics (dental age, DMFS) 'balanced'.
Clinical (VT) caries assessment by 1 examiner, diagnostic threshold = NCA. Radiographic assessment (postBW) by 1 examiner; diagnostic threshold = ER. State of tooth eruption included not reported. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "From lists for girls resp. boys in all classes each fourth child on the Vaxjo lists and each third child on the Ljungby lists was randomly selected for the respective groups."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The toothpaste was delivered in tubes with the word Toothpaste printed in different colours. During the period of investigation, only the manufacturer knew the code."

"...study was designed as a double-blind experiment."

Comment: Blind outcome assessment and use of placebo described. 

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 16% (75/469) in 2 years. Drop out by group: Not reported. Reasons for losses: orthodontic treatment (27), moved away (22), did not wish to continue (26, not reported by group).

Comment: Numbers lost are not unduly high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants continuing the study up to year 2 (children completing tests).

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (NCA) cl, reported at 2 years follow-up.
BLMD-DFS (clin).
MD-DFS (x-ray).
Proportion of children with new smooth surface caries.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 13.08 FD1, 12.90 FD2, 12.74 PL.

Dental age: 20.72 FD1, 21.21 FD2, 21.24 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "The dentifrice was distributed every second month in amounts calculated to meet the needs of the whole family, to ensure as far as possible that the participants did not have access to other toothpastes."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Gish 1966

Methods

Stratified random allocation; double-blind; placebo-controlled; 34% drop out after 3 years (study duration = 5 years). Reasons for attrition not reported; any differential group losses not assessable.

Participants

328 children analysed at 3 years (available at final examination).
Age range at start: 6-14 years (average = 9).
Surfaces affected at start: 3.9 DMFS.
Background exposure to fluoride: water.
Year study began: in/before 1963.
Location: USA.

Interventions

FT versus PL
(SnF2 group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Ca pyrophosphate.

Outcomes

3yDMFS increment - cl+xr.
Reported at 1, 2, 3, 4 and 5 years follow-ups.

DMFT.

Notes

Participants randomised (n = 500); numbers by group not reported.
Baseline characteristics (age, DMFS) 'balanced'.
Clinical (VT) caries assessment by 2 examiners, diagnostic threshold not reported. Radiographic assessment (5-7 BW); diagnostic threshold not reported. State of tooth eruption included not reported. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "The children were stratified by past caries experience and dental age, and then assigned at random to test or control groups."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The dentifrices were packed in plain, white, coded tubes. The code was not known by either the subjects or the examiners."

"...those in group 2 received an identical dentifrice minus the stannous fluoride."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 34, 4% (172/500) in 3 years. Drop out by group: Not reported. Reasons for losses: Not reported.

Comment: Numbers lost were not unduly high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data pertain to participants present at final examinations (completing the relevant follow-up exam).

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - cl+xr, reported at 1, 2, 3, 4 and 5 years follow-ups.
DMFT.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported: DFMS: 3.73 FD, 4.17 PL; Age: 9.27 FD, 9.25 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "All of the children and their families received as much dentifrice as they wished, and no instructions were given to either group as to oral hygiene or frequency of use of either product."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Glass 1978

Methods

Stratified random allocation; double-blind; placebo-controlled; 35% drop out after 3 years (study duration = 3 years). Natural losses, increased during 3rd year because an entire grade graduated; exclusions based on presence in all follow-up examinations; any differential group losses not assessable.

Participants

346 children analysed at 3 years (present for all examinations).
Age range at start: 6-11 years (average = 9).
Surfaces affected at start: 4.1 DFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1974.
Location: USA.

Interventions

FT versus PL
(SMFP group = 1000 ppm F).

School use/supervised, 1 g applied daily (appropriate toothpastes and toothbrushes also provided for home use).
Abrasive system: Ca carbonate.

Outcomes

3yNetDFS increment - (CA)cl+(ER)xr.
Reported at 1, 2 and 3 years follow-ups.

MD-DFS.
O-BL-DFS.
DFT.

CIR.
O-BL-CIR.
MD-CIR.

Notes

Participants randomised (n = 533); numbers by group not reported.
Baseline characteristics (age, DFS, DFT, SAR, TAR) 'balanced'.
Clinical (VT) caries assessment (FOTI used) by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E/U. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = ER. Reversals were small in both groups (about 6% of DFS increments) and equally common (NS different).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "The initial total of 533 subjects, stratified according to age and sex, were assigned at random to one of 2 groups."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "One group brushed with dentifrice containing MFP, the other with the same dentifrice without MFP."

"At no time during the clinical examinations or during the interpretation of the radiographs was the identity of the experimental and control group codes known to the examiner or his recorder."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 35% (187/533) in 3 years. Drop out by group: Not reported. Reasons for losses: Left school, exclusion based on presence at all examinations.

Comment: Numbers lost were not unduly high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data pertain to participants present at all examinations.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (CA)cl+(ER)xr, reported at 1, 2 and 3 years follow-ups.
MD-DFS.
O-BL-DFS.
DFT.

CIR.
O-BL-CIR.
MD-CIR.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 3.87 (4.22) FD, 4.38 (4.36) PL.

Age (months): 108.80 (17.21) FD, 110.16 (18.29) PL.

DFT: 2.32 (2.14) FD, 2.73 (2.45) PL.

SAR: 63.90 (27.63) FD, 61.63 (24.93) PL.

TAR: 11.30 (5.10) FD, 10.38 (4.48) PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "Subjects living at the same street address were assigned to the same group to avoid the presence of two dentifrices in the same household."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Glass 1983

Methods

Stratified random allocation; double-blind; placebo-controlled; 16% drop out after 2.5 years (study duration = 2.5 years). Natural losses; no losses due to any adverse effects; any differential group losses not assessable.

Participants

853 children analysed at 2.5 years (available at final examination).
Age range at start: 7-11 years (average = 9).
Surfaces affected at start: 2.1 DFS.
Background exposure to fluoride: water.
Year study began: 1976.
Location: USA.

Interventions

FT (2 groups) versus PL
(both SMFP groups = 1000 ppm F).

School use/supervised, daily (appropriate toothpastes and toothbrushes also provided for home use).
Abrasive system: IMP (main abrasive) in one SMFP and placebo toothpaste, Ca carbonate in the other SMFP toothpaste.

Outcomes

2.5yNetDFS increment - (CA)cl+(ER)xr.
Reported at 2.5 years follow-up.

DFT.
CIR.
Side effects.

Notes

Participants randomised (n = 1017); numbers by group not reported.
Baseline characteristics (age, DFS, DFT, SAR, TAR) 'balanced' (for DFT/DFS).
Clinical (VT) caries assessment by 2 examiners (independently); diagnostic threshold = CA; state of tooth eruption included = E/U. Radiographic assessment (2 postBW) by 2 examiners (independently); diagnostic threshold = ER. Results of one examiner chosen (findings consistent throughout).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "....within strata, subjects were assigned group codes using computer generated random permutations of the digits 1, 2 and 3."

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "One group of children brushed with a control dentifrice (no NaMFP), the other groups brushed with one of the dentifrices containing NaMFP."

"The study was conducted in a double-blind basis until the results had been analysed."

Comment: Use of placebo described, but blind outcome assessment not described but probably done since earlier report from same author clearly describe blind outcome assessment.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 16% (164/1017) in 2.5 years. Drop out by group: Not reported. Reasons for losses: Change of residence or school (no losses due to any adverse effect).

