PEDIATRIC DENTISTRYV 39 / NO 5SEP / OCT 17RECOMMENDATIONS: CLINICAL PRACTICE GUIDELINEUse of Silver Diamine Fluoride for Dental Caries Management in Children and Adolescents,Including Those with Special Health Care NeedsYasmi O. Crystal, DMD, MSc, FAAPD1 Abdullah A. Marghalani, BDS, MSD, DrPH2 Steven D. Ureles, DMD, MS3 John Timothy Wright, DMD, MS4 Rosalyn Sulyanto, DMD, MS5 Kimon Divaris, DDS, PhD6 Margherita Fontana, DDS, PhD7 Laurel Graham, MLS8Abstract: Background: This manuscript presents evidence-based guidance on the use of 38 percent silver diamine fluoride (SDF) for dental caries management in children and adolescents, including those with special health care needs. A guideline workgroup formed by the American Academy of Pediatric Dentistry developed guidance and an evidence-based recommendation regarding the application of 38 percent SDF to arrest cavitated carieslesions in primary teeth. Types of studies reviewed: The basis of the guideline’s recommendation is evidence from an existing systematic review "Clinicaltrials of silver diamine fluoride in arresting caries among children: A systematic review." (JDR Clin Transl Res 2016;1[3]:201-10). A systematic search wasconducted in PubMed /MEDLINE, Embase , Cochrane Central Register of Controlled Trials, and gray literature databases to identify randomized controlled trials and systematic reviews reporting on the effect of silver diamine fluoride and address peripheral issues such as adverse effects and cost. TheGrading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of the evidence and theevidence-to-decision framework was employed to formulate a recommendation. Results: The panel made a conditional recommendation regarding theuse of 38 percent SDF for the arrest of cavitated caries lesions in primary teeth as part of a comprehensive caries management program. After takinginto consideration the low cost of the treatment and the disease burden of caries, panel members were confident that the benefits of SDF applicationin the target populations outweigh its possible undesirable effects. Per GRADE, this is a conditional recommendation based on low-quality evidence.Conclusions and practical implications: The guideline intends to inform the clinical practices involving the application of 38 percent SDF to enhancedental caries management outcomes in children and adolescents, including those with special health care needs. These recommended practices arebased upon the best available evidence to-date. A 38 percent SDF protocol is included in Appendix II. (Pediatr Dent 2017;39(5):E135-E145)KEYWORDS:SILVER DIAMINE FLUORIDE, CLINICAL RECOMMENDATIONS, GUIDELINE, ANTI-INFECTIVE AGENTS, CARIOSTATIC AGENTS, SILVER COMPOUNDS, CARIES, TOPICAL FLUORIDES1 Dr.Yasmi O. Crystal, SDF workgroup chair, is a clinical associate professor of pediatricdentistry, at NYU College of Dentistry, New York, N.Y., USA; and a pediatric dentist inprivate practice, in New Yersey, N.J. and New York City, N.Y., USA. 2Dr. Abdullah A.Marghalani is a pediatric dental fellow, Division of Pediatric Dentistry, at the Universityof Maryland Dental School, Baltimore, Md., USA. 3Dr. Steven D. Ureles is an instructorin developmental biology, at the Harvard School of Dental Medicine/Boston Children’sHospital, Boston, Mass., USA; a pediatric dentist in private practice, New London County,Conn.; a clinical assistant professor, Department of Pediatric Dentistry, at the University of Connecticut School of Dental Medicine, Farmington, Conn.; and a MSc graduatestudent, Postgraduate Programme in Evidenced-Based Health Care Studies, NuffieldDepartment of Primary Care Health Sciences, at the University of Oxford, Oxford, UK.4Dr. John Timothy Wright is the Bawden Distinguished Professor, Department of PediatricDentistry School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, N.C.,USA. 5Dr. Rosalyn Sulyanto is an instructor, Developmental Biology, at the Harvard Schoolof Dental Medicine and Boston Children's Hospital, Boston, Mass., USA. 6Dr. KimonDivaris is an associate professor, Departments of Pediatric Dentistry, UNC School ofDentistry and Epidemiology, Gillings School of Global Public Health, at the University ofNorth Carolina-Chapel Hill, Chapel Hill, N.C., USA. 7 Dr. Margherita Fontana is a professor, Department of Cariology, Restorative Sciences, and Endodontics, at the Universityof Michigan School of Dentistry, Ann Arbor, Mich., USA. 8Ms. Laurel Graham is a seniorevidence-based dentistry manager, at the American Academy of Pediatric Dentistry,Chicago, Ill., USA.Correspond with Ms. Graham at [email protected] cite: Crystal YO, Marghalani AA, Ureles SD, et al. Use of silver diamine fluoride fordental caries management in children and adolescents, including those with specialhealth care needs. Pediatr Dent 2017;39(5):E135-E145.Scope and purposeThe guideline intends to inform