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Topical fluoride for caries prevention
Full report of the updated clinical recommendations and supporting systematic review
A Report of the Council on Scientific Affairs November 2013
This report is intended to assist practitioners with decision-making about the use of topical-fluoride caries preventive agents to prevent caries. The recommendations in this document are not intended to define a standard of care and rather should be integrated with a practitioner’s professional judgment and a patient’s needs and preferences.
© 2103 ADA Center for Evidence-Based Dentistry. All rights reserved.
Background. A panel of experts convened by the American Dental Association (ADA) Council on Scientific Affairs presents evidence-based clinical recommendations on professionally-applied and prescription-strength, home-use topical fluoride agents for caries prevention. These recommendations are an update of the 2006 ADA recommendations regarding professionally applied topical fluoride, and were developed by using a new process that includes conducting the systematic review of primary studies.
Types of studies reviewed. The authors conducted a search of MEDLINE and the Cochrane Library for clinical trials of professionally-applied and prescription-strength topical fluoride agents – including mouthrinses, varnishes, gels, foams, and pastes – with caries increment outcomes published in English through October 2012.
Results. The panel included 71 trials in 82 articles in its review and assessed the efficacy of various topical fluoride caries-preventive agents. The panel makes recommendations for further research.
Clinical Implications. The panel recommends the following for people at risk of developing dental caries: 2.26% fluoride varnish or 1.23% fluoride (APF) gel, or a prescription-strength, home-use 0.5% fluoride gel or paste or 0.09% fluoride mouthrinse for 6 years or older. Only 2.26% fluoride varnish is recommended for children younger than 6 years. The strengths of the recommendations for the recommended products varied from “in favor” to “expert opinion for”. As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner’s professional judgment and the patient’s needs and preferences.
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Authors and acknowledgments
Authors
Robert J. Weyant, DMD, DrPH; Sharon L. Tracy, PhD; Theresa (Tracy) Anselmo, MPH, BSDH, RDH;
Eugenio D. Beltrán-Aguilar, DMD, MPH, MS, DrPH; Kevin J. Donly, DDS, MS; William A. Frese, MD;
Philippe P. Hujoel, MSD, PhD; Timothy J. Iafolla, DMD, MPH; William Kohn, DDS; Jayanth Kumar,
DDS, MDH; Steven M. Levy, DDS, MPH; Norman Tinanoff, DDS, MS; J. Timothy Wright, DDS, MS;
Domenick Zero DDS, MS; Krishna Aravamudhan, BDS, MS; Julie Frantsve-Hawley RDH, PhD; Daniel
M. Meyer, DDS; for the American Dental Association Council on Scientific Affairs Expert Panel on
topical fluoride caries preventive agents
Robert J. Weyant is Professor and Chair, Department of Dental Public Health, School of Dental Medicine,
University of Pittsburgh, Pittsburgh, PA. He was the chair of the panel.
Sharon L. Tracy is Assistant Director, Center for Evidence-Based Dentistry, Division of Science, American Dental
Association, Chicago. Address reprint requests to Dr. Tracy.
Theresa Anselmo is the Oral Health Program Manager, San Luis Obispo Health Agency, San Luis Obispo, CA.
She represented the American Dental Hygienists’ Association on the panel.
Eugenio D. Beltrán-Aguilar is Senior Epidemiologist and Advisor to the Director, Division of Oral Health, Centers
for Disease Control and Prevention, Atlanta, GA. He represented the Centers for Disease Control and Prevention
on the panel.
Kevin J. Donly is Professor and Chair, Pediatric Dentistry at the University of Texas Health Science Center San
Antonio, San Antonio, TX. He represented the American Academy of Pediatric Dentistry on the panel.
William A. Frese is Assistant Professor of Pediatrics at the University of Illinois at Chicago, Chicago, IL. He
represented the American Academy of Pediatrics on the panel.
Philippe P. Hujoel is Professor of Periodontics, Department of Dental Public Health Sciences, School of Dentistry,
University of Washington, Seattle, WA.
Timothy J. Iafolla is a Public Health Analyst, Office of Science Policy and Analysis, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD. He represented NIDCR on the panel.
William Kohn is vice president of dental science and policy, Delta Dental Plans Association, Oak Park, IL.
Jayanth Kumar is Director, Oral Health Surveillance and Research, Bureau of Dental Health, New York State Department of Health, Albany, NY and Associate Professor, School of Public Health, University at Albany.
Steven M. Levy is the Wright-Bush-Shreves Endowed Professor of Research, Department of Preventive and
Community Dentistry, College of Dentistry, and a professor, Department of Epidemiology, College of Public
Health, University of Iowa, Iowa City, IA.
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Norman Tinanoff is Professor and Division Chief, Pediatric Dentistry, School of Dentistry, University of Maryland,
Baltimore, MD.
J. Timothy Wright is Professor and Chair, Department of Pediatric Dentistry, School of Dentistry, University of
North Carolina, Chapel Hill, NC
Domenick Zero is Professor and Chair, Department of Preventive and Community Dentistry, Director, Oral Health
Research Institute, Associate Dean for Research, Indiana University, School of Dentistry, Indianapolis, IN.
Krishna Aravamudhan is Senior Manager, Office of Quality Assessment and Improvement, Division of Dental
Practice, American Dental Association, 211 E. Chicago Ave., Chicago, IL 60611, e-mail
aravamudhank@ada.org.
Julie Frantsve-Hawley is Senior Director, Center for Evidence-based Dentistry, Division of Science, American
Dental Association, Chicago.
Daniel M. Meyer is Senior Vice President, Science/Professional Affairs, American Dental Association, Chicago.
Acknowledgments
The panel would like to acknowledge the efforts of the following individuals and their commitment in
helping complete this project.
Dr. Rocky Napier, ADA Council on Access, Prevention, and Interprofessional Relations (CAPIR)
Liaison; Ms. Jane McGinley, Manager, Fluoridation and Preventive Health Activities, ADA CAPIR Staff
Liaison; Dr. Douglas B. Torbush, ADA Council on Dental Practice (CDP) Liaison; Dr. C. Rieger Wood,
ADA Council on Dental Benefit Programs (CDBP) Liaison; Dr. William F. Robinson, ADA Council on
Dental Education and Licensure (CDEL) Liaison; Mr. Antanas Rasymas, ADA Library; Mr. Tom Wall,
ADA Health Policy Resources Center; Mr. Sam Cole, ADA Health Policy Resources Center.
The panel would like to thank the following individuals and organizations whose valuable input during
external peer review helped improve this report: Dr. Elliot Abt, Advocate Illinois Masonic Medical
Center; Dr. James Bader, University of North Carolina School of Dentistry; Dr. William H. Bowen,
University of Rochester School of Medicine and Dentistry; Dr. Albert Kingman, National Institute of
Dental and Craniofacial Research Center for Clinical Research; Dr. Stephen J. Moss, New York
University College of Dentistry; Dr. David G. Pendrys, University of Connecticut School of Dental
Medicine; Dr. Philip A. Swango, private dental consultant; Dr. Gary M. Whitford, Georgia Health
Sciences University School of Dentistry; Dr. Helen Worthington, Cochrane Oral Health Group,
University of Manchester School of Dentistry; the American Association for Dental Research (AADR);
the American Academy of Pediatric Dentistry (AAPD); the American Dental Hygienists’ Association
(ADHA); the National Institute of Dental and Craniofacial Research (NIDCR); the ADA Council on
Access, Prevention and Interprofessional Relations; the ADA Council on Communications; the ADA
Council on Dental Practice.
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The panel would like to thank the following individuals whose valuable input helped improve Table 1
and the chairside guide: Dr. Paul Fischl, Dr. Bob Kaspers, Dr. Dave Lewis, Dr. Dave McWhinnie, Dr.
Peter Neuhaus, and Dr. Maria Simon.
CDC Disclaimer: The work of the American Dental Association Council on Scientific Affairs Expert
Panel on Topical Fluoride Agents was supported in part by the U. S. Centers for Disease Control and
Prevention, Atlanta, GA. The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease Control and Prevention.
Disclosures: Robert J. Weyant, DMD, DrPH did not report any conflicts; Theresa (Tracy) Anselmo, MPH, BSDH, RDH served on the
Council on Public Health for the American Dental Hygienists' Association ending in June 2012; Eugenio D. Beltrán-Aguilar, DMD, MPH, MS,
DrPH is the Director of the American Board of Dental Public Health; Kevin J. Donly, DDS, MS is a Pediatric Dentistry Commissioner to the
ADA Commission on Dental Accreditation; William A. Frese, MD is the American Academy of Pediatrics Section VII Oral Health liaison and
also an advocate of oral health for the Illinois Oral Health Chapter of the American Academy of Pediatrics; Philippe P. Hujoel, MSD, PhD is a
Consultant to Delta Dental; Timothy Iafolla, DMD, MPH did not report any disclosures; William Kohn, DDS holds material financial interest in
a business that furnishes or is seeking to furnish goods or services to the ADA and publically represents Delta Dental Plans Association at
various meetings and events; Jayanth Kumar, DDS, MDH is the ASTDD Perinatal Committee Chair (2010 to present); Steven M. Levy, DDS,
MPH was the President of the American Board of Dental Public Health during the development of this report; Norman Tinanoff, DDS, MS is
on the Board of Trustees of the Dentaquest Foundation, an organization with a mission to improve access to oral health care, and receives no
compensation and occasionally does advocacy work for the University of Maryland Dental Action Coalition regarding oral health issues; J.
Timothy Wright, DDS, MS serves as a consultant to Edimer, which is a company working on ectodermal dysplasia protein therapy;
Domenick Zero, DDS, MS serves on the Johnson & Johnson Oral Care Advisory Board, receives compensation from Unilever for moderating
a symposium at the 2011 IADR Annual Meeting and consults on an ad hoc basis for GSK, Colgate, and P&G; Krishna Aravamudhan, BDS,
MS; Sharon L. Tracy, PhD; Julie Frantsve-Hawley RDH, PhD; Daniel M. Meyer, DDS have no disclosures.
Dr. Rocky Napier, ADA Council on Access, Prevention, and Interprofessional Relations (CAPIR) Liaison is a private practice dentist in Aiken,
South Carolina. He is also a member of the ADA Dental Practice Council, a mentor/local facilitator for the SC AAPD/OHS Head Start Dental
Home Initiative, a member of the Executive Board of the South Carolina Society of Pediatric Dentistry and a Liaison to the South Carolina
Dental Association. He is the Coordinator of the Aiken County Schools Dental Screening Program, and has been involved in several other
local dentistry-related organizations.
Dr. Douglas B. Torbush, ADA Council on Dental Practice Liaison is a Board Member of Fisher Foundation, which provides educational
loans/scholarships/grants to dental students and dental hygiene students in Georgia. He is also involved with Georgia Dental Associates
Legislative Awareness (LAW) Program, which lobbies Georgia Representatives on behalf of the patients of Georgia.
Dr. C. Rieger Wood, ADA Council on Dental Benefit Programs Liaison is the Dental Director of St. John Hospital Sapulpa and a part-time
Clinical Instructor at the University of Oklahoma College of Dentistry, Department of Operative Dentistry.
Dr. William F. Robinson, ADA Council on Dental Education and Licensure Liaison is a consultant for the Florida Board of Dentistry and the
Florida Department of Health.
Funding source: The ADA Council on Scientific Affairs commissioned this work and the Centers for
Disease Control and Prevention (CDC) partly funded this project.
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Introduction ...............................................................................................................................................................7
Clinical considerations and recommendations ....................................................................................................8
Balancing benefits with potential harms ...........................................................................................................9
Clinical Recommendations .............................................................................................................................. 10
Systematic review methods ................................................................................................................................ 12
Literature search ............................................................................................................................................... 12
Critical appraisal of included studies ............................................................................................................. 14
Data synthesis and meta-analysis ................................................................................................................. 15
Process for developing evidence statements ............................................................................................... 18
Deviations from the protocol ........................................................................................................................... 19
Methods for developing clinical recommendations .......................................................................................... 19
Results .................................................................................................................................................................... 22
Varnish: 2.26% and 0.1% fluoride .................................................................................................................. 23
Varnish (2.26% fluoride) .............................................................................................................................. 23
Evidence profiles: 2.26% fluoride varnish ................................................................................................. 26
Varnish (0.1% fluoride) ................................................................................................................................ 28
Evidence profiles: 0.1% fluoride varnish ................................................................................................... 30
APF gel (1.23% fluoride).................................................................................................................................. 31
General summary of results ........................................................................................................................ 31
Evidence statements .................................................................................................................................... 33
Evidence profiles: APF gel (1.23% fluoride) ............................................................................................. 34
APF foam (1.23% fluoride) .............................................................................................................................. 35
General summary of results ........................................................................................................................ 35
Evidence statements .................................................................................................................................... 35
Evidence profiles: APF foam (1.23% fluoride) ......................................................................................... 35
Prophylaxis pastes containing fluoride .......................................................................................................... 37
General summary of results ........................................................................................................................ 37
Evidence statements .................................................................................................................................... 38
Evidence profiles: prophylaxis pastes containing fluoride ...................................................................... 38
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Is prophylaxis prior to professional application of topical fluoride necessary? ........................................ 40
General summary of results ........................................................................................................................ 40
Evidence statements .................................................................................................................................... 41
Evidence profiles: Prophylaxis prior to APF gel (1.23% fluoride) application ...................................... 41
Prescription-strength, home-use (0.5% fluoride) gel/paste agents ........................................................... 43
General summary of results ........................................................................................................................ 43
Evidence statements .................................................................................................................................... 44
Evidence profiles: Prescription-strength, home-use (0.5% fluoride) gel/paste agents ...................... 45
Prescription-strength, home-use (0.09% fluoride) mouthrinse .................................................................. 47
General summary of results ........................................................................................................................ 47
Evidence statements .................................................................................................................................... 49
Evidence profiles: Prescription-strength, home-use (0.09% fluoride) mouthrinse .............................. 50
Stannous fluoride .............................................................................................................................................. 51
Erupting teeth .................................................................................................................................................... 51
Systematic review conclusions ........................................................................................................................... 51
Limitations .............................................................................................................................................................. 52
Regarding the evidence ................................................................................................................................... 52
Regarding this systematic review ................................................................................................................... 53
Future research ..................................................................................................................................................... 53
References ............................................................................................................................................................. 55
Appendix 1 – Clinical Recommendations – detailed presentation ................................................................ 61
Appendix 2 – Literature searches ...................................................................................................................... 62
Appendix 3 – Excluded studies at full-text stage ............................................................................................. 64
Appendix 4 – Study characteristics, bias scores, and outcomes data tables .............................................. 81
Appendix 5 - Pragmatic calculations for interpreting summary estimates clinically ................................. 118
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Introduction In 2006, the Council on Scientific Affairs (CSA) of the American Dental Association (ADA) published
recommendations for the use of professionally-applied topical fluorides for caries prevention.1 Fluoride
is the primary agent available for caries prevention. The local availability of fluoride to the tooth surface
has been shown to prevent caries by primarily three mechanisms2, 3: 1) inhibiting demineralization of
tooth enamel; 2) enhancing remineralization of tooth enamel prior to lesion progression; and 3)
inhibiting the enzyme activity of cariogenic bacteria.
The objective of this report is to update the evidence at the 5-year interval according to ADA policy and
address additional questions related to the use of prescription-strength, home-use topical fluorides. In
this review the authors evaluated sodium, stannous, and acidulated phosphate fluoride for professional
and prescription home use, including varnishes, gels, foams, rinses and prophylaxis pastes. Not
included in this report are: over-the-counter products, slow release delivery devices, dental materials
that release fluorides and products based on sodium monofluorophosphate (MFP), silver diamine
fluoride, and titanium tetrafluoride. Sodium monofluorophosphate is primarily a non-prescription, daily
use fluoride product. Silver diamine fluoride and titanium tetrafluoride are not currently available in any
products in the U.S. For the remainder of this manuscript, the term “topical fluoride(s)” will be used to
include professionally-applied as well as prescription-strength, home-use products.
This report is intended to assist practitioners with decision-making about the use of topical fluoride
caries preventive agents. The panel notes that lack of clinical data, changes in formulations across
time, and a wide variety of products can hamper decision-making. The recommendations in this
document do not purport to define a standard of care, but rather should be integrated with each
practitioner’s professional judgment and each patient’s needs and preferences.
The authors addressed three clinical questions:
1. In primary and permanent teeth, does the use of a topical fluoride compared to no topical
fluoride reduce the incidence of new lesions, or arrestA or reverseA existing coronal and/or root
caries?
A Although the original clinical questions asked about arresting and reversing coronal and/or root caries,
insufficient data were found to answer the question; therefore, these outcomes are not addressed in these clinical recommendations.
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2. For primary and permanent teeth, is one topical fluoride agent more effective than another in
reducing the incidence of, or arrestingA or reversingA coronal and/or root caries?
3. Does the use of prophylaxis before application of topical fluoride reduce the incidence of caries
to a greater extent than topical fluoride application without prophylaxis?
Although improved clinical outcomes such as reduced need for treatment, enhanced quality of life,
increased function, decreased pain and tooth loss, and improved esthetics are the ultimate goal of
preventive interventions, outcomes such as reductions in incidence and progression (“arrests” or
“reversals”)A of caries are commonly reported outcomes for topical fluorides and thus are the a priori
outcomes measures chosen for these clinical recommendations.
The panel notes that clinical trials generally test the efficacy of an intervention, which results in the best
possible outcome for the intervention because of the controlled nature of the trial and strict
inclusion/exclusion criteria for participants. These results do not necessarily equate to effectiveness of
an intervention, i.e. how the intervention works in routine practice, which typically includes patients with
comorbidities who may be taking multiple medications. The efficacy is almost always higher than the
effectiveness because of the presence of idealized conditions. Several different topical fluoride
modalities, including those planned for home use, have been reviewed in this document. Practitioners
can expect different compliance with treatment plans incorporating home-use products compared to
products applied by the practitioner. Cost, efficacy, and/or effectiveness related to the intended usage
environment also may vary.
Clinical considerations and recommendations The grading system4 used in this report is adapted from the United States Preventive Service Task
Force (USPSTF) system5 and differs markedly from the system used originally in the 2006 Clinical
Recommendations.1 The difference is that current clinical recommendations are based on synthesis of
primary evidence collected via a de novo systematic review; whereas the previous clinical
recommendations were primarily based on published systematic reviews, with additional studies
included if published after the most recent systematic review. Another difference is that these
recommendations are based on the net benefit of the intervention, i.e. a balance of benefits to potential
harms, in conjunction with the level of certainty in the evidence, whereas the previous
recommendations were based solely on the design6 of studies on benefits. This has resulted in some
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modifications to the strength assigned to the individual recommendations for products reviewed in this
report compared to the 2006 Clinical Recommendations.
The current grading system includes the use of expert opinion as a means of making clinical
recommendations or not making clinical recommendations when evidence was lacking, contradictory,
or judged to be at high risk of bias, so that the panel could not reliably estimate the net benefit of the
intervention. Practitioners should note the strength of the recommendations and endeavor to
understand the level of certainty in the underlying evidence, as well as the balance of benefits to
potential harms. They should discuss uncertainties in evidence with their patients, providing awareness
that there is usually some level of uncertainty in the evidence used for clinical decision-making.
A practitioner should consider a patient’s risk of experiencing disease when developing an optimal
caries prevention plan. Part of a patient’s risk includes whether the patient lives in an optimally
fluoridated community and uses fluoridated toothpaste. Patients at low risk for caries may not need
additional fluoride interventions, whereas caries in very high risk individuals appears at times to be
largely refractory to additional intensive preventive interventions.7, 8
Professional judgment is required to interpret the clinical relevance of all effect measures to the
individual patient. The combination of the patient’s caries risk status, the practitioner’s professional
judgment, and a patient’s needs and preferences should guide decision-making. Patient education,
assessment of readiness for change, dietary advice, other preventive modalities, and periodic clinical
examinations should be considered as a part of the caries prevention plan. In public health settings,
additional considerations include the feasibility and cost of the proposed intervention. The panel did not
include these issues in providing its clinical recommendations.
Balancing benefits with potential harms
When considering any intervention, the practitioner and patient must balance the potential benefits with
the potential harms. The panel considered harms reported by included articles as well as known
potential harms of fluoride use. Potential harms of topical fluorides include, but may not be limited to,
the following:
1. Nausea and vomiting associated with the ingestion of topical fluorides.9
2. Dental fluorosis (an esthetic concern) while tooth enamel is developing until about age 6, due to
daily ingestion of topical fluoride, such as from toothpaste or from prescription home use gels.
10
There is less of a concern with professionally-applied topical fluorides that have much longer
intervals between applications.10 Additionally, fluoride varnish has less potential for harms than
other forms of high concentration topical fluoride because the amount of fluoride that is placed in
the mouth with fluoride varnish is approximately one-tenth that of other professionally-applied
products.11
The panel judged that the benefits outweighed the potential for harms for all professionally-applied or
prescription-strength topical fluorides and age groups except for children under age 6, where the risk of
swallowing and associated events (particularly nausea and vomiting) outweighed the potential benefits
for all professionally-applied or prescription-strength topical fluorides except 2.26% fluoride varnish.
Clinical Recommendations
For individuals at elevated risk of developing dental caries, the panel made clinical recommendations
for the use of specific topical fluoride agents (as shown in Table 1); these recommendations are based
on the evidence statements and the balance of benefits with potential harm. The panel recommends
topical fluoride agents only for people at elevated risk for dental caries. Further details of the strength of
the clinical recommendations for each form of topical fluoride and age group are available in Appendix
1.
The panel recommends the following for people at risk of developing dental caries: 2.26% fluoride
varnish or 1.23% fluoride (APF) gel, or a prescription-strength, home-use 0.05% fluoride gel or paste or
0.09% fluoride mouthrinse for patients 6 years or older. Only 2.26% fluoride varnish is recommended
for children younger than 6 years. The strengths of the recommendations for the recommended
products varied from “in favor” to “expert opinion for”.
The panel judged that the benefits outweighed the potential for harm for all professionally applied and
prescription-strength, home-use topical fluoride agents and age groups except for children younger
than 6 years. In these children, the risk of experiencing adverse events (particularly nausea and
vomiting) associated with swallowing professionally applied topical fluoride agents outweighed the
potential benefits of using all of the topical fluoride agents except for 2.26 percent fluoride varnish.
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Table 1. Clinical recommendations for use of Professionally-applied or prescription-strength, home-use topical fluoride agents for caries
prevention in patients at elevated risk of developing caries
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Systematic review methods The authors represent a multidisciplinary panel of subject matter experts convened by the American Dental
Association (ADA) Council on Scientific Affairs (CSA). The panel conducted a comprehensive search of the
biomedical literature, screened the results of the search according to inclusion/exclusion criteria, critically
appraised the included studies, synthesized the data through meta-analyses where appropriate, evaluated the
level of certainty in the evidence regarding the magnitude of effect, and used a standardized process to
develop clinical recommendations. The supplemental materials (Appendices 2-4) contain further detailed
information for the interested reader as follows: Appendix 2 - search methods; Appendix 3 - detailed list of
excluded studies; and Appendix 4 - key information, risk of bias assessments, and extracted data from the
included studies.
Literature search
Two authors (KA and JF) used the strategy as presented in Appendix 2 to search MEDLINE through PubMed
and the Cochrane Library. In addition, two authors (KA and ST) hand-searched references of relevant recent
systematic reviews12-14 and other selected articles in order to include studies that might have been missed
through the electronic sources.
Figure 1 shows the process and results of the literature screening process. MEDLINE (through PubMed) was
searched from 1965 through March 4, 2011 resulting in 5,009 articles. An additional search of MEDLINE
(through PubMed) to identify articles on prescription-strength toothpaste was conducted on October 5, 2011 for
articles published since 1965 inclusive, which identified 23 articles. A second electronic database (The
Cochrane Library) was also searched from 1965 through March 4, 2011 resulting 1,281 articles. The electronic
database searches were all updated on August 30, 2012 resulting in 260 unique hits, for a total of 6,547
articles found. Through a hand-searching process, another 47 articles were identified for consideration.
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Two authors (KA and JF) independently screened the titles and abstracts using the inclusion and exclusion
criteria as shown in Table 2 and selected 402 articles for full-text review. One author (KA) reviewed the
manuscripts in full and identified articles for exclusion as reported in Appendix 3. Two members of the expert
panel (NT and TW) reviewed the reasons for exclusion and approved the final exclusion list. When a reviewer
was uncertain, she referred the papers to the expert panel members (NT and TW) for decision. Discrepancies
between reviewers were resolved by a third expert panel member and Chair of this workgroup (RW).
Figure 1: Flow diagram of the literature search and screening process
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Table 2. Inclusion/exclusion criteria
Inclusion criteria: Prospective human controlled clinical studies (randomized or non-randomized)
Fluoride agents requiring professional application or prescription
Studies that report caries incidence, arrest or reversal as outcomes
Exclusion criteria: Studies irrelevant to the topic
in vitro and animal studies
in situ studies using material surrogates (e.g., studies with removable appliances hosting enamel slabs)
Studies where the only reported outcome was increased salivary flow or reduction in Streptococcus mutans
Split-mouth designs
Cross-over design
Studies in which the experimental arm had other co-interventions (fluorides/OH instruction etc.) in which the control arm did not. (e.g., Exp: CHX + F; Control: F)
Studies that have sealants or toothpaste as the control group, except for studies that evaluated home use products
Studies reporting on fluoride-releasing dental materials
Studies reporting on slow release devices
Baseline caries data not reported
Abstracts only
Non English
Post-treatment results and effect of cessation of intervention
Products that are commercially available as OTC
APF Varnish
Studies that do not report the concentration of fluoride
Short-term (less than 1 year) studies unless the study reported frank cavitation in less than a year
Studies on products that are not commercially available in the U.S.
Critical appraisal of included studies: The grading system4 used in this report was adapted from the
United States Preventive Service Task Force (USPSTF) system5. The panel assessed the following four key
elements in their critical appraisal process: Randomization, allocation concealment, blinding and losses to
follow-up. All panel members participated in an orientation through a conference call to standardize the
application of the critical appraisal criteria. Each panel member received five to seven studies to review, along
with a standardized data abstraction form. Independent from the panel members, one of three authors (KA, JF,
or ST) duplicated the review and critical appraisal of all included studies independently and blinded to the
panel’s review. This ensured appraisal by two independent and blinded reviewers and standardized application
of the criteria by all reviewers. During a three-day face-to-face panel meeting, all panel members reviewed and
extensively discussed results from each study.
Each included trial was critically appraised according to the criteria displayed in Table 3, which are formatted
such that a “yes” response indicates low risk of bias. The number of “yes” answers was counted to provide a
risk of bias score. The numerical values of the risk of bias score generally can be interpreted as: 9-11 = low
15
risk of bias; 7-8 = moderate risk of bias; and 0-6 = high risk of bias. Note that studies were assessed based on
the methods they reported, sometimes without certain knowledge of the methods actually used.
Table 3. Criteria for assessment of individual study risk of bias
Data synthesis and meta-analysis
Choice of outcome measures. Caries increment was the primary outcome measure, which is the number of
newly decayed, missing and/or filled surfaces or teeth experienced by each participant per year compared to
baseline. Caries increment is derived from longitudinal and not cross-sectional studies. The panel adapted a
set of rules published in a Cochrane review of caries trials15 to select outcome data from each study for
subsequent analysis. Specifically, the panel chose data for "all surface types combined" over data for “specific
types (surfaces)" only; data for "all erupted and erupting teeth combined" over data for "erupted" only, and this
over data for "erupting only"; data from "clinical and radiological examinations combined" over data from
"clinical" only, and this over "radiological" only; DMFS (dmfs) scores over DFS (dfs) or DS (ds); netB caries
B Net caries increment is obtained by subtracting the number of reversals (negative increments) from the number of
positive caries increments (Broadbent and Thomson 2005). 16. Broadbent J. M., Thomson WM. For debate: problems with the DMF index pertinent to dental caries data analysis. Community Dent Oral Epidemiol 2005;33(6):400-9.
Were patients in both study arms recruited from the same
population at the same time?
Randomization reported (random sequence generation)?
Randomization procedure described?
Allocation concealment claimed?
Blinding (examiner, patient and statistician)?
Rate of losses to follow-up similar between treatment
groups?
Baseline caries status of those lost to follow-up similar to
those remaining?
Baseline caries status similar between treatment groups at
end of study or adjustment for confounding?
Sample size estimated a priori (to ensure sufficient power)?
Intention to treat* used?
Conflict of interest absent?
*As defined by study author(s)
16
increment data over crudeC (observed) increment data; and follow-up nearest to three years (often the one at
the end of the treatment period) over all other lengths of follow-up.