Comment: Numbers lost were not unduly high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced between groups. Caries data pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (CA)cl+(ER)xr, reported at 2.5 years follow-up.

DFT.
CIR.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 2.20 (2.91) FD1, 2.04 (2.63) FD2, 2.09 (2.53) PL.

TAR: 11.40 (4.82) FD1, 11.11 (4.14) FD2, 12.20 (5.11) PL.

SAR: 62.65 (25.54) FD1, 60.98 (22.27) FD2, 66.73 (26.63) PL.

Age: 8.80 (1.49) FD1, 8.65 (1.41) FD2, 8.89 (1.46) PL.

DFT: 1.59 (1.74) FD1, 1.51 (1.61) FD2, 1.61 (1.69) PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "Sufficient dentifrice was provided for home use by the entire family in order to minimize the chance of use of other than the dentifrice provided."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Hanachowicz 1984

Methods

Stratified random allocation; double-blind; placebo-controlled; 28% drop out after 3 years (study duration = 3 years). Natural losses and exclusions based on compliance; no differential group losses.

Participants

945 children analysed at 3 years (available at final examination and co-operative).
Age range at start: 10-12 years.
Surfaces affected at start: 5.4 DMFS.
Background exposure to fluoride: none reported.
Year study began: 1979.
Location: France.

Interventions

FT versus PL
(SMFP group = 1500 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Al oxide trihydrate.

Outcomes

3yNetDMFS increment - (E)(CA)cl+xr.
Reported at 3 years follow-up.

DMFT.
DMFS (U).
O-DMFS.
MD-DMFS.
BL-DMFS.
premolarDMFT.
premolarDMFS.
Proportion of children with new caries.
Compliance.

Notes

Participants randomised (n = 1318).
Baseline characteristics (DMFS) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA; radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold not reported. State of tooth eruption included = E/U. Consistency of clinical and x-ray diagnosis assessed by duplicate examinations of 6% sample (inter-examiner reproducibility ratios 0.24 for clinical and 0.13 for x-ray; intra-examiner reproducibility 0.27 for clinical and 0.14 for x-ray).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quotes: "After baseline examination, the children were stratified with regard to their examiner, caries experience..... Each child was then randomly allocated to the test or toothpaste group. In order that only one type of toothpaste was used in each household an exception was made where two children from one household were participating ...it was arranged for them to have the same toothpaste."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "Neither the subjects nor the examiners knew who was receiving the test or the control toothpaste."

"The control toothpaste was without sodium monofluorophosphate."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 19.5% in 3 years. Drop out by group: 186/659 FD, 185/659 FD. Reasons for losses: Family moved away (116), lack of co-operation (42) (by not brushing at least 5 times a week), refusal from final examination (30), refused consent for examination (21), moved to boarding school (18), discontinued (11), family difficulties (6), unacceptable taste of toothpaste (equally divided between groups {5}), illness (2), lost to follow-up (2), unacceptable abrasivity of toothpaste (not reported by group {1}).

Comment: Numbers lost were not unduly high for length of follow-up, and showed no differential loss between groups. It is unclear if reasons for missing data are acceptable and balanced between groups. Caries data pertain to participants present and co-operative at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (E)(CA)cl+xr, reported at 3 years follow-up.
DMFT.
DMFS (U).
O-DMFS.
MD-DMFS.
BL-DMFS.
premolarDMFT.
premolarDMFS.
Proportion of children with new caries.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported: DMFS: 5.36 FD, 5.43 PL.

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quotes: "In order that only one type of toothpaste was used in household, an exception was made where two children from one household were participating in the trial...it was arranged for them to have the same toothpaste."

"The distribution of the toothpastes was the responsibility of three ladies...Their duty was to visit each home every 5 weeks to supply the whole family with sufficient amounts of toothpaste. This was considered important to prevent the use of other commercial toothpastes."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Held 1968

Methods

Stratified random allocation; double-blind; placebo-controlled; 65% drop out after 3 years (study duration = 3 years). Reasons for high drop out due to age range at which many leave the institutions; no differential group losses.

Participants

63 children analysed at 3 years (available at final examination).
Age range at start: 15-16 years.
Surfaces affected at start: 14.3 DMFS.
Background exposure to fluoride: data not available for fluoridation status of site.
Year study began: 1962.
Location: France.

Interventions

FT versus PL
(NaF-SnF2 group = 1000 ppm F).

Institution use/supervised, twice a day.
Abrasive system: not clearly specified (silica used).

Outcomes

3yDMFS increment - (E) cl.
Reported at 3 years follow-up.

DMFT.
Annual CAR.

Notes

Participants randomised (n = 178).
Baseline characteristics (DMFS, DMFT) not balanced.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold not reported; state of tooth eruption included = E. Intra-examiner reproducibility checks done.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...distributed at random to 2 groups."

Comment: Translation of report not detailed enough to make a categorical decision regarding sequence generation.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "Double blind study."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Yes

Quotes: Overall drop out for length of follow-up: 64.6% in 3 years. Drop out by group: 54/86 FD, 61/92 PL. Reason for losses: Participants leaving school (due to age range at which many leave the institutions).

Comment: Numbers lost are unduly high for length of follow-up. Although no differential losses between groups are apparent and the only reason given for the missing data is acceptable and balanced between groups, this balance may have occurred by chance, because sample size is too small. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Unclear

Outcomes reported:
DMFS increment - (E) cl, reported at 3 years follow-up.
DMFT.
Annual CAR.

Comment: Trial protocol unavailable. Translation of methods section not detailed enough to make a categorical decision regarding selective outcome reporting.

Baseline characteristics balanced?

No

Prognostic factors reported: DMFS: 16.9 FD, 11.7 PL; DMFT: 7.9 FD, 5.7 PL.

Comment: Initial caries (DMFS) appears imbalanced.

Free of contamination/co-intervention?

Unclear

Translation of report not detailed enough to make a categorical decision regarding any contamination and/or co-intervention.



Held 1968a

Methods

Stratified random allocation; double-blind; placebo-controlled; 64% drop out after 3 years (study duration = 3 years). Reasons for high drop out due to age range at which many leave the institutions; no differential group losses.

Participants

36 children analysed at 3 years (available at final examination).
Age range at start: 15-16 years.
Surfaces affected at start: 9.6 DMFS.
Background exposure to fluoride: data not available for fluoridation status of site.
Year study began: 1961.
Location: France.

Interventions

FT versus PL
(NaF-SnF2 group = 1000 ppm F).

Institution use/supervised, twice a day.
Abrasive system: not clearly specified (silica used).

Outcomes

3yDMFS increment - (E) cl.
Reported at 3 years follow-up.

DMFT.
Annual CAR.

Notes

Participants randomised (n = 101).
Baseline characteristics (DMFS, DMFT) not balanced.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold not reported; state of tooth eruption included = E. Intra-examiner reproducibility checks done.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...distributed at random to 2 groups."

Comment: Translation of report not detailed enough to make a categorical decision regarding sequence generation.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "Double blind study."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Yes

Quotes: Overall drop out for length of follow-up: 64.4% in 3 years. Drop out by group: 33/52 FD, 32/49 PL. Reasons for losses: Participants leaving school (due to age range at which many leave the institutions).