the clinical practices involvingthe application of silver diamine fluoride (SDF) to enhancedental caries management outcomes in children and adolescents,including those with special health care needs. Silver diaminefluoride in this guideline’s recommendation refers to 38 percentSDF, the only formula available in the United States. These recommended practices are based upon the best available evidenceto-date. However, the ultimate decisions regarding diseasemanagement and specific treatment modalities are to be madeby the dental professional and the patient or his/her representative, acknowledging individuals’ differences in diseasepropensity, lifestyle, and environment.The guideline provides practitioners with easy to understandevidence-based recommendations. The American Academy ofPediatric Dentistry's (AAPD) evidence-based guidelines are beingABBREVIATIONSAAPD: American Academy of Pediatric Dentistry. CCTs: Controlledclinical trials. EBDC: Evidence-based dentistry committee. EPA: Environmental Protection Agency. GRADE: Grading of RecommendationsAssessment, Development and Evaluation. NaF: Sodium fluoride. NGC:National Guideline Clearinghouse. PICO: Population, intervention,control, and outcome. RCTs: Randomized control trials. SDF: Silverdiamine fluoride.Copyright 2017 American Academy of Pediatric Dentistry. All rights reserved.USE OF SDF FOR DENTAL CARIES MANAGEMENTE135

PEDIATRIC DENTISTRYV 39 / NO 5SEP / OCT 17produced in accordance with standards created by the NationalAcademy of Medicine (formerly known as the Institute of Medicine) and mandated by the National Guideline Clearinghouse (NGC), a database of evidence-based clinical practice guidelinesand related documents maintained as a public resource by theAgency for Healthcare Research and Quality (AHRQ) of theU.S. Department of Health and Human Services (USDHHS).Health intents and expected benefits or outcomes. Theguideline is based on analysis of data included in a recent systematic review and meta-analysis1 and summarizes evidence of thebenefits and safety of SDF application in the context of dentalcaries management, mainly its effectiveness in arresting cavitatedcaries lesions † 2 in the primary dentition. Its intent is to providethe best available information for practitioners and patientsor their representatives to determine the risks, benefits, and alternatives of SDF application as part of a caries managementprogram. Prevention of new caries lesion development and outcomes in permanent teeth, such as root caries lesion arrest, werenot the focus of this guideline; however, because they are ofinterest and relevant to caries management within the scopeof pediatric dentistry, they are mentioned and will be includedin future iterations of the guideline as the supporting evidencebase increases.Clinical questions addressed. The panel members used thePopulation, Intervention, Control, and Outcome (PICO)3 formulation to develop the clinical questions that will aid practitioners in the use of SDF in primary teeth with caries lesions.Does the application of SDF arrest cavitated caries lesions aseffectively as other treatment modalities in primary teeth?MethodsThis guideline adheres to the National Academy of Medicine'sguideline standards4 and the recommendations of the Appraisalof Guidelines Research and Evaluation (AGREE) instrument.5The guidance presented is based on an evaluation of the evidencepresented in a 2016 systematic review published by Gao andcolleagues.1† A caries lesion is a detectable change in the tooth structure that results fromthe biofilm-tooth interactions occurring due to the disease caries. It is theclinical manifestation (sign) of the caries process.Table 1.Search strategy. Literature searches were used to identifysystematic reviews that would serve as the basis of the guideline.Secondly, the results of the searches served as sources of evidenceor information on issues related to, but outside the context of,the PICO, such as cost, adverse effects, and patient preferences.Literature searches were conducted in PubMed /MEDLINE,Embase , Cochrane Central Register of Controlled Trials, grayliterature, and trial databases to identify systematic reviews andrandomized controlled trials of SDF. Search results were reviewedin duplicate at both the title and abstract and the full-text levelwhen warranted. Disagreements were resolved by consensus;if agreement could not be reached, the AAPD Evidence-BasedDentistry Committee (EBDC) overseeing the workgroup wasconsulted to settle the question. A detailed description of thesearch strategies is presented in Appendix I.Inclusion and exclusion criteria. The criteria used to identify publications for use in the guideline were determined bythe clinical PICO question. See Appendix I for search strategies. Publications which addressed the use of SDF to arrestcaries lesions in