When data on both the tooth surface-level and tooth-level were available, the panel extracted data for both.
Similarly, the panel extracted data for “dentinal/cavitated” caries lesions, as well as for "all stages" (these data
are presented in Appendix 3). The panel also extracted data for primary and permanent teeth separately.
Imputing variances. When needed and possible, the panel imputed non-reported standard deviations using a
linear regression equation. 15
Adjusting for cluster-randomization. Some studies used group randomization (groups such as schools or
classes as opposed to individuals receiving the same intervention). In some of these studies, the results were
not adequately adjusted for the unit of analysis being the cluster rather than the individual. Standard statistical
procedures for adjustment for clustering depend on the number of clusters and the intracluster correlation
coefficient (ICC).17 The ICC ranges from 0 to 1, with the smaller number indicating the smaller cluster effect
and vice versa; however, it is often not reported, thus requiring estimation. 17,18 The standardized mean
differenceD (SMD) for three ICC values (0, 0.1, and 0.2) were calculated, and the resulting effects on the SMD
are presented, when applicable.
Effect estimates. Individual study results were combined by meta-analysis when multiple papers using
comparable methods were included for the same fluoride agent, with the objective of obtaining a more powerful
estimate of the true effect size. The SMD between the treatment and control arms was used as the effect
estimate, since it indicates whether the intervention is effective (i.e., works or does not work) and allows
measures on a variety of scales to be combined.
Data on cavitated surfaces were used in the meta-analysis calculations when both surface- and tooth-level
cavitated data were extracted. When only all stages data were reported, those data were also included in the
C Crude caries increment is obtained by comparing the baseline and follow-up status of each surface (on a surface-by-
surface basis). It does not allow for reversals. (Broadbent and Thomson 2005).16. Ibid.
D Standardized mean difference is the difference in means divided by a standard deviation. The standard deviation is the
pooled standard deviation of outcomes. The SMD value does not depend on the measurement scale, so it is a useful metric when outcomes are measured on different scales. What it actually measures is the number of standard deviations between the means. [Cochrane Handbook, Meta-analysis of continuous data, http://www.cochrane-net.org/openlearning/html/modA1-4.htm.]
17
meta-analysis with cavitated data. When only tooth-level cavitated data were reported, the data were
summarized separately.
For individual studies judged to be too clinically heterogeneousE to combine into a meta-analysis, SMD
between the treatment and control arms in each study was used as the summary estimate. Individual study
results (as SMD), if present, are shown in a table along with the meta-analysis results, and not presented
graphically in a forest plot. All analyses were designed to assess superiority, not equivalence.
Clinical interpretation issues. Other systematic reviews on topical fluorides12-14 presented prevented fraction
(PF), number needed to treat (NNT), and SMD as their effect estimates. The panel chose a pragmatic
approach to summarize and interpret the data, which was to summarize one effect estimate (SMD), and then
provide conversions of that estimate into both PF and NNT for those more familiar with these effect estimates.
The methods are described in Appendix 5, and the results are presented in each topical fluoride section. The
methods originate from the observation14 that the character of DMFS data (that mean caries increments are
similar to their standard deviations) implies that meta-analysis of SMD (the difference between two means
divided by an estimate of the within-group standard deviation) is similar in magnitude to PF (the difference in
mean caries increments between the treatment and control groups divided by the mean increment of the
control group). The panel notes that the regression equation used to convert SMD to PF in Appendix 5 was
derived from studies on topical fluorides reviewed in this report and is not generalizable beyond this report. In
addition, the NNT in this report was based on an annual caries increment of 1 DMFS in the control group.
Generating forest plots. Random-effects meta-analyses were conducted throughout to generate forest plots
using Review Manager (RevMan) 5.1 software19 when there were two or more combinable trials. The random
effects method (rather than the fixed effect method) is recommended when trial data are taken from the
literature and likely do not represent the same population.20 The random effects model is more conservative in
that the variance is composed of both the within-study and between-studies sampling errors. Individual study
and summary effect estimates were weighted by the inverse of the variance according to standard methods.21
Statistical heterogeneity. Heterogeneity in study results typically arises from differences in study methodology
and/or differences in the clinical aspects of the trial, such as populations, time period of the study, and/or
E Clinical heterogeneity arises from variability in participants, interventions, and outcomes studied. [Cochrane Handbook
for Systematic Reviews of Interventions, Version 5.1.0 (updated March 2011), Editors: Julian PT Higgins and Sally Green.]
18
topical fluoride dose.22 The panel assessed heterogeneity from the forest plots based on the I2 statistic
generated by Review Manager19 software. The statistical heterogeneity was interpreted as23: I2<50% is low;
50<I2<75% is moderate; and I2>75% is high.
Process for developing evidence statements
The first step in this process was to systematically compare the 95% confidence interval of the summary effect
estimate to the null for each intervention. If the 95% confidence interval of the summary effect estimate
included the line of no effect (zero for difference measures such as SMD), the topical fluoride was judged not
to have an effect. If the 95% confidence interval of the summary effect estimate did not include the line of no
effect, the topical fluoride was judged to have a statistically significant effect.
The next step in the development of evidence statements was to classify the level of certainty in the summary
effect estimate as high, moderate, or low, according to a standardized grading system (Table 4). The level of
certainty refers to the probability that the panel’s assessment of the effect of an intervention is correct.4 The
criteria for assessment include the risk of bias of the included studies, number of studies, number of
participants, and statistical heterogeneity among the studies; the consistency in the magnitude and direction of
the effect; and the generalizability of the findings to the populations of interest. The possibility of publication
bias was not assessed, since there were not enough studies in any category to make a reliable judgment.
Table 4. Level of Certainty categories for summary effect estimates*
Level of Certainty in Effect Estimate
Description
High
The body of evidence usually includes consistent results from well-designed, well-conducted studies in representative populations. This conclusion is unlikely to be strongly affected by the results of future studies.
This statement is strongly established by the best available evidence.
Moderate
As more information becomes available, the magnitude or direction of the observed effect could change, and this change could be large enough to alter the conclusion.
This statement is based on preliminary determination from the current best available evidence, but confidence in the estimate is constrained by one or more factors, such as:
the number, size, or risk of bias of individual studies;
inconsistency** of findings across individual studies;
limited applicability due to the populations of interest; or
lack of coherence in the chain of evidence.
19
Low
More information could allow a reliable estimation of effects on health outcomes.
The available evidence is insufficient to support the statement or the statement is based on extrapolation from the best available evidence. Evidence is insufficient or the reliability of estimated effects is limited by factors such as:
the limited number or size of studies;
important flaws in study design or methods leading to high risk of bias;
inconsistency** of findings across individual studies;
gaps in the chain of evidence;
findings not applicable to the populations of interest; or
a lack of information on important health outcomes.
*Adapted from the United States Preventive Services Task Force system **Inconsistency of findings is a concept incorporating direction of effect, similarity of point estimates, overlapping of confidence intervals, and statistical heterogeneity. Statistical heterogeneity (I
2) is interpreted as
23: I
2<50% is low;
50<I2<75% is moderate; I
2>75% is high. Direction of effect and overlapping confidence intervals are also taken into
account.
Finally, the panel used a consensus method to generate statements that summarized the evidence, including
whether or not the intervention was shown to be beneficial, the level of certainty in the underlying evidence,
and other clinical information with respect to the population, dentition type, and frequency of application for
each topical fluoride agent that was reviewed. The evidence statements were approved by majority vote.
Deviations from the protocol
Although the panel was interested in the effect of topical fluoride agents on the arrest and reversal of caries
progression as stated in clinical question #1, insufficient evidence was found on these outcomes. Therefore,
the panel decided to focus the clinical recommendations only on the reduction of caries increment as a
measure of caries prevention.
Regarding clinical question #2, the panel was interested in the comparative effectiveness of different topical
fluoride agents. Because insufficient evidence was found on which to base clinical recommendations, the panel
was unable to address this question.
Methods for developing clinical recommendations The panel developed clinical recommendations and graded the strength of the recommendations according to
a standardized process. The expert panel ascertained the net benefit rating by judging the balance of benefits
to the potential for harms. For example, if a topical fluoride was found to be effective, and the benefits were
judged to outweigh the harms, the net benefit was “benefit outweighs harms.”
20
The panel used the criteria displayed in Table 5 to combine the Level of Certainty with the Net Benefit Rating
to arrive at the strength of the recommendation (Strong, In Favor, Weak, Expert Opinion For, Expert Opinion
Against, or Against). Table 6 shows the definitions of these strengths of recommendations.
Table 5. Balancing Level of Certainty and Net Benefit Rating to arrive at recommendation strength
Level of Certainty
Net Benefit Rating
Benefits outweigh
potential harms
Benefits balanced with
potential harms
No benefit or potential harms
outweigh benefits
High Strong In Favor Against
Moderate In favor Weak Against
Low Expert Opinion For¥ or Expert Opinion Against¥
¥The USPSTF system defines this category as insufficient evidence and makes I-Statements. They do not make recommendations when the level of certainty in the
evidence is low.
Table 6. Definitions for the strength of recommendation:*
Recommendation strength
Definition
Strong Evidence strongly supports providing this intervention
In Favor Evidence favors providing this intervention
Weak Evidence suggests implementing this intervention after alternatives have been considered.
Expert Opinion For¥ Evidence is lacking; the level of certainty is low. Expert Opinion guides this recommendation
Expert Opinion Against¥ Evidence is lacking; the level of certainty is low. Expert Opinion suggests not implementing this intervention
Against Evidence suggests not implementing this intervention or discontinuing ineffective procedures
*Adapted from the USPSTF system ¥The USPSTF system defines this category as insufficient evidence and makes I-Statements. They do not make recommendations when the level of
certainty in the evidence is low.
21
Note that as described in Table 4 for Low level of certainty (when evidence is insufficient or reliability of
estimated effects is limited) and Table 5, the expert panel can still make a recommendation based on their
collective judgment, based on the available evidence. Upon agreement that the level of certainty in the effect
was low, and when the panel decided to make a clinical recommendation, the language of that
recommendation was discussed and amended until a majority of the panel was satisfied, as assessed by vote.
A summary of the steps the panel took to translate the evidence into clinical recommendation strength levels is
presented at the end of each treatment section (subdivided by age/dentition) with the subheading “Evidence
Profiles”.24 The bulleted list includes: 1) the level of certainty in the effect estimate (column 1 in Table 5); 2) the
benefit of the treatment presented in three formats (standardized mean difference [SMD], prevented fraction
[PF], and number needed to treat [NNT]); 3) potential harms associated with the treatment; 4) the panel’s
judgment of the benefit-to-potential-harm balance (“net benefit rating”, columns 2 through 4 in Table 5); and 5)
the resulting strength of the recommendation from Table 5. By making the judgments explicit, the panel hopes
the reader can understand the reasoning behind the clinical judgments that were made to develop the clinical
recommendations. The panel’s judgments are based on the best available data. Some topical fluorides could
perform better than others in various situations. The panel notes that mean effects are just that, i.e., average
results; and some patients could experience a very large effect, while others experience little effect. Similarly,
small effects for an individual patient can have large public health effects if they apply to a large part of the
population.25
The panel approved clinical recommendations by a simple majority vote. The panel sought comments on this
report from other subject matter experts, methodologists, epidemiologists and end-users before finalizing the
recommendations. The ADA Council on Scientific Affairs approved the final report for publication.
22
Results The panel included 71 trials in 82 published papersF to assess the efficacy of various topical fluoride agents for
preventing caries. When possible, data from the studies were combined through a meta-analysis. Results of
the quality assessment and the data synthesis are presented below. Table 7 presents the fluoride
concentrations of each topical fluoride agent evaluated, both as concentration of fluoride ion and concentration
of sodium fluoride.
Table 7. Fluoride ion and sodium fluoride concentrations of topical fluoride agents
Topical Fluoride Agent % F- ion % NaF
Professionally-applied
2.26% fluoride varnish 2.26 5.0
0.1% fluoride varnish 0.1 N/A*
Acidulated phosphate fluoride (APF) gel (with 0.1 M phosphoric acid)
1.23 2.7
Acidulated phosphate fluoride (APF) foam (with 0.1 M phosphoric acid)
1.23** 2.7**
Prophylaxis paste containing fluoride (most as APF) 1.23 2.7
Prescription-strength, home-use
Prescription-strength gels/pastes with or without acidulation (0.1M phosphoric acid)
0.5 1.1
Prescription-strength mouthrinses 0.09 0.2
*0.09% difluorsilane **Concentration of fluoride before dispensed. When delivered as foam by combining gel with air, the total amount of fluoride in the foam product is reduced.
Some general considerations to take into account in reviewing the evidence include: First, some of the studies
were done before the 1970’s, when dental caries rates among children were higher,26 the percentage of the
population receiving fluoridated water was substantially lower,27 and the percentage of people using fluoridated
dentifrice was much lower28. Second, some studies were conducted in countries with different levels of
background fluoride exposure, other caries preventive efforts, and caries prevalence. Lastly, the study
populations often could not be categorized in terms of caries risk and the panel could not extrapolate to the risk
categories as defined today. Therefore, caution is advised when extrapolating the results to today’s high-risk
populations, such as children at high risk for early childhood caries.
F Note that there are several cases where one study was cited by several papers. All papers are cited for each study in
these cases.
23
Varnish: 2.26% and 0.1% fluoride
There are over 30 fluoride-containing varnish products on the market today, with varying compositions
(including resin, solvent, and presence of tricalcium phosphate [TCP]) and delivery systems. These
compositional differences lead to widely variable pharmacokinetics, the effects of which remain largely
untested clinically. Through its literature search process, the panel found clinical trials on four brand name
products and decided to summarize the results based on the percentage of fluoride, which was either 2.26% or
0.1%. Further research revealed that products identified with an identical brand name (Fluor Protector) had a
compositional change in 1987 from 0.7% fluoride to 0.1% fluoride29. Since the 0.7% fluoride product is no
longer available commercially, these trials30-34 were not eligible for inclusion in this review. Therefore, the data
are subdivided by 2.26% and 0.1% fluoride varnish.
Varnish (2.26% fluoride)
General summary of results
The panel identified 17 randomized and five non-randomized clinical trials that evaluated 2.26% fluoride
varnish. There were six randomized31-33, 35-39 and two non-randomized40, 41 clinical trials concerning the primary
dentition, 11 randomized31-33, 42-52 and two non-randomized53, 54 clinical trials concerning the permanent
dentition, and one controlled55 clinical trial that combined results for both dentitions. The control groups were
no treatment, oral health counseling, or placebo varnish. The studies were carried out in populations with
various levels of dental caries. The studies were conducted in many countries (Brazil, Canada, Hong Kong,
India, Kuwait, Netherlands, Poland, Spain, Sweden, U.K. and U.S.), with and without additional fluoride use or
other fluoride exposures (although most studies were in low fluoride areas), and with and without prior
prophylaxis. The ages of the children at baseline varied from 6 months to 8 years for studies of the primary
teeth; and 5 to 15 years for studies of the permanent teeth. The panel identified two studies50, 51 of root caries.
The age range in these two studies was 44 to 79 years. The varnish was professionally applied every 3 to 12
months, with the majority of studies applying varnish every 6 months.
The study characteristics, bias scores, and the extracted outcomes data are presented in Tables A through C
in Appendix 4. The bias scores ranged from 2 to 11 for the studies on primary and permanent teeth.
The panel combined the surface-level data for studies comparing varnish application to placebo or no
treatment into two meta-analyses, one each for the primary and permanent dentitions. These meta-analyses
are shown in Figures 2 and 3. Some studies were not included in the meta-analysis because the results for
primary and permanent teeth were combined55, only tooth-level data were reported53, and only data on the
occlusal surfaces of the first permanent molars were reported45.
24
The results of two root caries studies50, 51 were combined in a separate meta-analysis (Figure 4).
Table 8 summarizes the SMD from all the studies, separated into those results generated via meta-analysis
and those of individual studies (not included in the meta-analysis).
Figure 2. Standardized mean differences from meta-analysis of 2.26% fluoride varnish studies on
primary teeth [d(e/m)fs]
Notes: 1) Adjustment for cluster randomized trials (Grodzka) at ICC=0.1: -0.20 [-0.32, -0.08], I2=58%; at ICC=0.2: -0..20 [-0.32, -0.08], I
2=57%; 2) For
Clark, used Cochrane regression equation for imputing SD; 3) For Autio-Gold and Gugwad, calculated the change between baseline and final
measurements, assuming r=0.5 for SD calculation; 4) For Weintraub, ITT data used combining both treatment arms; 4) For Hardman, converted SE to
SD; 5) For Lawrence, used “adjusted means for aboriginal only” data, and converted SE (2.04) to SD using the adjusted difference according to SD =
SE/(sqrt(1/832+1/328)).
Figure 3. Standardized mean differences from meta-analysis of 2.26% fluoride varnish studies on
permanent teeth [DMFS]
Notes: 1) Koch-SE converted to SD using the adjusted difference according to SD = SE/(sqrt(1/60+1/61)); 2) Modéer-mean prevalence at 3 years adding
“Decayed 03” plus “Filled” data; and used Cochrane regression equation for imputing SD; 3) For Clark, used Cochrane regression equation for imputing
SD; 4) Tewari converted SE to SD using the same approach as for Koch SE; 5) Bravo added fissured and non-fissured means for total surface mean;
not cluster adjusted in this figure; used Cochrane regression equation for imputing SD; 6) Milsom used “Total DFS increment - Mean of cluster
summaries” data with the number of clusters used as the sample size.
Sensitivity analysis: Adjustment for cluster randomized trials (Bravo) at ICC=0.1: -0.37 [-0.52, -0.23], I2=65%; at ICC=0.2: -0.37 [-0.51, -0.22], I
2=64%
25
Figure 4. Standardized mean differences from meta-analysis of 2.26% fluoride varnish studies on
decayed root caries surfaces
Table 8. Summary of standardized mean differences from meta-analysis and individual studies for 2.26% fluoride varnish studies
Outcome Measures Number
and type* of studies
Number of participants**
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Meta-analysis results: Primary teeth
d(e/m)fs, increment or incidence †
6 RCT31-33,
35-39 and 2 CCT40, 41
3,409** -0.19 [-0.31, -0.08]
Meta-analysis results: Permanent teeth
D(M)FS, increment or incidence†
8 RCT31-33,
42-44, 46-49, 52 and 1 CCT54
2,574 -0.38 [-0.53, -0.24]
Root caries, meta-analysis results
Root caries increment 2 RCT50, 51 132 -0.67 [-1.14, -0.20]
Individual study results
Combined dentition 1 CCT55 390 DMFS + dmfs: -1.47 [-1.70, -1.25] DMFT + dmft: -1.15 [-1.37, -0.94]
DMFT 1 CCT53 77 -0.13 [-0.58, 0.32]
DS occlusal surfaces 1 RCT45 79 -0.54 [-1.06, -0.03] Notes: * RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized); **Including all participants (not using cluster-adjusted number of participants or numbers of clusters);
†all stages used if cavitated data not available; parentheses indicate that component was included in
some of the combined results and not others
The results of the meta-analyses for primary teeth (Figure 2) indicate that the application of 2.26% fluoride
varnish has a statistically significant effect (SMD -0.19 [95% CI: -0.31, -0.08]) on caries prevention as
measured by increment or incidence using surface-level data.
The results of the meta-analyses for permanent teeth (Figure 3) indicate that 2.26% fluoride varnish has a
statistically significant effect (SMD= -0.38 [95% CI: -0.53, -0.24]) on caries prevention as measured by
increment or incidence using surface-level data. Several studies provided data that could not be included in the
meta-analysis, the results of which are summarized in Table 8.
26
In addition, two RCTs on root caries indicated a statistically significant improvement in root caries prevention
as shown in Figure 4.
Evidence statements
The panel concluded with moderate certainty that there is a benefit of 2.26% fluoride varnish application
at least twice per year for caries prevention in the primary teeth among children aged 6 months to 8
years. This statement is based on meta-analysis of seven studies that ranged from low to high risk of bias and
included over 3,000 participants; however, it is noted that there was moderate statistical heterogeneity
(I2=58%) and inconsistency among the results of the studies.
The panel concluded with moderate certainty that there is a benefit of 2.26% fluoride varnish application
at least twice per year for caries prevention in the permanent teeth among children aged 5 to 15 years.
This statement is based on meta-analysis of nine studies that ranged from low to high risk of bias and included
over 4,500 participants; however, it is noted that there was moderate statistical heterogeneity (I2=68%) and
some inconsistency among the results of the studies.
The panel concluded with low certainty that there is a benefit of 2.26% fluoride varnish application at
least twice per year for root caries prevention in adults with root caries. This statement is based on meta-
analysis of two studies with low to moderate risk of bias that included only 132 participants, but there was low
statistical heterogeneity (I2=28%), showing a consistent effect between the two studies.
The panel identified no studies of the effect on coronal caries of 2.26% fluoride varnish on the permanent teeth
of adults over the age of 18.
Evidence profiles: 2.26% fluoride varnish
Primary teeth (children under age 6):
Level of certainty: Moderate
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.19 [-0.31, -0.08] o PF=0.22 o NNT for control rate of 1 dmfs per year = 4
Adverse events or harms: Little potential for harms if swallowed
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: In favor
Permanent teeth (children):
Level of certainty: Moderate
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.38 [-0.53, -0.24] o PF=0.36
27
o NNT for control rate of 1 DMFS per year = 3
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: In favor Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use Permanent teeth - root caries (adults):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.67 [-1.14, -0.20] o PF=0.58 o NNT for control rate of 1 DMFS per year = 2
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use
28
Varnish (0.1% fluoride)
General summary of results
The panel identified two non-randomized clinical trials56, 57 that evaluated 0.1% fluoride varnish on the
primary dentition and one randomized clinical trial58 on the permanent dentition. The control groups
received oral hygiene instruction or no treatment. The studies were carried out in Germany and Sweden
in populations with various baseline levels of dental caries. The ages of the children at baseline varied
from 4 to 5 years for primary dentition and 9 to 12 years for permanent dentition. The varnish was
professionally applied every 6 months for the primary dentition and every 4 months for the permanent
dentition. Additional fluoride use or other fluoride exposure was variable, and all studies included prior
prophylaxis.
The study characteristics, bias scores, and extracted outcomes data are presented in Tables D through
F in Appendix 4. The bias scores were 2 for the two clinical trials and 6 for the RCT.
The panel compared varnish application to no treatment in one meta-analysis for the primary dentition
as shown in Figure 5. Table 9 summarizes the meta-analysis results and also lists the single-study
results for the permanent dentition.
Figure 5. Standardized mean differences from meta-analysis of studies of 0.1% fluoride varnish
applied twice a year to primary teeth [d(e/m)fs]
Notes: Twetman and Petersson not cluster adjusted in figure.
Sensitivity analysis: Adjustment for cluster randomized trials (Twetman and Petersson) at ICC=0.1: -0.05 [-0.30, 0.20], I2=0%; at ICC=0.2: -0.05
[-0.40, 0.29], I2=0%
29
Table 9. Summary of standardized mean differences from meta-analysis and individual studies for 0.1% fluoride varnish
Outcome Measures
Number and type* of studies
Number of participants**
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Primary teeth, meta-analysis results
dfs increment or incidence
2 CCT56, 57 4,977 -0.11 [-0.27, 0.06]
Permanent teeth, individual study results
DMFS increment 1 RCT58 318 -0.15 [-0.37, 0.08] Notes: * RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized); **Including all participants (not using cluster-adjusted number of participants)
The estimate of effect of 0.1% fluoride varnish applied twice per year on the primary teeth shows no
statistically significant effect, as shown in Figure 5.
The estimate of effect of 0.1% fluoride varnish applied at least once per year on the permanent dentition
is not statistically significant, as shown in Table 9.
Evidence statement
The panel concluded with moderate certainty that there is no benefit of 0.1% fluoride varnish
application twice per year for caries prevention of primary teeth among children less than 6
years old. This statement is based on meta-analysis of two studies at high risk of bias with almost 5,000
participants; however, the results were inconsistent with high statistical heterogeneity (I2=79% without
cluster adjustment). Furthermore, when adjusted for clustering, the statistical heterogeneity was
eliminated (I2=0%).
The panel concluded with low certainty that there is no benefit of 0.1% fluoride varnish application
three times per year for caries prevention of permanent teeth among children aged 6-14 years
old. This statement is based on one study at high risk of bias with 318 participants.
The panel identified no studies on the effect of 0.1% fluoride varnish on coronal or root caries on the
permanent teeth of adults over the age of 18.
30
Evidence profiles: 0.1% fluoride varnish
Primary teeth (children under age 6):
Level of certainty: Moderate
Benefit: No
Adverse events or harms: Little potential for harms if swallowed
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Against
Permanent teeth (children):
Level of certainty: Low
Benefit: No
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion against use Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion against use Permanent teeth – root caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Unknown
Strength of clinical recommendation: Panel unable to make a recommendation
31
APF gel (1.23% fluoride)
General summary of results
The panel identified 11 randomized59-70 and four non-randomized 55, 71-75 clinical trials that evaluated APF gel
(1.23% fluoride as Acidulated Phosphate Fluoride [APF], 0.1 M phosphoric acid) quarterly, semiannually,
annually or biennually (one application observed after 2 years). The comparison groups received no treatment,
placebo, prophylaxis, or non-fluoride placebo gel. All studies except one71 were on permanent teeth. All
studies applied fluoride gel for four minutes.
The study characteristics, bias scores, and the extracted outcomes data are presented in Tables G through I in
Appendix 4. All studies were conducted on school-aged children (between 3 and 16 years old) except for
one69. One study69 was conducted on non-institutionalized adults at least 60 years of age and reported on root
caries. Ten studies were conducted in the U.S. and five elsewhere (India55 70, U.K.66, China65 and Canada67).
The bias scores of eight55, 59-61, 64, 66, 69, 71, 75 of the studies ranged from 3 to 6, and seven55, 56, 58, 60, 61 70, 72-74, 76
were rated as 7. Although most studies used blinded assessment of outcomes, these bias scores were driven
primarily by lack of reporting of the randomization procedure, allocation concealment, and use of intention-to-
treat analysis.
The panel combined the results of 12 studies on permanent teeth through a meta-analysis that was grouped by
frequency of application. Three of the studies were excluded from the meta-analysis because of clinical
heterogeneity (the participants were older adults and the outcome was root caries increment)69 and because of
non-comparable outcomes measures (results combined for primary and permanent teeth55; and primary teeth
only71). Figure 6 presents the results of the meta-analysis.
32
Figure 6. Standardized mean differences from meta-analysis of studies of APF gel (1.23% fluoride)
applied on permanent teeth [DMFS] grouped by frequency of application
Notes: Jiang not cluster-adjusted in figure because ICC is not known, but adjustment at ICC=0.1: -0.25 [-0.34, -0.17], I2=42%; and at ICC=0.2: -0.26 [-
0.35, -0.17], I2=42%.
The meta-analysis (Figure 6) shows statistically significant reduction of dental caries in permanent teeth with
professionally-applied 1.23% APF gel at 3- to 24-month intervals compared to no treatment, placebo, or
prophylaxis. All application frequencies had statistically significant overall effects.
Table 10 summarizes the standardized mean differences from all the studies, separated into those generated
via meta-analysis and those of individual studies (not included in the meta-analysis).
33
Table 10. Summary of standardized mean differences from meta-analysis and individual studies for professionally-applied APF gel (1.23% fluoride)
Outcome Measures Number and
Type* of studies Number of
participants**
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Meta-analysis results:
D(M)FS, increment or incidence†, all frequencies
10 RCT59-68, 70 / 2 CCT72-75
4,023 -0.25 [-0.33, -0.16]
Individual trial results:
dmfs increment 1 CCT71 255 -1.51 [-1.79, -1.23]
DMFS + dmfs increment, all stages
1 CCT55 390 -0.84 [-1.05, -0.63]
Root caries DMFS increment, adults older
than 60 1 RCT69 318 -0.22 [-0.44, -0.00]
Notes:* RCT = randomized controlled trial; CCT = controlled clinical trial; **Using non-cluster-adjusted participant numbers; †
All stages used if cavitated
data not available
Professionally-applied APF gel was shown to have a statistically significant effect on caries increment for the
mixed dentition55, as well as primary teeth71; however, the effect on root caries in adults older than 60 was
marginally statistically significant.69
Evidence statements
The panel concluded with low certainty that there is a benefit of APF gel (1.23% fluoride) application up
to every three months for 4G minutes for caries prevention in the primary dentition. This statement is
based on one study with a high bias score that included 255 participants.
