2 Topical Fluoride For Caries Prevention 2013 Update

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
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 practitioners
professional judgment and the patients needs and preferences.
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 practitioners professional judgment and a patients needs and preferences.
2013 ADA Center for Evidence-Based Dentistry. All rights reserved.

1
Authors and acknowledgments

Authors
Robert J. Weyant, DMD, DrPH; Sharon L. Tracy, PhD; Theresa (Tracy) Anselmo, MPH, BSDH, RDH;
Eugenio D. Beltrn-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. Beltrn-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.
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.
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. Beltrn-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.
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
Evidence profiles: APF foam (1.23% fluoride) ......................................................................................... 35
Prophylaxis pastes containing fluoride .......................................................................................................... 37
Evidence profiles: prophylaxis pastes containing fluoride ...................................................................... 38
5
Is prophylaxis prior to professional application of topical fluoride necessary? ........................................ 40

Evidence profiles: Prophylaxis prior to APF gel (1.23% fluoride) application ...................................... 41
Prescription-strength, home-use (0.5% fluoride) gel/paste agents ........................................................... 43
Evidence profiles: Prescription-strength, home-use (0.5% fluoride) gel/paste agents ...................... 45
Prescription-strength, home-use (0.09% fluoride) mouthrinse .................................................................. 47
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
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
practitioners professional judgment and each patients 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?
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.
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
8
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 patients risk of experiencing disease when developing an optimal
caries prevention plan. Part of a patients 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 patients caries risk status, the practitioners professional
judgment, and a patients 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.
9
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 0.5% 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.
10
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
11
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.
12
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
13
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
panels 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
14
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
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)
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
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.
15
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-by16. Ibid.
surface basis). It does not allow for reversals. (Broadbent and Thomson 2005).
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.cochranenet.org/openlearning/html/modA1-4.htm.]
16
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.]
17
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 panels 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.
18
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
2
23 2
confidence intervals, and statistical heterogeneity. Statistical heterogeneity (I ) is interpreted as : I <50% is low;
2
2
50<I <75% is moderate; I >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.
19
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
Net Benefit Rating
Level of Certainty
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
Strong
In Favor
Weak
Expert Opinion For
Expert Opinion Against
Against
Definition
Evidence strongly supports providing this intervention
Evidence favors providing this intervention
Evidence suggests implementing this intervention after alternatives have
been considered.
Evidence is lacking; the level of certainty is low. Expert Opinion guides this
recommendation
Evidence is lacking; the level of certainty is low. Expert Opinion suggests
not implementing this intervention
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.
20
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 panels
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 panels 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.
21
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
Professionally-applied
2.26% fluoride varnish
Acidulated phosphate fluoride (APF) gel (with 0.1 M
phosphoric acid)
Acidulated phosphate fluoride (APF) foam (with 0.1 M
phosphoric acid)
Prophylaxis paste containing fluoride (most as APF)
Prescription-strength, home-use
Prescription-strength gels/pastes with or without
acidulation (0.1M phosphoric acid)
Prescription-strength mouthrinses
% F- ion
% NaF
2.26
0.1
5.0
N/A*
1.23
2.7
1.23**
2.7**
1.23
2.7
0.5
1.1
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 1970s, 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 todays high-risk
populations, such as children at high risk for early childhood caries.
Note that there are several cases where one study was cited by several papers. All papers are cited for each study in
these cases.
22
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.
23
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], I2=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)).
permanent teeth [DMFS]
Notes: 1) Koch-SE converted to SD using the adjusted difference according to SD = SE/(sqrt(1/60+1/61)); 2) Moder-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], I2=64%
24
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

6 RCT31-33,
d(e/m)fs, increment or
35-39
and 2
3,409**
incidence
40, 41
CCT
Meta-analysis results: Permanent teeth
8 RCT31-33,
D(M)FS, increment or
42-44, 46-49, 52
2,574
incidence
and 1 CCT54
Root caries, meta-analysis results
Root caries increment
2 RCT50, 51
132
Individual study results
Combined dentition
1 CCT55
390
DMFT
DS occlusal surfaces
1 CCT53
1 RCT45
77
79
-0.19 [-0.31, -0.08]
-0.38 [-0.53, -0.24]
-0.67 [-1.14, -0.20]

DMFS + dmfs: -1.47 [-1.70, -1.25]
DMFT + dmft: -1.15 [-1.37, -0.94]
-0.13 [-0.58, 0.32]
-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.
25
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 metaanalysis 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):

o SMD=-0.38 [-0.53, -0.24]
o PF=0.36
26
o NNT for control rate of 1 DMFS per year = 3

Adverse events or harms: None if used as manufacturers recommend
Permanent teeth coronal caries (adults):

Level of certainty: No certainty (no studies)
Benefit: Unknown, but extrapolated from permanent teeth of children data
Strength of clinical recommendation: Expert opinion for use
Permanent teeth - root caries (adults):

Level of certainty: Low
o SMD=-0.67 [-1.14, -0.20]
o PF=0.58
27
Varnish (0.1% fluoride)

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%
28
Outcome
Measures
Number and
type* of
studies
Number of
participants**
Primary teeth, meta-analysis results

dfs increment or
2 CCT56, 57
4,977
incidence
Permanent teeth, individual study results
DMFS increment
1 RCT58
318

(negative favors intervention, positive
favors control)
-0.11 [-0.27, 0.06]
-0.15 [-0.37, 0.08]
Notes: * RCT = randomized controlled trial; CCT = controlled clinical trial (non-randomized); **Including all participants (not using clusteradjusted 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 (I 2=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.
29
Evidence profiles: 0.1% fluoride varnish

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
Benefit: No
Strength of clinical recommendation: Expert opinion against use
Permanent teeth root caries (adults):
Benefit: Unknown
Benefit-harm assessment (Net benefit rating): Unknown
Strength of clinical recommendation: Panel unable to make a recommendation
30
APF gel (1.23% fluoride)

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-totreat 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.
31
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).
32
professionally-applied APF gel (1.23% fluoride)
Outcome Measures
Number and
Type* of studies
Meta-analysis results:
D(M)FS, increment or
10 RCT59-68, 70 / 2
incidence, all
CCT72-75
frequencies
Individual trial results:
dmfs increment
1 CCT71
DMFS + dmfs
1 CCT55
increment, all stages
Root caries DMFS
increment, adults older
1 RCT69
than 60
Number of
participants**

favors control)
4,023
-0.25 [-0.33, -0.16]
255
-1.51 [-1.79, -1.23]
390
-0.84 [-1.05, -0.63]
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 614 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.
No studies were found on professionally-applied fluoride APF gels with an application time of less than 3 minutes.
33
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)
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
o SMD=-0.25 [-0.33, -0.16]
o PF=0.27
Benefit: Yes (smaller caries increment or incidence with topical fluoride use)
o SMD=-0.22 [-0.44, 0]
o PF=0.24
34
APF foam (1.23% fluoride)

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
dmfs increment
DMFS increment
Number and
type* of
studies
1 RCT77
1 RCT65
Number of
participants**
318
412

(negative favors intervention, positive favors control)
-1.26 [-1.50, -1.02]
-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)
o SMD=-1.26 [-1.50, -1.02]
Adverse events or harms: Potential for harm if swallowed
Both studies on professionally-applied fluoride APF foams used an application time of 4 minutes.
35

Benefit: No
Benefit: Unknown
36
Prophylaxis pastes containing fluoride

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)
37
Table 12. Summary of standardized mean differences from meta-analysis and individual studies of
prophylaxis pastes containing fluoride
favors control)
Individual study results of primary teeth data
Outcome
Measures
Number and
type* of studies
Number of
participants
defs increment,
cavitated lesions
1 CCT83
40
DMFS increment,
cavitated lesions
0.14 [-0.48, 0.76]
Meta-Analysis results of permanent teeth data

3 RCT78-80 and 2
-0.08 [-0.18, 0.02]
2,297
CCT81, 82
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-yearolds. 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 8-16year-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
Benefit: No
Benefit: No
Strength of clinical recommendation: Against
38


Benefit: Unknown
39
Is prophylaxis prior to professional application of topical fluoride necessary?

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)
40
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)
Number and
Number of
type* of
participants
studies
Individual study results of primary teeth data
defs increment,
1 RCT84
86
cavitated lesions
Meta-Analysis results of permanent teeth data
DMFS
2 RCT84-86 and
increment,
1,363
1 CCT87
cavitated lesions
Outcomes
Measure

0.03 [-0.39, 0.46]
0.00 [-0.11, 0.11]
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
Benefit: No
Adverse events or harms: No harms noted
Strength of clinical recommendation: Expert opinion (not necessary)
Benefit: No
Strength of clinical recommendation: Against (not necessary)
41

Benefit: Unknown, but extrapolated from permanent teeth of children data (no benefit)
Strength of clinical recommendation: Expert opinion (not necessary)

Benefit: Unknown
42
Prescription-strength, home-use (0.5% fluoride) gel/paste agents

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.
43
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
Number and
type* of
studies
d(e/m)fs increment
2 RCT93, 94, 96
D(M)FS incidence 6 RCT88, 90-9292,
9395, 97
or increment
Individual study results:
DMFT prevalence
1 CCT98
New root caries
1 RCT89
lesions
Outcome
Measures
Number of
participants

766
-0.15 [-0.30, -0.01]
2,669
-0.33 [-0.55, -0.12]
207
-0.45 [-0.75, -0.15]
138
N/A**
**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
44
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 studys 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.
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.
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
o SMD=-0.15 [-0.30, -0.01]
o PF=0.19
o NNT for control rate of 1 dmfs per year = 5
Strength of clinical recommendation: Expert opinion against use. Note that depending on individual
patient circumstances, benefits could outweigh potential harms.
o SMD=-0.33 [-0.55, -0.12]
o PF=0.33
45


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
46
Prescription-strength, home-use (0.09% fluoride) mouthrinse

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 metaanalysis.
47
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], I2=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, prescriptionstrength 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
48
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
D(M)FS, increment,
7 RCT99-107 /
daily, weekly and
1 CCT111
biweekly rinsing
D(M)FS, increment,
5 RCT99-104,
106
daily and weekly
/1
rinsing only
CCT111
Individual trial results:
DMFT prevalence
1 RCT110
[biweekly rinsing]
DMFS prevalence
1 RCT108
[weekly rinsing]
DMFT increment
1 CCT112
[biweekly rinsing]
Root caries increment,
daily rinsing, long1 RCT109
term-care elders
Coronal caries
increment, daily
1 RCT109
rinsing, long-term-care
elders
Number of
participants**