Comment: Numbers lost are unduly high for length of follow-up. Although no differential losses between groups are apparent and the only reason given for the missing data is acceptable and balanced between groups, this balance may have occurred by chance, because sample size is too small. Caries data used in analysis pertain to participants present at final examinations.

Free of selective reporting?

Unclear

Outcomes reported:
DMFS increment - (E) cl, reported at 3 years follow-up.
DMFT. Annual CAR.

Comment: Trial protocol unavailable. Translation of methods section not detailed enough to make a categorical decision regarding selective outcome reporting.

Baseline characteristics balanced?

No

Prognostic factors reported: DMFS: 11.0 FD, 8.0 PL; DMFT: 5.6 FD, 4.6 PL.

Comment: Initial caries (DMFS) appears imbalanced.

Free of contamination/co-intervention?

Unclear

Translation of report not detailed enough to make a categorical decision regarding any contamination and/or co-intervention.



Held 1968b

Methods

Stratified random allocation; double-blind; placebo-controlled; 62% drop out after 2 years (study duration = 3 years). Reasons for high drop out due to age range at which many leave the institutions; no differential group losses.

Participants

32 children analysed at 2* years (available at final examination).
Average age at start: 15 years.
Surfaces affected at start: 10.2 DMFS.
Background exposure to fluoride: data not available for fluoridation status of site.
Year study began: 1961.
Location: France.

Interventions

FT versus PL
(NaF group = 500 ppm F).

Institution use/supervised, twice a day.
Abrasive system: not clearly specified (silica used).

Outcomes

2y*DMFS increment - (E) cl.
Reported at 2 and 3 years follow-ups.

DMFT.
Annual CAR.

Notes

Participants randomised (n = 85).
Baseline characteristics (DMFS, DMFT) not balanced.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold not reported; state of tooth eruption included = E. Intra-examiner reproducibility checks done.
*Results for 3 years follow-up not considered due to very high drop-out rate.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...distributed at random to 2 groups."

Comment: Translation of report not detailed enough to make a categorical decision regarding sequence generation.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "Double blind study."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

No

Quotes: Overall drop out for length of follow-up: 62.4% in 2 years. Drop out by group: 30/44 FD, 23/41 PL. Reasons for losses: Participants leaving school.

Comment: Numbers lost are unduly high for length of follow-up, with differential losses between groups (68%, 56%). Reasons for the missing data are not balanced between groups. Caries data used in analysis pertain to participants present at each examination.

Free of selective reporting?

Unclear

Outcomes reported:
DMFS increment - (E) cl, reported at 2 years follow-up.
DMFT. Annual CAR.

Comment: Trial protocol unavailable. Translation of methods section not detailed enough to make a categorical decision regarding selective outcome reporting.

Baseline characteristics balanced?

No

Prognostic factors reported: DMFS: 13.7 FD, 7.0 PL; DMFT: 7.1 FD, 4.3 PL.

Comment: Initial caries (DMFS) appears imbalanced.

Free of contamination/co-intervention?

Unclear

Translation of report not detailed enough to make a categorical decision regarding any contamination and/or co-intervention.



Hodge 1980

Methods

Stratified random allocation; double-blind; placebo-controlled; 18% drop out after 3 years (study duration = 3 years). Reasons for attrition described with respective total numbers: 158 left school, 14 withdrawn by own choice, 8 lack of co-operation; any differential group losses not assessable.

Participants

799 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years.
Surfaces affected at start: 7.3 DMFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1976.
Location: UK.

Interventions

FT (3 groups) versus PL
(SMFP group = 1000 ppm F, both SMFP-NaF groups = 1450 ppm F).

School use/supervised, daily, for 1 min (appropriate toothpastes also provided for home use).
Abrasive system: alumina (in placebo toothpaste, SMFP and in one SMFP-NaF toothpaste), dicalcium phosphate (in another SMFP-NaF toothpaste).

Outcomes

3yNetDFS increment - (E) (CA)cl+(DR)xr.
Reported at 3 years follow-up.

DMFT.
Compliance.

Notes

Participants randomised (n = 979); numbers by group not reported.
Baseline characteristics (DMFS, DMFT, SAR) 'balanced' (DFS baseline data not reported).
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E/U; radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = DR. Reproducibility checks done in 10% sample clinically and radiographically (ICC of incremental data between 0.92 and 0.97).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Following the initial baseline examination, subjects were stratified according to school and sex, and randomly assigned to 1 of 4 groups."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "The trial was double-blind, neither the subjects nor the examiner knew who was receiving test or control products. The test and control dentifrices were indistinguishable in taste and appearance."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 18.4% (180/979) in 3 years. Drop out by group: Not reported. Reasons for losses: Changing school (184), moving away, withdrawal from study (14), exclusion due to lack of co-operation (7).

Comment: Numbers lost were not unduly high for the length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (E) (CA)cl+(DR)xr, reported at 3 years follow-up.
DMFT.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFT: 4.82 (3.02) FD1, 4.62 (3.12) FD2, 4.40 (2.84) FD3, 4.37 (2.62) PL.

DMFS: 7.81 (5.76) FD1, 7.63 (6.23) FD2, 6.97 (4.91) FD3, 6.93 (4.59) PL.

SAR: 90.61 (20.13) FD1, 88.05 (22.00) FD2, 90.00 (22.95) FD3, 87.09 (22.36) PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "Dentifrices were used daily in school, either immediately following morning or afternoon registration, the children being under the care of brushing supervisors."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Homan 1969

Methods

Stratified random allocation; double-blind; placebo-controlled; 19% drop out after 1.7 years (study duration = 1.7 years). Reasons for attrition not described; any differential group losses not assessable.

Participants

1874 children analysed at 1.7 years.
Age range at start: 7-13 years.
Surfaces affected at start: data not available nor obtainable.
Background exposure to fluoride: none.
Year study began: 1965.
Location: Australia.

Interventions

FT (3 groups) versus PL
(SnF2 and APF toothpaste concentrations not reported nor obtainable).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Ca pyrophosphate in one SnF2 toothpaste, calcium-free abrasive in the other SnF2 toothpaste and in the APF toothpaste; abrasive in placebo toothpaste not reported.

Outcomes

Caries increment data not reported nor obtainable.

Percentage DFS reductions by gender and age groups reported at 1.7 years follow-up.

Notes

Participants randomised (n = 2317); numbers by group not reported.
Baseline characteristics not reported.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA; state of tooth eruption included = E; radiographic assessment; diagnostic threshold = DR. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...children were equally divided by sex into two groups.....and randomly allocated to one of four coded dentifrices."

Quote from correspondence: "I do not recall method of randomisation."

Comment: Not enough information provided.

Allocation concealment?

Unclear

Quote from correspondence: "Yes. The allocation of subjects to groups and the distribution of dentifrices was completely independent of the clinical examiners."

Comment: Not enough information provided.

Blinding?
All outcomes

Yes

Quote from correspondence: "Neither investigators nor participants knew the toothpaste used by individual participants. This was achieved by packaging of all dentifrices used in the study in identical plain tubes......examiners were not provided with any information of the dentifrice used by any child examined." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 19.1% in 1.7 years (443/2317). Drop out by group: Not reported. Reasons for losses: Not reported.

Comment: Numbers lost were not unduly high for the length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced.