The panel concluded with moderate certainty that there is a benefit of APF gel (1.23% fluoride)
application up to every three months for 4G minutes for caries prevention in the permanent teeth of 6-
14 year olds. This statement is based on meta-analysis of 12 studies with moderate to high bias scores and
including over 4,000 participants; although there was some inconsistency, there was low statistical
heterogeneity (I2=43) between the studies.
The panel concluded with low certainty that there is a benefit of APF gel (1.23% fluoride) application 2
times per year for 4G minutes to prevent root caries. This statement is based on one study with a high bias
score including 318 participants.
G No studies were found on professionally-applied fluoride APF gels with an application time of less than 3 minutes.
34
The panel identified no studies on the effect of 2% NaF gel meeting study criteria. In addition, the panel
identified no studies of APF gel (1.23% fluoride) on the coronal surfaces of permanent teeth of adults over the
age of 18.
Evidence profiles: APF gel (1.23% fluoride)
Primary teeth (children under age 6):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-1.51 [-1.79, -1.23]
Adverse events or harms: Potential harms if swallowed
Benefit-harm assessment (Net benefit rating): Potential harms could outweigh benefits
Strength of clinical recommendation: Expert opinion against use
Permanent teeth (children):
Level of certainty: Moderate
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.25 [-0.33, -0.16] o PF=0.27 o NNT for control rate of 1 DMFS per year = 4
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: In favor Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use Permanent teeth - root caries (adults):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use) o SMD=-0.22 [-0.44, 0] o PF=0.24 o NNT for control rate of 1 DMFS per year = 4
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use
35
APF foam (1.23% fluoride)
General summary of results
The panel identified two randomized clinical trials65, 77 that evaluated APF foam (1.23% fluoride) in children
aged 3-7 years at baseline, one in the primary and the other in the permanent dentition. The comparison group
received either no treatment or placebo. Both studies were done in China.
The panel judged the bias score of one77 of the studies to be 9, while the other65 was judged to be 7. The study
characteristics, bias scores, and the extracted outcomes data are presented in Tables J through L in Appendix
4. The results for each study are shown in Table 11.
Table 11. Summary of standardized mean differences from individual studies for APF foam (1.23% fluoride)
Outcome Measures
Number and type* of studies
Number of participants**
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
dmfs increment 1 RCT77 318 -1.26 [-1.50, -1.02] †
DMFS increment 1 RCT65 412 -0.14 [-0.34, 0.04]‡ Notes:* RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized); **Using non-cluster adjusted numbers of participants; † Adjustment for cluster randomized trials (Jiang and Tai) at ICC=0.1: -1.26 [-1.68, -0.84]; at ICC=0.2: -1.25 [-1.79, -0.71]
Adjustment for cluster randomized trials (Jiang and Bian) at ICC=0.1: -0.14 [-0.59, 0.31]; at ICC=0.2: -0.14 [-0.75, 0.48]
Evidence statements
The panel concluded with low certainty that there is a benefit of APF foam (1.23% fluoride) application 2
times per year for 4H minutes for caries prevention in the primary dentition. This statement is based on
one study with a low bias score including 318 participants.
The panel concluded with low certainty that there is no benefit of APF foam (1.23% fluoride) application 2
times per year for 4H minutes for caries prevention in the permanent dentition of children. This
statement is based on one study with a moderate bias score including 412 participants.
Evidence profiles: APF foam (1.23% fluoride)
Primary teeth (children under age 6):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-1.26 [-1.50, -1.02]
Adverse events or harms: Potential for harm if swallowed
Benefit-harm assessment (Net benefit rating): Potential harms could outweigh benefits
Strength of clinical recommendation: Expert opinion against use
H Both studies on professionally-applied fluoride APF foams used an application time of 4 minutes.
36
Permanent teeth (children):
Level of certainty: Low
Benefit: No
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion against use Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion against use Permanent teeth - root caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Unknown
Strength of clinical recommendation: Panel unable to make a recommendation
37
Prophylaxis pastes containing fluoride
General summary of results
The panel identified three randomized78-80 and three non-randomized81-83 clinical trials that evaluated the
annual or semiannual application of prophylaxis pastes, most containing 1.23% fluoride as APF, for caries
prevention. These studies were all conducted in the 1960s-1970s. The comparison groups received pumice
prophylaxis or placebo paste. All studies except one83 (on children 3-5 years old at baseline) were on the
permanent teeth of children 8-16 years old at baseline.
The study characteristics, bias scores, and the extracted outcomes data are presented in Tables M through O
in Appendix 4. All of the studies were conducted in the U.S. The panel judged five of the studies to have bias
scores ranging from 3 to 5, and one with a bias score of 7.78 These judgments of quality were primarily driven
by lack of randomization; and if randomized, lack of reporting of the randomization procedure, allocation
concealment, and/or use of intention-to-treat analysis.
The panel combined the results of five of the studies through a meta-analysis. One of the studies83 was
excluded from the meta-analysis because of clinical heterogeneity (primary teeth). Two studies80, 81 reported
the results of two examiners separately; to be conservative, the data from the examiner with the largest
standard deviation were used. Standard deviations were imputed for two studies.82, 83 Figure 7 presents the
results of the meta-analysis on cavitated lesions of decayed surfaces. Table 12 summarizes the standardized
mean differences for both primary (one study) and permanent (5 studies) teeth.
Figure 7. Summary of standardized mean differences from meta-analysis of studies of prophylaxis
pastes containing fluoride on permanent teeth (DMFS)
38
Table 12. Summary of standardized mean differences from meta-analysis and individual studies of
prophylaxis pastes containing fluoride
Outcome Measures
Number and type* of studies
Number of participants
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Individual study results of primary teeth data
defs increment, cavitated lesions
1 CCT83 40 0.14 [-0.48, 0.76]
Meta-Analysis results of permanent teeth data
DMFS increment, cavitated lesions
3 RCT78-80 and 2 CCT81, 82
2,297 -0.08 [-0.18, 0.02]
Notes:* RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized)
Evidence statements
The panel concluded with low certainty that there is no benefit from prophylaxis paste containing
fluoride application for 4 minutes twice per year for caries prevention in the primary teeth of 3-5-year-
olds. This statement is based on one small study of 40 participants with a high bias score.
The panel concluded with moderate certainty that there is no benefit from prophylaxis paste containing
fluoride application for 4 minutes twice per year for caries prevention in the permanent teeth of 8-16-
year-olds. This statement is based on meta-analysis of six studies with moderate-to-high bias scores including
almost 2,300 participants that showed low statistical heterogeneity (I2=35%) but inconsistent beneficial effects.
No studies were identified that tested fluoride prophylaxis pastes on adult populations for caries preventive
effect.
Evidence profiles: prophylaxis pastes containing fluoride
Primary teeth (children under age 6):
Level of certainty: Low
Benefit: No
Adverse events or harms: Potential for harm if swallowed
Benefit-harm assessment (Net benefit rating): Potential harms could outweigh benefits
Strength of clinical recommendation: Expert opinion against use Permanent teeth (children):
Level of certainty: Moderate
Benefit: No
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Against
39
Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion against use Permanent teeth - root caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Unknown
Strength of clinical recommendation: Panel unable to make a recommendation
40
Is prophylaxis prior to professional application of topical fluoride necessary?
General summary of results
The panel identified two randomized84-86 and one non-randomized 87 clinical trials to assess whether
prophylaxis prior to professional application of topical fluoride impacts efficacy. All studies were of North
American children from 6-14 years of age at baseline. All studies reported data on permanent teeth, and one84
also reported data on primary teeth. All studies reported results on prophylaxis prior to APF gel (1.23%
fluoride) application.
The study characteristics, bias scores, and the extracted outcomes data are presented in Tables P through R
in Appendix 4. Two of the studies were judged to have bias scores of 3 and 685-87 and the other84 was 7. These
judgments of quality were primarily driven by lack of randomization; and if randomized, lack of reporting of the
randomization procedure, allocation concealment, blinding, and use of intention-to-treat analysis.
The panel combined the results on permanent teeth in a meta-analysis as shown in Fig. 8. Table 13
summarizes the standardized mean differences for both the primary (one study) and permanent (3 studies)
teeth.
Figure 8. Summary of standardized mean differences from meta-analysis of studies of prophylaxis
prior to professional application of APF gel (1.23% fluoride) on permanent teeth (DMFS)
41
Table 13. Summary of standardized mean differences from meta-analysis and individual studies of prophylaxis prior to professional application of APF gel (1.23% fluoride)
Outcomes Measure
Number and type* of studies
Number of participants
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Individual study results of primary teeth data
defs increment, cavitated lesions
1 RCT84 86 0.03 [-0.39, 0.46]
Meta-Analysis results of permanent teeth data
DMFS increment, cavitated lesions
2 RCT84-86 and 1 CCT87
1,363 0.00 [-0.11, 0.11]
Notes:* RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized)
Evidence statements
The panel concluded with low certainty that there is no benefit from conducting a prophylaxis prior to
APF gel (1.23% fluoride) application for caries prevention in primary teeth of children. This statement is
based on one small study of 86 participants with moderate bias score.
The panel concluded with moderate certainty that there is no benefit from conducting a prophylaxis prior
to APF gel (1.23% fluoride) application for caries prevention in the permanent teeth of 9-14-year-old
children. This statement is based on meta-analysis of three studies with moderate-to-high bias scores
including over 1,300 participants, consistent results, and no statistical heterogeneity (I2=0).
No studies were identified that tested prophylaxis prior to professional application of topical fluoride on adult
populations for caries preventive effect.
Evidence profiles: Prophylaxis prior to APF gel (1.23% fluoride) application
Primary teeth (children under age 6):
Level of certainty: Low
Benefit: No
Adverse events or harms: No harms noted
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion (not necessary) Permanent teeth (children):
Level of certainty: Moderate
Benefit: No
Adverse events or harms: No harms noted
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Against (not necessary)
42
Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data (no benefit)
Adverse events or harms: No harms noted
Benefit-harm assessment (Net benefit rating): No benefit
Strength of clinical recommendation: Expert opinion (not necessary) Permanent teeth - root caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown
Adverse events or harms: No harms noted
Benefit-harm assessment (Net benefit rating): Unknown
Strength of clinical recommendation: Panel unable to make a recommendation
43
Prescription-strength, home-use (0.5% fluoride) gel/paste agents
General summary of results
The panel reviewed the data for prescription-strength, home-use (0.5% fluoride) gels and pastes together. The
primary difference between gels and pastes is that pastes contain a small amount of an abrasive component.
The panel noted that only one study88 evaluated prescription-strength fluoride paste or gel (in this case it was
paste) in an unsupervised home environment, rather than by professional application in trays or with floss or in
a supervised school setting.
The panel identified eight randomized88-97 and one non-randomized 98 clinical trials meeting inclusion criteria on
prescription-strength (0.5% fluoride) paste or gel for home use. Six of the studies88, 91-95, 97, 98 were on
permanent teeth, one89 was on root caries, and two93, 94, 96 were on primary teeth.
The comparison group for all studies was either placebo, 0.125-0.145% fluoride paste, or no treatment. The
baseline age range of children was 2 to 15 for most of the studies, with one study including participants over
75.89 The studies were performed in Denmark, French Polynesia, Netherlands, Sweden, and the United States.
The study characteristics, bias scores, and the extracted outcomes data are presented in Appendix 4, Tables S
through U for the paste studies and V through X for gel studies. The bias scores of the studies ranged from 2
to 10.
Both meta-analyses (Figure 9 for primary teeth and Figure 10 for permanent teeth) show a statistically
significant reduction of dental caries with prescription strength 0.5% F paste or gel compared to no treatment,
placebo, or 0.125-0.145% fluoride paste.
Table 14 summarizes the standardized mean differences from all the studies, grouped into those generated via
meta-analysis and individual studies not included in the meta-analysis. The reasons that the individual studies
could not be included in the meta-analysis include data reported as DMFT98 and root caries data reported as
the number of new caries lesions89.
44
Figure 9. Standardized mean differences from meta-analysis of studies of prescription-strength (0.5% fluoride) paste or gel on primary teeth [d(e/m)fs]
Figure 10. Standardized mean differences from meta-analysis of studies of prescription-strength (0.5% fluoride) paste or gel on permanent teeth [D(M)FS]
Table 14. Summary of standardized mean differences from individual studies on prescription-strength (0.5% fluoride) paste or gel
Outcome Measures
Number and type* of studies
Number of participants
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Meta-analysis results:
d(e/m)fs increment 2 RCT93, 94, 96 766 -0.15 [-0.30, -0.01]
D(M)FS incidence or increment
6 RCT88, 90-9292,
9395, 97 2,669 -0.33 [-0.55, -0.12]
Individual study results:
DMFT prevalence 1 CCT98 207 -0.45 [-0.75, -0.15]
New root caries lesions
1 RCT89 138 N/A**
Notes:* RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized)
**Data reported as number of new lesions. For 0.5% paste, there were 18 new active lesions, and for the 0.145% control, there were 41 new active lesions. This was reported to be a statistically significant reduction at p<0.02. N/A=not applicable.
Evidence statements
Much of the data on these products are the result of supervised clinical trials where the product was
administered using tray applicators. Currently, these products are often used at home and applied with a tooth
45
brush. As currently used, there are no studies to support or refute the effect of 0.5% fluoride (home use gels or
drops) for caries prevention, and only one study’s protocol was unsupervised use.88 There are also no studies
directly comparing gels and pastes. Because there are little data on these products as they are currently used
and there are varied results for prescription-strength (0.5% fluoride), home-use products, the panel was limited
in their certainty with the body of evidence.
The panel concluded with low certainty that there is a benefit of prescription-strength (0.5% fluoride)
paste or gel application twice daily for caries prevention in the primary teeth. This statement is based on
meta-analysis of 776 participants in two studies, one with a low bias score and one with a high bias score, with
no statistical heterogeneity (I2=0%), but some inconsistency.
The panel concluded with low certainty that there is a benefit of prescription-strength (0.5% fluoride)
paste or gel application twice daily for caries prevention in the permanent teeth of 9-16 year olds. This
statement is based on meta-analysis of six studies with a range of low to high bias scores and showing
statistical heterogeneity (I2=86%) that included 2,669 participants.
The panel concluded with low certainty that there is a benefit of prescription-strength (0.5% fluoride)
paste or gel application twice daily in preventing root caries in adults. This statement is based on one
study with a high bias score including 138 participants.
The panel identified no studies on the effect of prescription-strength (0.5% fluoride), home-use products on
caries prevention in the permanent teeth of adults between the ages of 18 and 75.
Evidence profiles: Prescription-strength, home-use (0.5% fluoride) gel/paste agents
Primary teeth (children under age 6):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.15 [-0.30, -0.01] o PF=0.19 o NNT for control rate of 1 dmfs per year = 5
Adverse events or harms: Potential for harm if swallowed
Benefit-harm assessment (Net benefit rating): Potential harms could outweigh benefits
Strength of clinical recommendation: Expert opinion against use. Note that depending on individual patient circumstances, benefits could outweigh potential harms.
Permanent teeth (children):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.33 [-0.55, -0.12] o PF=0.33 o NNT for control rate of 1 DMFS per year = 3
Adverse events or harms: None if used as manufacturers recommend
46
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use Permanent teeth - root caries (adults):
Level of certainty: Low
Benefit: Yes (fewer new active lesions with topical fluoride use). o Benefit assessment based on data other than caries increment and calculations of PF, NNT,
MD not possible
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use
47
Prescription-strength, home-use (0.09% fluoride) mouthrinse
General summary of results
The panel identified ten randomized99-110 and two non-randomized 111, 112 clinical trials that evaluated
prescription-strength (0.09% fluoride) mouthrinse applications with daily, weekly, or biweekly (every 2 weeks)
applications. The majority of the studies compared the intervention to placebo mouthrinses, although some
compared the intervention to no treatment107, 111 or oral hygiene instruction (OHI) and prophylaxis101. All studies
were conducted on permanent teeth.
The study characteristics, bias scores, and the extracted outcomes data are presented in Tables Y through AA
in Appendix 4. All studies but one109 were conducted in school age children from 5 to 12 years of age. No adult
populations were studied except long-term-care elders (mean age 83 years) in one study109. In most studies,
fluoride rinsing was supervised by the teacher. In only one study110 were children enrolled based on their caries
risk status. Four of the studies were conducted in the United States. The panel judged the bias scores of the
included studies to range from 3 to 7 (high to moderate risk of bias).
The panel combined the results of eight of the studies through a meta-analysis that was subdivided by
frequency of application. Four studies were excluded from the meta-analysis because of clinical heterogeneity
(the participants were long-term-care elders109) and non-comparable outcomes measures (DMFT
prevalence110, DMFS prevalence108, and DMFT increment112). Figure 11 presents the results of the meta-
analysis.
48
Figure 11. Standardized mean differences from meta-analysis of prescription-strength (0.09% fluoride)
mouthrinse studies subgrouped by frequency of use on permanent teeth [D(M)FS]
Notes: 1) Heifetz-mean data are weighted averages of data from Examiners 1 and 2 and the number of control subjects is divided in half to account for two subgroups; 2) Driscoll-mean data are weighted averages of data from Examiners 1 and 2, SD imputed using Cochrane equation, and the number of control subjects is divided in half to account for two subgroups; 3) Ringelberg-number of control subjects is divided in half to account for two subgroups; and 4) Chikte and Torell – not adjusted for clustering in this figure because ICCs are not known, but adjustment at ICC=0.1: -0.22 [-0.30, -0.15], I
2=0%;
at ICC=0.2: -0.22 [-0.30, -0.14], I2=0%.
The meta-analysis of studies that reported surface-level caries increment in permanent teeth (Figure 11)
indicated that there is a statistically significant reduction in caries with the use of prescription strength fluoride
mouthrinse compared to placebo, no treatment, or OHI and prophylaxis. By frequency of use, daily and
weekly rinsing showed statistically significant effects, while biweekly rinsing did not.
Table 15 summarizes the SMDs for all the trials. The first two rows present the results from meta-analysis,
while the bottom five rows present the individual-trial results. With respect to the individual trials, prescription-
strength fluoride mouthrinse was shown to have a statistically significant effect on caries increment when
measured by DMFS prevalence108 and DMFT increment112. One study110 reported no statistically significant
effect of mouthrinse on DMFT prevalence using a biweekly rinsing protocol. In addition, one study109 showed a
49
statistically significant effect of daily rinsing on root caries increment for long-term care elders, while there was
no statistically significant effect on coronal caries.
Table 15. Summary of standardized mean differences (SMD) meta-analysis of prescription-strength (0.09% fluoride) mouthrinse studies and for individual studies not included in the meta-analysis.
Outcome Measures Number
and type* of studies
Number of participants**
Standardized Mean Difference [95% Confidence Interval]
(negative favors intervention, positive favors control)
Meta-analysis results:
D(M)FS, increment, daily, weekly and biweekly rinsing
7 RCT99-107 / 1 CCT111
4,374 -0.26 [-0.40, -0.13]
D(M)FS, increment, daily and weekly
rinsing only
5 RCT99-104,
106 / 1 CCT111
3,687 -0.20 [-0.27, -0.12]
Individual trial results:
DMFT prevalence [biweekly rinsing]
1 RCT110 273 0.17 [-0.08,0.41]
DMFS prevalence [weekly rinsing]
1 RCT108 377 -0.57 [-0.77, -0.36]
DMFT increment [biweekly rinsing]
1 CCT112 152 -0.38 [-0.70, -0.06]
Root caries increment, daily rinsing, long-term-care elders
1 RCT109 75 -0.54 [ -1.01, -0.08]
Coronal caries increment, daily
rinsing, long-term-care elders
1 RCT109 75 -0.16 [-0.62, 0.29]
Notes: *RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized); **Using non-cluster adjusted participant numbers
Evidence statements
The panel concluded with moderate certainty that there is a benefit of using prescription-strength (0.09%
fluoride) mouthrinse daily or weekly for caries prevention in permanent teeth among children aged 5-
12 years. This statement was based on meta-analysis of six moderate-to-high-risk-of-bias studies with over
3,600 participants; overall, these studies showed a consistent preventive effect and low statistical
heterogeneity (I2 = 17%).
The panel concluded with low certainty that there is a benefit of using prescription-strength (0.09%
fluoride) mouthrinse for root caries prevention among elders living in long-term-care facilities. This
statement is based on one study of 75 participants at high risk of bias showing a benefit of daily use of
prescription-strength (0.09% fluoride) mouthrinse to prevent root caries in an elderly population.
50
Finally, the panel identified no studies on prescription-strength (0.09% fluoride) mouthrinse in primary teeth or
in coronal caries of adults that met inclusion criteria.
Evidence profiles: Prescription-strength, home-use (0.09% fluoride) mouthrinse
Primary teeth (children under age 6):
Level of certainty: No certainty (no studies)
Benefit: Unknown
Adverse events or harms: Potential risk for nausea, vomiting, and dental fluorosis, if excessive material swallowed
Benefit-harm assessment (Net benefit rating): Potential harms could outweigh unknown benefits
Strength of clinical recommendation: Expert opinion against use
Permanent teeth (children):
Level of certainty: Moderate
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.26 [-0.40, -0.13] o PF=0.27 o NNT for control rate of 1 DMFS per year = 4
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: In favor Permanent teeth – coronal caries (adults):
Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use Permanent teeth - root caries (adults):
Level of certainty: Low
Benefit: Yes (smaller caries increment or incidence with topical fluoride use). o SMD=-0.54 [ -1.01, -0.08] o PF=0.48 o NNT for control rate of 1 DMFS per year = 2
Adverse events or harms: None if used as manufacturers recommend
Benefit-harm assessment (Net benefit rating): Benefits outweigh potential harms
Strength of clinical recommendation: Expert opinion for use
51
Stannous fluoride 1
Although the literature search included the search term “stannous fluoride”, no studies were found that used 2
prescription-strength concentration. Oral health providers often dispense or prescribe stannous fluoride 3
products, however, the fluoride concentration of these products is 0.1%, which is an over-the-counter 4
concentration and comparable to that in fluoride dentifrice. 5
Erupting teeth 6
Several trials52, 55, 79, 81, 104, 105, 111-113 utilizing various forms of topical fluoride agents reported results on erupting 7
teeth. The data were presented such that they could not be meaningfully aggregated. However, taken as a 8
whole, the data suggest a consistent benefit for use of fluoride varnish, rinse, and gel while teeth are erupting, 9
but due to methodological heterogeneity, it is impossible to estimate the effect. Additional studies are needed 10
to clarify these relationships. 11
Systematic review conclusions 12
Based on the studies that matched the inclusion criteria (Table 2 and Figure 1), the panel concluded that some 13
professionally-applied and prescription-strength topical fluoride agents are efficacious in preventing and 14
controlling tooth decay. These products include 2.26% fluoride varnishes, 1.23% fluoride gels, prescription-15
strength, home-use 0.5% fluoride gels/pastes, and prescription-strength, home-use 0.09% fluoride 16
mouthrinses. The panel did not find that 0.1% fluoride varnishes or prophylaxis pastes containing fluoride were 17
efficacious in preventing tooth decay and found insufficient evidence on 1.23% fluoride foams. Efficacious 18
means that the product is capable of preventing new carious lesions under the controlled setting of a clinical 19
trial. 20
21
52
Limitations
Regarding the evidence
The panel noted several limitations to the literature on topical fluoride for caries prevention.
1. Fluoride exposures. Most of the literature is from a time period prior to the fluoride exposures
(toothpastes, fluoridated water) occurring regularly in most areas in the U.S. today. Therefore, the effect
that was found when the background fluoride exposure was lower may not be the same as (and
probably is higher than) in current times when there are much greater exposures to multiple sources of
fluoride, such as toothpaste and fluoridated water. This means that the effects reported in the studies
may be overestimated for the current environment.
2. Study design, quality, and reporting. The time period also impacts the current assessment of the quality
of studies. Standards concerning clinical research in medicine and dentistry have been refined over the
past 10-15 years to minimize bias and increase transparency. Reporting methods were less refined,
leading to uncertainty regarding the conduct of the trials. For example, the reporting of appropriate
methods of randomization, sample allocation concealment, accounting for losses to follow-up, and lack
of intention-to-treat analyses typically were lacking. Studies not using an intention-to-treat analysis tend
to overestimate the magnitude of effect, whereas studies with other types of bias listed in Table 3 can
overestimate, underestimate, or have no effect on the magnitude of effect.
3. Outcomes measures. The panel identified caries incidence, arrest and reversal as three outcomes
worthy of assessment. Unfortunately, the caries outcomes reported in most trials did not permit the
panel to determine the effects of these agents on arrest or reversal (remineralization) of caries.
Similarly, the effect of topical fluorides on erupting teeth could not be assessed in a standardized
manner.
4. Patient characteristics. The panel found that available study findings provided limited information about
the caries risk status of participants. Furthermore, although conclusions were reported in the literature
specific to various age groups, these groupings do not represent biologically or behaviorally distinct
populations. Therefore, to make meaningful recommendations, the panel extrapolated the evidence to
standardized age ranges. Lastly, there were very few data regarding adults over 18 years old.
53
Regarding this systematic review
Further, this systematic review contains a number of potentially important limitations:
1. Publication bias. The competitive environment in which clinical trials are financed and conducted, as
well as the non-reporting of negative results by some investigators or publications, fosters publication
bias.114 There were not enough studies for an assessment of publication bias by visual inspection of a
funnel plot.
2. The panel attempted to capture all available evidence from controlled studies listed in only two
databases, namely PubMed and Cochrane, and included only studies published in English. Articles
published in other languages could have contributed additional data that were not considered in this
review.
3. Notwithstanding that randomized controlled clinical trials are considered the gold standard for
therapeutic interventions, in light of the paucity of such literature, the panel also considered non-
randomized studies.
Future research The panel recommends that multiple well-designed, appropriately powered, placebo-controlled RCT’s following
the Consolidated Standards of Reporting Trials (CONSORT) guidelines115 be conducted in the U.S. with
standardized reporting by age, dentition, and caries risk status. Standard methodologies for caries and fluoride
randomized controlled trials should be developed. The panel recommends that future trials be registered with
clinicaltrials.gov or equivalent registries. Specific areas of research recommendations are listed as follows:
1. Mechanisms of fluoride action and effects. Research is needed on various topical fluorides as to their
mechanism of action and caries-preventive effects when in use at the current level of background
fluoride exposure (fluoridated water and fluoride toothpaste) in the U.S. Fluoride strategies to induce
arrest or reversal of caries progression, as well as their specific effect on erupting teeth, are also
needed.
2. Populations. Research is needed concerning the following subpopulations: a) adults, between 18 and
65; b) high risk adults older than 65 (including people living in long-term-care facilities); c) extremely
54
high risk children and adults; d) U.S. specific populations; e) special needs populations (e.g., cognitive
disabilities, compromised self-care abilities, physical disabilities); and f) populations with chronic
disease (such as Sjögrens syndrome). Comparative effectiveness studies of different fluoride strategies
in these populations are also lacking. Lastly, studies of strategies to manage xerostomia-induced
coronal and root caries are needed.
3. Products and usage. Research is needed concerning the effectiveness and risks of specific products in
the following areas: a) self-applied, prescription-strength, home-use fluoride gels/toothpastes/drops; b)
2% NaF professionally-applied gel; c) alternative delivery systems, such as foam; d) optimal application
frequencies for fluoride varnish and gels; e) 1 minute application of APF gel; and f) combinations of
products (home-use and professionally-applied).
4. Measurement and outcomes. Development of measurements to evaluate caries arrest and reversal are
needed.
5. Economics. Caries prevention and economic benefit of topical fluoride in different risk populations.
6. Dissemination and implementation. Research on the best ways to help practitioners incorporate clinical
recommendations into practice.
55
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Appendix 1 – Clinical Recommendations – detailed presentation
Topical Fluoride Agent
Age Group or Dentition Affected
Younger than 6 Years (Primary teeth)
6-18 Years (Mixed dentition)
Older than 18 Years (Permanent Teeth)
Adult Root caries
Varnish, 2.26% fluoride
Every 3 to 6 months (In Favor)
Every 3 to 6 months (In Favor)
Every 3 to 6 months (Expert Opinion For)
Every 3 to 6 months (Expert opinion For)
Varnish, 0.1% fluoride Not recommended
(Against) Not recommended
(Expert Opinion Against) Not recommended
(Expert Opinion Against) Panel unable to make
recommendation
Professionally-applied 1.23% fluoride (APF) gel
Not recommended (Expert Opinion Against)
4‡ minutes every 3-6
months (In Favor)
4‡ minutes every 3 to 6
months (Expert Opinion For)
4‡ minutes every 3 to 6
months (Expert Opinion For)
Prophylaxis prior to 1.23% fluoride (APF) gel application
Not necessary for caries prevention
(Expert Opinion Against)
Not necessary for caries prevention (Against)
Not necessary for caries prevention
(Expert Opinion Against)
Panel unable to make recommendation
Fluoride foam (1.23%
fluoride as APF) Not recommended
(Expert Opinion Against) Not recommended
(Expert Opinion Against) Not recommended
(Expert Opinion Against) Panel unable to make
recommendation
Prophylaxis paste containing fluoride
Not recommended for caries prevention
(Expert Opinion Against)
Not recommended for caries prevention
(Against)
Not recommended for caries prevention
(Expert Opinion Against)
Panel unable to make recommendation
Prescription-strength (0.5% fluoride), home-use fluoride products (gel, paste)
Not recommended (Expert Opinion Against)
Twice daily (Expert Opinion For)
Twice daily (Expert Opinion For)
Twice daily (Expert Opinion For)
Mouthrinse, 0.09% fluoride
Not recommended (Expert Opinion Against)
At least weekly (In Favor)
At least weekly (Expert Opinion For)
Daily (Expert Opinion For)
‡No studies tested APF gel for less than 4 minutes.