(negative favors intervention, positive favors
control)
4,374
-0.26 [-0.40, -0.13]
3,687
-0.20 [-0.27, -0.12]
273
0.17 [-0.08,0.41]
377
-0.57 [-0.77, -0.36]
152
-0.38 [-0.70, -0.06]
75
-0.54 [ -1.01, -0.08]
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 512 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.
49
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
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
o SMD=-0.26 [-0.40, -0.13]
o PF=0.27
o SMD=-0.54 [ -1.01, -0.08]
o PF=0.48
50
1
2
Stannous fluoride
prescription-strength concentration. Oral health providers often dispense or prescribe stannous fluoride
products, however, the fluoride concentration of these products is 0.1%, which is an over-the-counter
concentration and comparable to that in fluoride dentifrice.
6
7
Erupting teeth
teeth. The data were presented such that they could not be meaningfully aggregated. However, taken as a
whole, the data suggest a consistent benefit for use of fluoride varnish, rinse, and gel while teeth are erupting,
10
but due to methodological heterogeneity, it is impossible to estimate the effect. Additional studies are needed
11
to clarify these relationships.
12
13
Systematic review conclusions
14
professionally-applied and prescription-strength topical fluoride agents are efficacious in preventing and
15
controlling tooth decay. These products include 2.26% fluoride varnishes, 1.23% fluoride gels, prescription-
16
strength, home-use 0.5% fluoride gels/pastes, and prescription-strength, home-use 0.09% fluoride
17
mouthrinses. The panel did not find that 0.1% fluoride varnishes or prophylaxis pastes containing fluoride were
18
efficacious in preventing tooth decay and found insufficient evidence on 1.23% fluoride foams. Efficacious
19
means that the product is capable of preventing new carious lesions under the controlled setting of a clinical
20
trial.
Although the literature search included the search term stannous fluoride, no studies were found that used
Several trials52, 55, 79, 81, 104, 105, 111-113 utilizing various forms of topical fluoride agents reported results on erupting
Based on the studies that matched the inclusion criteria (Table 2 and Figure 1), the panel concluded that some
21
51
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.
52
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 nonrandomized studies.
Future research
The panel recommends that multiple well-designed, appropriately powered, placebo-controlled RCTs 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
53
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 Sjgrens 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.
54
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60
Appendix 1 Clinical Recommendations detailed presentation

Topical Fluoride
Agent
Varnish, 2.26%
fluoride
Varnish, 0.1% fluoride
Professionally-applied
1.23% fluoride (APF)
gel
Prophylaxis prior to
1.23% fluoride (APF)
gel application
Fluoride foam (1.23%
fluoride as APF)
Prophylaxis paste
containing fluoride
Prescription-strength
(0.5% fluoride), homeuse fluoride products
(gel, paste)
Mouthrinse, 0.09%
fluoride
Younger than 6 Years

(Primary teeth)
Every 3 to 6 months
(In Favor)
Not recommended
(Against)
Not recommended
(Expert Opinion Against)
Not necessary for caries
prevention
Not recommended
Not recommended for
caries prevention
Age Group or Dentition Affected

6-18 Years
Older than 18 Years
(Mixed dentition)
(Permanent Teeth)
Every 3 to 6 months
Every 3 to 6 months
(In Favor)
(Expert Opinion For)
Not recommended
Not recommended
4 minutes every 3-6

4 minutes every 3 to 6
months
months
(In Favor)
prevention
prevention
(Against)
Not recommended
Not recommended
Not recommended for
Not recommended for
caries prevention
caries prevention
(Against)
Adult Root caries

Every 3 to 6 months
(Expert opinion For)
Panel unable to make
recommendation
4 minutes every 3 to 6
months
recommendation
recommendation
recommendation
Not recommended
Twice daily
Twice daily
Twice daily
Not recommended
At least weekly
(In Favor)
At least weekly
Daily
No studies tested APF gel for less than 4 minutes.
Table cell color legend.
61
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
62
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))
63
Appendix 3 Excluded studies at full-text stage

Citation
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.
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 Malm Study. Caries Res. 1991;25(4):304-10.
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.
Reason For
Exclusion
Only arrests data.
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.
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.
Self applied
prophy paste.
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.
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.
64
Ruiken R, Truin GJ, Knig 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.
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.
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.
Kllestl C. The effect of five years' implementation of caries-preventive methods in Swedish highrisk adolescents. Caries Res. 2005 Jan-Feb;39(1):20-6.
Kllestl C, Flinck A, Allebeck P, Holm AK, Wall S. Evaluation of caries preventive measures. Swed
Dent J. 2000;24(1-2):1-11.
Kllestl 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
outcome reported.
Percentile of DFS
scores. No idea
what the control
group was. No
information on
allocation of
schools/participan
ts.
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.
Multiple
interventions.
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.
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.
No baseline data.
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.
Clark DC, Robert G, Tessier C, Frchette 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.
Analysis of data
for a subset from
the Malm study
which we have
excluded.
Combination and
no relevant
control.
Control arm had
co-intervention
65
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.
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).
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.
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.
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.
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.
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.
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) 3951.
Wegner H. The clinical effect of application of fluoride varnish. Caries Res. 1976;10(4):318-20.
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.
Petchel KA, Mello AF. A school fluoride mouthrinse program. J Sch Health. 1977 Nov;47(9):557-8.
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.
Segreto VA, Jerman AC, Devlyn JE. Oral prophylaxis pellet: a stable stannous fluoride preparation.
Aeromed Rev. 1969 Jul;3:1-6.
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.
Special
population
Special case:
overdenture
abutments
Not prescription
strength
SDF versus
Toothbrushing.
Split mouth.
Multiple
interventions.
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.
Self-applied
1.23% APF with
brushing.
No concurrent
control group.
No control group.
Not a controlled
study.
No concurrent
control group.
Not a caries
study.
66
Horowitz HS. Caries prevention and fluoride preparations. Symp Pharmacol Ther Toxicol Group.
Review.
1974 Mar 21:36-43.
Hamp SE, Lindhe J, Fornell J, Johansson LA, Karlsson R. Effect of a field program based on systematicFluoride prophy
plaque control on caries and gingivitis in schoolchildren after 3 years.
paste and rinse.
Community Dent Oral Epidemiol. 1978 Jan;6(1):17-23.
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, Bertrn Mart L, Jorba Vives M, Gonzlez Svatetz CA, Agudo Trigueros A.
Not English.
Servei de Salut Escolar. IMS, Matar.
Hamp SE, Johansson LA. Dental prophylaxis for youths in their late teens. I. Clinical effect of different Multiple
preventive regimes on oral hygiene, gingivitis and dental caries. J Clin Periodontol.
interventions vary
1982 Jan;9(1):22-34.
by year.
Nishino M, Yoshida S, Sobue S, Kato J, Nishida M. Effect of topically applied ammoniacal silver
No clinical
fluoride on dental caries in children. J Osaka Univ Dent Sch. 1969 Sep;9:149-55.
evaluation.
Xhemnica L, Sulo D, Rroo R, Hysi D. Fluoride varnish application: a new prophylactic method in Albania.
Short term study
Effect on enamel carious lesions in permanent dentition. Eur J Paediatr Dent. 2008 Jun;9(2):93-6.
but they did report
cavitation.
However 6% NaF
and 6% CaF
varnish.
Ritter AV. Fluoride varnishes. J Esthet Restor Dent. 2003;15(4):256.
Multiple
interventions.
Johnson G, Almqvist H. Non-invasive management of superficial root caries lesions in disabled and
infirm patients. Gerodontology. 2003 Jul;20(1):9-14.
Lindhe J, Axelsson P. The effect of controlled oral hygiene and topical fluoride application on caries
Solution and
and gingivitis in Swedish schoolchildren. Community Dent Oral Epidemiol. 1973 1(1)
SMFP paste.
Weisz WS. The reduction of dental caries through use of a sodium fluoride mouthwash. J Am Dent
Patients over 10
Assoc. 1960 Apr;60:438-56.
years, Casecontrol 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.
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.
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.
Fure S, Lingstrm P. Evaluation of different fluoride treatments of initial root carious lesions in vivo.
Oral Health Prev Dent. 2009;7(2):147-54.
Ravald N, Birkhed D. Prediction of root caries in periodontally treated patients maintained with
different fluoride programmes. Caries Res. 1992;26(6):450-8.
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):3640.
SnF solution.
Multiple
interventions.
0.4% SnF.
SnF Solution vs.
Duraphat vs.
Carosolv +
Duraphat.
Duraphat vs.
0.05% Rinse vs.
0.4% SnF2
OTC comparisons
with Duraphat.
Solution. Teeth
surfaces were
kept wet with the
fluoride solution
for four minutes
by frequenterapplication.
67
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.
F vs. CHX.
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.
Birkeland JM, Jorkjend L. Effect of mouth rinsing and toothbrushing with fluoride solutions on caries
Rinse vs. F
among Norwegian schoolchildren. Community Dent Oral Epidemiol. 1975 Sep;3(5):201-7.
toothpaste.
Stecksn-Blicks C, Renfors G, Oscarson ND, Vivaldi-Rodrigues G, Demito CF, Bowman SJ, Ramos Split mouth.
AL. The effectiveness of a fluoride varnish in preventing the development of white spot lesions.
World Journal of Orthodontics. 2006 7(2):138-44.
Altenburger MJ, Schirrmeister JF, Wrbas KT, Klasser M, Hellwig E. Fluoride uptake and
In situ.
remineralisation of enamel lesions after weekly application of differently concentrated fluoride gels.
Caries Res. 2008 42(4):312-8.
Ferreira MA, Latorre Mdo R, Rodrigues CS, Lima KC. Effect of regular fluoride gel application on incipient
Short term WSL.
carious lesions. Oral Health & Preventive Dentistry. 2005 3(3):141-9.
Willmot DR. White lesions after orthodontic treatment: does low fluoride make a difference? Journal
Toothpaste and
of Orthodontics. 2004 31(3):235-42.
mouthrinse used
together
Combination.
Axelsson P, Lindhe J. Effect of fluoride on gingivitis and dental caries in a preventive program
SMFP.
based on plaque control. Community Dent Oral Epidemiol. 1975 3(4).
Vivaldi-Rodrigues G, Demito CF, Bowman SJ, Ramos AL. The effectiveness of a fluoride varnish in
Split mouth.
preventing the development of white spot lesions. World Journal of Orthodontics. 2006 7(2):138-44.
Ferreira JM, Arago AK, Rosa AD, Sampaio FC, Menezes VA. Therapeutic effect of two fluoride
Short-term WSL
varnishes on white spot lesions: a randomized clinical trial. Braz Oral Res. 2009 Oct-Dec;23(4):446- study.
51.
de Amorim RG, Leal SC, Bezerra AC, de Amorim FP, de Toledo OA. Association of chlorhexidine
Short Term WSL.
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.
Gontijo L, Cruz Rde A, Brando PR. Dental enamel around fixed orthodontic appliances after
Split mouth.
fluoride varnish application. Braz Dent J. 2007;18(1):49-53.
Stecksn-Blicks C, Renfors G, Oscarson ND, Bergstrand F, Twetman S. Caries-preventive
6 month WSL
effectiveness of a fluoride varnish: a randomized controlled trial in adolescents with fixed
study in ortho
orthodontic appliances. Caries Res. 2007;41(6):455-9. Epub 2007 Sep 7.
patients.
Tranaeus S, Al-Khateeb S, Bjrkman S, Twetman S, Angmar-Mnsson B. Application of
Short term QLF
quantitative light-induced fluorescence to monitor incipient lesions in caries-active children. A
study.
comparative study of remineralisation by fluoride varnish and professional cleaning. Eur J Oral Sci.
2001 Apr;109(2):71-5.
Tewari A, Chawla HS, Gopalakrishnan NS. Acidulated phosphate fluoride--3 1/2 years clinical trial
This paper
on the prevention of dental caries. J Indian Soc Pedod Prev Dent. 1986 Mar;4(1):15-24.
describes the use
of APF without
Tewari A, Chawla HS, Reddy VV. Efficacy of acidulated phosphate fluoride in the prevention of
stating exactly
dental caries--a 2 1/2 years study. J Indian Soc Pedod Prev Dent. 1983 Mar;1(1):20-7.
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.
68
Bordoni N, Bellagamba H, Doo 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.
Ogaard B, Rlla 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):1238.
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.
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.
Hass R. Effectiveness of a single application of stannous fluoride after toothbrushing. J Am Dent
Assoc. 1965 71(6).
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.
Zahran M. Effect of topically applied acidulated phosphate fluoride on dental caries. Community
Dent Oral Epidemiol. 1976 Nov;4(6):240-3.
McCombie F, Hole LW. Two year effect of supervised toothbrushing with an acidulated fluoridephosphate solution. J Can Dent Assoc (Tor). 1966 Feb;32(2):89-93.
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.
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.
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.
Not all the

