Randomized Controlled Trial of Interactive Parent-Targeted Text Messaging in Pediatric Clinics to Reduce Caries Among Urban Children
Phase: NA
Conditions: Caries, Dental, Health Behavior
Sponsor: Boston University

RCT of Interactive Parent-targeted text messaging in Pediatric Clinics to Reduce Caries  
Version 2.1 
Protocol #17-083-E 
29 March 2019 
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Randomized Controlled Trial of Interactive 
Parent-Targeted Text Messaging in Pediatric 
Clinics to reduce Caries among Urban Children  
 
NCT03294590 
NIDCR Protocol Number: 17-083-E 
NIDCR Grant Number: UH3DE025492-03  
Principal Investigator: Belinda Borrelli, PhD (Lead) 
                              belindab@bu.edu 
                        617-414-1116 
Co-Principal Investigator: Michelle Henshaw, DDS, MPH 
NIDCR Program Official: Darien Weatherspoon, DDS, MPH 
NIDCR Medical Monitor: Kevin McBryde, MD  
  
 
Draft or Version Number:  2.1 
29 March 2019 
 
 
Statistical Plan pages 43-38

RCT of Interactive Parent-targeted text messaging in Pediatric Clinics to Reduce Caries  
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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on 
Harmonisation guidelines for Good Clinical Practice (ICH E6), the Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), and the NIDCR 
Clinical Terms of Award. All personnel involved in the conduct of this study have 
completed human subjects protection training. 
 

RCT of Interactive Parent-targeted text messaging in Pediatric Clinics to Reduce Caries  
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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date:  
 
Name: Belinda Borrelli, PhD 
 
Title: Professor 
 
 
 
 
 
Signed: 
 
Date:  
 
Name: Michelle Henshaw, DDS, MPH 
 
Title: Professor 
 

RCT of Interactive Parent-targeted text messaging in Pediatric Clinics to Reduce Caries  
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TABLE OF CONTENTS 
PAGE 
STATEMENT OF COMPLIANCE ................................................................................................ 1 
SIGNATURE PAGE .................................................................................................................... 2 
TABLE OF CONTENTS .............................................................................................................. 3 
LIST OF ABBREVIATIONS ......................................................................................................... 6 
PROTOCOL SUMMARY ............................................................................................................. 8 
1 
KEY ROLES AND CONTACT INFORMATION ................................................................. 12 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....... 14 
2.1 
Background Information ........................................................................................ 14 
2.2 
Rationale .............................................................................................................. 14 
2.3 
Potential Risks and Benefits ................................................................................. 15 
2.3.1 
Potential Risks .......................................................................................... 15 
2.3.2 
Potential Benefits ...................................................................................... 16 
3 
OBJECTIVES ................................................................................................................... 17 
3.1 
Study Objectives ................................................................................................... 17 
3.2 
Study Outcome Measures .................................................................................... 17 
3.2.1 
Primary ...................................................................................................... 17 
3.2.2 
Secondary ................................................................................................. 18 
4 
STUDY DESIGN .............................................................................................................. 21 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................. 22 
5.1 
Subject Inclusion Criteria ...................................................................................... 22 
5.2 
Subject Exclusion Criteria ..................................................................................... 23 
5.3 
Strategies for Recruitment and Retention ............................................................. 24 
5.4 
Treatment Assignment Procedures ....................................................................... 27 
5.4.1 
Randomization Procedures (if applicable) ................................................. 27 
5.4.2 
Masking Procedures (if applicable) ............................................................ 27 
5.5 
Subject Withdrawal ............................................................................................... 27 
5.5.1 
Reasons for Withdrawal ............................................................................ 27 
5.5.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention ............................................................................................... 28 
5.6 
Premature Termination or Suspension of Study .................................................... 28 
6 
STUDY INTERVENTION .................................................................................................. 29 
6.1 
Study Behavioral or Social Intervention(s) Description .......................................... 29 
6.2 
Administration of Intervention ................................................................................ 29 
6.3 
Procedures for Training Interventionists and Monitoring Intervention Fidelity ........ 29 
6.4 
Assessment of Subject Compliance with Study Intervention ................................. 30 
7 
STUDY SCHEDULE ......................................................................................................... 31 
7.1 
Eligibility Determination ......................................................................................... 31 
7.2 
Enrollment/Baseline .............................................................................................. 31 
7.3 
Follow-up .............................................................................................................. 32 
7.4 
Final Study Visit (24 months + 31 days) ................................................................ 32 

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7.5 
Early Termination Visit .......................................................................................... 33 
7.6 
Unscheduled Visit ................................................................................................. 33 
8 
STUDY PROCEDURES /EVALUATIONS ........................................................................ 34 
8.1 
Study Procedures/Evaluations .............................................................................. 34 
8.2 
Laboratory Procedures/Evaluations ...................................................................... 36 
9 
ASSESSMENT OF SAFETY ............................................................................................ 37 
9.1 
Specification of Safety Parameters ....................................................................... 37 
9.1.1 
Unanticipated Problems ............................................................................ 37 
9.1.2 
Adverse Events ......................................................................................... 37 
9.1.3 
Serious Adverse Events ............................................................................ 37 
9.2 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 38 
9.3 
Characteristics of an Adverse Event ..................................................................... 38 
9.3.1 
Relationship to Study Intervention ............................................................. 38 
9.3.2 
Expectedness of SAEs .............................................................................. 38 
9.3.3 
Severity of Event ....................................................................................... 38 
9.4 
Reporting Procedures ........................................................................................... 39 
9.4.1 
Unanticipated Problem Reporting to IRB and NIDCR ................................ 39 
9.4.2 
Serious Adverse Event Reporting to NIDCR.............................................. 40 
10 
STUDY OVERSIGHT ....................................................................................................... 41 
11 
CLINICAL SITE MONITORING ........................................................................................ 42 
12 
STATISTICAL CONSIDERATIONS .................................................................................. 43 
12.1 
Study Hypotheses ................................................................................................. 43 
12.2 
Sample Size Considerations ................................................................................. 43 
12.3 
Planned Interim Analyses (if applicable) ............................................................... 45 
12.3.1 Safety Review ........................................................................................... 45 
12.3.2 Efficacy Review ......................................................................................... 45 
12.4 
Final Analysis Plan ............................................................................................... 45 
13 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................. 49 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................ 50 
15 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 51 
15.1 
Ethical Standard ................................................................................................... 51 
15.2 
Institutional Review Board .................................................................................... 51 
15.3 
Informed Consent Process ................................................................................... 51 
15.4 
Exclusion of Women, Minorities, and Children (Special Populations) .................... 53 
15.5 
Subject Confidentiality .......................................................................................... 53 
15.6 
Future Use of Stored Specimens and Other Identifiable Data ............................... 53 
16 
DATA HANDLING AND RECORD KEEPING ................................................................... 54 
16.1 
Data Management Responsibilities ....................................................................... 54 
16.2 
Data Capture Methods .......................................................................................... 54 
16.3 
Types of Data ....................................................................................................... 54 
16.4 
Schedule and Content of Reports ......................................................................... 55 
16.5 
Study Records Retention ...................................................................................... 63 
16.6 
Protocol Deviations ............................................................................................... 63 

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17 
PUBLICATION/DATA SHARING POLICY ........................................................................ 64 
18 
LITERATURE REFERENCES .......................................................................................... 65 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
AH 
Agile Health 
BIA 
Budget Impact Analysis 
BMC 
Boston Medical Center 
BRFQ 
Basic Research Factors Questionnaire 
CC 
Coordinating Center 
CFR 
Code of Federal Regulations 
CHC 
Community Health Center 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
CWT 
Child Wellness Text Message Program 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DMFS 
Decayed, missing, and filled tooth surfaces 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EHR 
Electronic Health Record 
FDA 
Food and Drug Administration 
FFR 
Federal Financial Report 
FWA 
Federalwide Assurance 
GCP 
Good Clinical Practice 
GSDM 
BU Goldman School of Dental Medicine 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IRB 
Institutional Review Board 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 