Table cell color legend.
62
Appendix 2 – Literature searches Primary search:
((DENTAL CARIES OR DENTAL CARIES ACTIVITY TESTS OR DENTAL CARIES
SUSCEPTIBILITY OR remineralisation OR demineralization OR remineralize OR remineralise
OR demineralize OR demineralise OR Tooth Demineralization OR tooth remineralization or
white spot) AND ("fluorides"[MeSH Terms] OR "fluorides"[All Fields] OR "fluoride"[All Fields])
OR APF[All Fields] OR (("silver"[MeSH Terms] OR "silver"[All Fields]) AND ("diamines"[MeSH
Terms] OR "diamines"[All Fields] OR "diamine"[All Fields])) OR ("tin fluorides"[MeSH Terms] OR
("tin"[All Fields] AND "fluorides"[All Fields]) OR "tin fluorides"[All Fields] OR ("stannous"[All
Fields] AND "fluoride"[All Fields]) OR "stannous fluoride"[All Fields]) OR (ACIDULATED[All
Fields] AND ("phosphates"[MeSH Terms] OR "phosphates"[All Fields] OR "phosphate"[All
Fields])) OR ("sodium fluoride"[MeSH Terms] OR ("sodium"[All Fields] AND "fluoride"[All Fields])
OR "sodium fluoride"[All Fields])) NOT (Review OR dentifrice OR in vitro OR in situ) LIMITS:
Humans, English
Secondary search (to identify dentifrice trials that also evaluated other agents of interest)
((DENTAL CARIES OR DENTAL CARIES ACTIVITY TESTS OR DENTAL CARIES
SUSCEPTIBILITY OR remineralisation OR demineralization OR remineralize OR remineralise
OR demineralize OR demineralise OR Tooth Demineralization OR tooth remineralization or
white spot) AND ("fluorides"[MeSH Terms] OR "fluorides"[All Fields] OR "fluoride"[All Fields])
OR APF[All Fields] OR (("silver"[MeSH Terms] OR "silver"[All Fields]) AND ("diamines"[MeSH
Terms] OR "diamines"[All Fields] OR "diamine"[All Fields])) OR ("tin fluorides"[MeSH Terms] OR
("tin"[All Fields] AND "fluorides"[All Fields]) OR "tin fluorides"[All Fields] OR ("stannous"[All
Fields] AND "fluoride"[All Fields]) OR "stannous fluoride"[All Fields]) OR (acidulated[All Fields]
AND ("phosphates"[MeSH Terms] OR "phosphates"[All Fields] OR "phosphate"[All Fields])) OR
("sodium fluoride"[MeSH Terms] OR ("sodium"[All Fields] AND "fluoride"[All Fields]) OR "sodium
fluoride"[All Fields]) AND (mouthwashes OR varnish* OR foam OR lacquer* OR laker* OR
lacker* OR lakk* laquer* OR duraphat OR fluor protector* flor* protector* OR gel* OR tray OR
paste* OR prophyla* OR mouthrins* OR mouth rins* OR rins* OR mouthwash* OR mouth wash*
mouth* rins* OR mouth* wash*)) Limits: Humans, English
Tertiary search (to identify trials that evaluated 5000ppm toothpaste) Limits: Humans, English
("Dentifrices"[Mesh]) AND ("fluorides"[MeSH Terms] OR "fluorides"[All Fields] OR "fluoride"[All
Fields]) AND 5000
63
Cochrane search strategy conducted March 4, 2011:
systematic[sb] AND ((DENTAL CARIES OR DENTAL CARIES ACTIVITY TESTS OR DENTAL CARIES
SUSCEPTIBILITY OR DMF* OR reminerali* OR deminerali* OR Tooth Demineralization OR tooth
remineralization or white spot) AND (FLUORIDE OR APF OR SILVER DIAMINE OR STANNOUS
FLUORIDE OR ACIDULATED PHOSPHATE OR SODIUM FLUORIDE))
64
Appendix 3 – Excluded studies at full-text stage
Citation Reason For
Exclusion
Chu CH, Lo EC, Lin HC. Effectiveness of silver diamine fluoride and sodium fluoride varnish in
arresting dentin caries in Chinese pre-school children. J Dent Res. 2002 Nov;81(11):767-70.
Lo EC, Chu CH, Lin HC. A community-based caries control program for pre-school children using
topical fluorides: 18-month results. J Dent Res. 2001 Dec;80(12):2071-4.
Only arrests data.
Frostell G, Birkhed D, Edwardsson S, Goldberg P, Petersson LG, Priwe C, Winholt AS. Effect of
partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries
development in preschool children: the Malmö Study. Caries Res. 1991;25(4):304-10.
Study primarily
about the effect of
sugar and not
designed to test
the effect of
Duraphat; too
many data
transformations
necessary to
account for the
non-sugar groups;
concerns for
validity if use only
the non-sugar
data.
Llodra JC, Rodriguez A, Ferrer B, Menardia V, Ramos T, Morato M.
Efficacy of silver diamine fluoride for caries reduction in primary teeth and first permanent molars of
schoolchildren: 36-month clinical trial. J Dent Res. 2005 Aug;84(8):721-4.
SDF versus no varnish; Not available in U.S.
Yee R, Holmgren C, Mulder J, Lama D, Walker D, van Palenstein Helderman W. Efficacy of silver
diamine fluoride for Arresting Caries Treatment. J Dent Res. 2009 Jul;88(7):644-7.
Various
concentrations;
Not available in
U.S.
Muhler JC, Spear LB Jr, Bixler D, Stookey GK. The arrestment of incipient dental caries in adults
after the use of three different forms of SnF2 therapy: results after 30 months. J Am Dent Assoc.
1967 Dec;75(6):1402-6.
Multiple
interventions.
Long JG. Self-applied fluoride paste; effect on dental caries. J Public Health Dent. 1972
Summer;32(3):161-4.
Woodhouse AD. A longitudinal study of the effectiveness of self applied 10 per cent stannous
fluoride paste for secondary school children. Aust Dent J. 1978 Oct;23(5):422-8.
Self applied
prophy paste.
Self applied.
Horowitz H, Bixler D. The effect of self-applied SnF2-ZrSIO4 prophylactic paste on dental caries:
Santa Clara County, Calif. J Am Dent Assoc. 1976 92(2).
Self applied.
Gish CW, Mercer VH, Stookey GK, Dahl LO. Self-application of fluoride as a community preventive
measure: rationale, procedures, and three-year results. J Am Dent Assoc. 1975 Feb;90(2):388-97.
Self applied.
65
Ruiken R, Truin GJ, König K, Vogels A, van 't Hof M. Clinical cariostatic effectiveness of a NaF rinse
in a low prevalence child population. Community Dent Oral Epidemiol. 1987 Apr;15(2):57-9.
No relevant
outcome reported.
Percentile of DFS
scores. No idea
what the control
group was. No
information on
allocation of
schools/participan
ts.
Zimmer S, Robke FJ, Roulet JF. Caries prevention with fluoride varnish in a socially deprived
community. Community Dent Oral Epidemiol. 1999 Apr;27(2):103-8.
Cohort study with
one school
starting the
varnish a year
after the other two
test schools.
Separate data not
available. Also
frequency of
application of
varnish different
between years.
Carlsson P, Struzycka I, Wierzbicka M, Iwanicka-Frankowska E, Bratthall D. Effect of a preventive
program on dental caries and mutans streptococci in Polish schoolchildren. Community Dent Oral
Epidemiol. 1988 Oct;16(5):253-7.
Multiple
interventions.
Källestål C. The effect of five years' implementation of caries-preventive methods in Swedish high-
risk adolescents. Caries Res. 2005 Jan-Feb;39(1):20-6.
Källestål C, Flinck A, Allebeck P, Holm AK, Wall S. Evaluation of caries preventive measures. Swed
Dent J. 2000;24(1-2):1-11.
Källestål C, Fjelddahl A. A four-year cohort study of caries and its risk factors in adolescents with
high and low risk at baseline. Swed Dent J. 2007;31(1):11-25.
No relevant
control group.
Varnish vs.
fluoride
toothpaste. No
other relevant
control group.
Ersin NK, Eden E, Eronat N, Totu FI, Ates M. Effectiveness of 2-year application of school-based
chlorhexidine varnish, sodium fluoride gel, and dental health education programs in high-risk
adolescents. Quintessence Int. 2008 Feb;39(2):e45-51.
No relevant
control group.
Powell LV, Persson RE, Kiyak HA, Hujoel PP. Caries prevention in a community-dwelling older
population. Caries Res. 1999 Sep-Oct;33(5):333-9.
No baseline data.
Peyron M, Matsson L, Birkhed D. Progression of approximal caries in primary molars and the effect
of Duraphat treatment. Scand J Dent Res. 1992 Dec;100(6):314-8.
Analysis of data
for a subset from
the Malmö study
which we have
excluded.
Badersten A, Egelberg J, Koch G. Effect of monthly prophylaxis on caries and gingivitis in
schoolchildren. Community Dent Oral Epidemiol. 1975 Feb;3(1):1-4.
Combination and
no relevant
control.
Clark DC, Robert G, Tessier C, Fréchette N, Le Blanc G, Boucher L, Maheux S, Le Blanc D. The
results after 20 months of a study testing the efficacy of a weekly fluoride mouthrinsing program. J
Public Health Dent. 1985 Fall;45(4):252-6.
Control arm had
co-intervention
66
Louw AJ, Carstens IL, Hartshorne JE, Blignaut RJ. Effectiveness of two school-based caries
preventive programmes. J Dent Assoc S Afr. 1995 Feb;50(2):43-9.
The baseline
between groups
was not
comparable. So
they threw out the
kids’ very high
caries in the test
group and then
compared the
groups.
Dreizen S, Brown LR, Daly TE, Drane JB. Prevention of xerostomia-related dental caries in
irradiated cancer patients. Journal of Dental Research. 1977 56(2).
Special
population
Toolson LB, Smith DE. A 2-year longitudinal study of overdenture patients. Part I: incidence and
control of caries on overdenture abutments. J Prosthet Dent. 1978 Nov;40(5):486-91.
Special case:
overdenture
abutments
DePaola PF, Soparkar P, Foley S, Bookstein F, Bakhos Y. Effect of high-concentration ammonium
and sodium fluoride rinses on dental caries in schoolchildren. Community Dent Oral Epidemiol.
1977 Jan;5(1):7-14.
Not prescription
strength
Braga MM, Mendes FM, De Benedetto MS, Imparato JC. Effect of silver diamine fluoride on
incipient caries lesions in erupting permanent first molars: a pilot study. J Dent Child (Chic). 2009
Jan-Apr;76(1):28-33.
SDF versus
Toothbrushing.
Split mouth.
Zickert I, Lindvall AM, Axelsson P. Effect on caries and gingivitis of a preventive program based on
oral hygiene measures and fluoride application. Community Dent Oral Epidemiol. 1982
Dec;10(6):289-95.
Multiple
interventions.
Ekstrand K, Martignon S, Holm-Pedersen P. Development and evaluation of two root caries
controlling programmes for home-based frail people older than 75 years. Gerodontology. 2008. p.
67-75.
Duraphat applied
once a month
based on whether
there was active
lesion at the
monthly visit. Not
a periodic
treatment.
Subjects used F
toothpaste also.
For control group
participants were
asked to brush
twice a day with a
similar F
toothpaste.
Horowitz HS, Heifetz SB, McClendon BJ, et al. Evaluation of self administered prophylaxis and
supervised toothbrushing with acidulated phosphate fluoride. CARIES RES (BASEL). 1974 8(1) 39-
51.
Self-applied
1.23% APF with
brushing.
Wegner H. The clinical effect of application of fluoride varnish. Caries Res. 1976;10(4):318-20. No concurrent
control group.
Ripa LW, Leske GS, Varma A. Effect of mouthrinsing with a 0.2 per cent neutral NaF solution on the
deciduous dentition of first to third grade school children. Pediatr Dent. 1984 Jun;6(2):93-7.
No control group.
Petchel KA, Mello AF. A school fluoride mouthrinse program. J Sch Health. 1977 Nov;47(9):557-8.
Not a controlled
study.
Ripa LW, Leske G. Effect on the primary dentition of mouthrinsing with a 0.2 percent neutral NaF
solution: results from a demonstration program after four school years. Pediatr Dent. 1981
Dec;3(4):311-5.
Ripa LW, Leske G. Effect on the primary dentition of mouthrinsing with a 0.2 percent neutral NaF
solution: results from a demonstration program after three school years. Pediatr Dent. 1980
Sep;2(3):184-9.
No concurrent
control group.
Segreto VA, Jerman AC, Devlyn JE. Oral prophylaxis pellet: a stable stannous fluoride preparation.
Aeromed Rev. 1969 Jul;3:1-6.
Not a caries
study.
67
Horowitz HS. Caries prevention and fluoride preparations. Symp Pharmacol Ther Toxicol Group.
1974 Mar 21:36-43.
Review.
Hamp SE, Lindhe J, Fornell J, Johansson LA, Karlsson R. Effect of a field program based on systematic
plaque control on caries and gingivitis in schoolchildren after 3 years.
Community Dent Oral Epidemiol. 1978 Jan;6(1):17-23.
Fluoride prophy
paste and rinse.
Composition of
prophy pastes
and treatments
varies between
the study years
and no
information on the
program for the
control kids.
Serra Pujol ME, Bosch Pou G, Bertrán Martí L, Jorba Vives M, González Svatetz CA, Agudo Trigueros A. Servei de Salut Escolar. IMS, Mataró.
Not English.
Hamp SE, Johansson LA. Dental prophylaxis for youths in their late teens. I. Clinical effect of different
preventive regimes on oral hygiene, gingivitis and dental caries. J Clin Periodontol.
1982 Jan;9(1):22-34.
Multiple
interventions vary
by year.
Nishino M, Yoshida S, Sobue S, Kato J, Nishida M. Effect of topically applied ammoniacal silver
fluoride on dental caries in children. J Osaka Univ Dent Sch. 1969 Sep;9:149-55.
No clinical
evaluation.
Xhemnica L, Sulo D, Rroço R, Hysi D. Fluoride varnish application: a new prophylactic method in Albania. Effect on enamel carious lesions in permanent dentition. Eur J Paediatr Dent. 2008 Jun;9(2):93-6.
Short term study
but they did report
cavitation.
However 6% NaF
and 6% CaF
varnish.
Ritter AV. Fluoride varnishes. J Esthet Restor Dent. 2003;15(4):256.
Johnson G, Almqvist H. Non-invasive management of superficial root caries lesions in disabled and
infirm patients. Gerodontology. 2003 Jul;20(1):9-14.
Multiple
interventions.
Lindhe J, Axelsson P. The effect of controlled oral hygiene and topical fluoride application on caries
and gingivitis in Swedish schoolchildren. Community Dent Oral Epidemiol. 1973 1(1)
Solution and
SMFP paste.
Weisz WS. The reduction of dental caries through use of a sodium fluoride mouthwash. J Am Dent Assoc. 1960 Apr;60:438-56.
Patients over 10 years, Case-control type analysis.
Houwink B, Dirks OB, Kwant GW. A nine-year study of topical application with stannous fluoride in identical twins and the caries experience five years after ending the applications. Caries Res. 1974;8(1):27-38.
SnF solution.
Roberts-Thomson KF, Slade GD, Bailie RS, Endean C, Simmons B, Leach AJ, Raye I, Morris PS. A comprehensive approach to health promotion for the reduction of dental caries in remote Indigenous Australian children: a clustered randomised controlled trial. Int Dent J. 2010 Jun;60(3 Suppl 2):245-9.
Multiple interventions.
Potter DE, Manwell MA, Dess R, Levine E, Tinanoff N. SnF2 as an adjunct to toothbrushing in an elderly institutionalized population. Spec Care Dentist. 1984 Sep-Oct;4(5):216-8.
0.4% SnF.
Fure S, Lingström P. Evaluation of different fluoride treatments of initial root carious lesions in vivo. Oral Health Prev Dent. 2009;7(2):147-54.
SnF Solution vs. Duraphat vs. Carosolv + Duraphat.
Ravald N, Birkhed D. Prediction of root caries in periodontally treated patients maintained with different fluoride programmes. Caries Res. 1992;26(6):450-8.
Duraphat vs. 0.05% Rinse vs. 0.4% SnF2 – OTC comparisons with Duraphat.
Cartwright HV, Lindahl RL, Bawden JW. Clinical findings on the effectiveness of stannous fluoride and acid phosphate fluoride as caries reducing agents in children. J Dent Child. 1968 Jan;35(1):36-40.
Solution. Teeth surfaces were kept wet with the fluoride solution for four minutes by frequenter-application.
68
Bijella MF, Bijella VT, Lopes ES, Bastos JR. Comparison of dental prophylaxis and toothbrushing prior to topical APF applications. Community Dent Oral Epidemiol. 1985 Aug;13(4):208-11.
Paper says APF solution but does not provide information on method of application. The control group did not get varnish and hence we cannot use it to answer the question on whether prior prophy is required.
Petersson LG, Magnusson K, Andersson H, Almquist B, Twetman S. Effect of quarterly treatments with a chlorhexidine and a fluoride varnish on approximal caries in caries-susceptible teenagers: a 3-year clinical study. Caries Res. 2000 Mar-Apr;34(2):140-3.
F vs. CHX.
Birkeland JM, Jorkjend L. Effect of mouth rinsing and toothbrushing with fluoride solutions on caries among Norwegian schoolchildren. Community Dent Oral Epidemiol. 1975 Sep;3(5):201-7.
Rinse vs. F toothpaste.
Stecksén-Blicks C, Renfors G, Oscarson ND, Vivaldi-Rodrigues G, Demito CF, Bowman SJ, Ramos AL. The effectiveness of a fluoride varnish in preventing the development of white spot lesions. World Journal of Orthodontics. 2006 7(2):138-44.
Split mouth.
Altenburger MJ, Schirrmeister JF, Wrbas KT, Klasser M, Hellwig E. Fluoride uptake and remineralisation of enamel lesions after weekly application of differently concentrated fluoride gels. Caries Res. 2008 42(4):312-8.
In situ.
Ferreira MA, Latorre Mdo R, Rodrigues CS, Lima KC. Effect of regular fluoride gel application on incipient carious lesions. Oral Health & Preventive Dentistry. 2005 3(3):141-9.
Short term WSL.
Willmot DR. White lesions after orthodontic treatment: does low fluoride make a difference? Journal of Orthodontics. 2004 31(3):235-42.
Toothpaste and mouthrinse used together – Combination.
Axelsson P, Lindhe J. Effect of fluoride on gingivitis and dental caries in a preventive program based on plaque control. Community Dent Oral Epidemiol. 1975 3(4).
SMFP.
Vivaldi-Rodrigues G, Demito CF, Bowman SJ, Ramos AL. The effectiveness of a fluoride varnish in preventing the development of white spot lesions. World Journal of Orthodontics. 2006 7(2):138-44.
Split mouth.
Ferreira JM, Aragão AK, Rosa AD, Sampaio FC, Menezes VA. Therapeutic effect of two fluoride varnishes on white spot lesions: a randomized clinical trial. Braz Oral Res. 2009 Oct-Dec;23(4):446-51.
Short-term WSL study.
de Amorim RG, Leal SC, Bezerra AC, de Amorim FP, de Toledo OA. Association of chlorhexidine and fluoride for plaque control and white spot lesion remineralization in primary dentition. Int J Paediatr Dent. 2008 Nov;18(6):446-51. Epub 2008 May 16.
Short Term WSL.
Gontijo L, Cruz Rde A, Brandão PR. Dental enamel around fixed orthodontic appliances after fluoride varnish application. Braz Dent J. 2007;18(1):49-53.
Split mouth.
Stecksén-Blicks C, Renfors G, Oscarson ND, Bergstrand F, Twetman S. Caries-preventive effectiveness of a fluoride varnish: a randomized controlled trial in adolescents with fixed orthodontic appliances. Caries Res. 2007;41(6):455-9. Epub 2007 Sep 7.
6 month WSL study in ortho patients.
Tranaeus S, Al-Khateeb S, Björkman S, Twetman S, Angmar-Månsson B. Application of quantitative light-induced fluorescence to monitor incipient lesions in caries-active children. A comparative study of remineralisation by fluoride varnish and professional cleaning. Eur J Oral Sci. 2001 Apr;109(2):71-5.
Short term QLF study.
Tewari A, Chawla HS, Gopalakrishnan NS. Acidulated phosphate fluoride--3 1/2 years clinical trial on the prevention of dental caries. J Indian Soc Pedod Prev Dent. 1986 Mar;4(1):15-24. Tewari A, Chawla HS, Reddy VV. Efficacy of acidulated phosphate fluoride in the prevention of dental caries--a 2 1/2 years study. J Indian Soc Pedod Prev Dent. 1983 Mar;1(1):20-7.
This paper describes the use of “APF” without stating exactly what the method of delivery is or what the concentration was. They use the word “painted” in the methods and in the discussion talk about other papers that have evaluated solution.
69
Bordoni N, Bellagamba H, Doño R, Piovano S, Marcantoni M, Squassi A. Effect of self-brushing with acidulated phosphate fluoride (pH 5.6) on dental caries in children. Acta Odontol Latinoam. 1994-1995;8(2):17-25.
Not all the children were examined. Incomplete study.
Ogaard B, Rølla G, Arends J, ten Cate JM. Orthodontic appliances and enamel demineralization. Part 2. Prevention and treatment of lesions. Am J Orthod Dentofacial Orthop. 1988 Aug;94(2):123-8.
Short term white spot ortho study - 4 week follow up.
Szwejda LF. Fluorides in community programs: a study for four years of the cariostatic effects of prophylactic pastes, rinses, and applications of various fluorides. J Public Health Dent. 1972 Spring;32(2):110-8. Szwejda LF. Fluorides in community programs: results after four years of study of various agents topically applied by two technics. J Public Health Dent. 1971 Summer;31(3):166-76.
NaF and APF solution but interventions varied between study years for all groups.
Szwejda LF. Fluorides in community programs; a study of four years of various fluorides applied topically to the teeth of children in fluoridated communities. J Public Health Dent. 1972 Winter;32(1):25-33.
Not commercially available products
Hass R. Effectiveness of a single application of stannous fluoride after toothbrushing. J Am Dent Assoc. 1965 71(6).
8% SnF Solution applied with cotton applicators.
Wellock WD, Maitland A, Brudevold F. Caries increments, tooth discoloration, and state of oral hygiene in children given single annual applications of acid phosphate-fluoride and stannous fluoride. Arch Oral Biol. 1965 May-Jun;10(3):453-60.
8% SnF and APF solution applied with cotton applicators and teeth kept wet for 4 minutes.
Zahran M. Effect of topically applied acidulated phosphate fluoride on dental caries. Community Dent Oral Epidemiol. 1976 Nov;4(6):240-3.
APF Fluoride solution (2% NaF in 0.15M phosphoric acid, pH 3.2) applied with a cotton applicator.
McCombie F, Hole LW. Two year effect of supervised toothbrushing with an acidulated fluoride-phosphate solution. J Can Dent Assoc (Tor). 1966 Feb;32(2):89-93.
Phosphate fluoride solution. Kids dipped toothbrush in solution and brushed teeth.
Averill HM, Averill JE, Ritz AG. A 2-year comparison of three topical fluoride agents. J Am Dent Assoc. 1967 Apr;74(5):996-1001. Averill HM, Averill JE, Ritz AG, Little MF. A two-year comparison of three topical fluoride agents. Am J Public Health Nations Health. 1967 Sep;57(9):1627-34.
2% aqueous NaF, 4% SnF and 2% APH. All solution coated several times onto the tooth with cotton applicators.
Mercer VH, Muhler JC. Comparison of single topical applications of sodium fluoride and stannous fluoride. J Dent Res. 1972 Sep-Oct;51(5):1325-30.
Paper calls it Solution and does not describe method of application. 8% SnF, 4% SnF, 0.4% SnF and 2% NaF.
Hyde EJ. Caries-inhibiting action of three different topically-applied agents on incipient lesions in newly erupted teeth: results after 24 months. J Can Dent Assoc (Tor). 1973 Mar;39(3):189-93.
8% SnF Solution and “APF solution”. No indication of method of application.
70
Horowitz HS, Heifetz SB. Evaluation of topical applications of stannous fluoride to teeth of children born and reared in a fluoridated community: interim report. J Dent Child. 1967 Jul;34(4):290-5.
Horowitz HS, Heifetz SB. Evaluation of topical applications of stannous fluoride to teeth of children born and reared in a fluoridated community: final report. ASDC J Dent Child. 1969 Sep-Oct;36(5):355-61.
8% SnF and 10% SnF. The paper clearly calls these solutions although method of application is not specified. Powder mixed with water just prior to application. Applied according to method described by Dudding and Muhler.
Burgess RC, Kreutzer J. Caries, prophylaxis, and fluorides. Appl Ther. 1966 Sep;8(9):760-4. Review.
Toth K. The methods and results of caries prevention with fluorides in Hungary and in Eastern European countries. Rev Belge Med Dent. 1972;27(4):521-7.
Review.
Fleming TJ. Use of topical fluoride by patients receiving cancer therapy. Curr Probl Cancer. 1983 Apr;7(10):37-41.
Caries not outcome.
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(9): 1648-54.
Evaluated 10% SnF. Paper calls it Solution but does not describe method of application.
Heifetz SB, Horowitz HS, Meyers RJ, Li SH. Evaluation of the comparative effectiveness of fluoride mouthrinsing, fluoride tablets, and both procedures in combination: interim findings after two years. Pediatric Dentistry. 1987 Jun;9(2): 121-5.
Rinse vs. F tab.
Myers RE, Mitchell DL. Fluoride for the head and neck radiation patient. Mil Med. 1988 Aug;153(8):411-3.
Review.
Mallatt ME, Morris P. Is prophylaxis really necessary prior to the application of fluoride for the prevention of caries? J Indiana Dent Assoc. 2006 Fall;85(3):20-1.
Review.
Richards W. Improving the oral health of young children through an evidence-based approach. Community Dent Health. 2006 Jun;23(2):124-5.
Letter.
Worthington H, Clarkson J. Cochrane Oral Health Group. The evidence base for topical fluorides. Community Dent Health. 2003 Jun;20(2):74-6.
Editorial.
Tinanoff N. Caries management in children: decision-making and therapies. Compend Contin Educ Dent. 2002 Dec;23(12 Suppl):9-13.
Review.
Martin AP. Silver fluoride use. Aust Dent J. 1997 Feb;42(1):66-7. Letter.
Miller MC, Truhe TF. Preventive dentistry for pediatric patients. J Calif Dent Assoc. 1995 Feb;23(2):42-4.
Review.
[No authors listed]. Researchers investigate methods to prevent caries on roots and crowns. J Am Dent Assoc. 1992 Nov;123(11):22, 24.
Announcement.
Raadal M, Laegreid O, Laegreid KV, Hveem H, Wangen K. Evaluation of a routine for prevention and treatment of fissure caries in permanent first molars. Community Dent Oral Epidemiol. 1990 Apr;18(2):70-3.
Combined topical fluoride and sealant.
Mallatt ME, Christen A. Is a prophylaxis really necessary prior to topical fluoride therapy? J Indiana Dent Assoc. 1989 Jan-Feb;68(1):33-5.
Review.
Mellberg JR, Lass A, Petrou I. Inhibition of artificial caries lesion formation by APF and neutral NaF office gels. Am J Dent. 1988 Dec;1(6):255-7.
In vitro study.
Bohannan HM, Klein SP, Disney JA, Bell RM, Graves RC, Foch CB. A summary of the results of the National Preventive Dentistry Demonstration Program. J Can Dent Assoc. 1985 Jun;51(6):435-41.
Multiple Interventions.