children were
examined.
Incomplete study.
Short term white
spot ortho study 4 week follow up.
NaF and APF
solution but
interventions
varied between
study years for all
groups.
Not commercially
available products
8% SnF Solution
applied with
cotton applicators.
8% SnF and APF
solution applied
with cotton
applicators and
teeth kept wet for
4 minutes.
APF Fluoride
solution (2% NaF
in 0.15M
phosphoric acid,
pH 3.2) applied
with a cotton
applicator.
Phosphate
fluoride solution.
Kids dipped
toothbrush in
solution and
brushed teeth.
2% aqueous NaF,
4% SnF and 2%
APH. All solution
coated several
times onto the
tooth with cotton
applicators.
Paper calls it
Solution and does
not describe
method of
application. 8%
SnF, 4% SnF,
0.4% SnF and 2%
NaF.
8% SnF Solution
and APF
solution. No
indication of
method of
application.
69
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 SepOct;36(5):355-61.
Burgess RC, Kreutzer J. Caries, prophylaxis, and fluorides. Appl Ther. 1966 Sep;8(9):760-4.
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.
Fleming TJ. Use of topical fluoride by patients receiving cancer therapy. Curr Probl Cancer. 1983
Apr;7(10):37-41.
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.
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.
Myers RE, Mitchell DL. Fluoride for the head and neck radiation patient. Mil Med. 1988
Aug;153(8):411-3.
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.
Richards W. Improving the oral health of young children through an evidence-based approach.
Community Dent Health. 2006 Jun;23(2):124-5.
Worthington H, Clarkson J. Cochrane Oral Health Group. The evidence base for topical fluorides.
Community Dent Health. 2003 Jun;20(2):74-6.
Tinanoff N. Caries management in children: decision-making and therapies. Compend Contin Educ
Dent. 2002 Dec;23(12 Suppl):9-13.
Martin AP. Silver fluoride use. Aust Dent J. 1997 Feb;42(1):66-7.
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.
Review.
Review.
Caries not
outcome.
Evaluated 10%
SnF. Paper calls it
Solution but does
not describe
method of
application.
Rinse vs. F tab.
Review.
Review.
Letter.
Editorial.
Review.
Letter.
Miller MC, Truhe TF. Preventive dentistry for pediatric patients. J Calif Dent Assoc. 1995
Feb;23(2):42-4.
[No authors listed]. Researchers investigate methods to prevent caries on roots and crowns. J Am
Dent Assoc. 1992 Nov;123(11):22, 24.
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.
Review.
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.
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):43541.
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.
In vitro 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.
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.
Letter.
Announcement.
Combined topical
fluoride and
sealant.
Multiple
Interventions.
Fluoride uptake
study.
Review.
70
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.
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.
Perry D, Newman MG. Uses of fluoride in dentistry. CDA J. 1985 Dec;13(12):31-6.
Rossy R, Tinanoff N. Topical fluoride therapy. J Clin Orthod. 1985 Jul;19(7):524-6.
Billings RJ, Brown LR, Kaster AG. Contemporary treatment strategies for root surface dental caries.
Gerodontics. 1985 Feb;1(1):20-7.
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.
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.
Silverstone LM. The significance of remineralization in caries prevention. J Can Dent Assoc. 1984
Feb;50(2):157-67.
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.
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.
Review.
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.
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.
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.
Osterbrock NL. Fluoride mouthrinsing in Cincinnati elementary schools. Cincinnati Dent Soc Bull.
1983 Sep;52(7):20-1.
Review.
Review.
Review.
No valid control
group.
Review.
Review.
In vitro evaluation.
Outcome not
caries.
Rinsing compared
to fluoridated
water.
Safety study
Caries not an
outcome.
Short term study
and OTC.
Review.
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.
Sposato AL, Leske GS, Ripa LW. The changing dental care patterns of participants in a schoolPrevalence study.
based fluoride mouthrinsing program. Pediatr Dent. 1983 Mar;5(1):53-6.
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.
Short-term cross
J Pedod. 1983 Spring;7(3):241-50.
over.
DePaola PF, Soparkar M, Van Leeuwen M, DeVelis R. The anticaries effect of single and combined
No baseline data.
topical fluoride systems in school children. Arch Oral Biol. 1980;25(10):649-53.
Spears ND, Goldstein C, Gordinier N, Crysler C. Effects of a thrice yearly application of fluoride
No baseline data
gel. Dent Hyg (Chic). 1978 Dec;52(12):569-72.
for both groups.
Malloy CM, Shannon IL. A single solution mixture of fluorides for treatment of cavity preparations.
In vitro.
Gen Dent. 1982 May-Jun;30(3):225-7.
Weisz WS. A two year study of the efficacy of a sodium fluoride mouth wash. Penn Dent J (Phila). 1947Not a controlled
Nov;5(2):36-43.
study.
Shannon IL. Fluoride treatment programs for high-caries-risk patients. Clin Prev Dent. 1982 MarReview.
Apr;4(2):11-20.
Sepp L. Fluoride varnishes in caries prevention. Proc Finn Dent Soc. 1982;78 Suppl 8:1-50.
Published
elsewhere.
Sepp L, Hausen H, Luoma H. Relationship between caries and fluoride uptake by enamel from
Split-mouth.
two fluoride varnishes in a community with fluoridated water. Caries Res. 1982;16(5):404-12.
Easley M. Rinsing with fluoride. A new, school-based program in Ohio. Ohio Dent J. 1981
Review.
Mar;55(3):36-41.
Poulsen S, Gadegaard E, Mortensen B. Cariostatic effect of daily use of a fluoride-containing
F supplement
lozenge compared to fortnightly rinses with 0.2% sodium fluoride. Caries Res. 1981;15(3):236-42.
study vs. rinse.
No other group.
Wade JR. Professional strength fluoride mouthrinses for use in dental offices. J Public Health Dent.
Letter.
1981 Winter;41(1):5-7.
Bissell GD, O'Shea RM, Mann J. Recruitment and participation in a school mouthrinse program. J
Caries not
Public Health Dent. 1980 Winter;40(1):57-63.
outcome.
Shannon IL. Responses of enamel, dentin, and root surfaces to mouthrinse concentrations of
Caries not
sodium fluoride and stannous fluoride. ASDC J Dent Child. 1980 Jan-Feb;47(1):17-20.
outcome.
71
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Shannon IL, Edmonds EJ. Topical applications of stannous fluoride: choice of concentration and
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Kolehmainen L, Kerosuo E. The clinical effect of application of a urethane lacquer containing silane
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DePaola PF. Combined use of a sodium fluoride prophylaxis paste and a spray containing
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Program
description.
Review.
Abstract.
In vitro.
Split mouth.
Combinations.
Procedure
description.
Caries not
outcome.
Report.
Very poor
reporting. No idea
what the control
group was,
although data for
a control group
is presented.
Combinations.
MFP.
0.05% OTC
mouthrinse.
Caries is not an
outcome.
Review.
OTC.
Not a trial.
Split mouth.
No caries.
Review.
No fluoride
agents.
Fluoride uptake.
Fluoride uptake.
Self-administered
TF.
No caries
outcome.
Fluoride tablets.
Review.
Abstract.
Split mouth.
Review.
72
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Feb;90(2):398-402.
Review.
No caries
outcome.
Review.
Fluoride retention.
Note.
No relevant
control group.
No F agent.
No caries
outcome.
No relevant
control group.
Abstract.
Abstract.
No caries
outcome.
Intervention not
consistent across
years.
Not controlled.
Investigative
varnish.
Combinations.
Not controlled.
Not on fluoride.
Combinations.
Split mouth.
Case reports.
Solution was
swallowed.
Phosflur rinse
OTC.
Phosflur OTC.
0.05% NaF rinse.
0.2% vs. 0.025% No relevant
control group.
100 ppm =
0.01% F ion OTC.
100 and 200 ppm
F ion
concentration
OTC.
73
Muhler JC, Stookey GK, Bixler D. Evaluation of the anticariogenic effect of mixtures of stannous
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molars. Aust Dent J. 1989 Oct;34(5):407-9.
Caries not
outcome.
Amine fluoride.
Combinations.
Children in test
group used F
prophy paste +
Duraphat and
control used only
Duraphat.
No relevant
agent.
Combination.
Unusual
concentration.
OTC
concentration.
0.1% SnF rinse
OTC
concentration.
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.
Split mouth.
The control group
was treated
based on dentists
judgment and on
an average
received 4 topical
fluoride
applications over
the 2 year study
period.
0.42% F vs.
1.23% APF for 4
weeks.
Testing a
chairside strep
test. Caries data
part of the original
paper is the one
below.
Silver fluoride
excluded
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Control group
received
semiannual 0.4%
NaF and test
received daily
0.1% NaF. OTC.
Many
combinations.
NPDDP paper.
0.05% NaF.
SnF prophy paste
and solution in the
test group and no
treatment control.
Split mouth.
Sepp L, Tuutti H, Luoma H. Three-year report on caries prevention of using fluoride varnishes for
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No control for the
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No control groups
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for the prevident
treatment; special
population; headto-head trial
Torell P, Gerdin PO. Fortnightly fluoride rinsing combined with topical painting of fluoride solutions
No concurrent
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Primary data is in
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Caries not an
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Cervitec.
Brnemark 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
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against test
varnish. No other
control group.
Birkeland JM, Torell P. Caries-preventive fluoride mouthrinses. Caries Res. 1978;12 Suppl 1:38-51.
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Vrbic V, Kosmelj B+KOSMELJ B, Ravnik C. A 3-year study among Yugoslavian schoolchildren on
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Non-English.
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Product not
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Letter.
Announcement.
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Not a controlled
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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.
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.
Nemes J, Bnczy 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.
Observational.
gaard 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.
gaard 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.
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.
Purdell-Lewis DJ, Arends J, Groeneveld A. The effect of differing concentrations of SnF2 on
demineralized enamel. Caries Res. 1978;12(1):43-51.
No baseline for
the control group.
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 schoolbased fluoride mouthrinsing program with implications for the use of sealants. J Public Health Dent.
1985;45(2):90-94.
Prevalence study.
Solution.
Not a clinical
study for
differences.
Observational.
No control for
fluoride.
Prevalence.
In vitro.
77
Shapira J, Stabholz A. A comprehensive 30-month preventive dental health program in a preadolescent population with Down's syndrome: a longitudinal study. Spec Care Dentist.
1996;16(1):33-37.
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.
Sledd JL. Applying fluoride varnish to pediatric patients to prevent caries. Northwest Dent. 2007
Jan-Feb;86(1):4, 66.
Sealant study.
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.
Not a fluoride
study.
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.
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.
Schirrmeister JF, Gebrande JP, Altenburger MJ, Mnting 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.
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):1824.
Sepp L, Pllnen L, Hausen H. Caries-preventive effect of fluoride varnish with different fluoride
concentrations. Caries Res. 1994;28(1):64-7.
Plaque scores.
Letter.
Fluoride solution
not currently
available.
Two week study.
Incorrect
outcomes
measure (no
data); specialized
populations
(orthodontic
patients that are
banded).
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.
0.1% APF rinse.