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NIDCR 
National Institute of Dental and Craniofacial Research, NIH, DHHS 
NIH 
National Institutes of Health 
OCTOM 
Office of Clinical Trials Operations and Management, NIDCR, NIH 
OHRP 
Office for Human Research Protections 
OHT 
Oral Health Text Message Program 
PHI 
Protected Health Information 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SCT 
Social Cognitive Theory 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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PROTOCOL SUMMARY 
Title: 
Randomized Controlled Trial of Interactive Parent-Targeted Text 
Messaging in Pediatric Clinics to reduce caries among Urban 
Children 
Précis: 
The aim of this study is to test an interactive parent-targeted text 
message-based intervention to reduce caries among children < 7 
years old, who are recruited from targeted pediatric clinics and 
receive pediatric care at those clinics. The design is predicated on 
the fact that sustainability of health behavior change is greatest if the 
intervention is integrated into existing channels (i.e., pediatric clinics) 
and woven into the fabric of people’s lives (e.g., text messages). 
Parent-child dyads will be randomized to Oral Health Text Messages 
(OHT) or Child Wellness Text Messages (CWT). The two 
interventions are matched on text message dose, duration and 
features. Participants in both groups will receive text messages for 
four months (2 per day in month 1; one per day in months 2-4), as 
well as weekly and monthly assessments delivered through text 
messaging. All participants will have an additional one-month text 
message ‘booster,’ one year after baseline. Surveys to assess oral 
health knowledge, behaviors, mediators, and moderators will be 
given at baseline, mid treatment (2 months) end of treatment (4 
months), one year, and 2 years after baseline. Caries will be 
assessed by clinical exam at baseline, and 12, and 24 months after 
baseline. Analyses will use longitudinal modeling strategies. We will 
collect quantitative and qualitative data for the budget impact 
analyses, assess mediators and moderators of the treatment effect, 
and assess changes in oral health behaviors for caregivers and their 
children. 
 
Objectives: 
 
Primary:  1. To test the efficacy of the OHT intervention. Parents of 
children <7 years old who attend one of four urban pediatric clinics 
will be randomized to receive either OHT or CWT. Caries will be 
objectively measured through clinical exam.  H1: Those receiving 
OHT will have lower 24 month incidence of caries vs. those receiving 
CWT.  2. To assess the mechanisms through which intervention 
effects occur (mediators). H2: OHT will differentially change Social 
Cognitive Theory constructs over time vs. CWT. We will test the 
mediational effect on caries.  Mediators will be assessed via self-
reported measures with good psychometric properties. 
 
Secondary:  1. To perform budget impact analyses of pediatric clinic 
adoption of the OHT intervention to determine the financial 
consequences of adoption, diffusion, and sustainability.  
2. Examine change in pediatric oral health behaviors (e.g. tooth 
brushing, diet, sugar sweetened beverages, fluoride toothpaste use, 
preventive dental visits, and ‘lift the lip’ oral assessment by parents).  
3. To assess the effect of the intervention on the parent’s oral health 
status, knowledge, attitudes, and behaviors (spill-over effect),  
4. To identify subpopulations for whom the intervention has the 
greatest effect (moderators; e.g., race/ethnicity, insurance coverage, 

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parent educational level, parent depressed mood, and child’s prior 
caries experience, intervention dose/engagement).  
  
Population: 
Participants will be 850 parent-child dyads, consisting of a parent 
and his/her child under the age of 7 who is attending one of our four 
targeted pediatric clinics (see below). Participants in our pilot RCT 
(n=55) were 96.3% female; Mean parent age =31.1; 73.6% below 
poverty level; 14.6% < high school education, 67.3% black, 9.1% 
White, 14.5% Hispanic, 9.1% other; mean child age =2.8.   
 
Phase: 
Phase III  
Number of Sites: 
Four pediatric clinics in urban and low income areas of Boston will 
serve as recruitment sites. Three sites are community health clinics 
(CHCs, Dorchester House and Codman Square and South End 
Community Health Center) and one site is a pediatric clinic in an 
urban safety net hospital (Boston Medical Center).  
Description of  
Intervention: 
We will recruit caregivers who speak either English or Spanish and 
have a child under the age of 7 years who attends one of our 
pediatric clinic partners. Caregivers who screen eligible will be 
consented into the study and complete a baseline survey. The index 
child will receive a baseline oral clinical exam. After these activities 
are completed, the parent will be enrolled into the study and 
randomized to receive either the OHT or the CWT intervention. 
Follow-up surveys will be administered through electronic and/or 
mobile platforms (e.g email, smartphone, or telephone) at 2- month 
(mid-treatment), 4- month (end of treatment), 12 and 24- month post 
baseline. Follow-up oral clinical examinations will occur at 12 and 
24- months post baseline. During the 4- month TM intervention, 
weekly and monthly assessments will also occur through the TM 
program.  A TM intervention ‘booster’ period of one month will also 
occur 12- months post baseline, after the 12 month assessment. 
Program features (quizzes, customization, personalization, tailoring,  
interactivity, problem solving photos/video, goal setting, and 
feedback and rewards), program structure (core and choice topics, 
assessments), engagement strategies (quizzes, rewards) and 
language preferences (English or Spanish) will be similar between 
the CWT and OHT.  Both study groups will also have three ‘weekly 
challenges’ over the 4- month intervention program, in which they 
can earn extra rewards and ‘unlock’ secret characters for performing 
the target behavior (OHT=brushing; CWT=reading).  
Study Duration: 
3 years 
Subject 
Participation 
Duration: 
2 years 

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Estimated Time to 
Complete 
Enrollment: 
12 months 

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Schematic of Study Design: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final Assessments 
Caries incidence (main outcome), secondary 
outcomes, mediators and moderators. 
Final Assessment 
24 months 
12 month 
Assessment 
4 month assessment 
(End of Treatment) 
2 Month 
Assessment 
(Mid-Treatment)  
Self-reported and clinical baseline assessments, plus variables needed 
for budget impact analyses, organizational level variables, secondary 
outcomes, mediators and moderators 
Self-reported baseline assessments plus assessments of program use, 
goals set/achieved, intervention dose, and program engagement  
 Self-reported baseline assessments (change in SCT variables & 
knowledge).  
OHT 
425 
 CWT 
 425 
Randomize N=850 
Baseline 
Screen potential participants by inclusion and exclusion criteria; obtain informed consent; 
conduct baseline survey and clinical exam: Caries (tooth surface level data collected by calibrated 
clinical examiners), Social Cognitive variables regarding child’s oral health (motivation, self-
efficacy, outcome expectations), Moderators from Fisher-Owens model (insurance, demographics, 
family size, perceived stress, physical safety/family issues, previous caries experience, parent oral 
health status, parent depressed mood, history of dental care, perception of dental visits, fluoride 
varnish, child oral health quality of life), Parent/child oral health behaviors (bottle/sippy cup use, 
diet, sugar sweetened beverages; tooth monitoring, fluoridated water/toothpaste; 
frequency/duration/timing of brushing or cleaning child’s mouth, preventive dental visits),  parent 
oral health knowledge and attitudes.
OHT or 
CWT Text 
Message 
Intervention 
(4 months) 
12-month Text Message 
Booster Session (conducted 
after 12-month assessment) 

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1 
KEY ROLES AND CONTACT INFORMATION 
 
Principal 
Investigator:   
Belinda Borrelli, Ph.D., (Lead PI) 
Professor, Boston University  
Henry M. Goldman School of Dental Medicine 
560 Harrison Avenue, 3rd floor 
Boston, MA  02118 
PH:  617-358-3358; FAX:  617-638-6381 
belindab@bu.edu 
 