Free of selective reporting?

Unclear

Outcomes reported: Caries increment (data not obtainable).

Percentage DFS reductions by gender and age group reported at 1.7 years follow-up.

Comment: Trial protocol or full text report (methods) unavailable. Not enough information provided.

Baseline characteristics balanced?

Unclear

No information provided.

Free of contamination/co-intervention?

Unclear

No information provided.



Howat 1978

Methods

Random allocation; double-blind; placebo-controlled; 12% drop out after 3 years (study duration = 3 years). Reasons for attrition described with respective total numbers (56 left school, 7 withdrawn by own choice, 2 lack of co-operation); no differential drop out - 65 failed to complete the trial, 39 in placebo group and 26 in fluoride group.

Participants

495 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years.
Surfaces affected at start: 7.4 DMFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1974.
Location: UK.

Interventions

FT versus PL
(SMFP group = 1000 ppm F).

School use/supervised, daily, for 1 min (appropriate toothpastes also provided for home use).
Abrasive system: silica zerogel.

Outcomes

3yNetDMFS increment - (E) (CA)cl+(DR)xr.
Reported at 3 years follow-up.

antDMFS.
postDMFS.
PF-DMFS.
MD-DMFS.
MD-BL-DMFS.
DMFT.
Compliance.

Notes

Participants randomised (n = 560); numbers by group not reported.
Baseline characteristics (DMFS, DMFT, SAR) 'balanced'.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E/U; radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = DR. Reproducibility checks done in 10% sample clinically and radiographically (ICC of incremental data between 0.96 and 0.99).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "The subjects were randomly allocated to test and control groups."

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "The trial was double-blind with neither the subjects nor the examiner being aware who was receiving test or control products.....dentifrices were indistinguishable in taste and appearance and their composition varied only in their fluoride content." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 11.6% (in 3 years). Drop out by group: 26/279 FD, 39/281 PL. Reasons for losses: Changing school (56), withdrawal from study by choice (7), exclusion due to lack of co-operation (2).

Comment: Numbers lost were not unduly high for the length of follow-up, with no differential losses between groups. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (E) (CA)cl+(DR)xr, reported at 3 years follow-up.
antDMFS.
postDMFS.
PF-DMFS.
MD-DMFS.
MD-BL-DMFS.
DMFT.       

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 7.42 (5.92) FD, 7.37 (5.59) PL.

DMFT: 4.63 (3.32) FD, 4.65 (3.17) PL.

SAR: 93.48 (19.74) FD, 92.81 (21.52) PL. 

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "Active and control dentifrices were used daily at school ...under the care of brushing supervisors... subjects were also given liberal supplies of the same dentifrice for home use....and independent checks of the dispensed dentifrices were carried out at regular intervals to assess the accuracy of the trial supervisors."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Jackson 1967

Methods

Random allocation; double-blind; placebo-controlled; 12% drop-out rate after 3 years (study duration = 3 years). Natural losses; no differential group losses.

Participants

871 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years. Surfaces affected at start: 8.7 DMFS.
Background exposure to fluoride: none reported.
Year study began: 1962.
Location: UK.

Interventions

FT versus PL
(SnF2 group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: dicalcium pyrophosphate.

Outcomes

3yDMFS increment - (E+U)(CA)cl.
Reported at 3 years follow-up.

DMFT.
Proportion of caries-free teeth/surfaces (by tooth type/ surface type) which developed caries.
Proportion of children who complained of tooth staining.
Compliance.

Notes

Participants randomised (n = 986).
Baseline characteristics (age, DMFS, DMFT, TAR, level of treatment, staining) 'balanced'.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E/U. Consistency of clinical diagnosis maintained by re-examination of 10% sample and calibration checks made against reserve examiner.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "Method used was stratification according to sex, age and school.....Age was calculated to a standard date...boys were paired according to age so that 2 groups were obtained in which mean age and distribution of age was as identical as possible. A coin toss determined whether the group should be nominated O and N."

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "The two groups were called O and N respectively. Whereas it was not known at the time which group was the control and which was the experimental group, it is now known that group O was that which received the stannous fluoride dentifrice."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 12% in 3 years. Drop out by group: 56/494 fluoride, 59/492 placebo. Reasons for losses: Not reported.

Comment: Numbers lost were not unduly high given length of follow-up with no differential losses between groups. It is unclear if the reasons for the missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (E+U)(CA)cl, reported at 3 years follow-up.
DMFT.
Proportion of caries-free teeth/surfaces (by tooth type/surface type) which developed caries.
Proportion of children who complained of tooth staining.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 8.42 (5.36) FD, 8.93 (5.87) PL.

DMFT: 5.43 FD, 5.14 PL.

Age: 11.7 FD, 11.7 PL.

Treatment index: 65 % FD, 64% PL.

TAR: 17.74 FD, 17.46 PL.

Staining: 19.9 FD, 18.7 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "The duties of the home visitors were to provide a continuous supply of toothpaste to each home for each member of the family...to encourage co-operation..."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



James 1967

Methods

Random allocation; double-blind; placebo-controlled; 23% drop-out rate after 3 years (study duration = 3 years). Reasons for drop out described with respective total numbers: moved away, unco-operative, not present on examination day, disliked toothpaste, staining of teeth, others; no differential group losses.

Participants

803 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years. Surfaces affected at start: 11 DFS.
Background exposure to fluoride: data not available for fluoridation status of site.
Year study began: 1962.
Location: UK.

Interventions

FT versus PL
(SnF2 group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: dicalcium pyrophosphate.

Outcomes

3yDFS increment - (E)
(CA)cl+(ER)xr.
Reported at 3 years follow-up.

DMFS.
DFT.
DMFT.
postMD-DFS.
Proportion of children with tooth staining.
Compliance.

Notes

Participants randomised (n = 1043).
Baseline characteristics (age, DFS, DFT, DMFS, DMFT) 'balanced'.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E/U. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = ER. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "These children were divided, by sex and by school, into 2 groups, using a random number technique for designation into groups. Each school therefore contained approximately equal numbers of test and control children, with similar representation of boys and girls."

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "Children in the test group were supplied with stannous fluoride...dentifrice, while the control dentifrice was identical in colour, texture and flavour."

"Nobody involved in the study, except the manufacturers, knew the identity of the test dentifrice, and the double-blind technique was maintained throughout the investigation."

"All radiographs were read by one of us at the end of the study without knowledge of group allocation."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 23% in 3 years. Drop out by group: 124/530 FD, 116/513 PL. Reasons for losses: Moved away (59 FD, 59 PL), unco-operative (31 FD, 24 PL), not present on examination day (27 both groups), disliked toothpaste (3 FD, 2 PL), staining of teeth (2 FD, 2 PL), others (18 FD, 13 PL).

Comment: Numbers lost were not unduly high given the length of follow-up with no differential losses between groups. It is unclear if reasons for the missing outcome data are acceptable and balanced between groups. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (E) (CA)cl+(ER)xr, reported at 3 years follow-up.
DMFS.
DFT.
DMFT.
postMD-DFS.

Proportion of children with tooth staining.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 10.73 FD, 11.32 PL.

Age: 11.35 FD, 11.35 PL. DFS: 10.73 FD, 11.32 PL.

