SUPUESTOS/HIPOTESIS FACTORES EXTERNOS

IDENTIFICATION OF REPORTS / STUDIES

Searching the core database in Reference Manager (using 'gel*' or 'fluoride gel*' or 'amine fluoride gel' or 'acidulated phosphate fluoride*' or 'acidulated fluorophosphate' or 'Elmex' as keywords combined with 'gel' or 'tray' in notes, and with 'gel' in titles and in all other fields) retrieved 694 records from MEDLINE, EMBASE, BIOSIS, SCISEARCH, SSCISEARCH, CINAHL, ERIC, ISTP and DISSERTATION ABSTRACTS. Searching LILACS (48 records), BBO (47 records), CCTR (86 records), SIGLE (6 records), and NIDR (24 records) databases produced a total of 211 records which were scanned outside Reference Manager. The last time LILACS and BBO were searched yielded 210 records (142 and 68 records respectively, also scanned outside Reference Manager). Searching OLD MEDLINE produced 545 records. Thus, 1670 records yielded by the original electronic searches for topical fluoride trials were scanned, but many of these were duplicates not merged in the core database. The specific MEDLINE search for fluoride gel trials performed without RCT filter produced 342 records, and the same specific search performed in the OHG specialised register produced 51 records. The search of non-electronic sources (reference lists of relevant studies, review articles or book chapters, and contacting authors) produced other 21 records for closer inspection. One of the six manufacturers of fluoride gel contacted, GAB A, provided a list of 409 records from a search performed in GALIDENT (Database of GAB A

Library in Dentistry) using the keyword 'amine fluoride'. However, search results from these and, if provided, from other manufacturers will be reported in updates of this review.

From the search results above, a total of 88 reports were considered potentially eligible, sought and assessed further (including some only available as abstracts).

SELECTION OF STUDIES

From the 88 reports that were sought for detailed assessment, 31 were considered immediately irrelevant for this review, mainly as a result of the interventions compared with or used in addition to fluoride gel. Forty studies (57 reports) are considered in this review; these comprise 34 reports relating to 25 included studies (one of the reports relates to a study treated as two independent trials), 20 reports relating to 13 excluded studies, and three reports relating to two studies waiting assessment (in Polish) which require translation. There are no reports of ongoing studies. Twelve non-English reports (nine studies) listed either under included or excluded studies have been fully assessed: five in German (by a German translator, with the contact reviewer), four in Portuguese (by the contact reviewer), one in Russian (by a Czech translator, with the reviewer), one in Bulgarian (by a Bulgarian translator, with the reviewer), and one in Hungarian (by a Hungarian translator, with the reviewer).

Fluoride gels f o r preven tin g dental caries in children and adolescents (THESIS C 16

See 'Characteristics of excluded studies' for the description of reasons for rejecting each study.

The 13 studies in this section were excluded for a variety o f reasons. Two studies were clearly not randomized/quasi-randomized or did not imply randomization (not stated and not possible); one of these also had a very high dropout rate. One study did not mention or indicate blind outcome assessment (but described use of random or quasi-random allocation). Attempts were made to contact the author of this study, but no reply was received so it was assumed that blinding had not been done, and the study was excluded. Two studies did not mention or indicate random or quasi­ random allocation or blind outcome assessment. The authors of these studies were contacted and due to a negative reply on blind outcome assessment, the studies were excluded. Three studies did not mention or indicate random or quasi-random allocation and blind outcome assessment. One of these also did not report main outcome data for control group. Attempts were made to contact the authors of these studies, but no replies were received so it was assumed that random allocation and blind assessment of outcome had not been done, and the studies were excluded.

Four studies had other fluoride-based interventions in addition to fluoride gel. One of these also did not state/indicate random or quasi-random allocation and blind outcome assessment; another was not randomized/quasi-randomized and the length of follow-up for the main outcome assessment was less than one year/school year; another had an 'inappropriate placebo' (not an inactive treatment), and another did not report any relevant outcome data. One study included institutionalised children with specific health problems.

INCLUDED STUDIES

See 'Characteristics o f included studies' table for details o f each study.

There are 25 trials included. The study conducted by Mart haler 1970 has been treated as two independent trials, since the results for the two age groups in the study have been reported

separately as distinct studies. All 34 reports were published between 1967 and 1999. The 25 trials were conducted between 1964 and 1996; 12 during the 1960s, seven during the 1970s, five during the 1980s and one in the 1990s. Twelve trials were conducted in USA (eight of these during the

1960's), five in Europe, four in Brazil, one in each of the following countries: Canada, Israel, Hawaii, and Venezuela. Six studies had more than one publication, one of these studies had six published reports. While three of the included studies clearly stated no involvement with any manufacturer of fluoride gel, 10 acknowledged assistance (product provision, etc) and/or partial support from fluoride gel manufacturers.

Design and methods

All the included studies used parallel group designs. Eight of these had more than one fluoride gel treatment group compared to a control, and among these, one trial had two treatment groups and two placebo control groups. With regard to type of control group used, nine trials used a no treatment control group, and the remaining 16 used a placebo control group, four of which used an inactive treatment other than gel ('placebo' solution). The study duration (indicated by the total length of follow-up as well as the treatment duration) ranged from one to four years among included trials: one lasted four years, nine lasted three years, 11 lasted around two years, and the remaining four lasted 1.5 years or one year. Studies were large with only four allocating less than 200 children to relevant study groups. The total number of children participating in the trials (given by the sample analysed at the end of the trial periods) was 7747, and ranged from 41 in the smallest trial to 631 in the largest trial. All participants were recruited from school settings.