Michelle Henshaw, DDS, MPH (Co-PI) 
Boston University 
Henry M. Goldman School of Dental Medicine 
560 Harrison Avenue, 3rd floor 
Boston, MA  02118 
PH:  617-358-6111; FAX:  617-638-6381 
mhenshaw@bu.edu 
Medical Monitor: 
Kevin D. McBryde, MD 
Medical Officer 
Division of Extramural Research 
National Institute of Dental and Craniofacial Research 
6701 Democracy Blvd., Rm. 638 
Bethesda, MD 20892-4878 
PH: 301-594-0170; FAX: 301-480-8319 
mcbrydekd@mail.nih.gov   
NIDCR Program 
Official:   
Darien Weatherspoon, DDS, MPH 
Director,  Health Disparities Research Program 
National Institute of Dental and Craniofacial Research 
6701 Democracy Blvd., Room 640 
MSC 4878 
Bethesda, MD 20892-4878 
Bethesda, MD 20817 (overnight mail or courier service) 

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PH: 301-594-5394; FAX: 301-480-8322 
darien.weatherspoon@nih.gov 
Clinical Site 
Investigators: 
William Adams, M.D., Professor 
Boston University School of Medicine, General Pediatrics 
88 East Newton Street, Vose Bldg., 3rd Floor 
Boston, MA  02118 
 
PH:  617-414-7707; FAX:  617-414-3687 
badams@bu.edu 
 
Timothy Heeren, Ph.D., Professor 
Boston University School of Public Health, Biostatistics 
801 Massachusetts Avenue, Crosstown Center 
Boston, MA  02118 
PH:  617-638-5172; FAX:  617-638-6484 
tch@bu.edu 
 
Institutions: 
Trustees of Boston University, BUMC 
Office of Sponsored Programs 
85 East Newton Street, M-921 
Boston, MA  02118-2340 
Diane Baldwin 
Assistant Vice President, Sponsored Programs 
PH:  617-638-4600; FAX:  617-638-4686 
bumc-era@bu.edu    
 
 

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2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE  
2.1 
Background Information 
The prevalence of caries in children is disproportionately high in racial and ethnic minorities 
(Dye et al., 2017). Pediatric clinics in urban and low income neighborhoods are an ideal venue 
to connect with parents who might not otherwise receive information on evidence-based oral 
health care for their child.  Mobile phone ownership is near saturation (95%) (Pew Research 
Center, 2017) and >85% of adults text message (TM), with no disparities by income, education, 
or ethnicity (Pew Research Center, 2017; Duggan & Rainie, 2012; Bennett et al., 2012; Fox and 
Duggan, 2012; Zickuhr & Smith, 2012).  The average number of daily texts is high (African-
Americans 70.1; Latinos 48.9; Whites 31.2; Smith, 2011; Zickuhr & Smith, 2012).  Using text 
messaging as an intervention platform and pediatric clinics as a channel for intervention could 
be an effective way to reach low income and ethnically diverse parents with an oral health 
behavior and caries prevention intervention.   Our program is called ‘iSMILE’ (Interactive Short 
Messages to Initiate Lasting Health Education). Throughout the protocol iSmile is used 
interchangeably with “RCT of Interactive Parent-targeted text messaging in Pediatric Clinics to 
Reduce caries” when referring to this study. Our study includes a theory-based, fully powered 
dose-matched design with objectively measured outcomes and hypothesized mediators.  The 
primary aim of the study is to test the efficacy of the Oral Health Text (OHT) message 
intervention by randomizing parents of children <7 years old attending pediatric clinic visits to 
receive either OHT or Child Wellness Texts (CWT).  We will also examine a behavioral ‘ripple 
effect’ from the intervention (i.e., improvement in the parent’s oral health behaviors), involve 
stakeholders on our advisory board, interview clinic decision makers, determine ways to 
integrate the intervention into work-flow and electronic health records (EHR), and perform 
budget impact analyses to aid in diffusion to other clinics. Thus, our multi-level project includes 
children, parents, providers, and clinic leadership.   
 
 
2.2 
Rationale 
Rationale for platform.  Text message interventions have been shown to be effective for 
changing health behaviors (Mason et al., 2015; Free et al., 2011; Saffari et al., 2014; Siopis et 
al., 2015; Finitsis et al., 2014) and are even more effective when integrated into clinic settings, 
such as pediatric clinics. Previous studies have shown that TMs have the following benefits: 1) 
access anytime/place, 2) ability to tailor content, timing, and intensity to users, 3) provision of 
real time coping strategies to users in everyday settings, 4) ability to support behavior change at 
key times, 5) few barriers to participation, 6) decreases the space/time gap between treatment 
and behavior, 7) interactive functionality in real time, 8) low participant burden, 9) reduces 
health care system cost (Chen et al., 2012; Guerriero et al., 2013), 10) ability to deliver 
intervention at key times (e.g., reminder to brush child’s teeth), 11) instant support and 
feedback, and 12) potential for cost effective dissemination.  Given that Blacks and Hispanics 
have the highest TM use, are likely to use texting to get health information, and also have 
children at highest risk for caries, this is an appropriate population in which to test a TM-based 
intervention intended to decrease caries incidence.  
Text Messaging vs. Other technologies:  1) Mobile apps:  Text messaging is superior in terms of 
popularity, simplicity, and world-wide scalability, because it is one of the most stable, 
transferable, cross-platform (phone, tablet, computer, etc.) methods available. Unlike apps, TMs 
do not require smartphones, and do not require users to download a program and accept ‘push’ 

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notifications. Only 53% of mobile phone owners and 29% of low income adults have smart 
phones (Fox & Duggan, 2012). Text messaging eliminates barrier points to entry by allowing 
anyone with a mobile phone to participate, regardless of make, model, or carrier. Users do not 
need to download anything to join. Also, text messaging is a conversation. A ‘push’ notification, 
such as with apps, is a one-way communication channel and users cannot respond directly. 
This creates a non-interactive experience, increasing the likelihood the user will turn off the 
push notifications or stop checking the app. Text messaging is highly interactive and inherently 
a two-way conversation. Users can text back and forth with our system, increasing engagement. 
2) Web-based interventions:  Short and low effort communications, such as text messaging, 
might be better for those who are less motivated to change. Web based interventions require 
more effort so less motivated parents are less likely to use them (Borland et al., 2013).  Web-
based studies on oral health promotion have had low usage rates (Hurling et al., 2013). TMs 
have wider reach than other electronic interventions (Abroms et al., 2012), have the advantage 
of instant transmission, and can prompt behavior at key times (e.g., nighttime brushing).   
Rationale for TM dose and duration. TM programs need to be of sufficient intensity and duration 
to affect behavior change, without being so burdensome that they cause drop out. We chose a 4 
month intervention because most studies with interventions lasting >3 months had better 
outcomes (Siopis et al., 2015; Brendryen & Kraft et al., 2008; Celik et al., 2014). In addition, our 
pilot data indicate that the length of the program is satisfactory to our target population. Because 
caries prevention involves numerous target behaviors, it necessitates a longer and more intense 
intervention than health behaviors that are focused on changing one behavior (e.g., smoking 
cessation).   
 
2.3 
Potential Risks and Benefits 
2.3.1 
Potential Risks 
This study poses minimal risk to the participant. Listed below are the risks:  
• 
The loss of privacy and confidentiality. 
• 
Some aspects of the assessments (e.g., answering questions about child care practices 
or the child sitting for the oral health assessment) may be uncomfortable or 
embarrassing. 
• 
Untreated dental disease may be identified during the oral health assessment which may 
cause anxiety for the caregiver. 
• 
There are two potential consequences of text messaging: accidents and thumb and joint 
pain. Texting while driving or walking could increase the risk of accidents. Frequent 
texting may increase the risk of thumb and joint pain. The number of texts involved in 
this study is not likely to result in thumb and joint pain. 
“Agile Health” (AH) is the company that will be programming our TM curriculum. Their 
database will contain the TMs including information on what TMs each participant has 
received, which texts participants have responded to, their actual responses, and feedback 
about individual messages. This database is HIPAA secured.   