head-to-head
data
Laswell HR, Pacher MW, Wiggs JS. Cariostatic effects of fluoride mouthrinses in a fluoridated
community. J Tenn Dent Assoc. 1975 Oct;55(4):198.
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 JanFeb;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.
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.
Sepp L, Pllnen L. Caries preventive effect of two fluoride varnishes and a fluoride mouthrinse.
Caries Res. 1987;21(4):375-9.
Koch G, Petersson LG, Rydn 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.
Too short of
follow-up (3 and 6
months); arrests
and reversals; did
not report
outcomes as
increments
Duraphat vs.
rinse; head-tohead
Duraphat vs.
Fluorprotector vs.
rinse; head-tohead
Head-to-head
78
Sepp L, Leppnen T, Hausen H. Fluoride varnish versus acidulated phosphate fluoride gel: a 3year 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
Flrio 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
Head-to-head
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.
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
0.3% NaF and
sodium fluoride or an acidulated phosphate-fluoride mouthwash. J Am Dent Assoc. 1973
APF; product
Aug;87(2):364-8.
concentrations
not available
commercially
Petersson LG, Arthursson L, Ostberg C, Jnsson G, Gleerup A. Caries-inhibiting effects of
Head-to-head
different modes of Duraphat varnish reapplication: a 3-year radiographic study. Caries Res.
varnish frequency
1991;25(1):70-3.
trial; no control
Weinstein P, Spiekerman C, Milgrom P Randomized equivalence trial of intensive and semiannual
Head-to-head
applications of fluoride varnish in the primary dentition. Caries Res. 2009;43(6):484-90. Epub 2009
varnish frequency
Dec 10.
trial; no control
Sepp L, Tolonen T. Scand J Dent Res. Caries preventive effect of fluoride varnish applications
Head-to-head
performed two or four times a year. 1990 Apr;98(2):102-5.
varnish frequency
trial; no control
Axelsson P, Paulander J, Nordkvist K, Karlsson R. Effect of fluoride containing dentifrice, mouthrinsing, 0.7% F
and varnish on approximal dental caries in a 3-year clinical trial. Community Dent Oral Epidemiol. 1987Fluorprotector
Aug;15(4):177-80.
composition no
longer available
van Eck AA, Theuns HM, Groeneveld A. Effect of annual application of polyurethane lacquer
0.7% F
containing silane-fluoride. Community Dent Oral Epidemiol. 1984 Aug;12(4):230-2.
Fluorprotector
composition no
longer available
Demito CF, Rodrigues GV, Ramos AL, Bowman SJ. Efficacy of a fluoride varnish in preventing
Split mouth; 6
white-spot lesions as measured with laser fluorescence. J Clin Orthod 2011;45(1):25-9; quiz 40.
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)
79
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
80
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)
Children
Duraphat every 4
months
Control
Prior
prophylaxis
?
Caries
risk
status as
stated by
authors
Baseline
score
Other F
exposure
for both
groups
Specificall
y recruited
patients
with caries
experience
?
Followup
duration
Outcome
measure
Diagnosti
c criteria
Reported
result
Adverse
events
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
32
months
DMFS all
teeth and all
surfaces
dfs only
first and
second
molars
Cavitated
Significant
favoring
varnish
Not
assessed
2 years
dmfs and
dmft all
teeth and
surfaces
Cavitated
WSL
Study
Design
Primary Dentition
AutioGold 2001
35
Clark
198531-33
Grodzka
1982 40
Gugwad,
201139
35
years
3-4
6-7
years
US
Canada
Poland
India
DMFS <
1;
Children
1. Durafluor 2.
Fluorprotector every six
months
No
varnish
Professional
Prophylaxis
Children
Duraphat every 6
months
No
treatment
Pumice
prophylaxis
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
Not Stated
Not stated
Baseline
dfs not
given
dmfs1 >
10
dmfs2>9.3
dmft1>6.5
dmft2>6.3
Dentifrices,
supplemet
s and
topical
fluoride
No topical
fluorides
No
No
defsp 5.35.5
defs 5.65.7
DMFS=0.
4-0.7
Yes
Not stated
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
Significant
favoring
Duraphat for
WSL dmft
ONLY
Primary defs
Control:
6.52
Varnish:
4.68
Not
assessed
RCT
RCT
GCCT (not
adjusted for
clustering)
Increments
Control:
0.89
Varnish: 0.99
p=0.03
Statistically
favors
varnish for
primary
teeth/surfac
es and no
difference
for
permanent
teeth/surfac
es *Note
that in
discussion
Not
reported
RCT
81
section the
authors note
that many
children did
not have
erupted
molars,
which may
have
affected the
permanent
teeth results
Not stated
Relatively
deprived
communit
y
Hardman
200736
6-8
United
Kingdom
d3ft > 2
dfs not
given
F milk; Fl
toothpaste
26
months
dfs
primary
molars all
surfaces
WS and
cavitated
Nonsignificant
difference
for large
WSL and
dentine
lesions;
significant
for small
WSL
No
2 years
defs All
teeth
Cavitated
and WSL
separatel
y
Significant
favoring
Duraphat
Not
assessed
CCT
No (but
post-hoc
per
baseline
score)
GRCT
(adjusted)
Children
Duraphat every 6
months
No
varnish
Unclear
No
treatment
Brushing
with special
powder
Not stated
ds < 1.5
F
toothpaste;
Some had
Fl
supplemen
ts
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)
Not Stated
ds = 0
F
toothpaste
and F
water
No (cariesfree)
2 year
dfs all
teeth and all
surfaces
Cavitated
and all
stages
Significant
favoring
varnish
None
observed
RCT
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
complicatio
ns
associated
with varnish
application
RCT
Cavitated
Significant
in favor of
varnish
Not
assessed
GRCT
(molar is the
unit of
analysis and
adjustment
for this BUT
allocation by
Holm
197941
Sweden
Children
Duraphat every six

months
Lawrence
200837
6
months
to 5
years
Canada
Children
Duraflor every 4- 6
months + counseling
Caregiver
Counselin
g
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
Prevalenc
e and
severity of
cariesis
among the
worst in
the
country
Nonfluoridated
community
Not
assessed
Permanent Dentition
Arruda
201242
Bravo
1997 43, 44,
116
7-14
6-8
Brazil
Spain
Children
Children
Cavity Shield (5% NaF

or 2.26% F); tested
application 1 and 2 times
per year combined
Duraphat every 6
months
Placebo
varnish
No
varnish
Toothbrushi
ng
Unclear
None
Not Stated
DFS
Test
6.15
Control
5.59
58.4% and
59.7% of
Test and
Control
received
Fluoridated
water
DMFS < 1
Not
investigate
d
No
12
months
DFS
Prevented
fraction
No
4 years
(2 year
data
available)
DMFS
first
permanent
molar all
surfaces
82
school
class)
Clark
198531-33
Holm and
Holst
1984 45
5
years
and 9
month
s
Ibricevic
200553
Koch
197546
Milsom
201147
Modeer
1984 48
Skold
200549
Canada
Children
1. Durafluor 2.
Fluorprotector every six
months
DMFS <
1;
No
varnish
Professional
Prophylaxis
No
treatment
Toothbrush
with special
cleansing
powder and
water
Not Stated
Baseline
dfs not
given
dmfs > 8
Sweden
Children
Duraphat every 6
months
Not Stated
NEWLY
ERUPTIN
G FIRST
MOLARS
DMFS=0
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)
15
Sweden
Adolescent
s
Duraphat every 6
months
No
treatment
Pumice
prophylaxis
High risk
DMFS >
20
7-8
yrs.
14
13
England
School
children
0.1ml Duraphat
(5% NaF) 3 X yr. on
permanent 1st molars
Sweden
Adolescent
s
Duraphat every three

months
Sweden
Children
Duraphat every 6
months, 3 times a year
within one week, 8 times
per year at 1 month
intervals during school
year
Yesno
treatment
No
No
treatment
Pumice
prophylaxis
Not Stated
Self
brushing
without
paste
Low,
Medium
and High
based on
SES,
caries and
water F
No
varnish
High Risk
Dentifrices,
supplemet
s and
topical
fluoride
Weekly
rinsing with
0.2% NaF,
0.4 0.9
ppm Water
F
No
32
months
DMFS all
teeth and all
surfaces
dfs only
first and
second
molars
No
2 years
after
eruption
of
permane
nt first
molar
DS Occlusal
surfaces of
first
permanent
molars
Cavitated
Cavitated
Unclear
No
2 years
DMFT all
teeth and all
surfaces
Cavitated
F rinse
every 2
weeks
No (posthoc based
on baseline
score)
1 year
DMFS all
teeth and all
surfaces
Cavitated
and WSL
No
No water
fluoridation
No
DFS > 2
Weekly F
rinse, Low
F water; F
toothpaste
s
No (posthoc based
on baseline
score)
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)
Significant
favoring
varnish
Significant
Favoring F
varnish
Nonsignificant
for healthy
children;
Significant
favoring
fluoride
varnish for
special
needs
Significant
favoring
varnish
(mainly for
low and
medium
risk)
Not
assessed
RCT
Not
assessed
RCT
(patient was
unit of
randomizati
on but looks
like results
are reported
for molars)
Not
assessed
CCT
Not
assessed
RCT
12 children
in
intervention
group
reported
adverse
reactions
(full details
online)
GRCT; 95
clusters in
each tx
3 yrs.
DFS
(primary)
DFT
(secondary)
cavitation
No
statistically
different
difference
between the
groups
3 years
DFS
premolars
and molars
proximal
surfaces
All
stages,
Cavitated
and WSL
Significant
favoring
varnish;
different
with
baseline risk
Not
assessed
3 years
DS
proximal
surfaces
from distal
of canine to
mesial of
second
molar
(radiographi
c)
All
stages,
WSL and
cavitated
separatel
y
Significant
favoring
varnish
None
observed
RCT
RCT
83
treated
with one F
varnish at
the yearly
check-up.
Fl
toothpaste
Schaeken
50
Tagliaferr
54
o, 2011
Tan
201051
Tewari
199052
44.4
6-8
Netherlan
ds
Brazil
Adults
Children
Duraphat every 3
months
Duraphat biannually
No
varnish
Professional
Prophylaxis
No
varnish
No;
Supervised
tooth
brushing
Low and
high risk
Unclear
> 60 root
lesions
High risk
dmft > 4.3;
DMFT>0.2
6
Low risk
dmfs +
DMFS=0
Varied
Yes
1 year
RCI
All Stages
Significant
favoring
varnish
None
observed
RCT
Fl water;
Fl Tooth
paste
Yes
2 years
DMFS
permanent
first molar
only
Cavitated
and WSL
Not
significant
Not
assessed
CCT
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
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
No
varnish
Professional
Prophylaxis
without F
3 years
DMFT/dmft;
DMFS/dmfs
all teeth
Cavitated
Significant
favoring
varnish
Mild
burning,
pungent
odor and
nausea with
APF
CCT
Combined Dentition
Shobha
198755
9 - 12
India
Children
Six monthly applications