primary teeth, regardless of language, meritedfull-text review; in vitro studies and studies of the use of SDFoutside of the guideline’s stated outcomes were excluded. Nonew randomized controlled trials were identified that warrantedupdating the meta-analysis found in the systematic review 1selected as the basis for this guideline.Assessment of the evidence. The main strength of thisguideline is that it is based on a systematic review of prospectiverandomized and controlled trials of SDF1. Evidence was assessedvia the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach6, a widely adoptedand peer reviewed system of evaluating study quality (Table 1).The guideline recommendation is based on the meta-analysis offour controlled trials (three randomized), extracted in duplicate,from a systematic review of SDF 1. Randomized (RCTs) andcontrolled clinical trials (CCTs) offer the highest level of clinical evidence; therefore, a recommendation based on a systematicreview and meta-analysis of graded RCTs/CCTs provides morereliable and accurate conclusions that can be applied towardspatient care.This guideline is limited by the small number of RCTsevaluating SDF, the heterogeneity of the included trials, andselection bias that may have been introduced by possibly poor QUALITY OF EVIDENCE GRADES ‡GradeDefinitionHighWe are very confident that the true effect lies close to that of the estimate of the effect.ModerateWe are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibilitythat it is substantially different.LowOur confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.Very LowWe have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.‡ Quality of evidence is a continuum; any discrete categorization involves some degree of arbitrariness. Nevertheless, advantages of simplicity, transparency, and vividness outweighthese limitations.Reprinted with permission. Quality of evidence and strength of recommendations. GRADE Handbook: Handbook for grading the quality of evidence and the strength of recommendations usingthe GRADE approach. Update October 2013. Available at: k/handbook.html”.E136USE OF SDF FOR DENTAL CARIES MANAGEMENT

PEDIATRIC DENTISTRYsequence generation 7,8 and selective reporting by one study 7.Weaknesses of this guideline are inherent to the limitationsfound in the systematic review 1 upon which this guideline isbased. Major limitations of the supporting literature includelack of calibration and/or evidence of agreement for examinersassessing clinical outcomes and unclear definitions or inconsistent criteria for caries lesion activity.9,10 Arguably, without a validand reliable method to determine lesion activity at baseline andfollow-up, misclassification bias is possible, especially becauseclinicians cannot be blinded with regard to SDF application(due to the dark staining).9,10 The absence of rigorous cariesdetection and activity measurement criteria in the reviewedliterature can decrease the validity of the reported results.9,10Other reviewers of the systematic review 1 noted similar andadditional limitations.9,10Formulation of the recommendations. The panel formulated this guideline collectively via surveys, teleconferences, andelectronic communications from January 2017–August 2017.The panel used the evidence-to-decision framework in an iterative manner to formulate the recommendations. Specifically,the main methods used were discussion, debate, and consensusseeking.11 To reach consensus, the panel voted anonymously onall contentious issues and on the final recommendation. GRADEwas used to determine the strength of the evidence.12Understanding the recommendations. GRADE ratesthe strength of a recommendation as either strong or conditional. A strong recommendation “is one for which guidelinepanel is confident that the desirable effects of an interventionoutweigh its undesirable effects (strong recommendation for anintervention) or that the undesirable effects of an interventionoutweigh its desirable effects (strong recommendation against anintervention).”6 A strong recommendation implies most patientswould benefit from the suggested course of action (i.e., eitherfor or against the intervention). A conditional recommendation“is one for which the desirable effects probably outweigh theundesirable effects (conditional recommendation for an intervention) or undesirable effects probably outweigh the desirableTable 2.V 39 / NO 5SEP / OCT 17effects (conditional recommendation against an intervention), butappreciable uncertainty exists.”6 A conditional recommendationimplies that not all patients would benefit from the intervention.The individual patient’s circumstances, preferences, and valuesneed to be assessed more than usual. Practitioners need to allocate more time for consultation along with explanation of thepotential benefits and harms to the patients and their caregiverswhen