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Confidentiality will be maintained by numerically coding all data with a unique identifier. All 
electronic data will be stored in password protected, secured computer systems at the CC. Data 
will be collected through 1) secure electronic data capture (EDC) 2) paper and pencil 
questionnaires (only used in the event of EDC failure).  Only the participant’s study identification 
number will appear on any paper data or transcripts. Any paper data will be placed in a locked 
file cabinet. The master-code (or key), that links the subject name with subject's study 
identification number will be saved to the password protected electronic file, saved on the 
Dental IT approval secure S drive; this will be saved separately from the actual study data (e.g., 
screener and survey data). Data will also be collected through the AH text message platform, 
which is HIPAA secure. These data will not be de-identified, because identifying parameters are 
needed to initiate and customize the program. The identifying parameters include parent first 
and last name, child first and last name, parent gender, child gender, child date of birth, parent 
date of birth, zip code, mobile number, and preferred language to send/receive text (English or 
Spanish). Data collected through the TM program that are identifiable are caries history, 
toothbrushing practices, reading practices, text message use, text message responses, 
motivation and confidence to engage in health habits, dental visits, child safety, and other child 
health and wellness behaviors.   
 
Participant information will be accessible only to research staff. Individually identifiable 
information will be destroyed seven years after the study has been concluded.  
 
It is possible that some aspects of the assessments or TMs (e.g., answering questions about 
child care practices) may be uncomfortable. Participants will be informed that they can refuse to 
answer any questions or text messages that make them uncomfortable. Participants will be 
clearly informed of the topics to be addressed when receiving the TMs: e.g. brushing your 
child’s teeth, visiting the dentist, etc.  If a child becomes uncomfortable or overly anxious at the 
time of the screening, child dissent will be honored by the clinical examiners and the screening 
will be stopped.   
 
All caregivers will receive a “report card” providing a summary of untreated dental decay found 
and a recommendation regarding the timing for seeking care. All caregivers are offered help in 
making a dental appointment and study staff will proactively follow up in cases with pain or 
infection to facilitate dental treatment. 
 
To prevent TM related injury, participants will be told that they should not view, send, or receive 
texts while driving or walking. During the pilot phase, there were no adverse events reported. 
 
2.3.2 
Potential Benefits 
Because both groups receive educational TMs, all participants may benefit (i.e., there is no 
‘assessment only’ control group). Participants may have increased knowledge about child 
health, changed attitudes about child health, and/or perform healthy behaviors to facilitate child 
health. Another potential benefit is that the child receives a brief oral health exam with possible 
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3 
OBJECTIVES 
3.1 
Study Objectives 
 
Primary Aims:    
 
1. To test the efficacy of the OHT intervention in a theory-based, fully powered, dose-matched 
design with objective clinical measurement of caries. Parents of children <7 years old attending 
one of our partner pediatric clinics will be randomized to receive either OHT or CWT. H1: Those 
receiving OHT will have lower 24- month incidence of caries vs. those receiving CWT, as 
assessed by clinical exam. Clinical exams will take place at baseline and 12-and 24- months 
later. 
 
2. To assess the mechanisms through which intervention effects occur (mediators). H2: OHT will 
differentially change Social Cognitive Theory constructs (motivation, self-efficacy, outcome 
expectations) over time vs. CWT. We will test the mediational effect on caries.  Mechanisms will 
be assessed through text messaging assessments during the intervention, and through self-
report surveys at baseline, and 2, 4, 12 and 24- months after baseline. 
 
Secondary Aims: 
 
1. To perform budget impact analyses of pediatric clinic adoption of the OHT intervention to 
determine the financial consequences of adoption, diffusion, and sustainability. The budget 
impact analyses will include interviews with key stakeholders. 
 
2. Examine change in pediatric oral health behaviors (e.g. tooth brushing, diet, sugar sweetened 
beverages, fluoride toothpaste use, preventive dental visits, and ‘lift the lip’ oral assessment by 
parents). These variables will be assessed at baseline, 4, 12, and 24 months after baseline. 
 
3. To assess the effect of the intervention on the parent’s oral health status, knowledge, 
attitudes, and behaviors (spill-over effect). These variables will be assessed at baseline, 4, 12, 
and 24 months after baseline. 
 
 
4. To identify subpopulations for whom the intervention has the greatest effect (moderators; 
e.g., race/ethnicity, insurance coverage, parent educational level, parent depressed mood, 
child’s prior caries experience and intervention dose/engagement). All moderators will be 
assessed at baseline, except for intervention dose/engagement, which will be assessed during 
the course of text message delivery. 
  
3.2 
Study Outcome Measures 
3.2.1 
Primary 
 
Caries Incidence:  Tooth surface level data in children, collected by calibrated clinical examiners 
(blind to treatment condition), utilizing the OHDC Modified ICDAS methodology, will allow 
calculation of caries incidence rates (development of a new cavitated lesion or filled surface in a 
previously sound tooth surface or tooth surface without a cavitated lesion). Data will be collected 
by clinical examiners at baseline, 12, and 24- months.   

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Mediators:  
Self-efficacy to perform oral health behaviors (12 items).  The overall self-efficacy score 
represents how sure participants are that they can engage in recommended behavior to take 
care of their children’s teeth.  The overall self-efficacy score is the mean response.  Items are 
scored on a 1-7 scale, 1 = not sure at all to 7 = extremely sure. This measure will be assessed 
at all measurement points (baseline and 2, 4, 12, 24 months) (Cronbach’s alpha = .92).  A one-
item measure of this construct will be assessed during the TM program.  
Motivation to perform oral health behaviors (12 items).  The overall motivation score 
represents how much participants want to engage in recommended behavior to take care of 
their children’s teeth.  The overall motivation score is the mean response.  Items are scored on 
a 1-7 scale, 1 = do not want to at all to 7 = very much want to. This measure will be assessed at 
all measurement points (Cronbach’s alpha = .88).  A one-item measure of this construct will be 
assessed during the TM program.   
Outcome expectations regarding oral health behaviors.  This measure assesses the 
degree to which participants perceive that performing the oral health behaviors (e.g., brushing) 
will lead to the desired outcome (e.g., reduced dental caries) in their children (Stewart et al., 
1997).  This measure will be assessed at all measurement points.  A one-item measure of this 
construct will be assessed during the TM program.   
Number of goals set and completed will be assessed during the TM program.  OHT will 
set goals to brush (or supervise brushing) their children’s teeth and CWT will set goals to read 
to their children.  Goals set and completed are automatically tracked in the AH TM platform 
system.  We will also assess whether or not participants ‘opt in’ to participating in ‘challenge 
weeks.’  For OHT, this will entail setting a goal of brushing every day, twice per day. For CWT, 
this will entail reading to their child every day. Both groups will be assessed each day for their 
adherence. 
3.2.2 
Secondary 
Budget impact analysis:  Measures and analyses will follow best practice guidelines (Mauskopf 
et al., 2007). Dental public and private insurance claims will be collected from each participating 
site. Labor Costs:  Labor time will be assessed for each dissemination scenario at each site and 
average salary for each personnel will be used to determine labor cost.  We will measure costs 
of interface development, implementation, and technical support.   
Pediatric oral health behaviors: 
Brushing. We will assess frequency, duration, timing, and supervision of brushing using 
items from the BRFQ (Albino et al., 2017). This measure will be assessed at all measurement 
points, and during the TM program.   
Bottle/sippy cup/cup use.  This measure will be assessed at all measurement points, and 
during the TM program.  We will use items from the BRFQ (Albino et al., 2017). 

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Diet (Food and Beverage Consumption Scale; Palmer et al., 2010; 31 food/beverage 
items). Participants are asked to assess their child’s food intake by selecting the frequency in 
which each food item is consumed over the past month on a five-point Likert scale, which is 
scored from 0-4 and measured by the following choices: Never/Rarely; 1-2 times/week; 3-6 
times/week; 1 time/day; 2 or more times/day.  The food items presented are divided into 6 food 
categories: cereal; fruits and vegetables; grains, breads, and pastas; dairy; snacks and sweets; 
and drinks. Each food category contains approximately 2 or more foods or beverages. The 
estimated cariogenicity score is composed of 5 cariogenic categories, calculated for each child 
by obtaining a weighted sum of the number of food items for each food category and dividing by 
the total food and beverage items. This measure will be assessed at baseline, 4, 12, and 24 
months after baseline. 
 