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All included trials reported that the participants were aged 15 or less at the start, with similar numbers from both sexes (with the exception of Ran 1991, who included male participants only in the study). The ages o f the children ranged from two to 15 years; 14 trials included participants who were 12 at start, and two trials included children younger than six years of age (in which deciduous teeth only were assessed for caries development). Decayed, missing and filled surfaces (DMFS) at baseline reported in all but three of the studies, ranged from 0.24 to 12.2, and was 3.7 defs in one of the two studies that reported data for deciduous teeth (where 'e' is teeth indicated for extraction). With regard to 'background exposure to other fluoride sources', all studies reported exposure or not to systemic sources, only five studies were conducted in fluoridated communities (water fluoridation in three and salt fluoridation in two studies); from the remaining 20 studies, no (or very low) exposure to fluoride dentifrices or to other fluoride sources was clearly reported in four studies, and substantial exposure to fluoride toothpaste (over 95%) was reported in three studies; exposure or not to fluoride toothpaste had to be assumed in the remaining 13 studies based on study location and year started, as described above. Information on dental treatment level could only be obtained from the most recently conducted study.

Interventions

Fourteen of the included trials reported gel application carried out by professionals and in the remaining 11 trials gel was self-applied under supervision (by dental personnel in four trials, by trained non-dental personnel in five trials and by mothers and dental personnel in another; data were not available for one of the studies). Gel was most usually administered using a tray (15 trials) or a brush (six trials), but the use of floss was reported in the most recent trial, and cotton

application was reported in two trials carried out in Brazil and in one from USA. A variety of fluoride gel types were used, including Acidulated Phosphate Fluoride (APF), Sodium Fluoride (NaF), Amine Fluoride (AmF) and Stannous Fluoride (SnF2) (used in the most recent study only). The fluoride concentrations ranged from 2425 ppm F (SnF2) to 12,500 ppm F (AmF and NaF). The common 12,300 ppm F APF gel concentration was used in at least 13 trials. The three studies which did not report the APF gel concentration are likely to have used the standard 12,300 ppm F, as all were carried out in the same country, started in consecutive years, and had APF gel applied by professionals once a year. The application frequency (times per year) ranged from once a year (the most common frequency of application, reported in seven studies) to 140 times a year (reported in the study of Englander 1967), but it varied greatly among the studies, with only five studies reporting 'twice a year' application frequency. With the exception of the study of Shem 1976 (with five consecutive - once a day or once a week applications in one year) all 14 studies where fluoride gel was professionally applied reported a frequency o f application of four times a year or less; likewise, with one exception (Trubman 1973) where frequency of application was four times a year, the 11 studies of self-applied gel reported a frequency o f application of five times a year or more. The amount of gel applied was reported in only a few studies (either in 'ml' or 'gr') and ranged from 1 to 4ml, and from 1 to 3mg. Where the application time was reported it ranged from two to 10 minutes, with 16 studies reporting three to five minutes gel application time. As regards the performance of some form of prior (professional or self-performed) tooth prophylaxis before administering the gel this was used in 16 studies; as long as performed with no paste or with a non-fluoride paste (if with a fluoride paste the trial would have been excluded), the prior

toothcleaning was considered by the reviewers as a possible part o f the technique of gel application and not as a separate intervention on its own.

Outcome measures

All 25 included trials reported caries increment data at the tooth surface level (D(M)FS reported in 23 trials, defs in the other two trials). Ten of the 23 trials reported caries increment data at the tooth level (D(M)FT) and both trials that reported caries increment data for deciduous teeth only

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(defs), also reported data at the tooth level (deft). With regard to the components of the DMFS index used (and types o f teeth/surfaces assessed), 18 trials reported DMFS data (one trial for first molars only and 17 trials for all tooth surface types), and other five reported DFS data (one trial for all approximal surfaces only and four trials for all tooth surface types), one of these also reported DS and FS data separately. Two of the 10 trials which reported D(M)FS data on specific teeth or tooth surfaces - first molars, occlusal, mesio-distal (approximal) and/or buco-lingual - did not report data on all tooth surfaces. Fourteen trials presented D(M)FS data at more than one follow- up time; 12 trials at one year follow-up time, 13 trials at two years, and nine trials at three years. In four trials, assessments o f D(M)FS increments were also made during a post-intervention follow- up period.

Clinical (all 25 trials) and radiographic examinations (five trials) provided the definition of different stages or grades of caries lesions. These have been grouped into two basic grades for each method of examination: NCA = non-cavitated incipient enamel lesions clinically visible as white spots or discoloured fissures; CA = lesions showing loss of enamel continuity that can be recorded clinically (undermined enamel, softened floor/walls) or showing frank cavitation; ER = any radiolucency in enamel/enamel-dentin junction; DR = radiolucency into dentin; 14 trials presented results using one caries grade only (CA/DR); the 11 remaining trials either did not report the grade (eight trials), in which case CA/DR was assumed, or reported both CA and NCA grades, in which case CA was chosen. Data on state o f tooth eruption considered were specified in 11 trials: data for teeth erupted at baseline only were reported in 10 trials and combined data for erupting and erupted teeth were reported in only one trial. Only the two studies of Marthaler 1970 did not use fiill mouth recording.

Data on the proportion of children developing new caries were reported in one trial and on the proportion of children not remaining caries-free in two trials. Adverse symptoms (nausea/ vomiting) were reported to have been assessed in three trials: two trials had useable data (one reported that there were no events, another reported that there were three participants from the treatment group who experienced one event each) but the remaining trial reported no clear data (the event was reported to have occurred 'in many subjects'). Other outcome measures were reported, but without complete or useable data: 'no side effects' was reported in one trial, and 'no etching of enamel' was reported in another trial. Data for unacceptability of treatment (as measured by dropouts/exclusions) were fully reported in six of the nine no treatment control trials.