Wei SH, Lau EW, Hattab FN. Time dependence of enamel fluoride acquisition from APF gels. II. In vivo study. Pediatr Dent. 1988 Sep;10(3):173-7.
Fluoride uptake study.
Tubert-Jeannin S, Riordan PJ. Association of caries experience in 12-year-old children in Heidelberg, Germany and Montpellier, France with different caries preventive measures. Community Dent Oral Epidemiol. 2003 Feb;31(1):75-6; author reply 77-8.
Letter.
Ripa LW. Caries prevention in children: the use of fluoride mouthrinses and pit and fissure sealants. N Y State Dent J. 1987 Feb;53(2):16-20.
Review.
71
Tewari A, Goyal A. Fluoride varnishes--a milestone discovery in the prevention of dental caries--I. J Indian Dent Assoc. 1986 Feb;58(2):55-6.
Review.
Billings RJ. Restoration of carious lesions of the root. Gerodontology. 1986 Spring;5(1):43-9.
Review.
Tewari A, Gauba K, Chandigarh PG. Fluoride. Critical appraisal of acidulated phosphate fluoride as a cariostatic agent. J Indian Dent Assoc. 1986 Jan;58(1):11-2.
Review.
Perry D, Newman MG. Uses of fluoride in dentistry. CDA J. 1985 Dec;13(12):31-6. Review.
Rossy R, Tinanoff N. Topical fluoride therapy. J Clin Orthod. 1985 Jul;19(7):524-6. Review.
Billings RJ, Brown LR, Kaster AG. Contemporary treatment strategies for root surface dental caries. Gerodontics. 1985 Feb;1(1):20-7.
No valid control group.
Clark DC, Hanley JA, Stamm JW, Weinstein PL. An empirically based system to estimate the effectiveness of caries-preventive agents. A comparison of the effectiveness estimates of APF gels and solutions, and fluoride varnishes. Caries Res. 1985;19(1):83-95.
Review.
Stamm JW, Bohannan HM, Graves RC, Disney JA. The efficiency of caries prevention with weekly fluoride mouthrinses. J Dent Educ. 1984 Nov;48(11):617-26.
Review.
Silverstone LM. The significance of remineralization in caries prevention. J Can Dent Assoc. 1984 Feb;50(2):157-67.
In vitro evaluation.
Vassilopoulou A, White GE. The effectiveness of a 0.4% stannous fluoride gel vs. a 0.1% stannous fluoride rinse on occlusal enamel. J Pedod. 1986 Winter;10(2):141-7.
Outcome not caries.
Holland T, O'Leary K, O'Mullane D. The effectiveness of a fortnightly mouthrinsing programme in the prevention of dental caries in school children. J Ir Dent Assoc. 1987;33(2-4):24-7.
Rinsing compared to fluoridated water.
McCall DR, Watkins TR, Stephen KW, Collins WJ, Smalls MJ. Fluoride ingestion following APF gel application. Br Dent J. 1983 Nov 19;155(10):333-6.
Safety study
Inaba D, Kawasaki K, Iijima Y, Taguchi N, Hayashida H, Yoshikawa T, Furugen R, Fukumoto E, Nishiyama T, Tanaka K, Takagi O. Enamel fluoride uptake from mouthrinse solutions with different NaF concentrations. Community Dent Oral Epidemiol. 2002 Aug;30(4):248-53.
Caries not an outcome.
Boyd CH, Boyd CM, Gallien GS Jr. A preliminary report: the effectiveness of 0.4% stannous fluoride on controlling dental caries. Ark Dent J. 1985 Dec;56(4):14-5.
Short term study and OTC.
Osterbrock NL. Fluoride mouthrinsing in Cincinnati elementary schools. Cincinnati Dent Soc Bull. 1983 Sep;52(7):20-1. Alacam T, Yilmaz T. In vivo remineralization of carious dentine treated with 10% solution of stannous fluoride. J Endod. 1983 Aug;9(8):313-5.
Review.
Sposato AL, Leske GS, Ripa LW. The changing dental care patterns of participants in a school-based fluoride mouthrinsing program. Pediatr Dent. 1983 Mar;5(1):53-6.
Prevalence study.
Donaldson KV. Rubber cup prophylaxis vs toothbrush cleaning. LDA J. 1983 Winter;41(4):9-11. Review.
Ramos-Gomez F, White GE. The effects of some remineralizing solutions on early occlusal lesions. J Pedod. 1983 Spring;7(3):241-50.
Short-term cross over.
DePaola PF, Soparkar M, Van Leeuwen M, DeVelis R. The anticaries effect of single and combined topical fluoride systems in school children. Arch Oral Biol. 1980;25(10):649-53.
No baseline data.
Spears ND, Goldstein C, Gordinier N, Crysler C. Effects of a thrice yearly application of fluoride gel. Dent Hyg (Chic). 1978 Dec;52(12):569-72.
No baseline data for both groups.
Malloy CM, Shannon IL. A single solution mixture of fluorides for treatment of cavity preparations. Gen Dent. 1982 May-Jun;30(3):225-7.
In vitro.
Weisz WS. A two year study of the efficacy of a sodium fluoride mouth wash. Penn Dent J (Phila). 1947 Nov;5(2):36-43.
Not a controlled study.
Shannon IL. Fluoride treatment programs for high-caries-risk patients. Clin Prev Dent. 1982 Mar-Apr;4(2):11-20.
Review.
Seppä L. Fluoride varnishes in caries prevention. Proc Finn Dent Soc. 1982;78 Suppl 8:1-50. Published elsewhere.
Seppä L, Hausen H, Luoma H. Relationship between caries and fluoride uptake by enamel from two fluoride varnishes in a community with fluoridated water. Caries Res. 1982;16(5):404-12.
Split-mouth.
Easley M. Rinsing with fluoride. A new, school-based program in Ohio. Ohio Dent J. 1981 Mar;55(3):36-41.
Review.
Poulsen S, Gadegaard E, Mortensen B. Cariostatic effect of daily use of a fluoride-containing lozenge compared to fortnightly rinses with 0.2% sodium fluoride. Caries Res. 1981;15(3):236-42.
F supplement study vs. rinse. No other group.
Wade JR. Professional strength fluoride mouthrinses for use in dental offices. J Public Health Dent. 1981 Winter;41(1):5-7.
Letter.
Bissell GD, O'Shea RM, Mann J. Recruitment and participation in a school mouthrinse program. J Public Health Dent. 1980 Winter;40(1):57-63.
Caries not outcome.
Shannon IL. Responses of enamel, dentin, and root surfaces to mouthrinse concentrations of sodium fluoride and stannous fluoride. ASDC J Dent Child. 1980 Jan-Feb;47(1):17-20.
Caries not outcome.
72
Pogozelski M, Rule JT, Macko DJ, Bailit HL. A neutral sodium fluoride mouthrinse program in two Connecticut communities. J Conn State Dent Assoc. 1980 Winter;54(1):13-4.
Program description.
Smith RS. Making the best use of topical fluoride applications. Dent Stud. 1979 May;57(8):86-90. Review.
Magness WS, Shannon IL, West DC. Office-applied fluoride treatments for orthodontic patients. J Dent Res. 1979 Apr;58(4):1427.
Abstract.
Shannon IL, Edmonds EJ. Topical applications of stannous fluoride: choice of concentration and duration of treatment. J Dent. 1979 Mar;7(1):9-14.
In vitro.
Kolehmainen L, Kerosuo E. The clinical effect of application of a urethane lacquer containing silane fluorine. A one-year study. Proc Finn Dent Soc. 1979;75(4):69-71.
Split mouth.
Heifetz SB, Franchi GJ, Mosley GW, MacDougall O, Brunelle J. Combined anticariogenic effect of fluoride gel-trays and fluoride mouthrinsing in an optimally fluoridated community. Clin Prev Dent. 1979 Jan-Feb;1(1):21-3, 28.
Combinations.
Cooley RL, Barkmeier WW. Reducing recurrent caries with topical stannous fluoride treatment of cavity preparations. Gen Dent. 1979 Jan-Feb;27(1):30-3.
Procedure description.
Tinanoff N, Wei SH, Parkins FM. Effect of a pumice prophylaxis on fluoride uptake in tooth enamel. J Am Dent Assoc. 1974 Feb;88(2):384-9.
Caries not outcome.
Messer HH. The anti-caries actions of topical fluorides. Northwest Dent. 1978 Nov-Dec;57(6):354-7. Report.
Maiwald HJ, Künzel W, Weatherell J. The use of a fluoride varnish in caries prevention. J Int Assoc Dent Child. 1978 Dec;9(2):31-5.
Very poor reporting. No idea what the control group was, although data for a “control” group is presented.
DePaola PF. Combined use of a sodium fluoride prophylaxis paste and a spray containing acidulated sodium fluoride solution. J Am Dent Assoc. 1967 Dec;75(6):1407-11.
Combinations.
Melsen B, Agerboek N, Rölla G. Topical application of 3% monofluorophosphate in a group of schoolchildren. Caries Res. 1979;13(6):344-9.
MFP.
Ripa LW, Leske GS, Forte F, Varma A. Effect of a 0.05% neutral NaF mouthrinse on coronal and root caries of adults. Gerodontology. 1987 Winter;6(4):131-6.
0.05% OTC mouthrinse.
Saunders WA, Wagner MJ. The metabolism of sodium fluoride in a vitamin preparation. J Dent Child. 1966 Mar;33(2):119-22.
Caries is not an outcome.
Beck DJ. Clinical trials of topical fluorides. N Z Dent J. 1974 Oct;70(322):275-81. Review.
Stratemann MW, Shannon IL. Control of decalcification in orthodontic patients by daily self-administered application of a water-free 0.4 per cent stannous fluoride gel. Am J Orthod. 1974 Sep;66(3):273-9.
OTC.
Westwater K. A study of the caries prevalence in first permanent molars of rural Zambian schoolchildren. J Dent. 1974 Sep;2(5):185-9.
Not a trial.
Hirschfield RE, Johnston LE. Decalcification under orthodontic bands. Angle Orthod. 1974 Jul;44(3):218-21.
Split mouth.
Andres CJ, Shaeffer JC, Windeler AS Jr. Comparison of antibacterial properties of stannous fluoride and sodium fluoride mouthwashes. J Dent Res. 1974 Mar-Apr;53(2):457-60.
No caries.
Fayle S, Roberts-Harry D. Fluoride mouthrinse. Br Dent J. 1996 Feb 24;180(4):129. Review.
Axelsson P, Lindhe J. The effect of a preventive programme on dental plaque, gingivitis and caries in schoolchildren. Results after one and two years. J Clin Periodontol. 1974;1(2):126-38.
No fluoride agents.
Mellberg JR, Nicholson CR. Fluoride uptake in vivo deciduous enamel of children from neutral Fluoride and APF mouthrinses. Caries Res. 1974;8(2):148-54.
Fluoride uptake.
Mellberg JR, Nicholson CR. Weekly mouth-rinsing with 3000 ppm of fluoride; the effect of concentration of fluoride in the enamel. J Public Health Dent. 1974 Winter;34(1):2-7.
Fluoride uptake.
Heifetz SB, Horowitz HS, Driscoll WS. Two-year evaluation of a self-administered procedure for the topical application of acidulated phosphate-fluoride; final report. J Public Health Dent. 1970 Winter;30(1):7-12.
Self-administered TF.
Gaum E, Cataldo E, Shiere F. Reaction of the gingiva to acidulated fluoride gel. ASDC J Dent Child. 1973 Nov-Dec;40(6):446-50.
No caries outcome.
Davies GN. Fluoride in the prevention of dental caries. A tentative cost-benefit analysis. 5. The cost-effectiveness of professionally-administered topical applications of fluoride solutions. Br Dent J. 1973 Sep 18;135(6):293-7.
Fluoride tablets.
Davies GN. Fluoride in the prevention of dental caries. A tentative cost-benefit analysis. Br Dent J. 1973 Sep 4;135(5):233-5.
Review.
Alexander WE, McDonald RE, Stookey GK. Effect of stannous fluoride on recurrent caries--results after 24 months. J Dent Res. 1973 Sep-Oct;52(5):1147.
Abstract.
Curson I. The effect on caries increments in dental students of topically applied acidulated phosphate fluoride (APF). J Dent. 1973 Jun;1(5):216-8.
Split mouth.
[No authors listed.] Professionally applied fluorides. Br Dent J. 1973 May 15;134(10):411-2. Review.
73
Ripa LW. Recommendations for the use of topical fluoride self-application techniques in a preventive office program. NY State Dent J. 1973 Apr;39(4):227-33.
Review.
Birkeland JM. Intra- and interindividual observations on fluoride ion activity and retained fluoride with sodium fluoride mouth rinses. Caries Res. 1973;7(1):39-55.
No caries outcome.
Englander HR. A perspective on prophylaxis of dental caries by topical fluoride. Dent Clin North Am. 1972 Oct;16(4):673-80.
Review.
Parkins FM. Retention of fluoride with chewable tablets and a mouthrinse. J Dent Res. 1972 Sep-Oct;51(5):1346-9.
Fluoride retention.
Miller JT, Shannon IL. A clinical report. Water-free stannous-fluoride gel and post-irradiation caries. J Public Health Dent. 1972 Spring;32(2):127.
Note.
DePaola PF, Aasenden R, Brudevold F. The use of topically applied acidulated phosphate-fluoride preceded by mild etching of the enamel: a one-year clinical trial. Arch Oral Biol. 1971 Oct;16(10):1155-63.
No relevant control group.
Zachrisson BU, Zachrisson S. Caries incidence and oral hygiene during orthodontic treatment. Scand J Dent Res. 1971;79(6):394-401.
No F agent.
Horowitz HS, Chamberlin SR. Pigmentation of teeth following topical applications of stannous fluoride in a nonfluoridated area. J Public Health Dent. 1971 Winter;31(1):32-7.
No caries outcome.
Scola FP. Self-preparation stannous fluoride prophylactic technique in preventive dentistry: report after two years. J Am Dent Assoc. 1970 Dec;81(6):1369-72.
No relevant control group.
Yardeni J, Hermel J. The anticariogenic effect of sodium fluoride. J Dent Res. 1969 Sep-Oct;48(5):965.
Abstract.
Swerdloff G, Shannon IL. Feasibility of the use of stannous fluoride mouthwash in a school system. ASDC J Dent Child. 1969 Sep-Oct;36(5):363-8.
Abstract.
Mellberg JR, Nicholson CR, Miller BG, Englander HR. Acquisition of fluoride in vivo by enamel from repeated topical sodium fluoride applications in a fluoridated area: a preliminary report. J Dent Res. 1968 Sep-Oct;47(5):733-6.
No caries outcome.
PePaola PF, Wellock WD, Maitland A, Brudevold F. The relationship of cariostasis, oral hygiene, and past caries experience in children receiving three sprays annually with acidulated phosphate-fluoride: three-year results. J Am Dent Assoc. 1968 Jul;77(1):91-4.
Intervention not consistent across years.
Murray JJ, Majid ZA. The prevalence and progression of approximal caries in the deciduous dentition in British children. Br Dent J. 1978 Sep 19;145(6):161-4. DePaola PF. Caries in our aging population: what are we learning? Cariology for the Nineties. (1993) University of Rochester Press, pp. 25-35.
Not controlled.
Lagutina NJ, Vorobjev VS, Grabetskij AA, Stepanov AV. Clinical evaluation of home fluoride-containing varnish. Quintessence Int Dent Dig. 1978 Feb;9(2):63-6.
Investigative varnish.
Fischman SL, English JA, Albino JE, Bissell GD, Greenberg JS, Juliano DB, O'Shea RM, Slakter MJ. A comprehensive caries control program--design and evaluation of the clinical trial. J Dent Res. 1977 Oct;56 Spec No:C99-103.
Combinations.
Shannon IL. A self-treatment program of chemical preventative dentistry for high-risk patients. Ariz Dent J. 1977;23(1):19, 26-9.
Not controlled.
Levine RS. An initial clinical assessment of a mineralising mouthrinse. Br Dent J. 1975 Apr 1;138(7):249-53.
Not on fluoride.
Geiger AM, Gorelick L, Gwinnett AJ, Griswold PG. The effect of a fluoride program on white spot formation during orthodontic treatment. Am J Orthod Dentofacial Orthop. 1988 Jan;93(1):29-37.
Combinations.
Seppä L, Hausen H, Tuutti H, Luoma H. Effect of a sodium fluoride varnish on the progress of initial caries lesions. Scand J Dent Res. 1983:91 (2).
Split mouth.
Hutton J, Koulourides T, Borden L. Evaluation of cariostatic disciplines for postradiation caries. Caries Res. 1982;16(5):390-7.
Case reports.
Aasenden R, DePaola PF, Brudevold F. Effects of daily rinsing and ingestion of fluoride solutions upon dental caries and enamel fluoride. Arch Oral Biol. 1972 Dec;17(12):1705-14.
Solution was swallowed.
Hirschfield RE. Control of decalcification by use of fluoride mouthrinse. ASDC J Dent Child. 1978 Nov-Dec;45(6):458-60.
Phosflur rinse OTC.
Frankl SN, Fleisch S, Diodati RR. The topical anticariogenic effect of daily rinsing with an acidulated phosphate fluoride solution. J Am Dent Assoc. 1972 Oct;85(4):882-6.
Phosflur OTC.
Rugg-Gunn AJ, Holloway PJ, Davies TG. Caries prevention by daily fluoride mouthrinsing. Report of a three-year clinical trial. Br Dent J. 1973 Oct 16;135(8):353-60.
0.05% NaF rinse.
Forsman B. The caries preventing effect of mouthrinsing with 0.025 percent sodium fluoride solution in Swedish children. Community Dent Oral Epidemiol. 1974;2(2):58-65.
0.2% vs. 0.025% - No relevant control group.
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. Br Dent J. 1977 Nov 15;143(10):333-8.
100 ppm = 0.01% F ion OTC.
Finn SB, Moller P, Jamison H, Regattieri L, Manson-Hing L. The clinical cariostatic effectiveness of two concentrations of acidulated phosphate-fluoride mouthwash. J Am Dent Assoc. 1975 Feb;90(2):398-402.
100 and 200 ppm F ion concentration OTC.
74
Muhler JC, Stookey GK, Bixler D. Evaluation of the anticariogenic effect of mixtures of stannous fluoride and soluble phosphates. ASDC J Dent Child. 1965 32(3).
Review.
Foster RD. Self-application of topically applied stannous fluoride: a feasibility study. J Am Dent Assoc. 1965 70(2).
Caries not outcome.
Alexander WE, McDonald RE, Stookey GK. Effectiveness of a stable 30 percent stannous fluoride solution in the prevention of recurrent dental caries. Journal of the Indiana Dental Association. 1969 48(4).
Applied to cavity walls.
Marthaler TM. Caries-inhibition after seven years of unsupervised use of an amine fluoride dentifrice. Br Dent J. 1968 124(11).
Amine fluoride.
Corbett JA, Shannon IL. Prevention of decalcification in orthodontic patients: a preliminary clinical trial with a mixture of fluorides. J Colo Dent Assoc. 1980 Mar;58(4):16-7.
Combinations.
Sköld L, Sundquist B, Eriksson B, Edeland C. Four-year study of caries inhibition of intensive Duraphat application in 11-15-year-old children. Community Dent Oral Epidemiol. 1994 Feb;22(1):8-12.
Children in test group used F prophy paste + Duraphat and control used only Duraphat.
McCormick J, Manson-Hing L, Wolff AE, Koulourides T. Remineralizing mouthwash rationale and a pilot clinical study. Ala J Med Sci. 1970 Jan;7(1):92-7.
No relevant agent.
Gray AS, Gunther DM, Munns PM. Fluoride paste and rinse in a school dental program. J Can Dent Assoc. 1980 46(10).
Combination.
Luoma H, Murtomaa H, Nuuja T, Nyman A, Nummikoski P, Ainamo J, Luoma AR. A simultaneous reduction of caries and gingivitis in a group of schoolchildren receiving chlorhexidine-fluoride applications. Results after 2 years. Caries Res. 1978;12(5):290-8.
Unusual concentration.
Hall GL. Stannous fluoride (0.1 percent) mouthwash study. SAM-TR-68-78. Tech Rep SAM-TR. 1968 Aug:1-2.
OTC concentration.
Swerdloff G, Shannon IL. A feasibility study of the use of a stannous fluoride mouthwash in a school preventive dentistry program. SAM-TR-67-52. Tech Rep SAM-TR. 1967 Jun:1-10.
0.1% SnF rinse – OTC concentration.
Brandt RS, Slack GL, Waller DF. The use of a sodium fluoride mouthwash in reducing the dental caries increment in eleven year old English school children. Proceedings of the British Paedodontic Society. 1972 (2).
Started with a group of kids. Found that baseline caries became different due to losses and so they decided to report only for matched pairs.
Murray JJ, Winter GB, Hurst CP. Duraphat fluoride varnish. A 2-year clinical trial in 5-year-old children. Br Dent J. 1977 Jul 5;143(1):11-7.
Split mouth.
Lindquist B, Edward S, Torell P, Krasse B. Effect of different carriers preventive measures in children highly infected with mutans streptococci. Scand J Dent Res. 1989 Aug;97(4):330-7.
The control group was treated based on dentists’ judgment and on an average received 4 topical fluoride applications over the 2 year study period.
Spak CJ, Johnson G, Ekstrand J. Caries incidence, salivary flow rate and efficacy of fluoride gel treatment in irradiated patients. Caries Res. 1994;28(5):388-93.
0.42% F vs. 1.23% APF for 4 weeks.
Twetman S, Petersson LG. Prediction of caries in pre-school children in relation to fluoride exposure. Eur J Oral Sci. 1996 Oct-Dec;104(5-6):523-8.
Testing a chairside strep test. Caries data part of the original paper is the one below.
Green E. A clinical evaluation of two methods of caries prevention in newly-erupted first permanent molars. Aust Dent J. 1989 Oct;34(5):407-9.
Silver fluoride excluded
75
Keltjens HM, Schaeken MJ, van der Hoeven JS, Hendriks JC. Caries control in overdenture patients: 18-month evaluation on fluoride and chlorhexidine therapies. Caries Res. 1990;24(5):371-5.
Control group received semiannual 0.4% NaF and test received daily 0.1% NaF. OTC.
Disney JA, Graves RC, Stamm JW, Bohannan HM, Abernathy JR. Comparative effects of a 4-year fluoride mouthrinse program on high and low caries forming grade 1 children. Community Dent Oral Epidemiol. 1989 Jun;17(3):139-43.
Many combinations. NPDDP paper.
Leverett DH, McHugh WD, Jensen OE. Dental caries and staining after twenty-eight months of rinsing with stannous fluoride or sodium fluoride. J Dent Res. 1986 Mar;65(3):424-7.
0.05% NaF.
Obersztyn A, Kolwinski K, Trykowski J, Starosciak S. Effects of stannous fluoride and amine fluorides on caries incidence and enamel solubility in adults. Aust Dent J. 1979 Dec;24(6):395-7.
SnF prophy paste and solution in the test group and no treatment control.
Seppä L, Tuutti H, Luoma H. Three-year report on caries prevention of using fluoride varnishes for caries risk children in a community with fluoridated water. Scand J Dent Res. 1982 Apr;90(2):89-94.
Split mouth.
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. J Am Dent Assoc. 1979 Feb;98(2):202-8.
Amine fluoride.
McConchie JM, Richardson AS, Hole LW, McCombie F, Kolthammer J. Caries-preventive effect of two concentrations of stannous fluoride mouthrinse. Community Dent Oral Epidemiol. 1977 Nov;5(6):278-83.
0.01 and 0.02% SnF OTC.
Boyd RL. Comparison of three self-applied topical fluoride preparations for control of decalcification. Angle Orthod. 1993 Spring;63(1):25-30.
All OTC concentrations.
McDonald SP, Sheiham A. A clinical comparison of non-traumatic methods of treating dental caries. Int Dent J. 1994 Oct;44(5):465-70.
Split mouth.
Bánóczy J, Nemes J. Effect of amine fluoride (AmF)/stannous fluoride (SnF2) toothpaste and mouthwashes on dental plaque accumulation, gingivitis and root-surface caries. Proc Finn Dent Soc. 1991;87(4):555-9.
No control for the NaF group.
Alexander SA, Ripa LW. Effects of self-applied topical fluoride preparations in orthodontic patients. Angle Orthod. 2000 Dec;70(6):424-30.
No control groups for the prevident treatment; special population; head-to-head trial
Torell P, Gerdin PO. Fortnightly fluoride rinsing combined with topical painting of fluoride solutions containing Al-, Fe-, and Mn-ions. Scand J Dent Res. 1977 Jan;85(1):38-40.
No concurrent control group.
Bawden JW, Granath L, Holst K, Koch G, Krasse P, Rootzén H. Effect of mouthrinsing with a sodium fluoride solution in children with different caries experience. Swed Dent J. 1980;4(3):111-7.
Primary data is in Koch 1967.
Seppä L. Fluoride content of enamel during treatment and 2 years after discontinuation of treatment with fluoride varnishes. Caries Res. 1984;18(3):278-81.
Caries not an outcome.
ten Cate JM, Shariati M, Featherstone JD. Enhancement of (salivary) remineralization by 'dipping' solutions. Caries Res. 1985;19(4):335-41.
In vitro study.
Ogaard B, Arends J, Rølla G. Action of fluoride on initiation of early root surface caries in vivo. Caries Res. 1990;24(2):142-4.
In vitro study.
Dénes J, Gábris K. Results of a 3-year oral hygiene programme, including amine fluoride products, in patients treated with fixed orthodontic appliances. Eur J Orthod. 1991 Apr;13(2):129-33.
Amine fluorides.
Wei SH, Kaqueller JC, Massler M. Remineralization of carious dentin. J Dent Res. 1968 May-Jun;47(3):381-91.
In vitro study.
J Orofac Orthop. 1997;58(4):206-13. Fluoride in combination of Cervitec.
Brånemark PI. Local tissue effects of sodium fluoride. Odontol Revy. 1967;18(3):273-94. No reason given.
Haugejorden O, Nord A. Caries incidence after topical application of varnishes containing different concentrations of sodium fluoride: 3-year results. Scand J Dent Res. 1991 Aug;99(4):295-300.
Duraphat tested against test varnish. No other control group.
Birkeland JM, Torell P. Caries-preventive fluoride mouthrinses. Caries Res. 1978;12 Suppl 1:38-51. Review paper.
Vrbic V, Kosmelj B+KOSMELJ B, Ravnik C. A 3-year study among Yugoslavian schoolchildren on caries reduction after topical application of 4% NaF-PO4. Community Dent Oral Epidemiol. 1974;2(4):163-5.
Non-standard fluoride concentration.
Radike AW, Gish CW, Peterson JK, King JD, Segreto VA. Clinical evaluation of stannous fluoride as an anticaries mouthrinse. J Am Dent Assoc. 1973 Feb;86(2):404-8.
0.1% SnF OTC.
Moreira BH, Guimaraes LO, Viera S, Piedade EF. [Fluoride mouthwashes in combination with fluoridation of the public water supply for the prevention of dental caries.] Revista Da Associacao Paulista de Cirurgioes Dentistas. 1981 35(4).
Non-English.
76
Molina XM, Rodriguez GP, Sepulveda MM, Urbina TR, Vargas SJ. [Increase of caries in a school children group that participated in a weekly mouth wash program with sodium fluoride 0.2.] Revista de la Facultad de Odontología de la Universidad de Chile. 1987: 5(2).
Non-English.
Mestrinho HD, et al. [Prevention of dental caries through topical application of APF gel with plastic trays.] Odontologo Moderno. 1983 (10).
Non-English.
Moreira BH,Tumang AJ. [Mouthwashes with 1 per cent sodium fluoride solutions in the prevention of dental caries.] Revista Brasileira de Odontologia. 1971 28(167).
Non-English.
Moreira BH,Tumang AJ. [Prevention of dental caries by means of mouthwashes with 0.1 solutions of sodium fluoride: results of a 2 year study.] Revista Brasileira de Odontologia. 1972 29(173).
Non-English.
Horowitz HS. Caries prevention and various fluoride preparations. Refuat Hapeh Vehashinayim. 1974 Oct;23:91-6.
Non-English.
Kukleva MP, Kondeva VK. Dynamics of caries activity and caries reduction in group prophylaxis with fluoride gel. Folia Med (Plovdiv). 2001;43(1-2):12-5.
Product not commercially available in U.S.
Marthaler TM. Improved oral health of schoolchildren of 16 communities after 8 years of prevention. I. Combining DMF data from the communities. Helv Odontol Acta. 1974 Oct;18(2):119-42.
Prevalence study.
Marthaler TM, König KG, Mühlemann HR. The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year. Helv Odontol Acta. 1970 Oct;14(2):67-77.