 
Sugar sweetened beverage consumption (15 items).  We will use the BEVQ-15 to 
assess sugar-sweetened beverages and total beverage energy intake (Hedrick et al., 2012). 
These measure will be assessed at baseline, 4, 12, and 24 months after baseline. 
Tooth monitoring.  We will assess the frequency of parental checking of child’s teeth for 
early signs of cavities. This will be assessed at all measurement points.  We will use items from 
the BRFQ (Albino et al., 2017). This measure will be assessed at baseline, 4, 12, and 24 
months after baseline. 
Fluoridated water/toothpaste. This measure will be assessed at baseline, 4, 12, and 24 
months after baseline. We will use items from the BRFQ (Albino et al., 2017). 
Preventive dental visits. This measure will be assessed at all measurement points, and 
monthly during the TM program.  We will use items from the BRFQ (Albino et al., 2017). 
Parental knowledge, attitudes and behavior regarding oral health: 
Parent oral health knowledge:  21 items. This measure assesses parental knowledge 
related to oral health hygiene routines and feeding practices.  The overall knowledge score 
represents the percentage of oral health knowledge items answered correctly.  We will use 
items from the BRFQ (Albino et al., 2017).This measure will be assessed at baseline, 4, 12, and 
24 months after baseline.  
Parent’s attitude toward their own and their child’s oral health.  We will use items from 
the BRFQ (Albino et al., 2017). This measure will be assessed at baseline, 4, 12, and 24 
months after baseline. 
Parent oral health behaviors.  12 items related to parental oral health behaviors, such as 
oral hygiene routines.   
Moderators from Fisher-Owens model:  
Demographics:  Insurance coverage, income, education, ethnicity, and family size, This 
measure will be assessed at baseline.  We will assess changes in mutable variables such as 
income and insurance at other measurement points.  We will use items from the BRFQ (Albino 
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Perceived stress (Herrero & Meneses, 2006):  We will use the 4-item version of the 
perceived stress scale (PSS). The PSS assesses the degree to which subjects perceive their 
environment and their experiences as stressful.  The scale correlates well with scores on life-
event measures, and has demonstrated adequate reliability (Cohen et al., 1983).  This measure 
will be assessed at baseline, 4, 12, and 24 months after baseline. 
 
Physical safety/family issues (Romano et al., 1991):  We will use the hassles scale 
which has been developed and validated on low income and ethnically diverse samples.  The 
scale assesses neighborhood safety and family issues. This measure will be assessed at 
baseline, 4, 12, and 24 months after baseline. 
Previous caries experience:  This measure will be assessed at baseline, 12 and 24- 
months via clinical exam utilizing a modified ICDAS  
Medical history:  This will be assessed at baseline, 12 and 24 months by the clinical 
examiner. 
Parent depressed mood:  We will use the short-form of the Center for Epidemiologic 
Studies Depression Scale (CESD-R- 10; Kohut et al., 1993).  The correlation between the long 
and short-forms is r=.91.  Cronbach’s alpha = .86.  This measure will be assessed at baseline, 
4, 12, and 24 months after baseline. 
History of dental care (parent and child). This measure will be assessed at baseline, 12 
and 24- months.  We will use items from the BRFQ (Albino et al., 2017).  
Perception of dental visits:    We will assess parental attitude toward taking their child to 
the dentist. This measure will be assessed at all measurement points.  We will use items from 
the BRFQ (Albino et al., 2017). 
Fluoride varnish. This measure will be assessed at baseline, 12 and 24- months.  We 
will use items from the BRFQ (Albino et al., 2017). 
Child oral health quality of life. We will use the Child Oral Health Impact Profile-Reduced 
scale (SF-19), which shows good reliability and validity to measure oral health related quality of 
life (Broder et al., 2012).  This measure will be assessed at baseline, 4, 12, and 24 months after 
baseline. 
Intervention Dose and Engagement: number of texts sent; percent of texts responded to, 
number of unprompted responses, use of program features, topics chosen, and goals 
set/completed. 
Program Satisfaction. We adapted the Mobile App Rating Scale (MARS; Stoyanov et al., 2015) 
to measure satisfaction with the text messaging program (e.g., would you recommend this 
program; ‘1’= not at all to ‘5’ definitely). Our other measures of program satisfaction that we 
adapted from the MARS are:  showing the TMs to others (yes/no); perceived helpfulness of TMs 
to family/friends; how much longer they want to receive the program; and satisfaction with each 
of the proposed program components (e.g., setting goals, choosing topics) and structure (e.g, 
time of day TMs received, frequency). The MARS also measures perceived impact of the 
intervention, and we adapted it for oral health.  We measure the perceived impact of the 
program on their own attitudes towards their child’s oral health and oral health practices. 

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Perceived impact on their own attitudes towards their child’s oral health is measured with six 
items on a scale of 1 (strongly disagree) to 5 (strongly agree; e.g., iSMILE has improved my 
attitude toward my child’s oral health) Perceived impact on oral health practices are measured 
with six items on a scale of 1 ‘not at all’ to 10 ‘very much.’ (e.g., ‘How much do you think that 
iSMILE had a positive impact on decreasing the amount of sugar sweetened beverages your 
child drinks.”). This measure will be assessed immediately after the conclusion of the fourth 
month text message program (at the 4-month follow-up).   
4  STUDY DESIGN 
This is a 2-arm, randomized controlled Phase III, single-center longitudinal trial. 850 parents or 
caregivers of children (< 7 years old) and their children with pediatric appointments at four 
targeted urban clinics will be recruited, consented, and subsequently randomized to OHT or 
CWT. We hypothesize that those randomized to the OHT group will have reduced incidence of 
caries as assessed by objective clinical exam 24- months after a baseline exam. Randomization 
will be a permuted block design, stratified by study site (Codman Square, Dorchester House, 
BMC, South End Community Health Center), and history of caries (no history of caries, any 
caries).  Because of the sparsity of Spanish speaking participants, with Spanish speakers 
primarily concentrated at one site, we will not stratify by site language (English, Spanish) but 
only on caries history to yield 8 strata.  CWT and OHT intervention arms will be matched on TM 
dose, duration and frequency, and employ identical features and engagement strategies for 
strong internal validity.  External validity will be supported by the fact that participants will be 
proactively recruited from an existing channel (pediatric clinic appointments) and use of the text 
message program in their everyday lives. Recruitment sites are located in urban, low-income 
areas, and the population is ethnically diverse and on public assistance.   
The approximate time to complete study enrollment is 1- year and the expected duration of 
subject participation is 2- years.  A clinical exam to assess caries will take place at baseline and 
12 and 24- months later. Clinical examiners are study staff and will be calibrated and blinded.  
Self-report surveys will take place at these time points, plus 2 and 4- months after baseline. 
These data will be captured through electronic data entry, in person, over the phone, or through 
an on-line link.  Weekly and monthly assessments will also occur during the 4- month TM 
program (from baseline through 4-months post-baseline). The coordinating center (CC) will be 
University of California at San Francisco.   
CWT or OHT TMs in either English or Spanish will be delivered in sets of two each day in Month 
1, and one set per day in Months 2-4, exclusive of brief assessments by text.   At month 12, 
participants will receive one month of ‘booster’ TMs (twice per day, exclusive of brief 
assessments by text).  Features include: quizzes, customization, personalization, tailoring, 
interactivity, problem solving photos/video, goal setting, and feedback and rewards using a 
gamification approach. There will also be three ‘weekly challenges’ over the 4- month program 
in which both groups can ‘opt-in’ and earn weekly rewards and ‘unlock’ secret characters for 
performing the core targeted behavior (brushing and reading for OHT and CWT respectively).  
Target behaviors (Reading for CWT and Brushing for OHT) will be assessed daily via TMs 
during challenge weeks.  Otherwise, both groups will be assessed weekly via TM on core topics 
(brushing for OHT; reading for CWT), motivation and confidence (to brush or to read).  Monthly 
assessments include dental visits (OHT) or safety (CWT). Both groups will have the ability to 
choose ‘choice topics’ each week and will receive the same engagement strategies (quizzes, 
rewards, birthday texts).  
 