of Duraphat
Not Stated
DMFS/dm
fs > 10
Low water
F
No
84
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?
Yes
Yes
No
Yes
Yes
Yes
Unclear
Unclear
No
No
Yes
Yes
No
No
No
No
Unclear
Unclear
Unclear
No
No
Yes
Yes
Yes
No
No
Unclear
Yes
Unclear
Unclear
Unclear
Unclear
Yes
Yes
Yes
Yes
Unclear
Examiner
Yes
Unclear
Yes
Yes
No
No
Yes
No
No
No
Examiner
Yes
No
Yes
No
No
Yes
Yes
Yes
Yes
Unclear
Examiner
Yes (ITT)
Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Primary Dentition
Autio-Gold
2001 35
Grodzka
1982 40
Gugwad
201139
Hardman36
Holm
197941
Lawrence
200837
Weintraub
2006 38
6
2
4
7
5
9
11
Yes
Yes
Yes
Examiner and
patient
Yes
Yes
Yes
No
Examiner and
patient
Yes
Unclear
Yes
Yes
No
Yes
Yes
Yes
No
Unclear
Examiner
Unclear
Unclear
Yes
No
No
Yes
Yes
Yes
No
Unclear
Examiner and
patient
Yes
Yes
Yes
No
No
Yes
Yes
Yes
No
Unclear
Unclear
Unclear
Unclear
Yes
No
No
Yes
Yes
No
No
No
No
Unclear
Unclear
Unclear
No
No
Yes
Unclear
Unclear
No
Unclear
Yes
Yes
Permanent Dentition
Arruda42
Bravo43, 44,
Clark31-33
Holm and
Holst 45
Ibricevic
200553
Koch
197546
Milsom
201147
Modeer
1984 48
Skold
200449
Schaeken50
116
2
4
10
5
6
7
Yes
Yes
No
No
unclear
Yes (min
LOF)
Yes
Yes
Yes
Yes
Yes
Yes
Unclear
Yes
Yes
Yes
Yes
Yes
No
No
Examiner
No
Unclear
Yes
No
No
Yes
Yes
Unclear
Yes
No
No
Yes
Yes (no
Yes
Yes
No
NA
No
Yes
Yes
Yes
Yes within
cohorts
Yes
Unclear
Unclear
No
Unclear
Provider and
examiner
Patient and
85
Tagliaferro,
201154
Tan 201051
Tewari
199052
7
11
7
examiner
loss)
Yes
No
No
No
Examiner
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Examiner
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Unclear
Examiner
Yes
Yes (min
loss)
Yes
Yes
No
No
Yes
No
No
Unclear
No
Yes
Yes
No
NA
Yes
Combined Dentition
Shobha
198755
Yes
Yes (min
loss)
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
3.05
4.25
59
4.05
4.40
83
0.54
4.1
59
1.47
4.0
83
Other available data
Primary Dentition
Caries prevalence dmfs cavitated 9month data
Autio-Gold 2001 35
Clark
Caries increment dmfs cavitated

calculated (baseline to 9 months)
Caries increment dmft cavitated 9month data
Use Table 1 data (cavitated); 9-month data;

Data for all stages including WSL available (in Table 2)
1.68
2.27
59
2.57
245
2.06
2.28
83
Cavitated increment assumed dfs 32

months
1.49
Net dmfs increment - cavitated
6.35
4.98
148
6.71
5.22
100
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
defs, 1 year BEFORE
5.67
5.40
106
5.63
4.02
105
defs, 1 year AFTER
4.68
4.95
106
6.52
7.31
105
2.36
2.82
234
Grodzka 1982 40
SD calculated from Cochrane equation in Clark 1985;

noted difference not stat sig
Radiographic data.
Gugwad 201139
OHI-S; deftp, deft, DMFT
86
defs, change (calculated)
-0.99
5.2
106
0.89
6.3
105
dfs caries increment WSL (d1fs)
0.71
1.57
334
1.12
2.02
330
dfs caries increment cavitated (d3fs)
1.52
2.39
334
1.49
2.36
330
Net defs increment-Cavitated
2.10
2.75
112
3.74
4.62
113
Net WSL(primary, surface) increment
0.81
2.56
112
0.92
3.07
113
MA; wsl = d2fs+d1fs; proportion of children with caries

increment in permanent dentition
Hardman 200736
calculated SD using Cochrane equation
already adjusted for clustering
Holm 197941
Surface specific data; prevalence data in table 4
Lawrence 200837
Mean net caries increment dmfs all

stages; Adjusted means, Aboriginal
children only
Unadjusted means available for intent-to-treat

population; stratification by age group.
11.00
31
832
13.48
31
328
SD calculated from adjusted difference column in

Table 3 of paper according to
SD = SE/(sqrt(1/832 + 1/328))
Weintraub 2006
dfs Incidence cavitated ITT group,

2x/year
0.7
dfs incidence- all stages ITT group

2x/year
1.4
2.1
87
1.7
3.1
100
1 application over 2 years; 3-4 applications over 2
years; Intended treatment group
38
3.1
87
2.7
3.4
100
Permanent Dentition
Arruda42
Bravo 1997 43, 44, 116
DFS increment, one and two

applications combined
95% CI
(3.54-5.67)
4.61
Prevented fraction, adjusted and unadjusted

generalized linear models
(6.26-9.18)
113
7.72
Calculated
4.39
Calculated
5.84
97
Children who received one or two applications

SD calculated from Cochrane equation
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
87
CLUSTER ADJUSTED (all significant at

all adjustments; picked conservative
ICC=0.2)
Clark 1985
31-33
DMFS caries increment DuraflorCavitated assumed
1.48
1.53
27
2.58
1.89
32
Used this in MA
Surface specific data; 32 month data used but 56

month data available
2.43
3.7
246
3.11
3.7
234
SD calculated from p value in Clark 1985
Holm and Holst 1984
Proximal only, occlusal only, depth of fissure, time to

caries from eruption
DS of first molars; Assumed prevalence,

Cavitated
1.44
2.32
50
3.29
3.65
59
DMFT caries increment - cavitated
0.35
0.69
43
0.47
1.13
34
Net DMFS increment cavitated
0.9
3.80
60
4.0
3.75
61
Net WSL (surface) increment
0.5
3.56
60
1.3
2.58
61
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
45
DECIDED SHOULD BE TOOTH-LEVEL

DATA SINCE ONLY 1 SURFACE
Ibricevic 200553
Koch 197546
DFS mean cavitated increment

DFT mean cavitated increment
Milsom 201147
Special Needs
By baseline prevalence and surface specific data

available. By caries risk also available.
Scores separately for each stage available;

progression data available; Progression data by caries
acitivity
DFS increment cavitated [03+F] (by

subtracting prevalence at baseline from
prevalence at 3 years)
1.4
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
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
2.3
87
2.0
2.8
107
SD for increment imputed via Cochrane regression

equation (2009)
Modeer 1984 48
Skold 200449
Use Cochrane regression equation to impute SD
88
Schaeken 1991 50
Root Caries increment surface cavitated
0.67
0.80
15
1.54
0.80
13
Caries increment DMFT cavitated (high

risk) Occlusal surfaces only
0.29
0.68
48
0.39
0.72
44
0.31
0.69
48
0.27
0.90
44
Caries increment DMFT all stages (high

Tagliaferro, 201154
Caries increment DMFT cavitated (low

0.29
43
0.12
0.40
42
0.09
0.29
43
0.14
0.42
42
0.33
1.04
91
0.57
1.39
86
Caries incidence Root-Cavitated root

surfaces
0.9
2.10
49
2.5
3.71
55
DMFS caries increment - all stages
0.554
4.58
311
2.163
4.12
307
DMFT caries increment - all stages
0.383
2.61
311
1.47
2.26
307
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
Caries increment all risks, all surfaces
Tan 201051
WSL data available; combined data available

0.09
Caries increment DMFT all stages (low

Calculated from p value in paper
Tewari 199052
Surface specific data; Teeth present at baseline vs

erupted during study
Combined Dentition
Shobha 1987
55
89
Table D: Characteristics of studies on 0.1% fluoride varnish
Citation
Age
Country
Special
Population?
Zimmer
200158
9
12
years
Germany
Children
Fluorprotector every 4
months + oral hygiene
instruction
Children
months
Twetman
199657
Petersson
1998 56
4-5
4-5
Sweden
Sweden
Children
Caries
risk
status as
state d
by
authors
Baseline
score
Other F
exposure for
both groups
Specifically
recruited
patients with
caries
experience?
Followup
duration
Outcome
measure
Diagnostic
criteria
Reported
result
Adverse
events
Study
Design
Intervention
(Dose/duration/frequency)
Control
Prior
prophylaxis?
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
No varnish
Pumice
prophylaxis
Not low
risk
dfs 0.181.0
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
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
months
No varnish
Pumice
prophylaxis
and floss
Low
caries
risk
90
Table E: Risk of bias assessment of studies on 0.1% fluoride varnish
Citation
Summary
risk of
bias score
Zimmer
200158
Twetman
199657
6
2
Were
patients in
both arms
recruited
from the
same
population at
the same
time?
Randomization
claimed
(random
sequence
generation)
Yes
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?
Yes
Yes
Unclear
Unclear
No
Yes
Yes
Unclear
No
Yes
No
No
No
No
Unclear
Yes (min
loss)
Unclear
Unclear
No
No
Yes
No
No
No
No
Unclear
No
Yes
Unclear
No
No
Yes
2
Petersson
1998 56
Table F Outcomes data from studies on 0.1% fluoride varnish
Citation
Zimmer 200158
Outcome measure (permanent/primary;

surface/tooth; outcome; all
stages/ws/cavitated)
Exp
mean
Exp SD
Exp n
Control
mean
Control
SD
Control
n
Mean increment DMFS All stages
6.18
3.92
187
9.14
4.50
131
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
Caries incidence dfs--Cavitated
1.07
1.96
442
1.53
2.55
374
Caries incidence - dft--Cavitated
0.65
1.40
442
1.09
1.85
374
Caries incidence dfs--Cavitated
1.30
2.46
2245
1.39
2.66
1916
Twetman 199657
Petersson 1998 56
Other available data
Prevalence data available
Approximal data; high F area
Approximal data
91
Table G: Characteristics of studies on professionally-applied 1.23% fluoride (APF) gel
Citation
Age
Agrawal
201170
9-16
years;
mean
age
experime
ntal
group
was
12.83,
and
control
was
12.94
Jiang and
Tai 2005 65
67
Hagan
198563
11 - 15
Country
Control
Prior
Prophyl
axis
Caries
risk
status as
state d by
authors
Baseline
score
(approxi
mate)
Other F
exposur
e for
both
groups
India
1.23% APF gel

(Fluorovil) + oral
health education
at baseline; gel
applied at
baseline and 6
months for 4
minutes
No
interventi
on + oral
health
educatio
n at
baseline
Assume
No
High risk;
underprivil
eged; low
SES
4.01 for
gel
group;
4.30 for
control
(DMFS)
Few
regularly
using
fluoride
dentifrice
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
Unites
States
8.12
United
States
Horowitz
1968,
1969,
72-74
1971
10-12
(grades
5-6)
United
States
8 - 12
Intervention
(Dose/duration/
frequency)
High risk
school
children
(underprivil
eged)
Trubman
1973 68
Bryan
196859,
1970 60
Special
Populatio
n?
United
States
Specifically
recruited
patients
with caries
experience
?
Follo
w-up
durat
ion
Compli
ance
Outcome
measure
Diagnosti
c criteria
Reported
result
Adverse
events
Study
Design
None
were
reported
GRCT,
n=1
cluster
per
interventi
on
Yes
6 and
12
mont
hs
Profess
ionally
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)
No
2
years
Profess
ional
applicat
ion
DMFS
first molar
Cavitated
Significant
favoring F for
smooth
surfaces only
None
observed
GRCT
(by class
and not
adjusted)
No
2
years
Profess
ional
applicat
ion
DMFS all
teeth
Cavitated
Statistically
significant
favoring F
3
episodes
of
nausea
or
vomiting
RCT
Children
1.23% APF gel