Amine Fluoride.
Marthaler TM. Caries-inhibiting effect of fluoride tablets. Helv Odontol Acta. 1969 Apr;13(1):1-13. Supplement study.
Koch G. Caries increment in schoolchildren during and two years after end of supervised rinsing of the mouth with sodium fluoride solution. Odontol Revy. 1969;20(3):323-30.
Post-treatment.
Hollender L, Koch G. Effect of local application of fluoride on initial demineralization of buccal surface of maxillary incisors. Clinical assessment from colour slides. Sven Tandlak Tidskr. 1976: 69 (1).
0.5% NaF rinse and photographs used to evaluate caries.
Arcieri RM, de Lourdes Carvalho M, Goncalves LM, Alfonso de Almeida H, Pereira AL, de Oliveira EM. [Incidence of dental caries in students after topical application of acidulated phosphate fluoride with or without fluoride mouthwashes: comparative study.] Revista do Centro de Ciencias Biomedicas Da Universidade Federal de Uberlandia. 1985: 1(1).
Non-English.
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.] Quintessenza. 1984: 35(1).
Non-English.
Effectiveness of fluoride gel. J Am Dent Assoc. 1989;119(1):10, 12, 172-174. Letter.
Researchers investigate methods to prevent caries on roots and crowns. J Am Dent Assoc. 1992;123(11):22, 24.
Announcement.
Abelson DC, Levin MP. Multiple use of fluoride for adult patients. N Y J Dent. 1977;47(5):146-148.
Not a clinical study.
Adler P. Fluorides and dental health. Monogr Ser World Health Organ. 1970;59:323-354.
Not a clinical study.
Andrus PL. The role of fluoride in the prevention of dental caries. Tex Med. 1982;78(12):57-61.
Review.
Brailsford SR, Fiske J, Gilbert S, Clark D, Beighton D. The effects of the combination of chlorhexidine/thymol- and fluoride-containing varnishes on the severity of root caries lesions in frail institutionalised elderly people. J Dent. 2002;30(7-8):319-324.
CHXF combination.
Brandt RS. Fluoride and dental caries. Practitioner. 1975;214(1281):388-389. Review.
Carberry FJ. Fluoride rinse. An alternative to restoration in Barbuda, West Indies. N Y State Dent J. 1999;65(2):34-38.
Not a clinical study.
Craig GG, Powell KR. Dental caries in susceptible fissures after prolonged fluoride application. Community Dent Oral Epidemiol. 1979;7(3):158-160.
Slow release.
Craig GG, Powell KR, Cooper MH. Caries progression in primary molars: 24-month results from a minimal treatment programme. Community Dent Oral Epidemiol. 1981;9(6):260-265.
Not a controlled study.
DePaola PF, Wellock WD, Maitland A, Brudevold F. The relationship of cariostasis, oral hygiene, and past caries experience in children receiving three sprays annually with acidulated phosphate-fluoride: three-year results. J Am Dent Assoc. 1968.
Sprays.
Dismer GA. Sodium fluoride mouthrinse. Three-year study. Ill Dent J. 1982;51(3):158-160.
Not a controlled study.
Driscoll WS, Nowjack-Raymer R, Heifetz SB, Li SH, Selwitz RH. Evaluation of the comparative effectiveness of fluoride mouthrinsing, fluoride tablets, and both procedures in combination: interim findings after five years. J Public Health Dent. 1990;50(1):13-17. Driscoll WS, Nowjack-Raymer R, Selwitz RH, Li SH, Heifetz SB. A comparison of the caries-preventive effects of fluoride mouthrinsing, fluoride tablets, and both procedures combined: final results after eight years. J Public Health Dent. 1992;52(2):111-116.
No control group.
77
Eckhaus B, Silverstein S, Fine J, Boriskin J. The community caries prevention demonstration program: fluoride mouthrinses for grades K-12. CDA J. 1982;10(1):43-47.
Not a controlled study.
Goggin G, O'Mullane DM, Welton H. The effectiveness of a combined fluoride mouthrinse and fissure sealant programme. J Ir Dent Assoc. 1991;37(2):38-40.
Combination.
Grissom DK, Dedenbostel RE, Cassel WJ, Murray RT. A comparative study of systemic sodium fluoride and topical stannous fluoride applications in preventive dentistry. ASDC J Dent Child. 1964. p. 314-322.
Supplements versus topical.
Harris R. Observations on the effect of eight per cent stannous fluoride on dental caries in children. Australian Dental Journal. 1963 Aug;8(4):335-340.
Solution.
Holve S. An observational study of the association of fluoride varnish applied during well child visits and the prevention of early childhood caries in American Indian children. Matern Child Health J. 2008;12 Suppl 1:64-67.
Not a clinical study for differences.
Horowitz HS, Heifetz SB, Meyers RJ, Driscoll WS, Korts DC. Evaluation of a combination of self-administered fluoride procedures for the control of dental caries in a nonfluoride area: findings after four years. J Am Dent Assoc. 1979 Feb;98(2):219-23.
Retrospective study.
Howell CL, Gish CW, Smiley RD, Muhler JC. Effect of topically applied stannous fluoride on dental caries experience in children. J Am Dent Assoc. 1955 Jan;50(1):14-7.
Solution.
Lesher D. Mouthrinsing project. Bull Mich Dent Hyg Assoc. 1976;6(1):13.
Announcement.
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. p. 275-285.
SMFP.
Marks RG, D'Agostino R, Moorhead JE, Conti AJ, Cancro L. A fluoride dose-response evaluation in an anticaries clinical trial. J Dent Res. 1992;71(6):1286-1291.
SMFP.
Marthaler TM. Reduction of caries, gingivitis and calculus after eight years of preventive measures--observations in seven communities. Helv Odontol Acta. 1972 Oct;16(2):69-83.
Observational.
Marthaler TM. Decrease of DMF-levels 4 years after the introduction of a caries-preventive program, observations in 5819 schoolchildren of 20 communities. Helv Odontol Acta. 1972 Oct;16(2):45-68.
Observational.
Nemes J, Bánóczy J, Wierzbicka M, Rost M. Clinical study on the effect of amine fluoride/stannous fluoride on exposed root surfaces. The Journal of Clinical Dentistry. 1992. p. 51-53.
No control for fluoride.
Øgaard B, Alm AA, Larsson E, Adolfsson U. A prospective, randomized clinical study on the effects of an amine fluoride/stannous fluoride toothpaste/mouthrinse on plaque, gingivitis and initial caries lesion development in orthodontic patients. European Journal of Orthodontics. 2006. p. 8-12.
Toothpaste study.
Øgaard B, Larsson E, Henriksson T, Birkhed D, Bishara SE. Effects of combined application of antimicrobial and fluoride varnishes in orthodontic patients. Am J Orthod Dentofacial Orthop. 2001;120(1):28-35.
No baseline for the control group.
Petchel KA, Mello AF. School-based weekly sodium fluoride rinse program. Results after three and one-half years. Clin Prev Dent. 1982;4(2):21-23.
Prevalence.
Purdell-Lewis DJ, Arends J, Groeneveld A. The effect of differing concentrations of SnF2 on demineralized enamel. Caries Res. 1978;12(1):43-51.
In vitro.
Ripa LW. Community- and school-based caries preventive programs. Participation of New York State children. N Y State Dent J. 1985;51(7):408-412.
Description.
Ripa LW, Leske GS, Forte F. The combined use of pit and fissure sealants and fluoride mouthrinsing in second and third grade children: one-year clinical results. Pediatr Dent. 1986;8(3):158-162.
Sealants study.
Ripa LW, Leske GS, Forte F. The combined use of pit and fissure sealants and fluoride mouthrinsing in second and third grade children: final clinical results after two years. Pediatr Dent. 1987;9(2):118-120.
Sealants study.
Ripa LW, Leske GS, Sposato A. The surface-specific caries pattern of participants in a school-based fluoride mouthrinsing program with implications for the use of sealants. J Public Health Dent. 1985;45(2):90-94.
Prevalence study.
78
Shapira J, Stabholz A. A comprehensive 30-month preventive dental health program in a pre-adolescent population with Down's syndrome: a longitudinal study. Spec Care Dentist. 1996;16(1):33-37.
Sealant study.
Sharma U, Jain RL, Pathak A. A clinical assessment of the effectiveness of mouthwashes in comparison to toothbrushing in children. J Indian Soc Pedod Prev Dent. 2004;22(2):38-44.
Plaque scores.
Sledd JL. Applying fluoride varnish to pediatric patients to prevent caries. Northwest Dent. 2007 Jan-Feb;86(1):4, 66.
Letter.
Sterritt GR, Frew RA, Rozier RG, Brunelle JA. Evaluation of a school-based fluoride mouthrinsing and clinic-based sealant program on a non-fluoridated island. Community Dent Oral Epidemiol. 1990;18(6):288-293.
Not a controlled study.
Toolson LB, Smith DE. A five-year longitudinal study of patients treated with overdentures. J Prosthet Dent. 1983;49(6):749-756.
Paper reporting on 2 year caries data included.
Leksell E. Evaluation of three caries preventive methods: a 3-year radiological study in Swedish urban school children with high caries risk. (Abstract). International Journal of Paediatric Dentistry /the British Paedodontic Society [and] the International Association of Dentistry for Children. 2003. p. 49.
Not a fluoride study.
Tewari A, Chawla HS, Utreja AK. Dental caries preventive effect of sodium fluoride and acidulated fluoride phosphate. 1 1/2 years clinical trial. J Indian Dent Assoc. 1983;55(4):133-8.
Fluoride “solution” not currently available.
Schirrmeister JF, Gebrande JP, Altenburger MJ, Mönting JS, Hellwig E. Effect of dentifrice containing 5000 ppm fluoride on non-cavitated fissure carious lesions in vivo after 2 weeks. Am J Dent. 2007 Aug;20(4):212-6.
Two week study.
Shannon IL, St Clair JR, Pratt GA, West DC. Stannous fluoride versus sodium fluoride in preventive treatment of orthodontic patients. Australian Orthodontic Journal. 1978;5(1):18–24.
Incorrect outcomes measure (no data); specialized populations (orthodontic patients that are banded).
Seppä L, Pöllänen L, Hausen H. Caries-preventive effect of fluoride varnish with different fluoride concentrations. Caries Res. 1994;28(1):64-7.
1.13% F varnish not available in U.S.
Packer MW, Laswell HR, Doyle J, Naff HH, Brown F. Cariostatic effects of fluoride mouthrinses in a non-fluoridated community. J Tenn Dent Assoc. 1975 Jan;55(1):22-6.
0.1% APF rinse. head-to-head data
Laswell HR, Packer MW, Wiggs JS. Cariostatic effects of fluoride mouthrinses in a fluoridated community. J Ky Dent Assoc. 1975 Oct;27(4):21-5. Laswell HR, Pacher MW, Wiggs JS. Cariostatic effects of fluoride mouthrinses in a fluoridated community. J Tenn Dent Assoc. 1975 Oct;55(4):198.
0.1% APF rinse. head-to-head data
Baysan A, Lynch E, Ellwood R, Davies R, Petersson L, Borsboom P. Reversal of primary root caries using dentifrices containing 5,000 and 1,100 ppm fluoride. Caries Res. 2001 Jan-Feb;35(1):41-6 Lynch E, Baysan A, Ellwood R, Davies R, Petersson L, Borsboom P. Effectiveness of two fluoride dentifrices to arrest root carious lesions. Am J Dent. 2000 Aug;13(4):218-20.
Too short of follow-up (3 and 6 months); arrests and reversals; did not report outcomes as increments
Kirkegaard E, Petersen G, Poulsen S, Holm SA, Heidmann J. Caries-preventive effect of Duraphat varnish applications versus fluoride mouthrinses: 5-year data. Caries Res. 1986;20(6):548-55.
Duraphat vs. rinse; head-to-head
Seppä L, Pöllänen L. Caries preventive effect of two fluoride varnishes and a fluoride mouthrinse. Caries Res. 1987;21(4):375-9.
Duraphat vs. Fluorprotector vs. rinse; head-to-head
Koch G, Petersson LG, Rydén H. Effect of fluoride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries. Swed Dent J. 1979;3(2):39-44.
Head-to-head
79
Seppä L, Leppänen T, Hausen H. Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical trial. Caries Res. 1995;29(5):327-30.
Head-to-head
Bruun C, Bille J, Hansen KT, Kann J, Qvist V, Thylstrup A. Three-year caries increments after fluoride rinses or topical applications with a fluoride varnish. Community Dent Oral Epidemiol. 1985 Dec;13(6):299-303.
Varnish vs. rinse; Head-to-head
Mellberg JR, Franchi GJ, Englander HR, Mosley GW, Nicholson CR. Short intensive topical APF applications and dental caries in a fluoridated area. Community Dent Oral Epidemiol. 1978 May;6(3):117-20.
Application methods not currently used in practice
Flório FM, Pereira AC, Meneghim Mde C, Ramacciato JC. Evaluation of non-invasive treatment applied to occlusal surfaces. ASDC J Dent Child. 2001 Sep-Dec;68(5-6):326-31, 301.
Head-to-head
Shern RJ, Duany LF, Senning RS, Zinner DD. Clinical study of an amine fluoride gel and acidulated phosphate fluoride gel. Community Dent Oral Epidemiol. 1976 Jul;4(4):133-6.
Application methods not currently used in practice
Pochanugool L, Manomaiudom W, Im-Erbsin T, Suwannuraks M, Kraiphibul P. Dental management in irradiated head and neck cancers. J Med Assoc Thai. 1994 May;77(5):261-5.
Head-to-head
Gallagher SJ, Glassgow I, Caldwell R. Self-application of fluoride by rinsing. J Public Health Dent. 1974 Winter;34(1):13-21.
Product concentrations not available commercially
Heifetz SB, Driscoll WS, Creighton WE. The effect on dental caries of weekly rinsing with a neutral sodium fluoride or an acidulated phosphate-fluoride mouthwash. J Am Dent Assoc. 1973 Aug;87(2):364-8.
0.3% NaF and APF; product concentrations not available commercially
Petersson LG, Arthursson L, Ostberg C, Jönsson G, Gleerup A. Caries-inhibiting effects of
different modes of Duraphat varnish reapplication: a 3-year radiographic study. Caries Res.
1991;25(1):70-3.
Head-to-head
varnish frequency
trial; no control
Weinstein P, Spiekerman C, Milgrom P Randomized equivalence trial of intensive and semiannual
applications of fluoride varnish in the primary dentition. Caries Res. 2009;43(6):484-90. Epub 2009
Dec 10.
Head-to-head
varnish frequency
trial; no control
Seppä L, Tolonen T. Scand J Dent Res. Caries preventive effect of fluoride varnish applications
performed two or four times a year. 1990 Apr;98(2):102-5. Head-to-head
varnish frequency
trial; no control
Axelsson P, Paulander J, Nordkvist K, Karlsson R. Effect of fluoride containing dentifrice, mouthrinsing, and varnish on approximal dental caries in a 3-year clinical trial. Community Dent Oral Epidemiol. 1987 Aug;15(4):177-80.
0.7% F
Fluorprotector
composition no
longer available
van Eck AA, Theuns HM, Groeneveld A. Effect of annual application of polyurethane lacquer containing silane-fluoride. Community Dent Oral Epidemiol. 1984 Aug;12(4):230-2.
0.7% F
Fluorprotector
composition no
longer available
Demito CF, Rodrigues GV, Ramos AL, Bowman SJ. Efficacy of a fluoride varnish in preventing
white-spot lesions as measured with laser fluorescence. J Clin Orthod 2011;45(1):25-9; quiz 40.
Split mouth; 6
month data and
only white spot
lesions (not frank
cavitation)
Milgrom PM, Tut OK, Mancl LA. Topical iodine and fluoride varnish effectiveness in the primary
dentition: a quasi-experimental study. J Dent Child (Chic) 2011;78(3):143-7. Varnish + iodine
vs. varnish alone,
no placebo group
(head to head)
80
Neumann AS, Lee KJ, Gussy MG, et al. Impact of an oral health intervention on pre-school children
< 3 years of age in a rural setting in Australia. J Paediatr Child Health 2011;47(6):367-72. Concentration of
fluoride in
toothpaste not
reported
Patil YB, Hegde-Shetiya S, Kakodkar PV, Shirahatti R. Evaluation of a preventive program based
on caries risk among mentally challenged children using the Cariogram model. Community Dent
Health 2011;28(4):286-91.
Combination of
therapies tested
based on
Cariogram risk
assessment
Wong MC, Lam KF, Lo EC. Analysis of multilevel grouped survival data with time-varying regression coefficients. Stat Med 2011;30(3):250-9.
Fluoride-related
data reported
previously
Divaris K, Rozier RG, King RS. Effectiveness of a school-based fluoride mouthrinse program. J
Dent Res 2012;91(3):282-7. Retrospective
Everett E. Fluoride and caries. Eur J Oral Sci 2011;119 Suppl 1:25-31. Not a trial
Guzman-Armstrong S, Chalmers J, Warren JJ. Ask us. White spot lesions: prevention and
treatment. Am J Orthod Dentofacial Orthop 2010;138(6):690-6. Not a trial
Karademir S, Akcam M, Kuybulu AE, Olgar S, Oktem F. Effects of fluorosis on QT dispersion, heart
rate variability and echocardiographic parameters in children. Anadolu Kardiyol Derg
2011;11(2):150-5.
Not topical
fluorides
Keim RG. Preventing and treating white-spot lesions. J Clin Orthod 2011;45(1):9-10.
Editorial / Not a
trial
Slade GD, Bailie RS, Roberts-Thomson K, et al. Effect of health promotion and fluoride varnish on
dental caries among Australian Aboriginal children: results from a community-randomized
controlled trial. Community Dent Oral Epidemiol 2011;39(1):29-43.
Co-intervention in
experimental arm
that control did
not have
81
Appendix 4 – Study characteristics, bias scores, and outcomes data tables
Table A: Characteristics of studies on 2.26% fluoride varnish
Citation Age Country Special
Population?
Intervention (Dose/duration/frequen
cy) Control
Prior prophylaxis
?
Caries risk
status as stated by authors
Baseline score
Other F exposure for both groups
Specifically recruited
patients with caries experience
?
Follow-up
duration
Outcome measure
Diagnostic criteria
Reported result
Adverse events
Study Design
Primary Dentition Autio-
Gold 2001 35
3 – 5 years
US Children Duraphat every 4
months No Tx
No prophylaxis
Low SES dmfs >
2.5; dmft > 1.98
0.8 ppm water F,
toothpaste No 9 months
dmfs, dmft, ds
Cavitated Significant favoring F
Not assessed
RCT
Clark 1985
31-33
7 Canada Children 1. Durafluor 2.
Fluorprotector every six months
No varnish
Professional Prophylaxis
Not Stated
DMFS < 1;
Baseline dfs not given
Dentifrices, supplemet
s and topical fluoride
No 32
months
DMFS – all teeth and all
surfaces dfs – only first and second molars
Cavitated Significant favoring varnish
Not assessed
RCT
Grodzka 1982
40
3 - 4 Poland Children Duraphat every 6
months No
treatment Pumice
prophylaxis Not stated
dmfs1 > 10
dmfs2>9.3 dmft1>6.5 dmft2>6.3
No topical fluorides
No 2 years
dmfs and dmft – all teeth and surfaces
Cavitated WSL
Significant favoring
Duraphat for WSL dmft
ONLY
Not assessed
GCCT (not adjusted for clustering)
Gugwad, 2011
39
6-7 years
India No
(children)
Cavity Shield (reportedly 5% NaF); 3 times a
week (once every two days in a week), once a
year; OHI at baseline
No treatment; OHI at baseline
Yes Not stated
defsp 5.3-5.5
defs 5.6-5.7
DMFS=0.4-0.7
Primary
defs Control:
5.63 Varnish:
5.67 p=0.95
Not reported
No 1 year
deft and defs; deftp and defsp
for posterior teeth;
DMFT and DMFS
WHO criteria,
including bitewings
Primary defs Control:
6.52 Varnish:
4.68
Increments Control:
0.89 Varnish: -
0.99 p=0.03
Statistically
favors varnish for
primary teeth/surfaces and no difference
for permanent teeth/surfac
es *Note that in
discussion
Not reported
RCT
82
section the authors note
that many children did
not have erupted molars,
which may have
affected the permanent
teeth results
Hardman 2007
36
6-8 United
Kingdom Children
Duraphat every 6 months
No varnish
Unclear
Not stated
“Relatively deprived communit
y”
“Prevalence and
severity of caries…is among the
worst in the
country”
d3ft > 2 dfs not given
F milk; Fl toothpaste
Non-
fluoridated community
No (but post-hoc
per baseline score)
26 months
dfs – primary
molars all surfaces
WS and cavitated
Non-significant difference for large WSL and dentine lesions;
significant for small
WSL
Not assessed
GRCT (adjusted)
Holm 1979
41
3 Sweden Children Duraphat every six
months No
treatment
Brushing with special
powder Not stated ds < 1.5
F toothpaste; Some had
Fl supplemen
ts
No 2 years defs – All
teeth
Cavitated and WSL separatel
y
Significant favoring Duraphat
Not assessed
CCT
Lawrence 2008
37
6 months
to 5 years
Canada Children Duraflor every 4- 6
months + counseling
Caregiver Counselin
g Unclear
High-risk (aboriginal children)
dmft > 6 No F water No 2 years dmfs – all
teeth and all surfaces
All stages Significant favoring F
varnish
None reported; one child allergic to
lanolin
GRCT (adjusted
data)
Weintraub 2006
38
6 – 44 months
US Children
low income
1. Duraphat + parental counseling 2x/year 2. Duraphat + parental counseling annual
Parental counselin
g
No
prophylaxis Not Stated ds = 0
F toothpaste
and F water
No (caries-free)
2 year dfs – all
teeth and all surfaces
Cavitated and all stages
Significant favoring varnish
None observed
RCT
Permanent Dentition
Arruda 2012
42 7-14 Brazil Children
Cavity Shield (5% NaF or 2.26% F); tested
application 1 and 2 times per year combined
Placebo varnish
Toothbrushing
None
DFS Test – 6.15
Control – 5.59
58.4% and 59.7% of Test and Control
received Fluoridated
water
No 12
months
DFS Prevented
fraction
ICDAS 1 and
above
Either 1 or 2 applications (combined)
stat sig better than placebo; post hoc analysis only 2
applications stat sig
better than placebo
None were reported; no participant removed owing to
complications
associated with varnish application
RCT
Bravo 1997
43, 44,
116
6 - 8 Spain Children Duraphat every 6
months No
varnish Unclear Not Stated DMFS < 1
Not investigate
d No
4 years (2 year
data available)
DMFS – first
permanent molar all surfaces
Cavitated Significant in favor of
varnish
Not assessed
GRCT (molar is the
unit of analysis and adjustment for this BUT allocation by
83
school class)
Clark 1985
31-33 7 Canada Children
1. Durafluor 2. Fluorprotector every six
months
No varnish
Professional Prophylaxis
Not Stated
DMFS < 1;
Baseline dfs not given
Dentifrices, supplemet
s and topical fluoride
No 32
months
DMFS – all teeth and all
surfaces dfs – only first and second molars
Cavitated Significant favoring varnish
Not assessed
RCT
Holm and Holst
1984 45
5 years and 9 month
s
Sweden Children Duraphat every 6
months No
treatment
Toothbrush with special cleansing
powder and water
Not Stated
dmfs > 8
NEWLY ERUPTING FIRST MOLARS DMFS=0
Weekly rinsing with 0.2% NaF, 0.4 – 0.9
ppm Water F
No
2 years after
eruption of
permanent first molar
DS - Occlusal
surfaces of first
permanent molars
Cavitated Significant Favoring F
varnish
Not assessed
RCT (patient was
unit of randomization but looks like results
are reported for molars)
Ibricevic 2005
53 6-15 Kuwait
Children (data for special needs
available)
Duraphat every 6 months
No varnish
Unclear High SES
DMFT < 1 (Healthy) DMFT <
1.5 (Special needs)
Unclear No 2 years DMFT – all
teeth and all surfaces
Cavitated
Non-significant for healthy children;
Significant favoring fluoride
varnish for special needs
Not assessed
CCT
Koch 1975
46 15 Sweden
Adolescents
Duraphat every 6 months
No treatment
Pumice prophylaxis
High risk DMFS >
20
F rinse every 2 weeks
No (post-hoc based on baseline
score)
1 year DMFS – all teeth and all
surfaces
Cavitated and WSL
Significant favoring varnish
(mainly for low and medium
risk)
Not assessed
RCT
Milsom 2011
47
7-8 yrs.
England School children
0.1ml Duraphat (5% NaF) 3 X yr. on
permanent 1st molars
Yes- no
treatment No High Risk No
No water fluoridation
No 3 yrs.
DFS (primary)
DFT (secondary)
cavitation
No statistically
different difference
between the groups
12 children in
intervention group
reported adverse reactions
(full details online)
GRCT; 95 clusters in
each tx
Modeer 1984
48 14 Sweden
Adolescents
Duraphat every three months
No treatment
Pumice prophylaxis
Not Stated DFS > 2
Weekly F rinse, Low F water; F toothpaste
s
No (post-hoc based on baseline
score)
3 years
DFS – premolars and molars
proximal surfaces
All stages,
Cavitated and WSL
Significant favoring varnish; different
with baseline risk
Not assessed
RCT
Skold 2005
49 13 Sweden Children
Duraphat every 6 months, 3 times a year
within one week, 8 times per year at 1 month
intervals during school year
No varnish
Self brushing without paste
Low, Medium and High based on
SES, caries and
water F
DFT – 0.6 – 2.65
Optimal water F in low risk
area. Low water F in medium and high
risk areas. 95% in all
groups were
No (Varied by SES
and water F)
3 years
DS – proximal surfaces
from distal of canine to
mesial of second molar
(radiographic)
All stages,
WSL and cavitated separatel
y
Significant favoring varnish
None observed
RCT
84
treated with one F varnish at the yearly check-up.
Fl toothpaste
Schaeken50
44.4 Netherlan
ds Adults
Duraphat every 3 months
No varnish
Professional Prophylaxis
Unclear > 60 root lesions
Varied Yes 1 year RCI All Stages Significant favoring varnish
None observed
RCT
Tagliaferro, 2011
54 6-8 Brazil Children Duraphat biannually
No varnish
No; Supervised
tooth brushing
Low and high risk
High risk dmft > 4.3; DMFT>0.2
6
Low risk dmfs +
DMFS=0
Fl water; Fl Tooth
paste Yes 2 years
DMFS permanent first molar
only
Cavitated and WSL
Not significant
Not assessed
CCT
Tan 2010
51 78.8
Hong Kong
Nursing home
residents
OHI + Duraphat every three months
OHI No
prophylaxis Not Stated
DFS (Root) > 2
Unclear No 3 years
RCI New
caries or fillings –
remaining teeth
Cavitated Significant favoring
NaF + OHI
None observed
RCT
Tewari 1990
52 9-12 India Children
2.26 % Duraphat for 4 min every 6 months
Placebo varnish of
double distilled water
Professional Prophylaxis
Not Stated DMFS > 2 Low water
F No 2.5 years
DMFS and DMFT – all
teeth and all surfaces
All stages Significant
favors Varnish
Not assessed
RCT
Combined Dentition
Shobha 1987
55 9 - 12 India Children
Six monthly applications of Duraphat
No varnish
Professional Prophylaxis
without F Not Stated
DMFS/dmfs > 10
Low water F
No 3 years DMFT/dmft; DMFS/dmfs – all teeth
Cavitated Significant favoring varnish
Mild burning, pungent odor and
nausea with APF
CCT
85
Table B: Risk of bias assessment of studies on 2.26% fluoride varnish
Citation Risk of
bias score
Were patients in both arms recruited from the
same population
at the same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects
assignment sequence
before and until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) –
Examiner, patient and statistician)
Rate of losses to follow-up similar
between tx groups
Baseline caries
status of those lost to
follow-up similar to
those remaining
Baseline caries status similar between tx
groups at end of study or
adjustment for confounding
Sample size
estimated apriori
Intention to treat used?
Conflict of
Interest absent?