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CWT include the Core Topics Reading and Child Safety, and the Choice Topics Physical 
Activity, Healthy Development, Secondhand Smoke, Safety Hazards, Sleep and Behavior, and 
Stress tips for parents. CWT participants earn weekly badges for reading to their child.  
Participants who are not reading to their child at recommended levels will received a graduated 
reward scheme, in which they will receive rewards for successive approximations of the 
recommended behavior.  The goal is to engage with reading to their child every day.  If they 
earn four different weekly badges (each badge specifying the reading goal achieved), they will 
earn a different ‘Book Buddy’ badge each month. They can also earn two ‘mystery book 
buddies’ for the completion of challenge weeks (Book buddies are anthropomorphized books). 
 
OHT include the Core topics Brushing and Visiting the Dentist, and the Choice topics Bedtime 
routine, Bottle/Sippy cup use, Sugar Sweetened Beverages, Healthy Eating, Getting Fluoride 
and Fun Facts. OHT participants earn weekly badges for brushing (or supervising brushing) 
their child’s teeth. Participants who are not brushing (or supervise brushing) their child’s teeth at 
recommended levels will received a graduated reward scheme, in which they will receive 
rewards for successive approximations of the recommended behavior. The goal is to brush their 
child’s teeth (or supervise brushing) 6-7 days per week, twice per day.  If they earn four different 
weekly badges (each badge specifying the brushing goal achieved), they will earn a different 
‘SuperTooth Hero’ badge each month and collect an entire family of SuperTooth heroes (Charlie 
Chew, Molly Molar, Faye Fluoride and Captain Chomp). They can also earn two ‘Secret Super 
Tooth Heroes’ for the completion of challenge weeks.  SuperTooth Heroes are 
anthropomorphized teeth wearing capes and holding toothbrushes. 
 
Substudies  
Because our comparison group (CWT) is an intervention, we would like to assess within- and 
between subject changes over time to gather pilot data for a future trial. The aim of this 
substudy would be to examine whether CWT parents increase their behaviors in two areas that 
reflect the core topics of the CWT intervention: reading to their child and child safety.  Core topic 
text messages are given once per day during month one (choice topics are also given once per 
day in month one) and 4 days per week during months 2-4 (choice topics are given 3 days per 
week during months 2-4). Choice topics for CWT are:   Physical Activity, Healthy Development, 
Secondhand Smoke, Safety Hazards, Sleep and Behavior, and Stress tips for parents. This 
substudy will have no impact on the main study.  We will analyze data from all participants in 
CWT and examine within subject changes over time, as well as whether or not they differentially 
changed in key variables (reading, safety) vs. OHT.  a separate analysis plan will be developed 
in the future. 
5  STUDY ENROLLMENT AND WITHDRAWAL 
5.1 Subject Inclusion Criteria 
In order to be eligible to participate in this study, the caregiver and child must meet all of the 
following criteria, as applicable: 
1. Provide informed consent for themselves and their child. 
2. Willing to comply with all study procedures and be available for the duration of the study  
3. Caregiver may be male or female, must be aged 18 or older (no upper age limit). 

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4. Caregiver must be a parent or legal guardian of a child less than 7 years old  
5. Enrolled child must have their first tooth showing. 
6. The child must receive medical care at one of the participating pediatric clinics (BMC, 
Dorchester House, Codman Square, South End Community Health Center).  
7. Speak, understand, and read either English or Spanish fluently.  
8. Have a mobile phone.  
9. Have used any type of text messaging at least one time in the past month.  
10. Have a mobile phone plan that includes unlimited text messaging.  
11. Score above the literacy cut-off, i.e. score less than or equal to 3 on the Single Item 
Literacy Screener (Morris et al., 2006) 
12. Ability to receive a test TM from the Agile Health system and ‘opting-in’ to program 
5.2 Subject Exclusion Criteria 
If the caregiver or child meets any of the following criteria, the dyad will be excluded from 
participation in this study: 
1. Participated in our usability trial or RCT pilot trial 
2. Substance abuse problems, as identified with the AUDIT-C screening tool and with 
questions about drug misuse.  
3. Diagnosis of serious mental illness (Bipolar Disorder, Mania, Manic-depressive disorder, 
Schizophrenia, Psychosis), self-reported.   
4. Children with severe congenital tooth malformations: at screening the caregiver will be 
asked if their child has known systemic diseases associated with abnormal tooth 
development or abnormal oral health status such as cleft lip or palate, amelogenesis 
imperfecta, or dentinogenesis imperfecta.   
5. Currently enrolled in another mobile phone study.  
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7. Plan on leaving the country for longer than two months during the 2- year study.  
8. Enrolled in an oral health study or child health and wellness study.  
9. Exclusion at the discretion of the Principal Investigator 
10. Children who cannot complete the baseline oral health exam. 
5.3 Strategies for Recruitment and Retention 
The study target population includes parents or legal guardians (>18 years old) of children (< 7 
years old) and their child with a pediatric appointment at one of the four participating clinical 
sites. 
 
The primary recruitment method for the study will be RAs, or other trained study 
personnel, identifying and recruiting participants in participating clinic waiting rooms (and other 
clinic spaces deemed appropriate by clinic partners). 
 
Additional strategies to identify potentially eligible participants may vary by site but include:  
(1) The site specific study champions and clinic staff and providers will identify potentially 
eligible participants, inform them about the study and direct them to a RA.  If the RA isn’t 
present, the clinic staff will give the participant a study pamphlet and/or permission to contact 
form for the iSmile study.  The permission to contact form may be printed with pre-populated the 
patient’s information (contact details), or given to the patient as a blank form.  
(2) iSMILE study staff will present the study at each clinical site at all-staff meetings to facilitate 
clinical staff and provider referral of  potentially eligible participants to the iSMILE study; 
(3) Bilingual study advertising, with RA contact information, will be on display in study clinics; 
(4) Bilingual study advertising inviting interested clinic patients to attend study information 
session phone calls to learn more about the study; 
(5) “Warm-hand-off” phone calls will be conducted by the clinic-employed study champion to 
potentially eligible participants prior to their scheduled clinic appointment to confirm their 
upcoming appointment and determine interest in the study (no cold calls will be made by our 
research staff). If the person is interested, the person will be referred to our study staff; 
(6) Partnering with other studies happening at participating clinics to facilitate referrals to iSmile; 
(7) Sending an informational letter from the Pediatric Medical Director to potential participants. 
(8) Distributing recruitment materials (flyers, brochures and permission to contact forms) at 
Head Start locations because many parents who visit Head Start also bring their children to 
receive care at one of our recruitment sites. 
 
 
Conducting “warm-hand-off” phone calls prior to a potentially eligible participants scheduled 
clinic visit will allow individuals the ability to plan for the extra time needed at their appointment 
to enroll and complete baseline study procedures. Research staff will identify subjects eligible 
for “warm-hand-off” phone calls from participating clinics' appointment schedule (part of the 
electronic health record (EHR). Research staff will have 'read-only' access to the EHR and they 
will not have access to the medical portion of the record. The parts of the EHR that we will have 
access to contains information on upcoming clinic appointments (date/time), name of parent and 
child, contact information, and age of child. The “warm-hand-off” phone call between clinic 
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to confirm their upcoming appointment and then determine their interest in learning more about 
the iSmile study. If the potentially eligible subject wants to learn more about the iSmile study 
over the phone, the clinical staff will hand the phone off to the iSmile RA. 
 