DFT: 6.12 FD, 6.48 PL. DMFT: 6.12 FD, 6.48 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "It was decided to supply the whole of the subject's family with the appropriate dentifrice to reduce the risk of other brands being used during the test period."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



James 1977

Methods

Stratified random allocation; double-blind; placebo-controlled; 19% drop out after 3 years (study duration = 3 years). Reasons for attrition not reported; exclusions based on presence in all follow-up examinations; any differential group losses not assessable.

Participants

782 children analysed at 3 years (present for all examinations).
Age range at start: 11-12 years.
Surfaces affected at start: 11.2 DMFS.
Background exposure to fluoride: data not available for fluoridation status of site.
Year study began: 1970.
Location: UK.

Interventions

FT versus PL
(SMFP group = 2400 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Al oxide trihydrate.

Outcomes

3yDMFS increment - (CA)cl+(ER)xr.
Reported at 3 years follow-up.

postMD-DMFS.
O-DMFS.
BL-DMFS.
O-BL-MDDMFS.
antDMFS.

Notes

Participants randomised (n = 964); numbers by group not reported.
Baseline characteristics (age, gender, DMFS) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA; radiographic assessment (2 postBW); state of tooth eruption included not reported. Inter- and intra- examiner reliability for clinical and radiographic diagnosis revealed by re-examination of 10% sample.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "After baseline examination, they were stratified by sex, school and level of caries experience and randomly allocated to one or other of two groups." 

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "...one of the groups was supplied with the dentifrice containing fluoride, while the other received the paste without it. The two dentifrices were identical in taste, appearance and texture, and the trial was conducted on a double-blind basis."

"After the analysis the code was broken...." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 18.9% (182/964) in 3 years. Drop out by group: Not reported. Reasons for losses: Exclusion due to absence from any examination.

Comment: Numbers lost were not unduly high for the length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants who took part in all examinations.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (E+U)(CA)cl, reported at 3 years follow-up.
postMD-DMFS.
O-DMFS.
BL-DMFS.
O-BL-MDDMFS.
antDMFS.

Proportion of caries-free teeth/surfaces (by tooth type/ surface type) which developed caries.

Proportion of children who complained of tooth staining.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported: DMFS: 11.0 FD, 11.4 PL; Mean age: 11.9 FD, 12.0 PL. 

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Unclear

Quote: "The appropriate pastes were distributed by home visitors to the children's homes.....they were not instructed to supervise or monitor the usage of the paste."

Comment: Not enough information provided.



Kinkel 1972

Methods

Random allocation; double-blind; placebo-controlled; 25% drop-out rate after 3 years (study duration = 7 years). Reasons for drop out not described; any differential group losses not assessable.

Participants

699 children analysed at 3 years.
Average age at start: 10 years. Surfaces affected at start: 2.2 DMFS.
Background exposure to fluoride: data not available.
Year study began: in/before 1969.
Location: Switzerland.

Interventions

FT versus PL
(SMFP group F concentration not reported).

Home use/unsupervised, daily frequency assumed.
Abrasive system: not reported.

Outcomes

3yDMFS increment - (CA)cl+(DR)xr.
Reported at 1, 2, 3, 4, 5 and 7 years follow-ups.

Notes

Participants randomised (n = 927); numbers by group not reported.
Baseline characteristics (DMFS) 'balanced'.
Clinical (V) caries assessment; diagnostic threshold = CA and NCA; state of tooth eruption included not reported. Radiographic assessment (2 postBW); diagnostic threshold = DR and ER.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...randomly allocated."

Comment: Translation of report not detailed enough to make a categorical decision regarding sequence generation.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "Double blind study."

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 24.6% (228/927) in 3 years. Drop out by group: Not reported. Reasons for losses: Not reported. 

Comment: Numbers lost were not unduly high for the length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Unclear

Outcomes reported: DMFS increment - (CA)cl+(DR)xr, reported at 1, 2, 3, 4, 5 and 7 years follow-ups.

Comment: Trial protocol unavailable. Translation of methods section not detailed enough to make a categorical decision regarding selective outcome reporting.

Baseline characteristics balanced?

Yes

Prognostic factors reported: DMFS: 2.21 fluoride, 2.29 placebo.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Unclear

Translation of report not detailed enough to make a categorical decision regarding any contamination and/or co-intervention.



Kleber 1996

Methods

Stratified random allocation; double-blind; placebo-controlled; 10% drop out after 1 year (study duration = 1 year). Main reasons for attrition: changes in residence, few exclusions for initiation of ortho treatment; no differential group losses.

Participants

156 children analysed at 1 year (available at final examination).
Age range at start: 10-11 years (average = 10.7).
Surfaces affected at start: 4.2 DMFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1994.
Location: USA.

Interventions

FT(+Alrins) versus PL(+Alrins) **
(NaF toothpaste = 1100 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: silica.

Outcomes

1yDMFS increment - (CA)cl+(ER)xr.
Reported at 0.6 and 1 year follow-ups.

DMFT.
Proportion of children remaining caries free.
Proportion of children with new DMFS.
Oral soft tissues lesions.
Compliance.

Notes

Participants randomised (n = 174).
Baseline characteristics (age, gender, DMFS, DMFT) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA; state of tooth eruption included = E/U. Radiographic assessment (postBW) by 2 examiners (independently); diagnostic threshold = ER.
Reversals were small in both groups and equally common. Results of 1 examiner chosen (findings consistent throughout).
**Rinsing with 500 ppm Al solutions performed daily at school in both relevant groups compared.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Subjects with evidence of caries activity were stratified according to age, gender...then randomly assigned to one of the balanced groups." 

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "A double blind comparison of three parallel groups of children... who used a test or placebo dentifrice for a twelve month period."

"Radiographs were scored independently by each examiner at a later date.."                   

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Yes

Quote: Overall drop out for length of follow-up: 10% in 1 year. Drop out by group: 10/87 FD, 8/87 PL. Reasons for losses: Changes in residence, exclusion based on orthodontic treatment. 

Comment: Numbers lost were not unduly high given the length of follow-up with no differential losses between groups. Reasons for the missing outcome data are acceptable. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (CA)cl+(ER)xr, reported at 0.6 and 1 year follow-ups.
DMFT.
Proportion of children remaining caries free.
Proportion of children with new DMFS.
Oral soft tissues lesions. 

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 5.06 (0.58) FD, 4.78 (0.50) PL.

DMFT: 3.31 (0.32) FD, 3.32 (0.27) PL.

Age: 10.7 FD, 10.6 PL.

Gender: 42 M, 45 F (FD); 42 M, 45 F (PL). 

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quote: "Sufficient quantities of the respective products were provided for the participants and their families to use throughout the study. Participants with the same telephone number or address were assigned to the same group to avoid confusion with different test products in the same household."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Koch 1990

Methods

Stratified random allocation; double-blind; 10.9% drop out (for all study groups combined) after 3 years (study duration = 3 years). Reasons for attrition: relocation, compliance, others; no differential group losses.

Participants

1035 children analysed at 3 years (available at final examination).
Age range at start: (11-12 years).
Surfaces affected at start: 9.9 DFS.
Background exposure to fluoride: water <0.1 ppm F in community.
Year study began: 1983.
Location: Iceland.

Interventions

FT (5 groups)  **  
250 ppm NaF
940 ppm F SMFP (no anti-calculus agent)
980 ppm F NaF (anti-calculus agent AHBP)
970 ppm F NaF (no anti-calculus agent)
940 ppm F NaF (anti-calculus agent AHBP).

