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Fluoride Varnishes for Dental Health: A Review of the Clinical Effectiveness, Cost-effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Oct 26.
A total of 382 citations were identified in the literature search. Following screening of titles and abstracts, 326 citations were excluded and 56 potentially relevant reports from the electronic search were retrieved for full-text review. Six potentially relevant publications were retrieved from the grey literature search. Of these potentially relevant articles, 43 publications were excluded for various reasons, while 19 publications met the inclusion criteria and were included in this report. Appendix 1 describes the PRISMA flowchart of the study selection.
Details of the characteristics of included publications are available in Appendix 2.
Five systematic reviews (SRs) were included in this report. 5–9 Four reviews focused on children 5–8 and one review included studies conducted in adults and children. 9 The SRs included randomized controlled trials (RCTs), 5–9 quasi-randomized studies, 8 non-randomized studies, 7,9 and controlled clinical trials. 9 The literature search date cut-offs were 2013, 8,9 2014, 5,7 and 2015 6 Nine RCTs 10–18 (five conducted in children, 10–13,15 two in adolescents and young adults, 17,18 and two in adults 14,16 ) were included in this review. One economic analysis 19 focused on fluoride use in children was identified. Four evidence-based guidelines were included in the review. 4,9,20,21
Authors of the systematic reviews were located in the United States, 6,7,9 Hong Kong, 5 Denmark, 7 and the United Kingdom. 8 The included RCTs were conducted in Denmark, 10 Iran, 11,12 Brazil, 13,14 Hong Kong, 15,16 and China. 17,18 The economic analysis was undertaken with a United States (Alaska) healthcare payer perspective. 19 The evidence-based guidelines were produced in the United States by the American Academy of Pediatric Dentistry 20 (AAPD), the American Dental Association 9 (ADA), and Institute for Clinical Systems Improvement 21 (ICSI) and in Scotland by the Scottish Intercollegiate Guidelines Network 4 (SIGN).
Four systematic reviews, 5–8 five RCTs, 10–13,15 one economic evaluation, 19 and three guidelines 4,20,21 were focused on the use of fluoride varnishes for children. The ages of children included in the publications ranged from six months 9 up to 16 years of age. 8 The ages of children included in the identified RCTs ranged from eight months 15 to 12 years, 13 with four of the five RCTs including children aged 36 months or younger. 10–12,15 The economic evaluation aimed to determine the cost-effectiveness of fluoride treatment for children from six to 60 months of age. 19
Two RCTs 17,18 included adolescents and young adults with patients aged 12 to 22 18 or 25 17 years of age. Two RCTs included adult patients. 14,16 One study included patients up to the age of 70 14 and one study included patients aged 26 to 75 years. 16 One guideline focused on dental interventions for patients of all ages. 9
Caries prevalence or incidence 7,9,16 measured by ICDAS (International Caries Detection and Assessment System) criteria, 10,15 or dmft (decayed, missing, or filled teeth) index 11
Caries increment change measured by damaged, missing, and filled surfaces (dmfs) score 8 Caries risk reduction 11 Tooth remineralization 6 Percentage of remineralized early enamel caries 5 Mean change in fluorescence and area of the lesions (QLF) 13,17 Reduction in size of white spot lesions 12,17 White spot lesion depth 18 Dentine sensitivity using US Public Health Service Criteria 14Cost was examined in one study looking at the cost-effectiveness of various fluoride treatments, including fluoride varnish, for the prevention of dental caries in Alaskan native children. 19 The authors modelled the used of water fluoridation, dental sealants, fluoride varnish, tooth brushing with fluoride toothpaste, or the conduct of an initial dental exams on children less than 18 months of age over a 10 year time horizon to evaluate the total cost of each intervention, as well as the cost per adverse health event (dental caries or full mouth dental restoration) avoided. Costs of existing dental procedures were obtained from Medicaid data. The authors assumed that all of the interventions had an ideal population coverage of 100 percent, that children were treated by a dentist or dental surgeon, that children would receive only one initial dental examination, and children would receive only one full mouth dental restoration per year.