for 4 minutes
every 6 months
Placebo
gel (no F
or acid)
Professio
nal brush
and floss
with no
paste
Not stated
DMFS >
4
Low
water F;
Some
children
received
professio
nally
applied fl
from
regular
dentists
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
prophyla
xis paste
Not Stated
DMFS >
2
Low
water F
No
3
years
Selfapplied
at
school
DMFT,
DMFS all
teeth
Cavitated
Significant
favoring F
Not
assesse
d
RCT
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
Profess
ionally
applied
DMFS all
teeth
Cavitated
Significant
favoring F
None
observed
CCT
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
Profess
ionally
applied
DMFS,
DMFT all
teeth
Cavitated
Significant
favoring F
Not
assesse
d
RCT
92
Unclear
DMFS >
2
Low
water F;
Unclear
dentifrice
exposure
No
2
years
Profess
ionally
applied
DMFS,
DMFT all
teeth
Cavitated
Significant
favoring F
Not
assesse
d
RCT
Pumice
Prophy
Unclear
DMFS >
2
No water
F
No
3
years
Profess
ionally
applied
DMFS,
DMFT - all
teeth and
surfaces
for 1M
Cavitated
Significant
favoring APF
Not
assesse
d
RCT
Placebo
rinse
Yessonic
scaler
Unclear
(root
caries
prevalence
of 69.7%)
DS > 1
F water
and F
toothpast
e
No
4
years
Profess
ionally
applied
Root
caries
DMFS
(Katz)
Cavitated
Significant
favoring F
Not
assesse
d
RCT
1.23% APF 4
minute gel biannual (every 6
months)
Non-F
Placebo
gel
No
prophyla
xis
High-risk
defs > 20
F
Toothpas
te
Yes (High
and veryhigh)
2
years
Profess
ionally
applied
DMFS all
teeth
All stages
Not significant
Not
assesse
d
RCT
Adolescents
1.23% APF gel 4

minutes every 6
months
No
treatmen
t
Professio
nal
brushing/
floss
Unclear
DMFS >
5
Low
water F
No
2
years
Profess
ionally
applied
DMFS all
teeth
Cavitated
Significant
Favoring F
Not
assesse
d
RCT
No gel
Professio
nal
prophyla
xis with
nonF
paste
Not Stated
DMFS/d
mfs >10
Low
water F
No
3
years
Profess
ionally
applied
DMFT/dmf
t;
DMFS/dmf
s all
teeth
Cavitated
Mild
burning,
pungent
odor and
nausea
with APF
CCT
Children
1. prophylaxis +
APF gel for 4
minutes single
application
No
treatmen
t
Prophy
Children
1.23% APF gel

for 4 minutes+
prophylaxis
annually
Prophy+
water
60
United
States
Seniors
1.2 % APF gel for

4 minutes
(Luride) +
placebo rinse
semi-annual
Olivier
1992 67
Canada
Children
Cobb 1980
11 - 14
US
Ingraham
1970 64
6 - 11
United
States
6 - 11
Unites
States
Wallace
1993 69
Cons 1970
62
61
Significant
favoring Naf
and APF
compared to
control
Shobha
55
1987
9 - 12
India
Children
Semi-annual
applications
of1.23% APF gel
Andruske
viciene
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
toothpast
e
No
3
years
Profess
ionally
applied
dmft and
dmfs
Cavitated
Significant
favoring APF
Not
assesse
d
CCT
Mainwarin
g 197866
11 - 12
UK
Children
1.23% APG gel

semi-annually for
4 min + brushing
with NonF paste
NonF
Gel +
brushing
with no-F
paste
Selfbrushing
Unclear
DFS > 5
Water F
< 0.3ppm
No
3
years
Profess
ionally
applied
DFS all
teeth and
surfaces
cavitated
Significant
favoring F
Not
assesse
d
RCT
Szwejda
197175
7-8
US
Children
1.23% APF
annual for 3
minutes
No gel
Pumice
prophyla
xis
Unclear
DFS < 2
No
No
2
years
Profess
ionally
applied
DFT, DFS
all teeth
and
surfaces
Cavitated
Nonsignificant
Not
assesse
d
CCT
93
Table H: Risk of bias assessment of studies on professionally-applied 1.23% fluoride (APF) gel
Randomization
claimed (random
sequence generation)
Randomization
procedure described
Allocation
concealment
(selection bias,
protects
assignment
sequence before
and until
allocation)
Citation
Summary risk
of bias score
Were patients
in both arms
recruited from
the same
population at
the same
time?
Agrawal 201170
Jiang 2005 65
7
7
Yes
Yes
Yes
Yes
Yes
Yes
Unclear
No
Hagan 198563
Yes
Yes
No
Unclear
Trubman 1973 68
Yes
Yes
No
Unclear
Yes
Yes
Yes
No
Unclear
Yes
Yes
yes
No
No
Yes
Yes
Yes
Yes
Unclear
Unclear
Unclear
Yes
Yes
No
No
Yes
Ingraham 1970
Cons 1970 62
Wallace 1993 69
6
7
6
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
unclear
Unclear
Unclear
Yes
Yes
Yes
unclear
Yes
Unclear
Yes
Yes
Yes
No
No
No
No
No
No
Yes
Yes
Yes
Olivier 1992 67
Yes
Yes
No
No
Yes
Yes
Yes
No
No
Yes
Yes
Yes
No
Unclear
Examiner
Examiner
Examiner
Provider and
examiner
Examiner
Unclear
No
No
Yes
Yes
No
No
Unclear
No
Yes
Yes
No
No
Yes
Yes
No
No
Unclear
Unclear
Yes
Yes (min
loss)
Yes (min
loss)
Unclear
Unclear
Unclear
No
NA
Yes
Yes
Yes
No
Unclear
Examiner and
patient
unclear
Unclear
Yes
No
No
Yes
Not clear
Not stated
No
No
Examiner
Not
stated
Not stated
Yes
No
No
Yes
Horowitz 1968,
1969, 197172-74
Bryan 1969, 1970
60
64
Cobb 1980
61
Shobha 198755
Andruskeviciene
2008 71
Mainwaring
197866
Szwejda 197175
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?
Examiner
Examiner
Examiner and
patient
Examiner and
patient
Yes
No
Unclear
Unclear
Yes
Yes
No
Yes
No
No
Yes
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
No
No
Yes
94
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
0.55
0.43
118
1.41
0.94
137
0.68
0.65
118
1.92
0.94
137
Other available
data
Primary Dentition
Andruskeviciene
2008 71
dmft increment
cavitated
dmfs increment
cavitated
Permanent Dentition
Agrawal 201170
DMFS as reported
(12 months)
4.32
1.439
120
4.63
1.484
119
Jiang and Tai

2005 65
Mean DMFS
increment cavitated
0.38
0.69
200
0.50
0.87
221
Hagan 198563
Mean DMFS
increment cavitated
3.08
3.85
108
4.40
3.86
103
2.74
3.13
145
4.21
4.12
166
1.29
1.57
145
1.67
1.67
166
3.06
2.97
182
3.62
3.00
170
6.51
6.75
182
8.61
7.95
170
2.01
2.54
103
3.63
3.33
105
4.56
4.50
103
7.26
4.76
105
1.84
2.24
56
3.13
2.70
63
0.84
1.05
56
1.76
0.79
63
1.50
1.67
278
1.99
1.94
311
3.14
3.83
278
3.82
5.11
311
Trubman 1973 68
Horowitz 1968,
1969, 197172-74
Bryan 1969, 1970

60
Ingraham 1970
Cons 1970 62
Mean DMFS
increment cavitated
Mean DMFT
increment cavitated
Mean DMFT
increment cavitated
Mean DMFS
increment
cavitated
Mean DMFT
increment cavitated
Mean DMFS
increment cavitated
64
Mean DMFS
increment cavitated
Mean DMFT
increment cavitated
Mean DMFT
increment Cavitated
Mean DMFS
increment Cavitated
IL data, 6 month
data
Smooth surface
and P and fissure
reported
Smooth surface
and P and fissure
reported
Reversals
Surface type;
reversal
95
Wallace 1993 69
DMFS incrementCavitated
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
5.28
0.66
115
8.15
0.87
78
4.86
2.58
195
6.89
3.33
195
7.45
3.01
195
10.36
3.86
195
Prevalence data
available
7.10
5.62
315
8.27
6.62
316
Reversals
1.23
1.22
148
1.27
0.75
170
2.07
2.43
148
2.15
2.22
170
Cobb 1980 61
Shobha 198755
Mainwaring 197866
Szwejda 197175
DMFS increment
cavitated
DMFT + dmft
Caries Increment- all
stages
DMFS + dmfs caries
increment all
stages
Net DFS increment
cavitated
Caries incidence
DMFT cavitated
Caries Incidence
DFS Cavitated
Table J: Characteristics of studies on 1.23% fluoride (APF) foam
Citation
Age
Jiang
and Tai
2005 65
67
Jiang
and
Bian
200577
3-4
years
Country
China
China
Special
Population?
Intervention
(Dose/duration/
frequency)
Children
1.23% APF
Foam for 4
minutes every 6
months
Children
1.23% APF
foam for 4
minutes every 6
months
Control
Prior
prophylaxis?
Caries
risk
status
as
stated
by
authors
No Tx
No
prophylaxis
Not
Stated
No
prophylaxis
Not
Stated
Placebo
Baseline
score
(approximate)
Other F
exposure
for both
groups
Specifically
recruited
patients
with caries
experience?
Followup
duration
Compliance
Outcome
measure
No
2 years
Professional
application
No
2 years
Professional
application
Low
DMFS > 7
water F
dmfs > 2
22% F
toothpaste;
low water
F; no
community
programs
Diagnostic
criteria
Reported
result
Adverse
events
Study
Design
DMFS
first
molar
Cavitated
Significant
favoring F
for smooth
surfaces
only
None
observed
GRCT
(by class
and not
adjusted)
dmfs all
teeth and
all
surfaces
Cavitated
Significant
favoring
approximal
surfaces
only
None
observed
GRCT (p
values at
cluster
level)
96
Table K: Risk of bias assessment of studies on 1.23% fluoride (APF) foam
Citation
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?
Yes
Yes
No
Examiner
No
Unclear
Yes
Yes
No
Yes
Yes
Yes
Yes
Examiner and
patient
Yes
Unclear
Yes
Yes
No
Yes
Summary risk of bias

score
Were patients in both

arms recruited from
the same population at
the same time?
Randomization
claimed (random
sequence generation)
Yes
Yes
Jiang
and Tai
2005 65
Jiang
and
Bian
200577
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

200577
dmfs Increment
Cavitated
3.8
0.9
167
5.0
1.0
151
By tooth surfaces
97
Table M: Characteristics of studies on prophylaxis pastes containing fluoride