recommendations are rated as conditional. Practitioners’expertise and judgment as well as patients’ and their caregivers’needs and preferences establish the suitability of the recommendation to individual patients. The strength of a recommendationpresents different implications for patients, clinicians, and policymakers (Table 2).RecommendationsThe SDF panel supports the use of 38 percent SDF for thearrest of cavitated caries lesions in primary teeth as part of acomprehensive caries management program. (Conditionalrecommendation, low-quality evidence)Summary of findingsThe recommendation is based on data from a meta-analysis ofdata extracted from RCTs and CCTs of SDF efficacy with various follow-up times and controls (Table 3). Based on thepooled estimates of SDF group, approximately 68 percent (95percent confidence interval [95% CI] 9.7 to 97.7) of cavitatedcaries lesions in primary teeth would be expected to be arrestedtwo years after SDF application (with once or twice a yearapplication). Using data with longest follow-up time (at least30 months follow-up; n 2,567 surfaces from one RCT7 andone CCT8), SDF had 48 percent higher (95% CI 32 to 66)success rate in caries lesion arrest compared to the controls (76percent versus 51 percent arrested lesions, in absolute terms).In other words, 248 more cavitated caries lesions would be expected to arrest by treatment with SDF compared to controltreatments, per 1000 surfaces after at least 30 months followup. Considering the stratum with most data (n 3,313 surfacesIMPLICATIONS OF STRONG AND CONDITIONAL RECOMMENDATIONS FOR DIFFERENT USERS OF GUIDELINESStrong recommendationConditional recommendationFor patientsMost individuals in this situation would want the recommendedcourse of action and only a small proportion would not.The majority of individuals in this situation would want the suggestedcourse of action, but many would not.For cliniciansMost individuals should receive the recommended course of action.Adherence to this recommendation according to the guidelinecould be used as a quality criterion or performance indicator. Formaldecision aids are not likely to be needed to help individuals makedecisions consistent with their values and preferences.Recognize that different choices will be appropriate for different patients, and that you must help each patient arrive at a managementdecision consistent with her or his values and preferences. Decisionaids may well be useful helping individuals making decisions consistentwith their values and preferences. Clinicians should expect to spendmore time with patients when working towards a decision.For policymakersThe recommendation can be adapted as policy in most situationsincluding for the use as performance indicators.Policymaking will require substantial debates and involvement ofmany stakeholders. Policies are also more likely to vary betweenregions. Performance indicators would have to focus on the fact thatadequate deliberation about the management options has taken place.Reprinted with permission. GRADE Handbook: Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. Update October 2013.Available at: k/handbook.html”.USE OF SDF FOR DENTAL CARIES MANAGEMENTE137

PEDIATRIC DENTISTRYV 39 / NO 5SEP / OCT 17from three RCTs and one CCT, with follow-up of 24 monthsor more), similar estimates of relative and absolute efficacywere produced (i.e., RR 1.42 [95% CI 1.17 to 1.72]) and 72percent versus 50 percent arrested lesions, in absolute terms.Other follow-up and application frequency strata are listed in thesummary of findings (Table 3). The range of estimates of SDFefficacy between the included trials was categorically wide.Rates of arrest on untreated groups may seem unusually high,and this may be due to background fluoride exposure. In oneof the trials 7, all participants (i.e., both the SDF-treated andcontrol children) received 0.2 percent sodium fluoride (NaF)rinse every other week in school, while in other trials, childrenwere either given fluoride toothpaste13 or reported use of fluoridetoothpaste 8. The panel determined the overall quality of theevidence for this comparison was low or very low, owing toserious issues of risk of bias (unclear method for randomization,selective reporting, and high heterogeneity) in the includedstudies. No studies were identified regarding the arresting effectof SDF on cavitated caries lesions in adult patients. The panelsuggests that similar treatment effects may be expected for otherage groups, but the lack of evidence informing this recommendation restrained the panel from providing an evidence-basedrecommendation.The panel made a conditional recommendation regardingthe use of SDF for the arrest of cavitated caries lesions in primaryteeth as part of a comprehensive caries management program.After taking in consideration the low cost of the treatment andthe