All five of the SRs included in this review clearly described an a priori design, a comprehensive literature search strategy, assessed the scientific quality of the included studies, and considered the scientific quality of the included studies when formulating their conclusions. 5–9 It was unclear whether Weyant et al. 9 performed duplicate study selection and data extraction. The other four SRs clearly stated that selection and data extraction were done in duplicate. 5–8 Only the SR by Lenzi et al. 6 clearly stated that the grey literature was included in their literature search strategy. The review by Marinho et al. 8 was the only one to provide a clear list of included and excluded studies. The reviews by Gao 5 and Weyant 9 did not provide detailed characteristics of the studies included in their analysis. It was unclear whether Weyant et al. 9 used appropriate methods to combine the findings of the studies included in their review and they did not mention whether the likelihood of publication bias was assessed. Of the five included SRs, only the review by Twetman et al. 7 did not clearly indicate whether the authors had potential conflicts of interest.
The aim, research questions, interventions and comparators, clinical outcomes, and study results were clearly described in all of the included RCTs. 10–18 Block or cluster randomization was done in four studies 10,11,15,16 while five RCTs randomized individuals. 12–14,17,18 Randomization was achieved using computer software, 15,17 sequentially numbered, opaque, sealed envelopes, 14 random number tables, 12,18 and a randomization list. 13 In three studies, randomization was done by a third party not involved in the conduct of the study. 11,15,18 The exact method of random allocation was not described in two RCTs. 10,16
Appropriate sample size and statistical power calculations were described in seven studies. 10,11,13,15–18 A lack of appropriate power calculations could results in uncertainty of the validity of the study results and the ability of the study to detect a true change in the population.
Four studies included patients, 10,14 and providers 10,11,14 or outcome assessors 11 who were not blinded to randomization. The lack of blinding of assessors could possibly impact their interpretation of the clinical outcomes and lead to bias in the reported results. Patients who were lost to follow-up were adequately described in seven studies. 10–12,15–18
Potential confounding factors that could impact the applicability of results to the general population were described and accounted for in only three studies. 10,16,17 Anderson et al. 10 stratified dental clinics based on socioeconomic level, geographic area, and size of the clinic prior to randomization in an effort to have treatment and control groups that were as similar to each other as possible.
Seven studies recruited patients from a single treatment centre, or limited geographic or socioeconomic area which may have limited the generalizability of their overall findings as the study sample may not be representative of the general population as a whole. 12–18 Similarly, limited sample size (as determined by the authors) of two studies may have reduced the generalizability of their results. 11,16 Specific patient characteristics were not described by Restrepo, 13 Memarpour, 12 Du, 18 or Camilotti 14 which may limit the generalizability of their findings as we do not have a clear understanding of the exact characteristics of the original treatment population.
The cost-effectiveness analysis by Atkins, et al. 19 appeared to be generally well conducted. The authors clearly stated the research question and economic importance of the analysis. The analysis was undertaken from a justified perspective appropriate to the question and scenario (health care payer) and the time horizon and discounting values (10 years, 3%) applied to resource costs were clearly identified. Costs and quantity of resources were reported separately and all relevant costs were considered. Sensitivity analyses were undertaken examining the minimum and maximum effectiveness of the interventions at both current and the ideal population coverage levels. The main limitation of this analysis is that it was conducted to examine the cost effectiveness of preventing dental caries and full mouth dental reconstructions in a very limited population of Alaska Native children in a specific geographic region. As such, the results cannot reasonably be generalized to any other region or population. The methods may help to inform approaches future cost-analyses in other regions. The evaluation assumed 100% coverage of children, and all interventions provided by a dentist or dental surgeon, and that children would receive one full mouth dental restoration per year, which may not be reflective of actual practice.