Primary Dentition
Autio-Gold 2001
35
6 Yes Yes No Yes Yes Yes Unclear Unclear No No Yes
Grodzka 1982
40
2 Yes No No No No Unclear Unclear Unclear No No Yes
Gugwad 2011
39
4 Yes Yes No No Unclear Yes Unclear Unclear Unclear Unclear Yes
Hardman36
7 Yes Yes Yes Unclear Examiner Yes Unclear Yes Yes No No
Holm 1979
41
5 Yes No No No Examiner Yes No Yes No No Yes
Lawrence 2008
37
9 Yes Yes Yes Unclear Examiner Yes (ITT) Unclear Yes Yes Yes Yes
Weintraub 2006
38
11 Yes Yes Yes Yes
Examiner and patient
Yes Yes Yes Yes Yes Yes
Permanent Dentition
Arruda42
8
Yes Yes Yes No Examiner and
patient Yes Unclear Yes Yes No Yes
Bravo43, 44,
116
5 Yes Yes No Unclear Examiner Unclear Unclear Yes No No Yes
Clark31-33
7
Yes Yes No Unclear Examiner and
patient Yes Yes Yes No No Yes
Holm and Holst
45
4 Yes Yes No Unclear Unclear Unclear Unclear Yes No No Yes
Ibricevic 2005
53
2 Yes No No No No Unclear Unclear Unclear No No Yes
Koch 1975
46
4 Yes Yes No No unclear
Yes (min LOF)
Unclear Unclear No Unclear Yes
Milsom 2011
47
10 Yes Yes Yes Yes Yes Yes Unclear Yes Yes Yes Yes
Modeer 1984
48
5 Yes Yes No No Examiner No Unclear Yes No No Yes
Skold 2004
49
6 Yes
Yes within cohorts
Unclear Unclear Provider and
examiner Yes Unclear Yes No No Yes
Schaeken50
7 Yes Yes No Unclear Patient and Yes (no Yes Yes No NA No
86
examiner loss)
Tagliaferro, 2011
54
7 Yes No No No Examiner Yes Yes Yes Yes No Yes
Tan 201051
11 Yes Yes Yes Yes Examiner Yes Yes Yes Yes Yes Yes
Tewari 1990
52
7 Yes Yes No Unclear Examiner
Yes (min loss)
Yes Yes No No Yes
Combined Dentition
Shobha 1987
55
6 Yes No No Unclear No
Yes (min loss)
Yes Yes No NA Yes
Table C: Outcomes data from studies on 2.26% fluoride varnish
Citation Outcome measure (permanent/primary;
surfact/tooth; outcome; all stages/ws/cavitated)
Exp mean
Exp SD Exp n Control mean
Control SD Control
n Other available data
Primary Dentition
Autio-Gold 2001 35
Caries prevalence dmfs – cavitated – 9-
month data 3.05 4.25 59 4.05 4.40 83
Use Table 1 data (cavitated); 9-month data;
Data for all stages including WSL available (in Table 2)
Caries increment dmfs – cavitated –
calculated (baseline to 9 months) 0.54 4.1 59 1.47 4.0 83
Caries increment dmft – cavitated – 9-
month data 1.68 2.27 59 2.57 2.28 83
Clark Cavitated increment assumed dfs – 32
months 1.49
2.36 245 2.06
2.82 234
SD calculated from Cochrane equation in Clark 1985; noted difference not stat sig
Grodzka 1982 40
Net dmfs increment - cavitated 6.35 4.98 148 6.71 5.22 100
Radiographic data.
Net dmft increment - cavitated 2.04 1.98 148 2.46 2.13 100
Net dmfs increment – WSL 6.24 4.75 148 6.89 5.08 100
Net dmft increment – WSL 1.91 2.04 148 2.51 2.20 100
Gugwad 201139
defs, 1 year BEFORE 5.67 5.40 106 5.63 4.02 105
OHI-S; deftp, deft, DMFT
defs, 1 year AFTER 4.68 4.95 106 6.52 7.31 105
87
defs, change (calculated) -0.99 5.2 106 0.89 6.3 105
Hardman 200736
dfs caries increment – WSL (d1fs) 0.71 1.57 334 1.12 2.02 330 MA; wsl = d2fs+d1fs; proportion of children with caries
increment in permanent dentition
dfs caries increment – cavitated (d3fs) 1.52 2.39 334 1.49 2.36 330 calculated SD using Cochrane equation
already adjusted for clustering
Holm 197941
Net defs increment-Cavitated 2.10 2.75 112 3.74 4.62 113
Surface specific data; prevalence data in table 4
Net WSL(primary, surface) increment 0.81 2.56 112 0.92 3.07 113
Lawrence 200837
Mean net caries increment – dmfs all stages; Adjusted means, Aboriginal
children only 11.00 31 832 13.48 31 328
Unadjusted means available for intent-to-treat population; stratification by age group.
SD calculated from adjusted difference column in Table 3 of paper according to
SD = SE/(sqrt(1/832 + 1/328))
Weintraub 2006 38
dfs Incidence – cavitated – ITT group, 2x/year
0.7 2.1 87 1.7 3.1 100
1 application over 2 years; 3-4 applications over 2 years; Intended treatment group
dfs incidence- all stages – ITT group 2x/year
1.4 3.1 87 2.7 3.4 100
Permanent Dentition
Arruda42
DFS increment, one and two
applications combined 4.61
95% CI (3.54-5.67)
Calculated 4.39
113 7.72
(6.26-9.18)
Calculated 5.84
97
Prevented fraction, adjusted and unadjusted generalized linear models
Children who received one or two applications
SD calculated from Cochrane equation
Bravo 1997 43, 44, 116
DMFS caries increment – fissure cavitated)
1.33 1.82 98 2.13 2.06 116 Fissured vs non-fissured surfaces
DMFS caries increment – smooth (cavitated)
0.15 0.83 98 0.45 1.22 116 Fissured vs non-fissured surfaces
Calculated: Total fissure and smooth DMFS caries increment, cavitated
1.48 1.53 98 2.58 1.89 116 Fissure and smooth means added; SD for sum increment calculated via: Cochrane formula for
combining groups
88
CLUSTER ADJUSTED (all significant at all adjustments; picked conservative
ICC=0.2) 1.48 1.53 27 2.58 1.89 32 Used this in MA
Clark 198531-33
DMFS caries increment Duraflor-
Cavitated assumed 2.43 3.7 246 3.11 3.7 234
Surface specific data; 32 month data used but 56 month data available
SD calculated from p value in Clark 1985
Holm and Holst 1984 45
DS of first molars; Assumed prevalence, Cavitated
DECIDED SHOULD BE TOOTH-LEVEL DATA SINCE ONLY 1 SURFACE
1.44 2.32 50 3.29 3.65 59
Proximal only, occlusal only, depth of fissure, time to caries from eruption
Use Cochrane regression equation to impute SD
Ibricevic 200553
DMFT caries increment - cavitated 0.35 0.69 43 0.47 1.13 34 Special Needs
Koch 197546
Net DMFS increment cavitated 0.9 3.80 60 4.0 3.75 61 By baseline prevalence and surface specific data
available. By caries risk also available. Net WSL (surface) increment 0.5 3.56 60 1.3 2.58 61
Milsom 201147
DFS mean cavitated increment
DFT mean cavitated increment
DFS 0.65 DFT 0.36
2.15 0.91
1270 DFS 0.67 DFT 0.35
2.10 0.90
1320
Cluster DFS data 0.66 0.73 94 0.63 0.66 95
Cluster DFT data 0.36 0.35 94 0.33 0.30 95
Modeer 1984 48
DFS increment – cavitated [03+F] (by
subtracting prevalence at baseline from
prevalence at 3 years)
1.4 2.3 87 2.0 2.8 107
Scores separately for each stage available; progression data available; Progression data by caries
acitivity
SD for increment imputed via Cochrane regression equation (2009)
Used in MA – 3-year DFS (proximal
surfaces on premolars and molars)
Decayed 03 plus Filled
2.5 3.1 87 3.7 3.9 107 Baseline not subtracted to be consistent with other
studies (Autio-Gold and Petersson 1991); Cochrane regression equation for SD
Skold 200449
Permanent approximal surface-Caries
incidence – all stages, application frequency = every 6 months
0.79 1.67 190 1.85 2.89 181 By risk category; by different intervals and caries
prevalence by WSL and cavitated
89
Schaeken 1991 50
Root Caries increment surface cavitated 0.67 0.80 15 1.54 0.80 13 Calculated from p value in paper
Tagliaferro, 201154
Caries increment DMFT cavitated (high
risk) Occlusal surfaces only 0.29 0.68 48 0.39 0.72 44
WSL data available; combined data available
Caries increment DMFT all stages (high
risk) – Occlusal surfaces only 0.31 0.69 48 0.27 0.90 44
Caries increment DMFT cavitated (low
risk) Occlusal surfaces only 0.09 0.29 43 0.12 0.40 42
Caries increment DMFT all stages (low
risk) – Occlusal surfaces only 0.09 0.29 43 0.14 0.42 42
Caries increment all risks, all surfaces 0.33 1.04 91 0.57 1.39 86
Tan 201051
Caries incidence – Root-Cavitated root
surfaces 0.9 2.10 49 2.5 3.71 55
Tewari 199052
DMFS – caries increment - all stages 0.554 4.58 311 2.163 4.12 307 Surface specific data; Teeth present at baseline vs
erupted during study DMFT – caries increment - all stages 0.383 2.61 311 1.47 2.26 307
Combined Dentition
Shobha 198755
DMFT + dmft – caries increment– all stages – at 3 years
3.72 1.99 195 6.89 3.33 195
DMFS + dmfs – caries increment– all stages – at 3 years
5.55 2.53 195 10.36 3.86 195
90
Table D: Characteristics of studies on 0.1% fluoride varnish
Citation Age Country Special
Population?
Intervention
(Dose/duration/frequency) Control
Prior
prophylaxis?
Caries
risk
status as
state d
by
authors
Baseline
score
Other F
exposure for
both groups
Specifically
recruited
patients with
caries
experience?
Follow-
up
duration
Outcome
measure
Diagnostic
criteria
Reported
result
Adverse
events
Study
Design
Zimmer
200158
9 –
12
years
Germany Children
Fluorprotector every 4
months + oral hygiene
instruction
Oral
hygiene
instruction
Professional
Fluoridated
prophylaxis
paste
High-risk
dmft and
DMFT >
0
Unclear Yes 2 years DMFS
WSL, All
stages and
Cavitated
Significant
for smaller
lesions
Not
assessed RCT
Twetman 1996
57
4 - 5 Sweden Children Fluorprotector every 6
months No varnish
Pumice prophylaxis
Not low risk
dfs 0.18-1.0
0.1 ppm water F, used F toothpaste and some got
F tabs
No 2 years dfs, dft,
dfsa Cavitated
Significant favoring F
Not assessed
GCCT
Petersson
1998 56
4 - 5 Sweden Children
Fluorprotector every 6
months No varnish
Pumice
prophylaxis
and floss
Low
caries
risk
dfs>1
0.1 ppm
water F for
most; 10% in
1.2 ppm F
area, used F
toothpaste
and some got
F tabs
No 2 years dfs Cavitated Not
significant
Not
assessed GCCT
91
Table E: Risk of bias assessment of studies on 0.1% fluoride varnish
Citation Summary
risk of bias score
Were patients in both arms recruited from the
same population at
the same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects
assignment sequence
before and until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) –
Examiner, patient and statistician)
Rate of losses to follow-up similar
between tx groups
Baseline caries
status of those lost to
follow-up similar to
those remaining
Baseline caries status similar between tx
groups at end of study or
adjustment for confounding
Sample size
estimated apriori
Intention to treat used?
Conflict of
Interest absent?
Zimmer 2001
58
6 Yes Yes Yes Unclear Unclear No Yes Yes Unclear No Yes
Twetman 1996
57
2 No No No No Unclear
Yes (min loss)
Unclear Unclear No No Yes
Petersson
1998 56
2 No No No No Unclear No Yes Unclear No No Yes
Table F Outcomes data from studies on 0.1% fluoride varnish
Citation Outcome measure (permanent/primary;
surface/tooth; outcome; all stages/ws/cavitated)
Exp mean
Exp SD Exp n Control mean
Control SD
Control n
Other available data
Zimmer 200158
Mean increment – DMFS All stages 6.18 3.92 187 9.14 4.50 131
Prevalence data available Mean increment – DMFS WSL 3.96 4.97 187 6.53 5.71 131
Mean increment – DMFS Cavitated 2.22 2.49 187 2.61 2.85 131
Twetman 199657
Caries incidence – dfs--Cavitated 1.07 1.96 442 1.53 2.55 374
Approximal data; high F area
Caries incidence - dft--Cavitated 0.65 1.40 442 1.09 1.85 374
Petersson 1998 56
Caries incidence – dfs--Cavitated 1.30 2.46 2245 1.39 2.66 1916 Approximal data
92
Table G: Characteristics of studies on professionally-applied 1.23% fluoride (APF) gel
Citation Age Country Special
Population?
Intervention (Dose/duration/
frequency) Control
Prior Prophyl
axis
Caries risk
status as state d by authors
Baseline score
(approximate)
Other F exposur
e for both
groups
Specifically recruited patients
with caries experience
?
Follow-up duration
Compliance
Outcome measure
Diagnostic criteria
Reported result
Adverse events
Study Design
Agrawal 2011
70
9-16 years; mean age
experimental
group was
12.83, and
control was
12.94
India
High risk school
children (underprivil
eged)
1.23% APF gel (Fluorovil) + oral health education at baseline; gel
applied at baseline and 6 months for 4
minutes
No intervention + oral
health educatio
n at baseline
Assume No
“High risk”; “underprivileged”; “low
SES”
4.01 for gel
group; 4.30 for control (DMFS)
Few regularly
using fluoride
dentifrice
Yes
6 and 12
months
Professionally applied
DFMT, DMFS, IL (incipient lesion)
All stages
No statistically significant
differences at 12 months in
cavitated data; (statistically significant difference,
improvement for gel group, in IL at 6 and 12
months)
None were
reported
GRCT, n=1
cluster per
intervention
Jiang and Tai 2005
65
6 – 7 China Children 1.23% APF for 4 minutes gel every
6 months No Tx
No professio
nal prophyla
xis
Not Stated DMFS >
7 Low
water F No
2 years
Professional
application
DMFS – first molar
Cavitated
Significant favoring F for
smooth surfaces only
None observed
GRCT (by class and not
adjusted)
Hagan 1985
63
11 - 15 Unites States
Children 1.23% APF gel for 4 minutes
every 6 months
Placebo gel (no F or acid)
Professional brush and floss with no paste
Not stated DMFS >
4
Low water F; Some
children received professio
nally applied fl
from regular dentists
No 2
years
Professional
application
DMFS – all teeth
Cavitated Statistically significant favoring F
3 episodes
of nausea
or vomiting
RCT
Trubman 1973
68
8.12 United States
Children
1.23% APF gel for 4 minutes +
nonfluoride prophylaxis paste four times during
school year
Placebo gel (non
F) + nonF
prophy paste
Self brushing
with prophylaxis paste
Not Stated DMFS >
2 Low
water F No
3 years
Self-applied
at school
DMFT, DMFS – all
teeth Cavitated
Significant favoring F
Not assesse
d RCT
Horowitz 1968, 1969,
197172-74
10-12 (grades
5-6)
United States
Children 1.23% APF gel for 4 minutes
annually Prophy
Prophy with
standard paste (no fluoride)
Unclear DMFS >
8 Low
water F No
3 years
Professionally applied
DMFS –all teeth
Cavitated Significant favoring F
None observed
CCT
Bryan 1968
59,
1970 60
8 - 12
United States
Children
Single application of Phosphate fluoride gel
(1.23% APF) for 4 minutes +
prophylaxislaxis
Prophy Prophy Unclear DMFS >
5 Low
water F No
2 years
Professionally applied
DMFS, DMFT – all
teeth Cavitated
Significant favoring F
Not assesse
d RCT
93
Ingraham 1970
64
6 - 11 United States
Children
1. prophylaxis + APF gel for 4
minutes single application
No treatmen
t Prophy Unclear
DMFS > 2
Low water F; Unclear
dentifrice exposure
No 2
years
Professionally applied
DMFS, DMFT – all
teeth Cavitated
Significant favoring F
Not assesse
d RCT
Cons 1970 62
6 - 11
Unites States
Children
1.23% APF gel for 4 minutes+
prophylaxis annually
Prophy+ water
Pumice Prophy
Unclear DMFS >
2 No water
F No
3 years
Professionally applied
DMFS, DMFT - all teeth and surfaces for 1M
Cavitated Significant
favoring APF
Not assesse
d RCT
Wallace 1993
69
60 United States
Seniors
1.2 % APF gel for 4 minutes (Luride) +
placebo rinse semi-annual
Placebo rinse
Yes-sonic scaler
Unclear (root
caries prevalence of 69.7%)
DS > 1
F water and F
toothpaste
No 4
years
Professionally applied
Root caries DMFS (Katz)
Cavitated Significant favoring F
Not assesse
d RCT
Olivier 1992
67 6 Canada Children
1.23% APF 4 minute gel bi-
annual (every 6 months)
Non-F Placebo
gel
No
prophyla
xis High-risk defs > 20
F Toothpas
te
Yes (High and very-
high)
2 years
Professionally applied
DMFS – all teeth
All stages Not significant Not
assessed
RCT
Cobb 1980 61
11 - 14 US Adol-
escents
1.23% APF gel 4 minutes every 6
months
No treatmen
t
Professional
brushing/floss
Unclear DMFS >
5 Low
water F No
2 years
Professionally applied
DMFS – all teeth
Cavitated Significant Favoring F
Not assesse
d RCT
Shobha 1987
55 9 - 12 India Children
Semi-annual applications
of1.23% APF gel No gel
Professional
prophylaxis with nonF paste
Not Stated DMFS/dmfs >10
Low water F
No 3
years
Professionally applied
DMFT/dmft;
DMFS/dmfs – all teeth
Cavitated
Significant favoring Naf
and APF compared to
control
Mild burning, pungent odor and nausea
with APF
CCT
Andruskeviciene 2008
71
3 - 7 Lithuani
a Children
Toothbrushing with F paste OR 1.23% APF gel every 4 months
No tx Unclear Unclear dmft > 3 F
toothpaste
No 3
years
Professionally applied
dmft and dmfs
Cavitated Significant
favoring APF
Not assesse
d CCT
Mainwaring 1978
66 11 - 12 UK Children
1.23% APG gel semi-annually for 4 min + brushing with NonF paste
NonF Gel +
brushing with no-F
paste
Self-brushing
Unclear DFS > 5 Water F
< 0.3ppm No
3 years
Professionally applied
DFS – all teeth and surfaces
cavitated Significant favoring F
Not assesse
d RCT
Szwejda 1971
75 7 - 8 US Children
1.23% APF annual for 3
minutes No gel
Pumice prophyla
xis Unclear DFS < 2 No No
2 years
Professionally applied
DFT, DFS – all teeth
and surfaces
Cavitated Nonsignificant Not
assessed
CCT
94
Table H: Risk of bias assessment of studies on professionally-applied 1.23% fluoride (APF) gel
Citation Summary risk of bias score
Were patients in both arms
recruited from the same
population at the same
time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects
assignment sequence before
and until allocation)
Blinding (ascertainment bias, protects sequence after allocation) – Examiner, patient and statistician)
Rate of losses to follow-up
similar between tx
groups
Baseline caries status of those lost to follow-up
similar to those
remaining
Baseline caries status similar between tx
groups at end of study or
adjustment for confounding
Sample size estimated
apriori
Intention to treat used?
Conflict of Interest absent?
Agrawal 201170
7 Yes Yes Yes Unclear Examiner Yes Unclear Yes No No Yes
Jiang 2005 65
7 Yes Yes Yes No Examiner No Unclear Yes Yes No Yes
Hagan 198563
7 Yes Yes No Unclear Examiner and
patient Yes Yes Yes No No Yes
Trubman 1973 68
7 Yes Yes No Unclear Examiner and
patient Yes Yes Yes No No Yes
Horowitz 1968, 1969, 1971
72-74
7 Yes Yes Yes No Unclear Yes Yes yes No No Yes
Bryan 1969, 1970 60
6 Yes Yes Yes Unclear Unclear Unclear Yes Yes No No Yes
Ingraham 1970 64
6 Yes Yes No unclear Examiner Yes unclear Yes No No Yes
Cons 1970 62
7 Yes Yes No Unclear Examiner Yes Yes Yes No No Yes
Wallace 1993 69
6 Yes Yes No Unclear Examiner Yes Unclear Yes No No Yes
Olivier 1992 67
7 Yes Yes No No Provider and
examiner Yes Yes Yes No No Yes
Cobb 1980 61
5 Yes Yes No Unclear Examiner Yes Unclear Unclear No No Yes
Shobha 198755
5 Yes No No Unclear No Yes (min
loss) Yes Yes No No Yes
Andruskeviciene 2008
71
4 Yes No No Unclear Unclear Yes (min
loss) Unclear Unclear No NA Yes
Mainwaring 1978
66
5 Yes Yes No Unclear Examiner and
patient unclear Unclear Yes No No Yes
Szwejda 197175
3 Not clear Not stated No No Examiner Not
stated Not stated Yes No No Yes
95
Table I: Outcomes data from studies on professionally-applied 1.23% fluoride (APF) gel
Citation Outcome measure Exp mean Exp SD Exp n Control mean Control SD Control n Other available
data
Primary Dentition
Andruskeviciene 2008
71
dmft increment cavitated
0.55 0.43 118 1.41 0.94 137
dmfs increment cavitated
0.68 0.65 118 1.92 0.94 137
Permanent Dentition
Agrawal 201170
DMFS – as reported
(12 months) 4.32 1.439 120 4.63 1.484 119
IL data, 6 month data
Jiang and Tai 2005
65
Mean DMFS increment –cavitated
0.38 0.69 200 0.50 0.87 221 Smooth surface
and P and fissure reported
Hagan 198563
Mean DMFS
increment cavitated 3.08 3.85 108 4.40 3.86 103
Smooth surface and P and fissure
reported
Trubman 1973 68
Mean DMFS increment cavitated
2.74 3.13 145 4.21 4.12 166
Reversals Mean DMFT
increment cavitated 1.29 1.57 145 1.67 1.67 166
Horowitz 1968, 1969, 1971
72-74
Mean DMFT increment cavitated
3.06 2.97 182 3.62 3.00 170
Surface type; reversal
Mean DMFS increment cavitated
6.51 6.75 182 8.61 7.95 170
Bryan 1969, 1970 60
Mean DMFT increment cavitated
2.01 2.54 103 3.63 3.33 105
Mean DMFS increment cavitated
4.56 4.50 103 7.26 4.76 105
Ingraham 1970 64
Mean DMFS increment cavitated
1.84 2.24 56 3.13 2.70 63
Mean DMFT increment cavitated
0.84 1.05 56 1.76 0.79 63
Cons 1970 62
Mean DMFT increment Cavitated
1.50 1.67 278 1.99 1.94 311
Mean DMFS increment - Cavitated
3.14 3.83 278 3.82 5.11 311
96
Wallace 1993 69
DMFS increment-
Cavitated 0.27 2.71 147 0.91 2.99 171
Reversed lesions, new lesions
Olivier 1992 67
DMFS increments –
All stages 2.94 3.09 224 3.24 3.13 207
Surface level data available
Cobb 1980 61
DMFS increment –
cavitated 5.28 0.66 115 8.15 0.87 78
Shobha 198755
DMFT + dmft – Caries Increment- all
stages 4.86 2.58 195 6.89 3.33 195
DMFS + dmfs caries increment – all
stages 7.45 3.01 195 10.36 3.86 195
Prevalence data available
Mainwaring 197866
Net DFS increment
cavitated 7.10 5.62 315 8.27 6.62 316 Reversals
Szwejda 197175
Caries incidence DMFT cavitated
1.23 1.22 148 1.27 0.75 170
Caries Incidence DFS Cavitated
2.07 2.43 148 2.15 2.22 170
Table J: Characteristics of studies on 1.23% fluoride (APF) foam
Citation Age Country Special
Population?
Intervention (Dose/duration/
frequency) Control
Prior prophylaxis?
Caries risk
status as
stated by
authors
Baseline score
(approximate)
Other F exposure for both groups
Specifically recruited patients
with caries experience?
Follow-up
duration Compliance
Outcome measure
Diagnostic criteria
Reported result
Adverse events
Study Design
Jiang and Tai 2005
65
6 – 7 China Children
1.23% APF Foam for 4
minutes every 6 months
No Tx No
prophylaxis Not
Stated DMFS > 7
Low
water F No 2 years
Professional application
DMFS – first
molar Cavitated
Significant favoring F for smooth surfaces
only
None observed
GRCT (by class and not
adjusted)
Jiang and Bian
200577
3-4 years
China Children
1.23% APF foam for 4
minutes every 6 months
Placebo No
prophylaxis Not
Stated dmfs > 2
22% F toothpaste; low water
F; no community programs
No 2 years Professional application
dmfs – all teeth and
all surfaces
Cavitated
Significant favoring
approximal surfaces
only
None observed
GRCT (p values at cluster level)
97
Table K: Risk of bias assessment of studies on 1.23% fluoride (APF) foam
Citation Summary risk of bias
score
Were patients in both arms recruited from
the same population at the same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects
assignment sequence before
and until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) –
Examiner, patient and statistician)
Rate of losses to follow-up
similar between tx
groups
Baseline caries status of those lost to follow-up similar to
those remaining
Baseline caries status similar between tx
groups at end of study or
adjustment for confounding
Sample size estimated
apriori
Intention to treat used?
Conflict of Interest absent?
Jiang and Tai 2005
65
7 Yes Yes Yes No Examiner No Unclear Yes Yes No Yes
Jiang and Bian
200577
9 Yes Yes Yes Yes Examiner and
patient Yes Unclear Yes Yes No Yes
Table L: Outcomes data from studies on 1.23% fluoride (APF) foam
Citation Outcome measure Exp mean Exp SD Exp n Control mean Control SD Control n Other available
data
Jiang and Tai 2005
65
DMFS increment – permanent first molar cavitated
0.39 0.65 191 0.50 0.87 221 Smooth surface
and Pit and fissure caries
Jiang and Bian 2005
77
dmfs Increment Cavitated
3.8 0.9 167 5.0 1.0 151 By tooth surfaces
98
Table M: Characteristics of studies on prophylaxis pastes containing fluoride
Citation Age Country Special
population? Intervention (Dose/duration/
frequency) Control
Caries risk
status as
stated by
authors
Baseline score
(approximate)
Other F exposure for both groups
Subjects included based on
presence of caries
experience?
Follow-up
duration
Outcome measure (record smooth vs. pit
and fissure)
Diagnostic criteria
Reported result
Adverse events
Study Design
Peterson 1969
80
10 - 13 United States
Children APF paste applied annually with a
rubber cup
Annual pumice
prophylaxis Unclear DMFS >4
Two data sets with
fluoridated and non-
fluoridated communities
No 2 years
DMFS, DMFT – all teeth
and surfaces
Cavitated Nonsignificant
difference Not
assessed RCT
Barenie 1976
81
9 - 14 Unites States
Children Semiannual prophylaxis with APF paste for 4 minutes for two years
Placebo paste
Unclear DMFS > 5 Low fluoride
area No 2 years
DMFS, DMFT, all teeth and
all surfaces
Cavitated Nonsignificant
difference Not
assessed CCT
Schutze 1974
83
3 - 5 United States
Children APF paste (Luride) for 4 minutes
every 6 months
Pumice prophylaxis
every 6 months
Unclear defs > 2 Fluoridated
Water No 2 years
defs – all teeth and surfaces
Cavitated Nonsignificant
difference Not
assessed CCT
DePaola 1973
79
10 - 13 United States
Children
1.26% fluoride ion from ammonium fluorosilicate prophylaxis paste
(Luride) applied semiannually for 4 mins
Placebo paste
Unclear DFS > 6 Fluoridated dentifrice
No 2 years
DFS, DFT – all teeth and surfaces
Cavitated Significant difference favoring F
Not assessed
RCT
Horowitz 1966
82
8 - 10 United States
Children 8.9% SnF prophylaxis paste for 4
minutes Lava
pumice Unclear DMFS > 5 Low water F No 2 years
DMFS, DMFT – all teeth
and surfaces
Cavitated Nonsignificant
difference Not
assessed CCT
Beiswanger 1979
78
8 - 16 United States
Children 9% SnF paste for 4 minutes +
placebo solution
Placebo paste + placebo solution
Unclear DMFS > 5
F dentifrice; Varying levels of natural water
fluoride levels
No 3 years
DMFS, DMFT – all teeth and all
surfaces
Cavitated Nonsignificant
difference Not
assessed RCT
99
Table N: Risk of bias assessment of studies on prophylaxis pastes containing fluoride
Citation Summary risk of bias
score
Were patients in both arms recruited
from the same population at the
same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects assignment sequence before and
until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) – Examiner, patient and statistician)
Rate of losses to follow-up similar
between tx
groups
Baseline caries
status of those lost to follow-up similar to those
remaining
Baseline caries status
similar between tx groups at
end of study or
adjustment for
confounding
Sample size
estimated apriori
Intention to treat used?