Caries
risk
status
as
stated
by
authors
Baseline
score
(approximate)
Other F
exposure
for both
groups
Subjects
included
based on
presence of
caries
experience?
Followup
duration
Outcome
measure
(record
smooth
vs. pit
and
fissure)
Diagnostic
criteria
Reported
result
Adverse
events
Study
Design
DMFS >4
Two data
sets with
fluoridated
and nonfluoridated
communities
No
2 years
DMFS,
DMFT
all teeth
and
surfaces
Cavitated
Nonsignificant
difference
Not
assessed
RCT
No
2 years
DMFS,
DMFT, all
teeth and
all
surfaces
Cavitated
Nonsignificant
difference
Not
assessed
CCT
Special
population?
Intervention (Dose/duration/
frequency)
Control
Children
APF paste applied annually with a

rubber cup
Annual
pumice
prophylaxis
9 - 14
Unites
States
Children
Semiannual prophylaxis with APF

paste for 4 minutes for two years
Placebo
paste
Unclear
DMFS > 5
Low fluoride
area
Schutze
197483
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
197379
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
196682
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
9% SnF paste for 4 minutes +

placebo solution
Placebo
paste +
placebo
solution
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
Citation
Age
Country
10 - 13
United
States
Barenie
197681
Peterson
196980
Beiswanger
197978
8 - 16
United
States
Children
Unclear
Unclear
98
Table N: Risk of bias assessment of studies on prophylaxis pastes containing fluoride
Citation
Peterson
1969
Barenie
1976
Schutze
1974
DePaola
1973
Horowitz
1966
Beiswanger
1979
Summary
risk of bias
score
Rate of
losses to
follow-up
similar
between
tx
groups
Baseline
caries
status of
those lost
to followup 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?
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)
Yes
Yes
No
Unclear
Yes
Yes
Unclear
Not
Reported
No
No
Yes
Yes
No
No
Unclear
Examiner and
patient
Unclear
Unclear
Yes
No
No
Yes
Yes
No
No
No
No
Unclear
Unclear
Yes
No
No
Yes
Yes
Yes
No
Unclear
Examiner and
patient
Unclear
Unclear
Yes
No
No
Yes
Yes
No
No
Unclear
Unclear
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Unclear
Examiner and
Patient
Yes
Unclear
Yes
No
No
Yes
Blinding
(ascertainment
bias, protects
sequence after
allocation)
Examiner,
patient and
statistician)
4
3
5
5
7
99
Table O: Outcomes data from studies on prophylaxis pastes containing fluoride

Citation
Peterson 1969
Barenie 1976
Outcome measure
Exp mean
Exp SD
Exp n
Control mean
Control SD
Control n
Mean Increment
DMFS Cavitated
Examiner A Fargo
2.63
3.14
256
3.00
4.37
252
Mean Increment
DMFS Cavitated
Examiner B Fargo
2.31
256
2.72
2.75
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
Mean Increment
DMFS Cavitated
Examiner B
Moorhead
2.47
Mean Increment
DMFT Cavitated
Examiner A
Moorhead
2.02
Mean Increment
DMFT Cavitated
Examiner B
Moorhead
1.34
Mean increment
DMFS cavitated
examiner 1
7.67
202
4.18
3.28
202
2.93
4.05
Surface data;
examiner B visual
and x-ray; cannot
combine data for
meta-analysis
205
4.01
202
2.30
1.93
205
2.12
202
1.55
1.71
7.16
205
4.51
Other available
data
205
1.92
181
7.15
6.07
152
Surface data;
newly erupted,
reversals. Cannot
100
Mean increment
DMFS cavitated
examiner 2
Mean increment
DMFT cavitated
examiner 1
Mean increment
DMFT cavitated
examiner 2
5.30
6.38
179
4.93
5.26
150
3.98
3.50
181
3.78
2.98
152
3.00
3.08
179
2.73
2.55
150
combine data for

meta-analysis
Surface, anterior
vs posterior
Schutze 1974
Mean increment
defs cavitated
4.64
4.41*
20
4.04
4.09*
20
Mean increment
DFT cavitated
2.36
2.15
151
2.92
2.68
169
DePaola 1973
*SD imputed using

Cochrane
equation
Erupted;
Mean increment
DFS cavitated
4.99
4.41
151
6.32
5.41
169
Mean increment
DMFT cavitated
1.63
NA
227
1.51
NA
222
Reversals
*Imputed using
Cochrane
equation
Horowitz 1966
Mean increment
DMFS cavitated
4.08
4.41*
227
3.85
3.98*
222
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
Beiswanger 1979
101
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
(approximat
e)
Other
exposu
re for
both
groups
Specifically
recruited
patients with
caries
experience?
Followup
duration
Outcome
measure
Diagnosti
c 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)
Nonsignifican
t difference
Not
assessed
RCT
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
Nonsignifican
t difference
Not
assessed
CCT
Johnston
1995 84
6 -11
Canada
Children
1.23% APF gel biannual +

prophylaxis
No
prophyla
xis + bi
annual
APF
Very high risk
defs > 10
Unclear
Yes
3 years
defs +
DMFS and
defs all
teeth and all
surfaces
Cavitated
Nonsignifican
t difference
Not
assessed
RCT
Houpt 1983
102
Table Q: Risk of bias assessment of studies on professional prophylaxis prior to fluoride application
Citation
Ripa
1984 85
Houpt
1983 87
Johnston
1995 84
Summary
risk of
bias score
6
3
7
Blinding
(ascertainment
bias, protects
sequence after
allocation)
Examiner,
patient and
statistician)
Rate of
losses
to
followup
similar
between
tx
groups
Baseline
caries
status of
those lost
to followup 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?

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)
Yes
Yes
No
Unclear
Unclear
Yes
Yes
Yes
No
No
Yes
Yes
No
No
No
No
Unclear
Unclear
Yes
No
No
Yes
Yes
Yes
Yes
Unclear
Examiner and
patient
Unclear
Unclear
Yes
Yes
No
Yes
103
Table R: Outcomes data from studies on professional prophylaxis prior to fluoride application
Outcome measure
Citation
Ripa 1984 85
Exp mean
Exp SD
Exp n
Control mean
Control SD
Control n
Mean DMFT
increment Cavitated
2.02
2.35
324
2.01
2.14
314
Mean DMFS
increments
Cavitated
3.33
4.35
324
3.19
3.62
314
Caries incidence
DMFS cavitated
2.05
3.4
269
2.14
3.4
381
Caries incidence
DMFT cavitated
0.94
1.6
269
1.19
1.8
381
Other data
available
Self-prophylaxis
and specific teeth
surfaces
Self-prophylaxis
Houpt 1983 87
defs increment
cavitated
Johnston 1995
2.25
2.72
47
2.17
2.25
39
2.22
3.13
45
2.50
2.40
30
84
DMFS increment
cavitated
Biannual;
defs+DMSF for 67 year olds;
Reversals in text
104
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?
Followup
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#
Not
described
Single
blind
RCT
Not
reported
RCT
Favors 5000
ppm dentifrice
(p<0.01)
compliant;
caries
progression
(not incidence,
p=0.4)
Nordstrom
201088
Ekstrand
200889
1416yr
75+
year
olds;
mean
age
81.6
Sweden
Denmark
adolescent
Home-based
frail elderly
with active
root caries
5000 ppm
dentifrice
2yr
1gr 2Xday
Unsupervised
5,000 ppm F
toothpaste
2x/day/pea size
amount /
unsupervised
1450ppm
dentifrice
1450 ppm
F
toothpaste
2x/day/pea
size
amount
no
F Varnish
group has
their teeth
brushed by a
dental
hygienist
before
application
High
Low/moderate
root
caries activity
DFS 5.84
5.83
Group 1 137 (total),

81 (active),
56
(arrested)
Group 2
133, 82, 51,
respectively
Group 3
125, 77, 48,
respectively
0.1ppm
water
F vanish tx
10%
supplements
0.5 ppm F in
drinking
water
yes
2yr
DFS
Cavitated
Enamel only
P=0.01 noncompliant
(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)
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
105
Cutress
199298
10-15
years
French
Polynesia
5000 ppm/200
times a
year/once
daily/supervised
in school
no
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
Nordstrom
201088
Summary risk
of bias score

arms recruited from the
same population at the
same time?
Randomization
claimed (random
sequence
generation)
Yes
Yes
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*
Yes
No
Single blind
(Examiner)
Similar
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?
Similar
Yes
Yes
No
Yes
No
No
Yes
No
No
Yes
6
Ekstrand,
200889
Cutress
199298
Yes
Yes
Yes
Unclear
Examiner and
patient
No
Unclear
no significant
inter-group
difference
concerning
number of active
lesions or
arrested lesions
Yes
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
106
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
DFS Incidence
(combined
compliance groups)
1.12
1.23
104
1.46
1.61
107
DFS progression
(combined
compliance groups)
1.28
1.50
104
2.13
2.10
107
Nordstrom 201088
Other available
data
Prevalence data;
proximal
incidence;
Compliance A vs
B; proximal
progression;
prevented fraction
Total number of
lesions
New active and

arrested lesions
Ekstrand, 200889
Change in status of
baseline active and
arrested lesions
New active / New

Arrested
Group 2 = 64
NA
Group 2 18 / 18
Mean DMFT
12 years, 5000 ppm,

mean=2.7
Combined, 2.6
NA
Group 3 = 54
Group 3 41 / 11
11 years, 5000 ppm,

mean=2.6
Cutress 199298
New active / New

Arrested
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
Calculated
combined SD=4.2
11 years, 1250
ppm, n=46
12 years, 1250
ppm, n=19
Characterization
of the participants
as to whether the
root caries status
became better,
stayed stable or
worsened during
the study
% DMFT; tooth
level DMFT
Combined, 4.2
107
Table V: Characteristics of studies on prescription-strength 0.5% fluoride (home-use) gels
Citation
Age
Country
Special
Populatio
n?
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
4.5
6.5
Netherlan
ds
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
Statisticall
y
significant
favoring
NaF
Not
assessed
RCT
Truin 2005
91
Truin
200792
9.5
11.5
Netherlan
ds
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
197197
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
26
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
Children
1. 1:1 % NaF
gel with 0.1M
phosphate
everyday; 2. 1:1
NaF gel
everyday
(excluding
summer break)
for 6 minutes
Cavitated
Significant
favoring F
vs control.
No
significant
difference
for APF vs
neutral
None
observed
RCT
All stages,
WSL,
Cavitated
Significant
favoring F.
The
majority of
caries
incidence
was
attributable
to incipient
lesions
Not
assessed
RCT
93
Englander
1967 117
Gisselsson
199990
11 14
13
Unites
States
Sweden
Children
1% NaF or 1%
Snf four times a
year; applied
with floss
No tx
Placebo
No
prophylaxis
No
prophylaxis
Unclear
Unclear
DMFS >
10
DFS > 2
Low water
F; F-free
toothpaste
F
toothpaste
and low
water F
No
No
21 months
3 years
Supervised
application
in school
settings
Professional
ly applied
DMFS all
teeth
DFS
approxmal
from
canine to
2M
108
Table W: Risk of bias assessment of studies on prescription-strength 0.5% fluoride (home-use) gels
Citation
Van
Rijkom
2004 94
Truin 2005
Sample
size
estimated
apriori
Intention
to treat
used?
Conflict of
Interest
absent?
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)
Yes
Yes
Yes
Examiner,
patient and
statistician
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
Examiner and
patient
Yes
Unclear
Yes
Yes
Yes
Yes
Summary
risk of
bias
score
Were patients in
both arms
recruited from
the same
population at the
same time?
Randomization
claimed (random
sequence
generation)
10
Yes
93
Truin 2005
91
Truin
200792
Baseline
caries
status of
those lost
to followup similar
to those
remaining
Baseline
caries
status
similar
between tx
groups at
end of study
or
adjustment
for
confounding
Rate of
losses
to
followup
similar
between
tx
groups
10
Englander
197197
Yes
Yes
No
Unclear
Examiner
Unclear
Unclear
Yes
No
No
Yes
Englander
1978 96
yes
Yes
No
Unclear
Unclear
Yes
Unclear
Unclear
No
No
Yes
Englander
1967 117
Yes
Yes
No
Unclear
Examiner
Unclear
Unclear
yes
No
No
Yes
Yes
Yes
No
Unclear
Examiner and
patient
No
Unclear
Yes
No
No
Yes
Gisselsson
199990
109
Table X: Outcomes data from studies on prescription-strength 0.5% fluoride (home-use) gels
Citation
Van Rijkom 2004