The four included guidelines 4,9,20,21 clearly described their overall objectives, population of interest, and target users. The health benefits and side effects appear to have been considered when forming the recommendations. The recommendations provided are specific, easily identifiable, and propose varied options for patient management. The composition of the AAPD guideline group was not clearly specified so it is unclear whether the group was composed of individuals from relevant professional groups. 20 Only the SIGN guideline clearly indicated that they incorporated the views and opinions of patients into their guideline. 4 The SIGN and ICSI guidelines considered potential resource implications of implementing the recommendations and also provide guidance as to how the recommendations could be put into practice. 4,21
The search strategy used for the AAPD guideline was not described. 20 The SIGN, ADA, and ICSI groups undertook a systematic search of the literature to support their guidelines. 4,9,21 Additionally, the methods of critical appraisal and methods of evaluating the strength and quality of the included studies were not described. 20 The remaining three guidelines evaluated the level of evidence and grade of recommendations using established methodologies. The SIGN50, 4 USPSTF, 9 and GRADE 21 methods were used. The SIGN guideline was the only guideline that clearly indicated it was externally reviewed prior to publication. 4 The SIGN, ADA, and ICSI guidelines all described procedures for updating the document. 4,9,21 None of the four included guidelines described methods of guideline validation.
Five SRs 5–9 and seven RCTs 4,11–13,15,16,18 evaluated the clinical effectiveness of fluoride varnished for dental health.
Four SRs 5–8 examined the use of fluoride varnish versus no treatment or a placebo treatment for the prevention of dental caries in children.
Gao et al. 5 systematically reviews studies of professionally applied fluoride treatment for preventing and improving dental caries in children. Six RCTs were identified regarding remineralization and meta-analysis was conducted on four of those RCTs that examined the same intervention and comparator. 5 In the meta-analysis, the overall percentage of remineralization was 63.6% greater than no treatment (95% confidence interval [CI], 36.0% to 91.2%; P <0.001). 5 The authors indicated that all six RCTs included in the review demonstrated an effectiveness of fluoride varnish for remineralization of early childhood caries (ECC). 5 Comparators studied in the individual trials included chlorhexidine and no treatment but the comparative effectiveness of fluoride versus those comparators were not reported in the review.
Lenzi et al. 6 identified three studies for meta-analysis comparing fluoride varnish (Duraphat, Fluorniz, or Fluoridin) with no treatment for the reversal of enamel carious lesions in children with a mean age from three to 12 years. The number of fluoride applications ranged from two quarterly applications to four weekly applications. The overall mean difference was a decrease of 2.04 (95% CI, −3.25 to −0.84; P = 0.0009) in the number of enamel carious lesions in the varnish versus control or no treatment group. 6 In the meta-analysis, there was a statistically higher decrease in caries prevalence in the fluoride varnish group as compared to the no treatment group. Despite a high level of heterogeneity identified in the meta-analysis, the authors concluded that fluoride varnish was an effective product to stop the progression of enamel carious lesions in both primary and permanent teeth. 6
Marinho et al. 8 included 22 RCTs and quasi-randomized studies (13 analyzing permanent and 10 analyzing primary teeth) in their review. Data on 9,595 children up to the age of 16 years were included in the analysis. Various fluoride varnishes (Duraphat, Fluoridin, Lawefluorid, Fluor Protector, Cavity Shield, Duroflor) were compared with no treatment or placebo treatment. Pooled decayed, missing, and filled surfaces (dmfs) scores showed a prevented fraction estimate for permanent tooth surfaces of 43% (95% CI, 30% to 57%; P < 0.0001) when comparing fluoride varnish with placebo or no treatment. 8 The pooled dmfs prevented fraction estimate for primary tooth surfaces was 37% (95% CI, 24% to 51%; P <0.0001). 8 The authors indicated that both analyses were based on moderate quality evidence. The authors concluded that fluoride varnish was effective for inhibiting caries development in both primary and permanent teeth. 8
Tewtman et al. 7 undertook a review of self- and professionally-applied fluoride and other dental products for the prevention and management of ECC in children less than three years of age. Six studies (seven publications) were identified regarding the use of 5% sodium fluoride varnish applied professionally two to four times per year combined with oral health education. Due to heterogeneity identified in the included studies and moderate to high risk of bias, the authors were not able to statistically combine results and provided a narrative synthesis of the evidence. The authors concluded that the findings of the identified studies provided limited quality evidence that fluoride toothpaste and fluoride varnish were each effective for the prevention of ECC when compared with no treatment or a placebo. 7 The authors did not compare the effectiveness of fluoride varnish with that of fluoride toothpaste.