The iSmile study team will partner with other studies happening at participating clinics to 
facilitate referrals to iSmile. The iSmile team has learned of the other co-occurring studies 
happening in each of the participating clinics that overlap with the target iSmile recruitment 
population. From these co-occurring studies, iSmile has worked with each applicable study 
contact to determine if cross recruitment is feasible. For those studies for which cross 
recruitment is feasible, co-occurring study staff members will screen their potential participants 
per their IRB approved protocol. For potential participants who screen ineligible for other co-
occurring studies, the co-occurring study staff conducting screening will inform the individual 
that they may be eligible for the iSmile study. If an iSmile study staff member is available, the 
potential participant will be directly introduced to the iSmile study staff member to hear more 
about the study and potentially complete the IRB approved screening and enrollment process. If 
an iSmile study staff member is not available to tell the potential participant more about the 
study, the co-occurring study staff member will inform the potential participant that they can 
complete a paper permission to contact form and a member of the iSmile study staff will contact 
them shortly to tell them more about the study. Each participating clinical site has designated its 
own secure location for completed permission to contact forms to be stored on site until an 
iSmile study staff member is able to collect them. After collection, iSmile study staff will attempt 
to contact all potential participants to tell them more about the study. After successfully, or 
unsuccessfully, attempting to contact the potential participant, all completed permission to 
contact forms will be store in a locked filing cabinet in the Research Project Manager’s office. 
 
The informational letter being sent from each pediatric clinic, from the Pediatric Medical 
Director, will inform parents of children under age 7 that the health center is partnering with 
Boston University to develop a text message program. Study staff contact information is also 
included in the letter, should the parent be interested in assessing eligibility or asking questions 
about the study. 
 
If participants do not have time to be screened at the clinic, we will collect their contact 
information and the participant will be screened over the phone. Participants who are called will 
be guided through the consent process over the phone and we will obtain verbal  consent over 
the phone (seeking a waiver of documentation of consent) until they can provide signed consent 
at the time of the clinical exam. This is so participants can spend less time doing study 
procedures at the clinic. Clinic staff will also refer potentially interested participants to RAs.  
Study staff will perform screening and informed consent (in a private space or on the phone, 
prior to their appointment).  Participants will be told that, in order to be eligible for the study, they 
must be willing to receive TMs about their child’s health, have a phone that is able to 
send/receive text messages from our system, give permission for the index child to have dental 
exam, opt-in to the program, and receive one of two different TM programs. If there is more than 
one child < 7 years old in the same family, we will systematically choose the youngest as the 
index child for the study. If there is more than one parent present, we will choose the one that 
spends the most time with the child. Those who are eligible to participate will be asked to sign 
an electronic informed consent form, complete contact information and child demographic 
information with study staff who will verbally collect information via direct entry, and 
subsequently complete a self-report baseline assessment via electronic data capture (with 

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paper copies as back-up) and the baseline oral assessment. Study staff will take all possible 
steps to ensure that the participant is clear that the baseline questionnaire will ask questions 
regarding themselves and the child in the study (youngest child under the age of 7 years old 
with at least one tooth showing i.e., child for whom the informed consent had been collected). 
Once the baseline questionnaire and oral assessment are completed, REDCAP will 
automatically randomize participants into OHT or CWT, and this code as well as the TM 
personalization options will be transferred to the AH system so the first TM (OHT or CWT) will 
occur within 24 hours after randomization. The automization of randomization will ensure that 
the RAs are blind to treatment condition. 
The enrolled parent/caregiver will receive $60 for assessment contacts that include a self-report 
instrument and an oral health assessment conducted by the study clinical examiner (baseline 
and 12 and 24- months), $40 for assessment contacts which only include the self-report 
instrument (2 and 4- months after baseline), an additional $40.00 if the 12 and 24 month plus 
either the 2 or 4 month assessments are completed, or $70.00 if all 4 assessments are 
completed.  Thus, the total possible compensation for each parent who is a participant is 
$330.00. If at any point during the study following baseline it is determined that a participant will 
not be able to complete the 12 or 24 month oral health exam because they moved out of the 
area, we would still like to compensate the participant for completing the 12 or 24 month follow 
up surveys without the oral health exam. The participant would then be compensated with a $40 
gift card instead of $60, which is comparable to compensation at 2 and 4 months when 
participants are expected to only complete surveys. In addition, individuals who move out of the 
area and their situation is deemed by study research staff to be impossible to complete the oral 
health assessment are still eligible for bonus payment. 
 
During the text message program, participants will be given brief weekly assessments.  Each 
time they provide an answer to these questions, their name will be entered into a monthly raffle 
for $100.00. Every time that they answer one of these questions, they will have another entry 
into the raffle, increasing their chances of winning each month, for a maximum of four chances.  
Therefore, if they answer each of the four weekly questions per month, they will have four 
entries into the raffle that month.  After the name is drawn for that month, a new month will 
begin and all previous entries will be cleared.   Because they will receive text messages over 
the course of four months, they will have four chances to win.   
 
Assessments will be completed online, on participant’s smartphone, on the phone, or in person.  
 
To prevent dropout during the 4- month intervention period, we will personalize TMs, avoid TM 
redundancy, vary TM  content and frequency, use participant’s name and use fun TM quizzes, 
with the answers provided the following day. After the intervention period, we will use various 
cohort maintenance procedures as outlined in Albino et al (2017) to enhance retention (e.g., 
send birthday cards, contact six times/year to find out address changes) and also track 
participants through their contact with the pediatric clinics (i.e. identification of upcoming child 
wellness appointments through the clinic’s electronic scheduling system. Guidance from the AB 
will also assist in the development of retention strategies. 
 
In addition to direct compensation for their participation in the study, participants will also have 
be compensated for their transportation to and from participating clinical sites.  As the Baseline 

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enrollment process is long, not all families who begin the enrollment process are able to 
complete it in one day. To help facilitate enrollment, the study will compensate participants in 
the form of a $10 gift card for their transportation to and from participating clinical sites for 
participants who need to return to complete their enrollment process in a second visit. In 
addition, the study will provide the same $10 gift card compensation t for participant 
transportation to and from participating clinical sites for enrollees to complete the 12 and 24 
month oral health assessments at the clinic site.  
5.4  Treatment Assignment Procedures 
5.4.1. Randomization Procedures  
In order to randomly assign participants to treatment groups at baseline, we will be using a 
permuted randomized block design (random sized blocks of 2 or 4 participants), stratified by 
study site (Codman Square, Dorchester, BMC, South End Community Health Center), and 
history of caries (no history of caries, any caries).  Because of the sparsity of Spanish speaking 
participants, with Spanish speakers primarily concentrated at one site, we will not stratify by site 
language (English, Spanish) but only on caries history to yield 8 strata. The randomization list 
will be created using REDCap. Participants will be randomized by the web-based REDCap 
randomization module. Once the baseline questionnaire and oral assessment are completed, 
REDCap will automatically randomize participants into OHT or CWT, and this code as well as 
the TM personalization options from the baseline questionnaire will be transferred via secure 
API to the AH system so the first TM (OHT or. CWT) will occur within 24 hours after 
randomization. The automization of randomization will ensure that the RAs who have contact 
with participants are blind to treatment condition. The clinical examiners who will be collecting 
the primary outcome data will also be blinded.  A detailed plan for maintenance of 
randomization codes, including the timing and procedures for planned and unplanned breaking 
of randomization codes is described in the MOP.  
5.4.2 Masking Procedures  
All study staff collecting data, including the clinical examiners and RAs, will be blind to treatment 
condition.  The  Project Director and PIs will not be blind to treatment condition, because they 
will need to monitor inbound text messages for any responses that the automated system does 
not recognize. Unmasking procedures are detailed in the MOP. 
5.5 Subject Withdrawal 
Subjects are free to withdraw from the study at any time. During the TM  program, the 
participant can text ‘stop’ at any time and the  messages will cease. After the TM program, 
participants can e-mail iSMILE, or call or text  iSMILE, to state that they want to withdraw from 
the program. If a study subject requests to be withdrawn from the study, the research team will 
attempt to ascertain the reason for withdrawal. The Principal Investigators will also have the 
option to withdraw a participant if continued participation is not in the best interest of the 
participant. 
5.5.1 Reasons for Withdrawal 
We anticipate that reasons for a subject’s withdrawal may include one or more of the following:  