Home use/unsupervised, daily frequency assumed.
Abrasive system: NaF silica; SMFP CaHPO42H2O.

Outcomes

3yNet DFS increment cl+xr
Reported at 3 years follow-up.

DFS increment by surface.
DFT increment.
New lesions only and restorations.
Gingival health (gingival bleeding index).
Compliance.
Adverse reactions.

Notes

Participants randomised (n = 1161).
Baseline characteristics (age, gender, DFS) 'balanced'.
Clinical examinations performed by 2 examiners. Prior to each exam, both dentists examined 20 of their assigned children at random who were re-examined at least 1 day later to gauge consistency. ICC of at least 0.75 for acceptable reliability but exact values not stated.
**1000 ppm F groups combined for analysis. Groups with anti-calculus agents excluded from analysis.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: " ...randomly assigned to one of five treatment groups."

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quotes: "...unsupervised double-blind study."

"...dentifrices were purchased and refilled in laminated tubes to ensure dentifrices were identical."

 

Incomplete outcome data addressed?
All outcomes

Unclear

Comment: Reasons for attrition stated. Attrition rate was low after 3 years, 11% overall and similar in all toothpaste groups. Query compliance as reason for withdrawal and this negates ITT analysis, although only 23/1146 (2%) withdrew or were withdrawn for this reason.

Free of selective reporting?

Yes

Comment: Results reported DFT, DFS, on different surface types.

Baseline characteristics balanced?

Yes

Comment: Balance of age, gender, DFS.

Free of contamination/co-intervention?

Unclear

Comment: Insufficient information.



Lima 2008

Methods

Random allocation; single-blind; 25% drop-out rate after 1 year (study duration = 1 year). Reasons for attrition: moved away from study area, children leaving nursery setting; no differential group losses.

Participants

90 children analysed at 1 year (available at final examination).
Age range at start: 2-4 years (average = 3).
Surfaces affected at start: 5.1 DMFS.
Background exposure to fluoride: water <0.3 ppm F in community.
Year study began: in/before 2006.
Location: Brazil.

Interventions

FT (500 ppm NaF) versus FT (1100 ppm NaF).

School use/supervised daily frequency; home use/unsupervised, daily frequency assumed.
Abrasive system: none reported.

Outcomes

Number of lesions becoming active/cavities or inactive by initial caries status.

Notes

Participants randomised (n = 120).
Baseline characteristics (age, gender, caries status) 'balanced'.
Clinical caries assessment by single examiner; intra-examiner agreement assessed by second clinical exam in 10% of the sample after 15 days (Kappa 0.95).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "..randomised single-blind clinical trial."

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quotes: "..randomised single-blind clinical trial" "The study was blinded only for the examiner..."

Comment: Examiner was blinded to the treatment allocation.

Incomplete outcome data addressed?
All outcomes

Yes

Comment: Reasons for attrition stated. Attrition rate was moderate after 1 year, 25% overall and similar in both toothpaste groups and unlikely to be related to intervention.

Free of selective reporting?

Yes

Comment: All pre-specified outcomes reported (progression and arresting of lesions by toothpaste group and inital caries status).

Baseline characteristics balanced?

No

Comment: More males in 1100 ppm F group than females (26:18 versus 23:23), lower mean activated non-cavitated caries lesions in 500 ppm F group (2.5 (1.5 sd) versus 5.3 (6.5 sd)).

Free of contamination/co-intervention?

Unclear

Comment: Possible contamination in school brushing sessions but unlikely under supervision. Possible contamination at home brushing.



Lind 1974

Methods

Stratified random allocation; double-blind; placebo-controlled; 17% drop-out rate after 3 years (study duration = 3 years). Main reasons for drop out: moved away, sickness; exclusions based on presence in one interim examination; no differential group losses.

Participants

1167 children analysed at 3 years (available at intermediate and final examination).
Age range at start: 7-12 years (average = 10).
Surfaces affected at start: 5.1 DMFS.
Background exposure to fluoride: water.
Year study began: 1970.
Location: Denmark.

Interventions

FT versus PL
(SMFP group = 2400 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Al oxide trihydrate.

Outcomes

3yNetDMFS increment - (E+U) (CA)cl+(DR)xr.
Reported at 1, 2, and 3 years follow-ups.

DMFT.
ECSI.

Notes

Participants randomised (n = 1407).
Baseline characteristics (age, DMFS, DMFT) 'balanced'.
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA/NCA; radiographic assessment (2 postBW) by 2 examiners; diagnostic threshold = ER/DR; state of tooth eruption included = E/U. Inter-examiner diagnostic error reported to have no effect on results; reversal rates small and similar in both groups.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "...children were stratified according to age, sex...The experimental and control groups were formed using random assignment. Children from the same household were allocated to the same treatment group to ensure that only one type of dentifrice entered the household during the trial period." 

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quote: "The trial was in...a double-blind design...The only persons who, of necessity, knew the allocation code of the dentifrices were the factory personnel who manufactured the dentifrices. The packages containing the dentifrices differed only in the color of the neutral text." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 17% in 3 years. Drop out by group: 127/719 fluoride, 113/688 placebo. Reasons for losses: Sickness, change of address and exclusions from analysis due to presence at the first, fourth and at least one other intermediate examination (not reported by group).

Comment: Numbers lost were not unduly high given the length of follow-up, and show no differential loss between groups. Reasons for missing data are acceptable, but it is unclear if they are balanced. Caries data used in the analysis pertain to participants present for the first, last and at least one other follow-up exam.

Free of selective reporting?

Yes

Outcomes reported:
DMFS increment - (E+U) (CA)cl+(DR)xr, reported at 1, 2, and 3 years follow-ups.
DMFT.
ECSI. 

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DMFS: 9.32 FD, 9.24 PL.

Mean age: 10.04 FD, 9.99 PL.

DMFT: 5.51 FD, 5.44 PL. 

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quote: "Children from the same household however, were allocated to the same treatment group to ensure that only one type of dentifrice entered the household during the trial period."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Lu 1987

Methods

Stratified random allocation: double-blind; 55% drop out (for all study groups combined) after 3 years (study duration = 3 years). Reasons for attrition not reported; any differential group losses not assessable.

Participants

2055 children analysed at 3 years (available at final examination).
Age range at start: 7-15 years (average = 10).
Surfaces affected at start: 4.0 DMFS.
Background exposure to fluoride: water <0.3 ppm F in community.
Year study began: in/before 1983.
Location: USA.

Interventions

FT (3 groups)**
1100 ppm F NaF
2800 ppm F SMFP
2800 ppm F NaF.

Home use/unsupervised: daily frequency assumed.
Abrasive system: silica.

Outcomes

3yDMFS increment - cl+xr
Reported at 3 years follow-up.

DMFT increment.

Notes

Participants randomised (n = 4494)
Baseline characteristics (age, sex, DMFS, DMFT) 'balanced'.
Analysis of covariance undertaken. Clinical examination by 1 examiner.

** 2800 ppm F groups combined for analysis.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: " . .assigned at random . .."

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quotes: " double-blind clinical study." "Toothbrushes and assigned dentifrices labelled with the subjects name and unique identification number were supplied by the study's sponsor in plain white 2,7 oz tubes every 6 months."