Weyant et al. 9 undertook a systematic review to support the development and update of the American Dental Association (ADA) guidelines regarding topical fluoride products for caries prevention. Topical fluorides, including 2.26% and 0.1% fluoride varnish, were compared with placebo, no treatment, or oral health counseling. Six RCTs and two non-randomized studies were identified for fluoride varnish use on primary teeth (children aged six months to eight years), 11 RCTs and two non-randomized studies were identified for permanent teeth (participants aged five to 79 years), and one controlled clinical trial examined both primary and permanent teeth. 9 The results of the analysis of the included studies were not clearly presented in the SR.
Based on the analysis of the included studies, the authors and the guideline panel concluded (with moderate certainty) that patients up to 18 years of age may benefit from the application of 2.26% fluoride varnish application at least twice a year for the prevention of dental caries. For adults, the guideline group concluded (with a low level of certainty) that 2.26% fluoride varnish may be beneficial to prevent root caries if applied at least twice a year. 9 For 0.1% fluoride varnish, the guideline group concluded (low to moderate certainty) that there was no benefit of twice or three times yearly application for caries prevention in children less than 18 years of age. 9
One RCT by Xin et al. 16 compared the use of fluoride varnish (Duraphat) and a placebo gel in 85 adults with Sjögren’s syndrome, which results in dry mouth. All participants received oral health education at baseline. The type (enamel, dentin, or arrested) and number of caries lesions were recorded at 12 and 24 months. A higher mean number of new caries lesions were observed in the control group at the end of the study; however, the differences between groups were not statistically significant. The authors determined that there was no sufficient evidence to recommend for or against the quarterly use of fluoride varnish to prevent new dental caries in adults with Sjögren’s syndrome. 16
Four RCTs 4,11,12,15 compared fluoride varnish plus a standard dental health intervention with the dental health intervention alone for reduction of dental caries in children.
Anderson et al. 4 undertook a non-blinded cluster RCT. Dental clinics were clustered and randomized and children attending the clinics born in 2010 received either topical fluoride varnish (Duraphat) over five visits (every six months) and family dental health education or dental health education alone. Clinical exams were conducted on all children at 12, 24, and 36 months of age. 10 The ICDAS score was measured at baseline (12 months), 24 and 36 months of age. No significant difference in the number of dental caries was observed between groups at 12, 24, or 36 months of age, thus the authors concluded that there was no additive effect fluoride varnish intervention for the prevention of dental caries.