Conflict of
Interest absent?
Peterson 1969
5 Yes Yes No Unclear Yes Yes Unclear
Not Reported
No No Yes
Barenie 1976
4 Yes No No Unclear
Examiner and patient
Unclear Unclear Yes No No Yes
Schutze 1974 3 Yes No No No No Unclear Unclear Yes No No Yes
DePaola 1973
5 Yes Yes No Unclear
Examiner and patient
Unclear Unclear Yes No No Yes
Horowitz 1966 5 Yes No No Unclear Unclear Yes Yes Yes No No Yes
Beiswanger 1979
7 Yes Yes Yes Unclear
Examiner and Patient
Yes Unclear Yes No No Yes
100
Table O: Outcomes data from studies on prophylaxis pastes containing fluoride
Citation Outcome measure Exp mean Exp SD Exp n Control mean Control SD Control n Other available
data
Peterson 1969
Mean Increment DMFS Cavitated
Examiner A Fargo 2.63
3.14 256 3.00
4.37 252
Surface data; examiner B visual and x-ray; cannot combine data for
meta-analysis
Mean Increment DMFS Cavitated
Examiner B Fargo 2.31
2.75
256 2.72
3.73 252
Mean Increment DMFT Cavitated
Examiner A Fargo 1.66
1.87 256 1.80
2.02 252
Mean Increment DMFT Cavitated
Examiner B Fargo 1.36
1.76 256 1.68
1.97 252
Mean Increment DMFS Cavitated
Examiner A Moorhead
3.54 3.28
202 4.18 4.51
205
Mean Increment DMFS Cavitated
Examiner B Moorhead
2.47 4.05
202 2.93 4.01
205
Mean Increment DMFT Cavitated
Examiner A Moorhead
2.02 1.93
202 2.30 2.12
205
Mean Increment DMFT Cavitated
Examiner B Moorhead
1.34 1.71
202 1.55 1.92
205
Barenie 1976 Mean increment DMFS cavitated
examiner 1 7.67 7.16 181 7.15 6.07 152
Surface data; newly erupted,
reversals. Cannot
101
Mean increment
DMFS cavitated
examiner 2 5.30 6.38 179 4.93 5.26 150
combine data for meta-analysis
Mean increment
DMFT cavitated
examiner 1 3.98 3.50 181 3.78 2.98 152
Mean increment
DMFT cavitated
examiner 2 3.00 3.08 179 2.73 2.55 150
Schutze 1974 Mean increment defs cavitated
4.64 4.41* 20 4.04 4.09* 20
Surface, anterior vs posterior
*SD imputed using Cochrane equation
DePaola 1973
Mean increment DFT cavitated
2.36 2.15 151 2.92 2.68 169
Erupted;
Mean increment DFS cavitated
4.99 4.41 151 6.32 5.41 169
Horowitz 1966
Mean increment DMFT cavitated
1.63 NA 227 1.51 NA 222 Reversals
*Imputed using Cochrane equation
Mean increment DMFS cavitated
4.08 4.41* 227 3.85 3.98* 222
Beiswanger 1979
Mean Increment DMFT cavitated
2.87 3.42 139 3.46 3.68 141
Mean Increment DMFS Cavitated
4.47 6.25 139 5.26 7.01 141
102
Table P: Characteristics of studies on professional prophylaxis prior to fluoride application
Citation Age Countr
y Special
population?
Intervention (Dose/duration/
frequency) Control
Caries risk status as stated by authors
Baseline score
(approximate)
Other exposure for both
groups
Specifically recruited
patients with caries
experience?
Follow-up
duration
Outcome measure
Diagnostic criteria
Reported result
Adverse events
Study Design
Ripa 1983, 1984
85, 86
10 - 14
United States
Children Professional Prophylaxis +
APF bi annual (data for self-prophylaxis available)
No prophyla
xis + APF
No Stated DMFS > 4 Low
water F No 3 years
DMFS, DMFT – all
teeth and all surfaces
Cavitated (Radike)
Nonsignificant difference
Not assessed
RCT
Houpt 1983 87
9 -13
United States
Children Professional Prophylaxis +
APF bi annual (data for self-prophylaxis available)
No prophyla
xis + APF
Not Stated DMFS > 2 0.2 ppm
water fluoride
No 2 years
DMFS, DMFT – all
teeth and all surfaces
Cavitated Nonsignificant difference
Not assessed
CCT
Johnston 1995
84
6 -11 Canada Children 1.23% APF gel biannual +
prophylaxis
No prophylaxis + bi annual APF
Very high risk defs > 10 Unclear Yes 3 years
defs + DMFS and defs – all
teeth and all surfaces
Cavitated Nonsignificant difference
Not assessed
RCT
103
Table Q: Risk of bias assessment of studies on professional prophylaxis prior to fluoride application
Citation Summary
risk of bias score
Were patients in both arms recruited from the same population at the
same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects assignment sequence before and
until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) – Examiner, patient and statistician)
Rate of losses
to follow-
up similar
between tx
groups
Baseline caries
status of those lost to follow-up similar to those
remaining
Baseline caries status similar
between tx groups at
end of study or
adjustment for
confounding
Sample size
estimated apriori
Intention to treat used?
Conflict of Interest absent?
Ripa 1984
85
6 Yes Yes No Unclear Unclear Yes Yes Yes No No Yes
Houpt 1983
87
3 Yes No No No No Unclear Unclear Yes No No Yes
Johnston 1995
84
7 Yes Yes Yes Unclear
Examiner and patient
Unclear Unclear Yes Yes No Yes
104
Table R: Outcomes data from studies on professional prophylaxis prior to fluoride application
Citation Outcome measure
Exp mean Exp SD Exp n Control mean Control SD Control n Other data available
Ripa 1984 85
Mean DMFT increment Cavitated
2.02 2.35 324 2.01 2.14 314 Self-prophylaxis
and specific teeth surfaces
Mean DMFS increments Cavitated
3.33 4.35 324 3.19 3.62 314
Houpt 1983 87
Caries incidence – DMFS cavitated
2.05 3.4 269 2.14 3.4 381 Self-prophylaxis
Caries incidence – DMFT cavitated
0.94 1.6 269 1.19 1.8 381
Johnston 1995 84
defs increment cavitated
2.25 2.72 47 2.17 2.25 39
Biannual; defs+DMSF for 6-
7 year olds; Reversals in text
DMFS increment cavitated
2.22 3.13 45 2.50 2.40 30
105
Table S: Characteristics of studies on prescription-strength 0.5% fluoride (home-use) pastes
Citation Age Country Special
population?
Intervention (Dose/duration/
frequency) Control
Prior prophylaxis? Make a note if Fluoride
prophylaxis paste was
used.
Caries risk status as stated by authors
(record any risk
indicators)
Baseline caries
score for groups
Other F exposure for both groups
Subjects included based on
presence of caries
experience?
Follow-up
duration
Outcome measure (record
tooth vs. surface,
smooth vs. pit and fissure)
(record if only
specific teeth
evaluated)
Diagnostic criteria
(cavitated only, All stages,
WSL only)
Reported result
(Statistical significance
of result)
Adverse events
Study Design#
Nordstrom 2010
88
14-16yr
Sweden adolescent
5000 ppm dentifrice
2yr 1gr 2Xday
Unsupervised
1450ppm dentifrice
no High DFS 5.84
5.83
0.1ppm water
F vanish tx 10%
supplements
yes 2yr DFS Cavitated
Enamel only
Favors 5000 ppm dentifrice
(p<0.01) compliant;
caries progression
(not incidence, p=0.4)
P=0.01 non-
compliant (progression);
p<0.05 (incidence)
For combined
groups (compliant and non-compliant) no difference in incidence
(p=0.08); favors 5000
ppm for progression (p<0.001)
Not described
Single blind RCT
Ekstrand 2008
89
75+ year olds; mean age 81.6
Denmark
Home-based frail elderly with active root caries
5,000 ppm F toothpaste 2x/day/pea size amount / unsupervised
1450 ppm F toothpaste 2x/day/pea size amount
F Varnish group has their teeth
brushed by a dental
hygienist before
application
Low/moderate root
caries activity
Group 1 - 137 (total), 81 (active),
56 (arrested) Group 2 –
133, 82, 51, respectively Group 3 –
125, 77, 48, respectively
0.5 ppm F in drinking water
Yes 8 mos after
baseline
Root surfaces
with lesions
Cavitated Also
evaluated caries activity
using a new system
based on texture, contour,
location and color of root
caries lesions
Significant reduction in number of active root
caries lesions between group
1 and 2 vs. group 3
(p < 0.02) FAVORS 5000 ppm dentrifice
Not reported
RCT
106
Cutress
199298
10-15 years
French Polynesia
no
5000 ppm/200 times a
year/once daily/supervised
in school
1250ppm F toothpaste
No High None Xylitol in 1 treatment
group No 3 year
Mean DMFT
WHO - cavitated
Not provided Not
discussed CCT
# RCT – group of subjects were randomly allocated; CCT – group of subjects were divided but word “random” not used in the paper; GRCT – a
group of school classes or communities were randomly allocated; GCCT – group of school classes or communities were divided but word “random”
not used in the paper
Table T: Risk of bias assessment of studies on prescription-strength 0.5% fluoride (home-use) pastes
Citation Summary risk of bias score
Were patients in both arms recruited from the same population at the
same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment (selection bias, protects assignment sequence
before and until allocation) e.g. opaque
enveloped holding assignment number
Blinding (ascertainment bias, protects sequence after allocation) –
Examiner, patient and statistician)
Rate of losses to follow-up
similar between tx
groups*
Baseline caries status of those lost to follow-up similar to those
remaining*
Baseline caries status similar between tx
groups at end of study or adjustment for
confounding*
Sample size
estimated apriori
Intention to treat used?*
Conflict of
Interest absent?
Nordstrom 2010
88
9 Yes Yes Yes No
Single blind (Examiner)
Similar Similar Yes Yes No Yes
Ekstrand, 2008
89
6
Yes Yes Yes Unclear Examiner and
patient No Unclear
no significant inter-group difference concerning
number of active lesions or
arrested lesions
No No Yes
Cutress 1992
98
2 Yes Unclear Unclear Unclear Unclear Unclear Unclear Unclear No No Yes
107
Table U: Outcomes data from studies on prescription-strength 0.5% fluoride (home-use) pastes
Citation Outcome measure Exp mean Exp SD Exp n Control mean Control SD Control n Other available
data
Nordstrom 201088
DFS Incidence (combined
compliance groups) 1.12 1.23 104 1.46 1.61 107
Prevalence data; proximal
incidence; Compliance A vs
B; proximal progression;
prevented fraction
DFS progression (combined
compliance groups) 1.28 1.50 104 2.13 2.10 107
Ekstrand, 200889
New active and arrested lesions
Change in status of baseline active and
arrested lesions
New active / New Arrested
Group 2 18 / 18
NA Group 2 = 64
New active / New Arrested
Group 3 41 / 11
NA Group 3 = 54
Total number of lesions
Characterization of the participants as to whether the root caries status became better, stayed stable or worsened during
the study
Cutress 199298
Mean DMFT
11 years, 5000 ppm, mean=2.6
12 years, 5000 ppm, mean=2.7
Combined, 2.6
Calculated combined SD=3.2
11 years, 5000 ppm, n=77
12 years, 5000 ppm, n=65
11 years, 1250 ppm, mean=4.2
12 years, 1250 ppm, mean=4.2
Combined, 4.2
Calculated combined SD=4.2
11 years, 1250 ppm, n=46
12 years, 1250 ppm, n=19
% DMFT; tooth level DMFT
108
Table V: Characteristics of studies on prescription-strength 0.5% fluoride (home-use) gels
Citation Age Country Special
Population?
Intervention (Dose/duration
/ frequency) Control
Prior Prophylaxis
Caries risk status as stated by authors
Baseline score
(approx.)
Other F exposure for both groups
Specifically recruited
patients with caries
experience?
Follow-up duration
Compliance Outcome measure
Diagnostic criteria
Reported result
Adverse events
Study Design
Van Rijkom 2004
94
Truin 2005 93
4.5 – 6.5
Netherlands
Children
1% NaF for 4 min every 6
months (applied in a tray)
Placebo No
prophylaxis Low risk DMFS = 0
Low water F
Low risk (no cavitated lesions at baseline)
4 years Professional application
DMFS and dmsf– all
teeth Cavitated
Statistically
significant favoring
NaF
Not assessed
RCT
Truin 2005 91
Truin 2007
92
9.5 – 11.5
Netherlands
Children
1% NaF for 4 minutes every 6 months (applied
in a tray)
Placebo No
professional prophylaxis
Low risk DMFS = 0
Low water F
Fluoride Toothpast
e
Low risk (no cavitated lesions at baseline)
4 years Professional application
DMFS – all teeth
Cavitated Not
significant Not
assessed RCT
Englander 1971
97
11 - 15
United States
Children
1.1% NaF gel with 0.1M
phosphate for 3 minutes 3 days
a week
No Tx No
prophylaxis Unclear DMFS > 3 1ppm F
No (although low risk
population)
27-31 months
Supervised application in school settings
DMFS – all teeth
Cavitated Significant favoring F
Not assessed
RCT
Englander 1978
96
2 – 6 United States
Children
1:1% NaF gel with 0.1M phosphate
thrice weekly for 3 minutes
Placebo No
prophylaxis Low caries increment
defs > 2
1 ppm F in water; F
free toothpaste
No 28 months
Supervised application in school settings
defs cavitated Not
significant Not
assessed RCT
Englander 1967
117
11 - 14
Unites States
Children
1. 1:1 % NaF gel with 0.1M
phosphate everyday; 2. 1:1
NaF gel everyday (excluding
summer break) for 6 minutes
No tx No
prophylaxis Unclear
DMFS > 10
Low water F; F-free
toothpaste No 21 months
Supervised application in school settings
DMFS – all teeth
Cavitated
Significant favoring F vs control.
No significant difference for APF vs
neutral
None observed
RCT
Gisselsson 1999
90
13 Sweden Children
1% NaF or 1% Snf four times a
year; applied with floss
Placebo No
prophylaxis Unclear DFS > 2
F toothpaste
and low water F
No 3 years Professional
ly applied
DFS – approxmal
from canine to
2M
All stages, WSL,
Cavitated
Significant favoring F.
The majority of
caries incidence
was attributable to incipient
lesions
Not assessed
RCT
109
Table W: Risk of bias assessment of studies on prescription-strength 0.5% fluoride (home-use) gels
Citation
Summary risk of bias
score
Were patients in both arms
recruited from the same
population at the same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects
assignment sequence before
and until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) – Examiner, patient and statistician)
Rate of losses
to follow-
up similar
between tx
groups
Baseline caries
status of those lost to follow-up similar to those
remaining
Baseline caries status similar
between tx groups at
end of study or
adjustment for
confounding
Sample size
estimated apriori
Intention to treat used?
Conflict of Interest absent?
Van Rijkom 2004
94
Truin 2005 93
10 Yes Yes Yes Yes Examiner, patient and statistician
Yes Yes Yes No Yes Yes
Truin 2005 91
Truin 2007
92
10 Yes Yes Yes Yes
Examiner and patient
Yes Unclear Yes Yes Yes Yes
Englander 1971
97
5 Yes Yes No Unclear Examiner Unclear Unclear Yes No No Yes
Englander 1978
96
4 yes Yes No Unclear Unclear Yes Unclear Unclear No No Yes
Englander 1967
117
5 Yes Yes No Unclear Examiner Unclear Unclear yes No No Yes
Gisselsson 1999
90
6 Yes Yes No Unclear
Examiner and patient
No Unclear Yes No No Yes
110
Table X: Outcomes data from studies on prescription-strength 0.5% fluoride (home-use) gels
Citation Outcome measure Exp mean Exp SD Exp n Control mean Control SD Control n Other available
data
Van Rijkom 2004 94
Truin 2005 93
Mean Increment DMFS Cavitated
0.78 1.48 340 1 1.47 336 Surface scores available, Percent progressed and
regressed Mean Increment dmfs Cavitated
1.80 3.13
340 2.34 3.67
336
Truin 2005 91
Truin
200792
Mean Increment DMFS Cavitated
0.94 1.57 269 1.18 2.17 261
Surface scores
available, Percent
progressed and
regressed; second
molar only data
available
Englander 197197
Mean DMFS increment –
cavitated 1.57 2.62 337 2.20 2.97 220
Examination
specific data
available
Englander 1978 96
Mean defs
increments - cavitated
1.79 2.61 (calculated) 46 2.11 2.86 (calculated) 44 Surface scores
available
Englander 1967 117
Mean Increment NaF vs control
DMFS - cavitated 0.89 4.18 151 4.39 4.47 195
Mean Increment Acidulated NaF vs.
control DMFS - cavitated
1.10 3.47 154 4.39 4.47 195
Mean Increment NaF & APF DMFS
cavitated 1.00 3.84 305 4.39 4.47 195
Mean Increment NaF vs. Control
DMFT - cavitated 0.90 1.84 151 2.75 2.37 195
111
Mean Increment Acidulated NaF vs.
Control DMFT - cavitated
1.00 1.99 154 2.75 2.37 195
Mean Increment NaF & APF DMFT
cavitated 0.95 1.92 305 2.75 2.37 195
Gisselsson 199990
Incidence DFS (all stages)
2.78 3.73 97 3.98 4.63 98
Incidence DS
(WSL) 2.26 3.24 97 3.48 4.31 98
Incidence DS (cavitated)
0.12 0.79 97 0.12 0.85 98
112
Table Y: Characteristics of studies on 0.09% fluoride mouthrinse
Citation Age Country Special
Population?
Intervention (Dose/
duration/ frequency)
Control
Caries risk
status as
stated by
authors
Baseline score
(approximate)
Other F exposure for both groups
Specifically recruited patients
with caries experience?
Follow-up
duration Compliance
Outcome measure
Diagnostic criteria
Reported result
Adverse events
Study Design
Wyatt 2004
109
83 Canada Long-term care elders
Daily rinsing 0.2% NaF
Placebo Unclear DMFS > 100 Some used F
toothpaste No 2 years
Similar between groups
Coronal and root caries
Incidence and
reversals all teeth
and surfaces
Cavitated Significant favoring
NaF
Not assessed
RCT
Van Wyk 1986
108
12 -13
South Africa
Children
Weekly rinsing with 0.2% NaF
rinse
Placebo Unclear DFS > 8
Low water F; topical
fl and fl tablets
were noted when
present
No 3 years Supervised DFS – all teeth and surfaces
Cavitated Significant favoring
NaF
Not assessed
RCT
Driscoll 1981
99,
1982100
12.8
United States
Children
Weekly and daily rinsing
with 0.2% NaF for one
minute
Placebo Unclear DMFS > 4 Optimum water F
No 30
months Supervised
DMFS – all teeth
Cavitated Significant favoring
NaF
Not assessed
RCT
Heifetz 1981
102, 103
10 - 12
Unites States
Children
Weekly and daily rinsing with 0.2%
NaF for one minute
Placebo Unclear DMFS > 5 Non F No 3 years Supervised DMFS – all teeth
Cavitated
Significant favoring NaF vs control.
No significant difference between weekly
and daily
Not assessed
RCT (data
reported by
examiner)
Craig 1981
101
11 - 12
New Zealand
Children
Weekly rinsing with 0.2% NaF +
OHI and prophylaxis
OHI and Prophylaxis
high DFS > 10 No No 21
months Unknown
DFS –all teeth
Cavitated Significant favoring
NaF
Not assessed
RCT
Ringelberg 1982
106
12.5 United States
Children
Weekly and daily rinsing
with 0.2%NaF for one minute
Placebo Unclear DMFS > 4 Low water
F No 2 years Supervised
DMFS – all teeth
Cavitated Not
significant Not
assessed RCT
113
Horowitz 1971
104
6 & 10
United States
Children
Weekly rinsing with 0.2% NaF
for 1 minute
Placebo monthly
Unclear (low ses)
6 yr olds DMFS > 0.79;
10 yr olds DMFS > 6.36
Low water F
No 20
months Supervised
DMFS, DMFT
Cavitated Significant favoring
NaF
Not assessed
RCT
Torell 1965
107
10 Sweden Children
Bi-weekly Rinsing with 0.2% NaF
rinse
No treatment
Unclear DMFS > 14 Low water
F No 2 years Supervised
DMFS all teeth
Cavitated Significant favoring
NaF
Not assessed
GRCT (adjusted
for clustering in meta-analysis)
Poulsen 1983
105
7 - 9
Denmark Children Bi-weekly
rinsing with 0.2% NaF
Placebo Unclear DMFS> 3 Low water F, Used F toothpaste
No 3 years Supervised DMFS all teeth and surfaces
Cavitated
Significant for teeth erupting
during the trial
Not assessed
RCT
Chikte 1996
111
6 -12
South Africa
Children Weekly
rinsing with 0.2% NaF
No rinse Unclear DMFS < or = 1
Low water F;
Supervised daily F
tooth paste brushing
No 3 years Supervised
DMFS and
DMFT all teeth and surfaces
All stages Significant favoring F
rinse
Not assessed
GCCT (adjusted
for clustering in meta-analysis)
Liefde 1989
110
5-8 New
Zealand Children
Bi-weekly rinsing with 0.2% NaF
Placebo
High-risk
based on
caries score
deft >3 and decayed first permanent
molar
Low water F
Yes 3 years Supervised DMFT Cavitated Non
significant Not
assessed RCT
Corpus 1973
112
8 - 10
Philippines Children Bi-weekly
rinsing with 0.2% NaF
Placebo Unclear DMFT > 1.38 Low water
F, No F toothpaste
No 2 years Supervised DMFT All Stages Not
significant None
observed CCT
114
Table Z: Risk of bias assessment of studies on 0.09% fluoride mouthrinse
Citation Risk of
bias score
Were patients in both arms recruited from the
same population
at the same time?
Randomization claimed (random
sequence generation)
Randomization procedure described
Allocation concealment
(selection bias, protects assignment sequence before and
until allocation)
Blinding (ascertainment bias, protects
sequence after allocation) – Examiner, patient and statistician)
Rate of losses to follow-up similar
between tx groups
Baseline caries
status of those lost to
follow-up similar to
those remaining
Baseline caries status
similar between tx
groups at end of study or adjustment
for confounding
Sample size
estimated apriori
Intention to treat used?
Conflict of
Interest absent?
Wyatt 2004109
6
Yes Yes Unclear Unclear Examiner and
patient Unclear Yes No Yes No Yes
Van Wyk 1986
108
6 Yes Yes Unclear Unclear Examiner and
patient Yes Unclear Yes No No Yes
Driscoll 1982
100
7 Yes Yes No Unclear Examiner and
patient Yes Yes Yes No No Yes
Heifetz 1981
102
5 Yes Yes No Unclear Examiner Unclear Unclear Yes No No Yes
Craig 1981101
5 Yes Yes No Unclear Unclear Yes Unclear Yes No No Yes
Ringelberg 1982
106
5 Yes Yes Yes Unclear Examiner and
patient Unclear Unclear Unclear No No Yes
Horowitz 1971 104
7 Yes Yes No Unclear Examiner Yes Yes Yes No No Yes
Torell 1965107
6 Yes Yes No No Examiner Yes Unclear Unclear Yes No Yes
Poulsen 1983
105
7 Yes Yes No Unclear Examiner and
patient Yes
(small) Yes Yes No No Yes
Chikte 1996111
3 Yes No No No No Yes Unclear Unclear No No Yes
Liefde 1989 110
5 yes Yes No Unclear
Examiner and patient
yes Unclear Unclear No No Yes
Corpus 1973 112
4 Yes No No No Unclear Yes Yes Unclear No No Yes
115
Table AA: Outcomes data from studies on 0.09% fluoride mouthrinse
Citation Outcome measure Exp mean Exp SD Exp n Control mean Control SD Control n Other available
data
Wyatt 2004109
Caries increment – crown DMFS
cavitated 0.4 2.5 39 0.8 2.4 36
Root increment; Reversals; Root
reversals Caries increment –
root DMFS cavitated 0.3 3.1 39 2.2 3.8 36
Van Wyk 1986108
DFS increment -
cavitated 4.6 4.4 185 7.5 5.7 192
Prevalence difference; SD estimated from
Cochrane equation
Driscoll 1982100
Mean DMFS increment –
cavitated weekly rinsing-- examiner 1
2.01 2.78 81 2.58 3.19 77
Surface level ; daily rinsing
SD were not stated; imputed according to the
Cochrane Equation
Mean DMFS increment –
cavitated weekly rinsing-- examiner 2
0.85 1.73 84 1.89 2.69 74
Mean DMFS increment –
cavitated weekly rinsing-- calculated
combined data
1.42 2.30 165 2.24 2.96 151
Mean DMFS increment –
cavitated daily rinsing-- examiner 1
1.86 2.67 102 2.58 3.19 77
Mean DMFS increment –
cavitated daily rinsing-- examiner 2
0.95 1.84 106 1.89 2.69 74
116
Mean DMFS increment –
cavitated daily rinsing-- calculated
combined data
1.76 2.59 208 2.24 2.96 151
Heifetz 1981102, 103
Mean DMFS increment Cavitated
weekly rinsing-- examiner 1
2.25 3.94 97 3.61 6.06 87
Surface level ; daily rinsing;
reversal in 2 yr results
Mean DMFS increment Cavitated
weekly rinsing-- examiner 2
3.39 3.94 102 4.43 4.98 117
Mean DMFS increment –
cavitated weekly rinsing-- calculated
combined data
2.83 3.94 199 4.08 5.47 204
Mean DMFS increment Cavitated
daily rinsing-- examiner 1
1.90 4.03 88 3.61 6.06 87
Mean DMFS increment Cavitated
daily rinsing-- examiner 2
2.94 3.41 107 4.43 4.98 117
Mean DMFS increment –
cavitated daily rinsing-- calculated
combined data
2.47 3.90 195 4.08 5.47 204
Craig 1981101
DFS caries
increment Cavitated 1.8 2.7 49 2.6 3.1 48
Surface level score available;
Ringelberg 1982
106
DMFS increment Cavitated weekly
2.66 3.98 253
3.34 4.42 249 Daily rinse; approximal
DMFS increment 2.58 3.85 257
117
Cavitated daily
Horowitz 1971 104
DMFS increment cavitated—6 year
old 1.08
1.96 133 1.29
1.89 123
DMFT, eruption, surface
DMFS increment cavitated—10 year
old 1.65
2.77 98 2.92
4.20 110
DMFS increment cavitated—
calculated combined 1.32 1.74 231 2.06 3.20 233
DMFT increment cavitated—6 year
old 0.54 1.15 133 0.72
1.00 123
DMFT increment cavitated—10 year
old 0.79 1.68 98 1.63
2.62 110
DMFT increment cavitated—
calculated combined 0.64 1.40 231 1.15 1.94 233
Torell 1965107
DMFS increment-
cavitated 5.10 4.93 160 10.02 6.75 162
Poulsen 1983105
Mean DMFS increment-cavitated
1.75 2.37 191 1.83 2.20 174
Data by erupting and erupted teeth and by surfaces.
Mean DMFS increment-caviated, Newly erupted teeth
0.73 1.31 191 0.99 1.52 174
Chikte 1996111
DMFS increment -
Cavitated 1.054 2.54 603 1.245 2.65 642
Surface level data available;
eruption; tooth type; prevalence’
Liefde 1989 110
DMFT prevalence
cavitated 2.9 1.2 101 2.7 1.2 172
Mean score in proximal and anterior teeth
available; high and low caries risk; defs tooth
score
Corpus 1973 112
DMFT all stages caries increment
1.12 1.34 80 1.68 1.61 72 erupting
118
Appendix 5 - Pragmatic calculations for interpreting summary
estimates clinically The standardized mean difference (SMD) is the chosen summary estimate.
The relationship of the absolute value of the SMDs to prevented fractions (PF) was investigated.
A correlation equation was generated from topical fluoride systematic reviews (Marinho et al12-14,
118) as follows:
The equation to convert SMD to PF is: PF=0.75*│SMD│+ 0.08 Note that this equation is not generalizable to studies of outcomes other than DMFS and should not be extrapolated beyond the ranges of SMD and PF used in its generation. To convert PF to number needed to treat (NNT), the following equation was used (assuming
“prevented fraction” is equivalent to “preventive fraction”):
PF=1-RR;
RR=ERt/ERc => ERt=RR(ERc)
NNT=1/(ERc-ERt) = 1/(ERc-RR(ERc)) = 1/(ERc*(1-RR)) = 1/(ERc*PF)
Where RR is the risk ratio; ER is the event rate; ERc is the control event rate; ERt is the
treatment event rate. For example, if for an at-risk population, the ERc is set at 1 DMFS per
year, then NNT = 1/PF.
Recommended