Incomplete outcome data addressed?
All outcomes

No

Comment: No reasons for attrition reported and 3-year withdrawals are high 53%, 55%, 55% in the 1100, 2800 SMFP, 2800 NaF groups.

Free of selective reporting?

Yes

Comment: DMFT, DMFS increments over 3 years.

Baseline characteristics balanced?

Yes

Comment: Balance of age, gender, DMFS, DMFT at baseline. Adjusted analysis (analysis of covariance).

Free of contamination/co-intervention?

Yes

Comment: Toothpaste given at school in named tube for home use for all the family. Contamination unlikely.



Mainwaring 1978

Methods

Stratified random allocation; double-blind; placebo-controlled; 18% drop out (for all study groups combined) after 3 years (study duration = 3 years). Natural losses; any differential group losses not assessable.

Participants

1107 children analysed at 3 years (available at final examination).
Age range at start: 11-12 years.
Surfaces affected at start: 7.9 DFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1974.
Location: UK.

Interventions

FT (2 groups) versus PL
(both SMFP groups = 1000 ppm F).

Home use/unsupervised, for 1 min, daily frequency assumed.
Abrasive system: Ca carbonate in all toothpastes.

Outcomes

3yNetDFS increment - (E)(CA)cl+(ER)xr.
Reported at 3 years follow-up.

PF-DFS .
postMD-DFS.
CIR.

Notes

Participants randomised (numbers for relevant groups not reported).
Baseline characteristics (age, SAR, DFS) 'balanced'.
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = ER. Intra-examiner reproducibility checks for DFS in 10% sample (ICC for VT/XR over 0.95); error variance less than 5% of total variance; reversal rate less than 5% of observed DFS increment in all groups.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Participants were stratified according to age, sex and then randomly assigned to one of the treatment groups; children from the same family were assigned to the same group."  

Comment: Not enough information provided.

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "The study was of double-blind design, neither examiner nor participants knowing the identity of the treatment group to which the subjects had been allocated."

"...control group were provided with non-fluoride toothpaste." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 18.4% 386/2104 in 3 years (for all 5 groups). Drop out by group: Not reported. Reasons for losses: Not reported.

Comment: Numbers lost were not unduly high given length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (E)(CA)cl+(ER)xr, reported at 3 years follow-up.
PF-DFS.
postMD-DFS.
Caries incidence rate.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
Mean age: 142.2 months (for each group).

SAR: 87.73 (20.95) FG, 89.38 (20.94) PL.

DFS: 8.19 (6.01) FG, 7.59 (5.56) PL. 

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quote: "Sufficient toothpaste was delivered by specifically appointed home visitors at monthly intervals to the subjects' homes for total family requirements."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Mainwaring 1983

Methods

Stratified random allocation; double-blind; placebo-controlled; 19% drop out (for all study groups combined) after 4 years (study duration = 4 years). Natural losses, no losses due to any adverse effects; any differential group losses not assessable.

Participants

682 children analysed at 4 years (available at final examination).
Age range at start: 11-12 years.
Surfaces affected at start: 6.9 DFS.
Background exposure to fluoride: none reported.
Year study began: in/before 1978.
Location: UK.

Interventions

FT (2 groups)** versus PL
(SMFP group = 1000 ppm F, SMFP-NaF group = 1000 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: Ca carbonate in all toothpastes.

Outcomes

4yNetDFS increment - (CA)cl+(ER)xr.
Reported at 4 years follow-up.

O-DFS.
MD-DFS.
postMD-DFS.
MD-BL-DFS.

Notes

Participants randomised (numbers for relevant groups not reported).
Baseline characteristics (age, SAR, DFS, FS) 'balanced'.
Clinical (VT) caries assessment (FOTI used) by 1 examiner; diagnostic threshold = CA; state of tooth eruption included not reported. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = ER. Intra-examiner reproducibility checks for DFS in 10% sample (ICC for VT/XR over 0.95).
**Ca glycerophosphate/SMFP toothpaste group not considered (additional non-F active agent in this group only).

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Yes

Quote: "The subjects were stratified according to age and sex, and assigned by means of a table of random numbers to one of four dentifrice groups. Siblings were assigned to the same group."

Allocation concealment?

Unclear

No information provided.

Blinding?
All outcomes

Yes

Quotes: "At no time during the study was the identity of these groups known to the examiner, the subjects or anyone directly associated with the study."

"Control group received dentifrice without fluoride." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quotes: Overall drop out for length of follow-up: 19% 210/1133 in 4 years (all 4 groups). Drop out by group: Not reported. Reasons for losses: Moving away from the area (and no losses due to any adverse effects).

Comment: Numbers lost were not unduly high for the length of follow-up. Any differential losses between groups are not assessable. Reasons for missing outcome data are acceptable but it is unclear if they are balanced between groups. Caries data used in analysis pertain to participants present at final examination.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (CA)cl+(ER)xr, reported at 4 years follow-up.
O-DFS.
MD-DFS.
postMD-DFS.
MD-BL-DFS.

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
DFS: 7.38 (0.37) FD1, 6.85 (0.35) FD2, 6.30 (0.34) PL.

FS: 4.87 (0.26) FD1, 4.35 (0.26) FD2, 4.12 (0.27) PL.

SAR: 91.60 (1.38) FD1, 93.04 (1.39) FD2, 90.49 (1.46) PL.

Comment: Initial caries appears balanced between groups.

Free of contamination/co-intervention?

Yes

Quote: "The dentifrices were delivered to the subjects homes by home visitors calling at monthly intervals. At each visit, sufficient toothpaste was provided to satisfy the needs of the whole family."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Marks 1994

Methods

Stratified random allocation; double-blind; 31.8% drop out (for all study groups combined) after 3 years (study duration = 3 years). Reasons for attrition not reported; no differential group losses.

Participants

5474 children analysed at 3 years (available at final examiation).
Age range at start: 6-14 (average = 9).
Surfaces affected at start: 2.5 DMFS.
Background exposure to fluoride: water <0.3 ppm F in community.
Year study began: 1983.
Location: USA.

Interventions

FT (5 groups)
1000 ppm F, 1500 ppm F, 2000 ppm F, 2500 ppm F all SMFP, 2000 ppm F NaF.

Home use/supervised toothbrushing at school, daily frequency.
Abrasive system: silica.

Outcomes

3yDMFS increment - cl xr.
Reported at 3 years follow-up.

DMFT increment.
DFS interproximal increment.
Compliance.

Notes

Participants randomised (n = 8027).
Baseline characteristics (age, gender, sound surfaces, DMFS, DMFT, DFS Inter) 'very well balanced'.
Clinical caries assessment by 1 examiner. Analysis of covariance adjusting for baseline age, gender and DMFS. This is a re-analysis of a previous study with inclusion of 2000 ppm NaF group.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: " . .block randomisation scheme was used to balance study groups for age, gender and baseline experience.. .."

Allocation concealment?

Unclear

Comment: Insufficient information.

Blinding?
All outcomes

Yes

Quotes: "double-blind caries trial."

"All dentifrices were identical in appearance and flavour."

Comment: Although not stated examiners probably blinded to group.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: "Attrition rates ranged from 29.9 per cent in 1000 ppm group to 34.5 in 2000 ppm NaF group and the overall attrition rate over all groups was 31.8 per cent."