Memarpour et al. 11 compared no treatment versus oral hygiene information and education versus fluoride varnish (DuraShield) plus education. One study examined the use of fluoride varnish for the prevention of ECC in children aged 12 to 24 months with two varnish applications at baseline and six months of follow-up. 11 Children in the fluoride varnish group had 31% fewer caries at 12 months as compared to the no treatment group. Both the varnish and education alone groups had significantly reduced caries incidence as compared to the no treatment group (P < 0.001); however, there were no significant differences reported between the two intervention groups. 11
Jiang et al. 15 conducted an RCT comparing one-time oral parental oral hygiene education with hands on parental toothbrushing training with or without semi-annual fluoride varnish (Clinpro White Varnish) application for children less than three years of age at a low risk of dental caries. New dental caries were classified by ICDAS criteria as Level 1 (non-cavitated and cavitated lesions) or Level 2 (cavitated lesions only). At 24 months, the overall incidence of Level 1 caries was 13.7% (57 of 417 [control = 11.9%, hands-on = 11.8%, varnish = 17.5%]) and Level 2 caries was 8.4% (35 of 415 [control = 8.2%, hands-on = 6.9%, varnish = 10.2%])). 15 There were no statistically significant differences in the incidences of early childhood caries between the three study groups. The study was conducted in an area with public water supply fluoridation. The authors concluded that the use of fluoride varnish in this population of low risk children in an optimally fluoridated area may not be effective for the prevention of ECC. 15
Restrepo et al. 13 conducted an RCT to evaluate the use of fluoride varnish (Duraphat, weekly application for four weeks) versus usual home care and placebo varnish for the remineralization of teeth with molar incisor hypomineralization (MIH) in children aged nine to 12 years. The most severe lesion was treated in each patient. The observed mean lesion volume and mean percentage of fluorescence loss were similar between the varnish and control groups at all five visits. 13 The authors concluded that four applications of fluoride varnish had no favorable effect on the remineralization of MIH lesions as compared to the control treatment. 13
A second study by Memarpour et al. 12 examined fluoride varnish (DuraShield, three applications quarterly) versus no treatment plus placebo varnish) versus oral hygiene counseling alone for the remineralization of white spot lesions (WSL) on primary teeth of children aged 12 to 36 months. 12 The mean area of the WSL and dmft scores were reported. The mean area of WSL increased over time in the no treatment group and was significantly greater after 8 months (P = 0.001) but there was no significant difference observed in that group between eight and 12 months (P = 0.221). 12 The mean WSL size decreased significantly over time in the fluoride varnish group (P <0.001) and there were significant differences in dmft only at 12 months (P <0.001) between the control, fluoride varnish, and oral hygiene groups. 12 The authors observed that dmft did not change significantly over time in the varnish or oral hygiene groups but decreased in the control group and concluded that four applications of fluoride varnish in combination with oral hygiene education were effective to decrease the area of WSL. 12
One parallel group RCT, conducted by Du et al., 18 assessed the use of fluoride varnish (Duraphat, applied monthly for six months) versus saline placebo for the remineralization of WSL after fixed orthodontic treatment in patients aged 12 to 22 years. The depth of the WSL was assessed using a DIAGNOdent pen. 18 Lesion depth scores were significantly lower in the fluoride group as compared to the control group at both three and 6 months follow-up. 18 The authors concluded that the use of fluoride varnish was effective for the reversal of WSL after the removal of orthodontic brackets and they suggested the use of fluoride varnish should be considered as a routine measure in these cases. 18
Two RCTs 14,17 were identified that compared fluoride varnishes with other topical fluoride treatments.
He et al. 17 conducted a three-arm parallel RCT in patients aged 12 to 25 years who had recently completed orthodontic therapy and had at least one maxillary anterior tooth. The application of fluoride varnish (Duraphat) was compared with fluoride film (Sheer) and placebo. Participants in all groups received oral hygiene education and were required to use fluoridated toothpaste daily. Lesion volume was significantly reduced in the varnish, film, and control groups after six months. 17 There was a significantly greater decrease in lesion volume in the varnish group as compared to the film group. Although both fluoride varnish and fluoride film resulted in significant improvements in WSLs, the authors concluded that lesion volume decrease was greater with fluoride and fluoride varnish was determined to be significantly more effective than fluoride film or placebo.
One 14 year old boy suffered from nausea after swallowing fluoride varnish at one treatment. 17 No other adverse events were reported in any of the publications included in this review.
Camilotti et al. 14 conducted an RCT comparing four fluoride varnishes (Duraphat [50 mg NaF], Fluorniz [5.0g% NaF], Duofluorid XII [6% NaF + 6% CaF], Fluorophat [2% NaF]), sodium fluoride, potassium oxalate, and placebo for the improvement of dentin sensitivity in adult patients (18 to 70 years of age). All of the fluoride varnish treatments resulted in significant improvements in sensitivity scores from baseline; however, Duraphat and Flurophat resulted in the greatest improvements in mean sensitivity scores at final reassessment 30 days after the last treatment. 14 There was some improvement in sensitivity scores in the placebo group but this change was not significant. The authors had originally hypothesized that there would be no difference in effectiveness between the different fluoride varnish treatments; however, they concluded that the final results disproved this theory.