94
Truin 2005 93
Outcome measure
Exp mean
Exp SD
Exp n
Control mean
Control SD
Control n
Mean Increment
DMFS Cavitated
0.78
1.48
340
1.47
336
Mean Increment
dmfs Cavitated
1.80
3.13
2.34
3.67
340
336
Other available
data
Surface scores
available, Percent
progressed and
regressed
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
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
Englander 1967
117
110
Gisselsson 199990
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
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
111
Table Y: Characteristics of studies on 0.09% fluoride mouthrinse
Citation
Wyatt
2004109
Age
83
Country
Canada
Special
Population?
Intervention
(Dose/
duration/
frequency)
Long-term
care elders
Daily rinsing
0.2% NaF
Placebo
Placebo
Van Wyk
1986108
12 13
South
Africa
Children
Weekly
rinsing with
0.2% NaF
rinse
Driscoll
198199,
1982100
12.8
United
States
Children
Weekly and
daily rinsing
with 0.2%
NaF for one
minute
Heifetz
1981102, 103
10 12
Unites
States
Craig
1981101
11 12
New
Zealand
12.5
United
States
Ringelberg
1982106
Control
Placebo
Caries
risk
status
as
stated
by
authors
Baseline
score
(approximate)
Other F
exposure
for both
groups
Specifically
recruited
patients
with caries
experience?
Followup
duration
Compliance
Outcome
measure
Diagnostic
criteria
Reported
result
Adverse
events
Study
Design
Cavitated
Significant
favoring
NaF
Not
assessed
RCT
DMFS > 100
Some
used F
toothpaste
No
2 years
Similar
between
groups
Coronal
and root
caries
Incidence
and
reversals
all teeth
and
surfaces
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
Unclear
DMFS > 4
Optimum
water F
No
30
months
Supervised
DMFS
all teeth
Cavitated
Significant
favoring
NaF
Not
assessed
RCT
Cavitated
Significant
favoring
NaF vs
control.
No
significant
difference
between
weekly
and daily
Not
assessed
RCT
(data
reported
by
examiner)
Unclear
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
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
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
112
Horowitz
1971 104
6&
10
United
States
Torell
1965107
10
Poulsen
1983105
79
Denmark
Chikte
1996111
612
South
Africa
Sweden
Children
Weekly
rinsing with
0.2% NaF
for 1 minute
Placebo
monthly
Children
Bi-weekly
Rinsing with
0.2% NaF
rinse
No
treatment
Children
Bi-weekly
rinsing with
0.2% NaF
Children
Weekly
rinsing with
0.2% NaF
Liefde
1989 110
5-8
New
Zealand
Children
Bi-weekly
rinsing with
0.2% NaF
Corpus
1973 112
810
Philippines
Children
Bi-weekly
rinsing with
0.2% NaF
Placebo
Unclear
(low
ses)
Unclear
Unclear
6 yr olds
DMFS > 0.79;
10 yr olds
DMFS > 6.36
Low water
F
DMFS > 14
Low water
F
DMFS> 3
Low water
F, Used F
toothpaste
No
No
No
No
20
months
Supervised
DMFS,
DMFT
Supervised
DMFS all
teeth
Supervised
DMFS all
teeth and
surfaces
3 years
Supervised
DMFS
and
DMFT all
teeth and
surfaces
2 years
3 years
No rinse
Unclear
DMFS < or = 1
Low water
F;
Supervised
daily F
tooth paste
brushing
Placebo
Highrisk
based
on
caries
score
deft >3 and

decayed first
permanent
molar
Low water
F
Yes
3 years
Supervised
DMFT
Placebo
Unclear
DMFT > 1.38
Low water
F, No F
toothpaste
No
2 years
Supervised
DMFT
Cavitated
Significant
favoring
NaF
Not
assessed
RCT
Cavitated
Significant
favoring
NaF
Not
assessed
GRCT
(adjusted
for
clustering
in metaanalysis)
Cavitated
Significant
for teeth
erupting
during the
trial
Not
assessed
RCT
All stages
Significant
favoring F
rinse
Not
assessed
GCCT
(adjusted
for
clustering
in metaanalysis)
Non
significant
Not
assessed
RCT
Not
significant
None
observed
CCT
Cavitated
All Stages
113
Table Z: Risk of bias assessment of studies on 0.09% fluoride mouthrinse

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)
Yes
Yes
Unclear
Unclear
Yes
Yes
Unclear
Unclear
Yes
Yes
No
Unclear
Yes
Yes
No
Unclear
Examiner
Yes
Yes
No
Unclear
Yes
Yes
Yes
Unclear
Unclear
Examiner and
patient
Yes
Yes
No
Unclear
Yes
Yes
No
No
Yes
Yes
No
Unclear
Yes
No
No
No
yes
Yes
No
Unclear
Yes
No
No
No
Citation
Risk of
bias
score
Wyatt 2004109
Van Wyk
1986108
Driscoll
1982100
Heifetz
1981102
Craig 1981101
Ringelberg
1982106
Horowitz 1971
104
107
Torell 1965
Poulsen
1983105
Chikte 1996111
Liefde 1989
110
Corpus 1973
112
Blinding
(ascertainment
bias, protects
sequence after
allocation)
Examiner,
patient and
statistician)
Examiner and
patient
Examiner and
patient
Examiner and
patient
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?
Unclear
Yes
No
Yes
No
Yes
Yes
Unclear
Yes
No
No
Yes
Yes
Yes
Yes
No
No
Yes
Unclear
Unclear
Yes
No
No
Yes
Yes
Unclear
Yes
No
No
Yes
Unclear
Unclear
Unclear
No
No
Yes
Examiner
Yes
Yes
Yes
No
No
Yes
Examiner
Examiner and
patient
No
Examiner and
patient
Yes
Yes
(small)
Yes
Unclear
Unclear
Yes
No
Yes
Yes
Yes
No
No
Yes
Unclear
Unclear
No
No
Yes
yes
Unclear
Unclear
No
No
Yes
Unclear
Yes
Yes
Unclear
No
No
Yes
114
Table AA: Outcomes data from studies on 0.09% fluoride mouthrinse

Citation
109
Wyatt 2004
Van Wyk 1986108
Driscoll 1982100
Outcome measure
Exp mean
Exp SD
Exp n
Control mean
Control SD
Control n
Caries increment
crown DMFS
cavitated
0.4
2.5
39
0.8
2.4
36
Caries increment
root DMFS cavitated
0.3
3.1
39
2.2
3.8
36
DFS increment cavitated
4.6
4.4
185
7.5
5.7
192
Mean DMFS
increment
cavitated weekly
rinsing-- examiner 1
2.01
2.78
81
2.58
3.19
77
Mean DMFS
increment
cavitated weekly
0.85
1.73
84
1.89
2.69
74
Other available
data
Root increment;
Reversals; Root
reversals
Prevalence
difference; SD
estimated from
Cochrane
equation
Surface level ;
daily rinsing
Mean DMFS
increment
cavitated weekly
rinsing-- calculated
combined data
1.42
2.30
165
2.24
2.96
151
Mean DMFS
increment
cavitated daily
1.86
2.67
102
2.58
3.19
77
Mean DMFS
increment
cavitated daily
0.95
1.84
106
1.89
2.69
74
SD were not
stated; imputed
according to the
Cochrane
Equation
115
Mean DMFS
increment
cavitated daily
combined data
1.76
2.59
208
2.24
2.96
151
Mean DMFS
increment Cavitated
weekly rinsing-examiner 1
2.25
3.94
97
3.61
6.06
87
Mean DMFS
increment Cavitated
weekly rinsing-examiner 2
3.39
3.94
102
4.43
4.98
117
2.83
3.94
199
4.08
5.47
204
Mean DMFS
increment
cavitated weekly
combined data
Heifetz 1981
Surface level ;
daily rinsing;
reversal in 2 yr
results
102, 103
Mean DMFS
increment Cavitated
daily rinsing-examiner 1
1.90
4.03
88
2.94
3.41
107
2.47
3.90
DFS caries
increment Cavitated
1.8
DMFS increment
Cavitated weekly
2.66
DMFS increment
2.58
Mean DMFS
increment Cavitated
daily rinsing-examiner 2
Mean DMFS
increment
cavitated daily
combined data
Craig 1981101
Ringelberg
1982106
3.61
6.06
87
4.43
4.98
117
195
4.08
5.47
204
2.7
49
2.6
3.1
48
Surface level
score available;
3.98
253
3.34
4.42
249
Daily rinse;
approximal
3.85
257
116
Cavitated daily
Horowitz 1971
104
Torell 1965107
Poulsen 1983
105
Chikte 1996111
DMFS increment
cavitated6 year
old
DMFS increment
cavitated10 year
old
DMFS increment
cavitated
calculated combined
DMFT increment
cavitated6 year
old
DMFT increment
cavitated10 year
old
DMFT increment
cavitated
calculated combined
DMFS incrementcavitated
Mean DMFS
increment-cavitated
Mean DMFS
increment-caviated,
Newly erupted teeth
DMFS increment Cavitated
1.08
133
1.29
1.96
1.65
98
2.92
2.77
1.32
1.74
123
1.89
110
4.20
231
2.06
3.20
233
DMFT, eruption,
surface
0.54
1.15
133
0.72
123
1.00
0.79
1.68
98
1.63
110
2.62
0.64
1.40
231
1.15
1.94
233
5.10
4.93
160
10.02
6.75
162
1.75
2.37
191
1.83
2.20
0.73
1.31
191
0.99
1.52
174
1.054
2.54
603
1.245
2.65
642
Surface level data

available;
eruption; tooth
type; prevalence
174
Data by erupting
and erupted teeth
and by surfaces.
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
117
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.
118

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2 Topical Fluoride For Caries Prevention 2013 Update

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Topical fluoride for caries

2013 ADA Center for Evidence-Based Dentistry. All rights reserved.

Authors and acknowledgments

Is prophylaxis prior to professional application of topical fluoride necessary? ........................................ 40

Clinical considerations and recommendations

Balancing benefits with potential harms

Systematic review methods

Table 2. Inclusion/exclusion criteria

Prospective human controlled clinical studies (randomized or non-randomized)

Studies irrelevant to the topic

Table 3. Criteria for assessment of individual study risk of bias

Were patients in both study arms recruited from the same

*As defined by study author(s)

Data synthesis and meta-analysis

Process for developing evidence statements

The body of evidence usually includes consistent results from well-designed,

As more information becomes available, the magnitude or direction of the

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.

More information could allow a reliable estimation of effects on health

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.

Deviations from the protocol

Methods for developing clinical recommendations

Benefits balanced with

No benefit or potential harms

Expert Opinion For or Expert Opinion Against

Table 6. Definitions for the strength of recommendation:*

*Adapted from the USPSTF system

Varnish: 2.26% and 0.1% fluoride

Standardized Mean Difference

Meta-analysis results: Primary teeth

-0.19 [-0.31, -0.08]

-0.38 [-0.53, -0.24]

-0.67 [-1.14, -0.20]

Permanent teeth (children):

o NNT for control rate of 1 DMFS per year = 3

Permanent teeth coronal caries (adults):

Permanent teeth - root caries (adults):

Varnish (0.1% fluoride)

Notes: Twetman and Petersson not cluster adjusted in figure.

Primary teeth, meta-analysis results

Standardized Mean Difference

Evidence profiles: 0.1% fluoride varnish

APF gel (1.23% fluoride)

Standardized Mean Difference

-0.25 [-0.33, -0.16]

-1.51 [-1.79, -1.23]

-0.84 [-1.05, -0.63]

-0.22 [-0.44, -0.00]

APF foam (1.23% fluoride)

Standardized Mean Difference

Permanent teeth (children):

Prophylaxis pastes containing fluoride

0.14 [-0.48, 0.76]

Meta-Analysis results of permanent teeth data

Permanent teeth coronal caries (adults):