Comment: No reasons given for losses.

Free of selective reporting?

Yes

Comment: DMFT, DMFS, DFS on interproximal surfaces increments over 3 years reported.

Baseline characteristics balanced?

Yes

Comment: Balance of age, gender, baseline caries. Analysis of covariance adjusting for baseline age, gender and DMFS.

Free of contamination/co-intervention?

Unclear

Comment: Daily supervised toothbrushing and normal home use so contamination unlikely. Insufficient information.



Marthaler 1965

Methods

Random allocation; double-blind; placebo-controlled; 43% drop out (for all study groups combined) after 3 years (study duration = 7 years). Exclusions based on variation in toothpaste provision and presence in follow-up examinations; any differential group losses not assessable.

Participants

269 children analysed at 3 years (present for all examinations).
Age range at start: 6-9 years (average = 8).
Surfaces affected at start: 3.3 DMFS.
Background exposure to fluoride: salt (suboptimal).
Year study began: 1958.
Location: Switzerland.

Interventions

FT versus PL
(AmF group = 1250 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: IMP.

Outcomes

3yNetDFS increment - (CA)cl+(DR)xr.
Reported at 1.5, 3, 5 and 7 years follow-ups.

postMD-DFS.
antMD-DFS.
BL-DFS.
O-DFS.
DMFT.
FT.
FS.
MT.
Compliance.

Notes

Participants randomised (numbers for relevant groups not reported).
Baseline characteristics (age, DMFS, DMFT) 'balanced' (DFS baseline data not reported).
Clinical (V) caries assessment by 1 examiner; diagnostic threshold = CA and NCA; state of tooth eruption included not reported. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = DR and ER; partial recording. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Randomisation was carried out with the aid of the alphabetical class lists. The dentifrices were assigned to the children listed in this way, in a fixed order according to the code numbers printed on the tubes. The numbers in turn had been randomly assigned to the dentifrices A, B, C, D, E. In this way a random assignment of the dentifrices throughout the school was obtained."

Comment: Not enough information provided.

Allocation concealment?

Yes

Central allocation described.

Blinding?
All outcomes

Yes

Quotes: "...the examinations were carried out without knowledge of the dentifrice used by the children."

"Tubes and content were only distinguishable with the aid of a small mark printed on the neutral tube." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

Unclear

Quote: Overall drop out for length of follow-up: 43% 256/589 drop out (for all 5 groups) after 3 years. Drop out by group: Not reported. Reasons for losses: Exclusions based on variation in toothpaste provision and presence in follow-up examinations (not reported by group).

Comment: Numbers lost were high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants present for all examinations.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (CA)cl+(DR)xr, reported at 3 years follow-up.
postMD-DFS.
antMD-DFS.
BL-DFS.
O-DFS.
DMFT.
FT.
FS.
MT.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported: Mean age: 7.6 FD, 7.6 PL; DMFS: 3.45 FD, 3.19 PL; DMFT: 2.39 FD, 2.27 PL.

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "In order to exclude exchange of tubes at the start of the study, two tubes of dentifrices...were sent to the parents. The parents were told that upon returning the empty tubes, their child could get new dentifrice at the local school dental clinic."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Marthaler 1965a

Methods

Random allocation; double-blind; placebo-controlled; 66% drop out (for all study groups combined) after 3 years (study duration = 3 years). Main reason for high drop out: children leaving public school on completion of last compulsory year; exclusions based on variation in toothpaste provision and presence in all follow-up examinations; any differential group losses not assessable.

Participants

74 children analysed at 3 years (present for all examinations).
Age range at start: 11-14 years (average = 13).
Surfaces affected at start: 18.9 DMFS.
Background exposure to fluoride: salt (suboptimal).
Year study began: 1958.
Location: Switzerland.

Interventions

FT versus PL
(AmF group = 1250 ppm F).

Home use/unsupervised, daily frequency assumed.
Abrasive system: IMP.

Outcomes

3yNetDFS increment - (CA)cl+(DR)xr.
Reported at 3 years follow-up.

postMD-DFS.
antMD-DFS.
BL-DFS.
O-DFS.
DMFT.
FT.
FS.
MT.
Compliance.

Notes

Participants randomised (numbers for relevant groups not reported).
Baseline characteristics (age, DMFS, DMFT) 'balanced' (DFS baseline data not reported).
Clinical (V) caries assessment by 1 examiner; diagnostic threshold = CA and NCA; state of tooth eruption included not reported. Radiographic assessment (2 postBW) by 1 examiner; diagnostic threshold = DR and ER; partial recording. Diagnostic errors not reported.

Risk of bias

Item

Authors' judgement

Description

Adequate sequence generation?

Unclear

Quote: "Randomisation was carried out with the aid of the alphabetical class lists. The dentifrices were assigned to the children listed in this way, in a fixed order according to the code numbers printed on the tubes. The numbers in turn had been randomly assigned to the dentifrices A, B, C, D, E. In this way a random assignment of the dentifrices throughout the school was obtained."

Comment: Not enough information provided.

Allocation concealment?

Yes

Central allocation described.

Blinding?
All outcomes

Yes

Quotes: "...the examinations were carried out without knowledge of the dentifrice used by the children."

"Tubes and content were only distinguishable with the aid of a small mark printed on the neutral tube." 

Comment: Blind outcome assessment and use of placebo described.

Incomplete outcome data addressed?
All outcomes

No

Quote: Overall drop out for length of follow-up: 66.5% 246/370 (for all 4 groups) in 3 years. Drop out by group: Not reported. Reasons for losses: Children completing school; exclusions based on variation in toothpaste provision and presence in follow-up examinations, including those unsatisfactorily radiographed (not reported by group).

Comment: Numbers lost are unduly high for length of follow-up. It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants present for all examinations.

Free of selective reporting?

Yes

Outcomes reported:
DFS increment - (CA)cl+(DR)xr, reported at 1.5, 3, 5 and 7 years follow-ups.
postMD-DFS.
antMD-DFS.
BL-DFS.
O-DFS.
DMFT.
FT.
FS.
MT.

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way.

Baseline characteristics balanced?

Yes

Prognostic factors reported:
Mean age: 12.8 FD, 12.5 PL.

DMFS: 18.5 FD, 19.34 PL.

DMFT: 9.93 FD, 10.25 PL. 

Comment: Initial caries appears balanced.

Free of contamination/co-intervention?

Yes

Quote: "In order to exclude exchange of tubes at the start of the study, two tubes of dentifrices...were sent to the parents. The parents were told that upon returning the empty tubes, their child could get new dentifrice at the local school dental clinic."

Comment: There is sufficient indication overall of prevention of contamination/co-intervention.



Marthaler 1970

Methods

Random allocation; placebo-controlled; 18% drop out (for all study groups combined) after 3 years (study duration = 3 years). Exclusions based on use of orthodontic bands and presence in all follow-up examinations; any differential group losses not assessable.

Participants

100 children analysed at 3 years (present for all examinations).
Age range at start: 6-7 years (average = 7).
Surfaces affected at start: 1 DMFS.
Background exposure to fluoride: salt (suboptimal).
Year study began: 1966.
Location: Switzerland.

Interventions

FT versus PL
(AmF group = 1250 ppm F).

Home use/unsupervised, twice/three times a day/680 times a year estimated.
Abrasive system: IMP.