One economic evaluation by Atkins et al. 19 was identified. The authors were interested in the cost-effectiveness of various dental interventions for Alaska native children ages six to sixty months of age. The aim was to reduce the number of carious teeth and full mouth dental reconstructions in the population. The analysis was modeled over a 10 year time horizon with a 3% discounting rate and was undertaken from the healthcare payer perspective. Cost-effectiveness was determined by calculating the cost-effectiveness ratio of the cost per prevented adverse health outcome. The authors concluded that a fluoride varnish program could result in 133 averted dental caries and averted costs of $195,347 in year 1. The authors concluded that fluoride varnish was a cost-effective solution with a 10 year total discounted cost of $1,252,021 USD to provide fluoride varnish to 100 percent of the population. However, in this geographical area, a general water fluoridation program was considered to be the most cost-effective solution for the prevention of ECC. 19
Four evidence-based guidelines were identified regarding the use of fluoride varnish treatment in a dental office setting for the prevention and control of dental caries. 4,9,20,21 Three of these guidelines focused on patients 18 years of age and under 4,20,21 and one included patients of all ages. 9
The American Academy of Pediatric Dentistry guidelines 20 indicate that topical five percent sodium fluoride varnish and 1.23 percent fluoride gel preparations can effectively be used to reduce caries in children determined to be at risk and these children should receive a professionally applied fluoride treatment at minimum every six months. The Institute for Clinical Systems Improvement 21 guideline recommends fluoride for the prevention of dental caries in children from birth to 18 years of age. No frequency of treatment is provided but it is recommended children at high risk of cavities receive fluoride varnish if the facilities to deliver the fluoride in a clinic setting are available. 21
The Scottish Intercollegiate Guidelines Network 4 guideline recommends that a topical fluoride varnish should be applied at least twice per year in all children. Based on a balance of safety and effectiveness data, the American Dental Association 9 (ADA) recommends 2.26% fluoride varnish as the only topical fluoride option for children less than six years of age. Based on expert opinion, 2.26% fluoride varnish is recommended every three to six months for children up to 18 years of age. The ADA guideline also suggests that all patients who are determined to be at low risk of developing dental caries may not require the addition of topical fluoride treatment to their dental health care treatment if they also use fluoridated toothpaste and consume fluoridated water. 9
Based on expert opinion, the ADA recommends that patients older than 18 years of age and adults with root caries should receive 2.26% fluoride varnish at least every three to six months.
Weyant et al. 9 noted that their review included studies that included patients from different countries with and without additional fluoride use, with and without fluoridated public water supply, and with or without prophylaxis, making it difficult to determine the exact effect of the interventions of interest. Three of the nine RCTs 10,11,15 reported whether the study was conducted in an area with fluoridation of the public water supply. One study 10 was conducted in Denmark with a non-fluoridated water supply. Two studies conducted in Iran 11 and Hong Kong 15 reported water supplies with 0.5 and
Anderson et al. 10 indicated that cluster randomization may have been a limitation of their study. They suggested that individual randomization could have been preferable to demonstrate effectiveness but the cluster randomization of dental clinics was more practical. Stratification was undertaken in an effort to minimize confounders. Lack of blinding of providers and assessors may have resulted in interpretation bias of the results. The use of the standardized ICDAS tool was meant to minimize that probability. The overall study dropout rate of 25% was greater than expected but was evenly distributed between the intervention and control groups.
Jiang et al. 15 indicated that a high proportion of the children participating in the study came from families of middle and high socioeconomic status. Children in this population are generally at lower risk of developing dental caries and therefore the make-up of the study population may have limited its generalizability to the population as a whole.
This review focused on the application of varnish in a dental office setting. Varnish may also be applied in community, school, and medical office settings and may be applied by primary care physicians, nurses, and dental hygienists/assistants in the absence of the supervision of a dentist. Examining the use of fluoride varnish in other practice settings may be of interest for future research.
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