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• 
Does not have time to participate.  
• 
Does not want to receive TMs.  
• 
Does not feel the need for health information.  
• 
His/her child is not in their custody at the present time.  
• 
They are going out of the country permanently or for an extended period of time.  
A study subject may be withdrawn from study participation by the investigative team if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the 
best interest of the subject. 
• 
The subject meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
 
5.5.2  Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
We will attempt to obtain a final child oral health assessment and study questionnaires from all 
subject caregivers, including those who withdraw from the study for any reason. We will also 
attempt to perform an oral assessment on the child at the time of withdrawal if a subject 
withdraws early (before 24 months of participation). We will make a minimum of 5 attempts to 
contact the caregiver in cases of withdrawal and those who relocate. At the time of withdrawal, 
study staff will review procedures for contacting the study team in case an AE or UP occurs. 
Once a participant has been randomized, and begins the program, replacement of that 
participant is not allowed if the participant withdraws prematurely. If the participant becomes 
ineligible (e.g., child no longer lives with them), then we will replace the subject but only if the 
study is within the specified recruitment period. 
5.6  Premature Termination or Suspension of Study 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause.  
Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to investigator and NIDCR.   If the study is 
prematurely terminated or suspended, the principal investigator will promptly inform the IRB and 
will provide the reason(s) for the termination or suspension. Circumstances that may warrant 
termination include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects. 
• 
Insufficient adherence to protocol requirements. 
• 
Data that are not sufficiently complete and/or evaluable.  

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• 
Determination of futility. 
 
 
 
 
6 STUDY INTERVENTION 
6.1 Study Behavioral or Social Intervention(s) Description 
The intervention is an interactive, parent-targeted TM program to reduce caries among low 
income families visiting urban pediatric clinics. Caregivers and their children under the age of 7 
attending pediatric visits at one of our clinic partners will be randomized to receive one of two 
dose-equivalent TM interventions: Oral Health Texts (OHT) or Child Wellness Texts (CWT). The 
intervention includes a theory based, fully powered dose-matched design with an objectively 
measured clinical outcome. The CWT intervention is matched to OHT intervention on: 1) 
number of core modules and ability to choose from a menu of options for additional topics, 2) 
number of TMs and program duration 3) engagement strategies and 4) program features.  For 
the OHT group, the two core topics are Brushing and Visiting the Dentist. In addition to the 
required OHT Core topics, caregivers can choose from the following menu of topics: Bedtime 
Routine, Bottle/Sippy Cup Use, Sugar Sweetened Beverages, Healthy Eating, Getting Fluoride 
(tap water and toothpaste) and Fun Facts.  For the CWT group, the two core topics are Reading 
and Child Safety.   In addition to these required Core topics, caregivers can choose from the 
following menu of topics: Physical Activity, Healthy Development, Secondhand Smoke, Safety 
Hazards, Sleep and Behavior and Stress Tips for You.  
6.2 Administration of Intervention 
The TM intervention is automated and interactive.  The program will begin sending TMs within 
24- hours of randomization.  Both OHT and CWT will be 4-months in duration, with a  1-month 
booster session that will occur 12 months after baseline (8 months after the end of the 4 month 
program).  TMs will be delivered approximately twice each day in Month 1, and once per day in 
Months 2-4 (exclusive of brief assessment questions which occur several times per week).  
During the booster session (at 12 months after baseline), TMs will be delivered approximately 
twice per day, exclusive of brief assessment questions. Brief assessment questions will occur 
several times per week.  The number of texts, dose, and duration will be equivalent between the 
two groups. Participants in both groups will choose ‘choice topics’ each week, and will be 
assessed weekly via TM on core topics (brushing for OHT; reading for CWT) and mediators 
(motivation, self-efficacy and outcome expectations).  Monthly assessments include dental visits 
(OHT) or safety (CWT)
6.3 Procedures for Training Interventionists and Monitoring Intervention Fidelity 
The intervention will not utilize human providers. TM interventions are delivered exactly as 
designed, resulting in a 100% reliable intervention, providing confidence in the obtained results. 
However, because the project director will be able to respond to TMs, we will review a 
proportion of the responses to ensure that there is no treatment contamination. Because our 

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outcome data is collected by a clinical examiner, this data collection will be digitally recorded by 
an RA to ensure that no oral health advice or education is given during that time. 
6.4 Assessment of Subject Compliance with Study Intervention 
The AH Platform keeps track of all TMs sent and received, including both unprompted 
responses and expected responses from participants.  This includes responses to assessment 
questions, responses to weekly topic choices, and responses to the interactive intervention 
features of the TM programs. The study team will receive regular reports from AH as outlined in 
the MOP.  The study team will review the reports and monitor compliance based on overall 
response rates and response rates to assessment questions.   
 

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7. STUDY SCHEDULE 
The schedule of general study activities for individuals in both the intervention (OHT) and the 
dose matched control arm (CWT) is outlined in the following table. Once a subject has been 
determined eligible and has consented to study activities, a baseline survey and the clinical oral 
health assessment will occur.  After baseline activities are completed, the intervention and 
control activities will be delivered via text messaging for 4- months.  Study questionnaires will be 
administered at 2 months (mid treatment) and again at the end of the intervention (4 months).  
Study activities are described in greater detail below.  
 
Experimental 
and Control 
Baseline 
2 M (-14 days or 
+31 days) 
4 M (-14 
days or +31 
days)  
12 M (-14 days 
or + 60 days) 
24 M (-14 days 
or + 60 days) 
Eligibility 
Screening (pre-
baseline) 
X 
 
 
 
 
Questionnaires 
X 
X 
X 
X 
X 
Oral 
Assessment 
X 
 
 
X 
X 
TMs (OHT & 
CWT delivery) 
X 
X 
X 
X 
 
7.1 Eligibility Determination  
Subjects who express an interest in study participation will talk on the phone or meet in person 
with a RA or other appropriate study staff who will determine eligibility based on a series of 
eligibility questions (see Section 5). Those who are deemed eligible will continue with the 
consent process conducted by the RA.   
7.2 Enrollment/Baseline 
Subjects will be enrolled in the study after signing an electronic informed consent form and 
completing all baseline activities. For some participants, these activities will occur on the same 
day as eligibility determination and consent. For others, screening and review of consent 
procedures may take place over the phone (prior to their clinic appointment), and documentation 
of informed consent, the baseline questionnaire, and the oral assessment will occur at in person.     
 
The following activities will occur at baseline: 
• 
Informed consent 
• 
Opt-in to Agile Health system 
• 
Contact information and demographic information 
• 
Completion of Baseline Questionnaire  

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• 
Conduct oral health assessment of child  
• 
Randomize participant to OHT or CWT  
• 
TM Intervention will begin after randomization 
7.3 Follow-up  
Follow-up assessments will occur approximately at 2, 4, 12 and 24- months following the 
baseline visit.  For the 2 and 4 month survey, participants completing the survey within 14 days 
prior to or 31 days after the target date will be considered compliant with the study schedule.  
Oral health assessments of children and surveys at 12 and 24- months occurring within -14 days 
prior to or 60 days after the target follow-up date will be considered compliant with the study 
follow-up schedule.  Surveys will be completed through electronic data capture, either in-person, 
on-line, or via weblink. If the person requests that the survey be conducted via interview, we will 
oblige and administer the survey verbally and the RA will input data directly into the electronic 
data capture system. 
Baseline – 4 months:  
The intervention will be delivered to caregivers via daily TM for 4- months. However, there are 
no study visits associated with the intervention delivery.   
2 and 4 month assessments (-14 days/+ 31 days):  
• 
Record adverse events as reported by subject or observed by investigator. 
• 
Self-report questionnaire 
12 month assessment (12 months -14 days/+ 60days) 
• 
Record adverse events as reported by subject or observed by investigator. 
• 
Self-report questionnaire 
• 
Conduct oral health assessment of child 
7.4 Final Study Visit (24 months -14 days + 60 days) 
The final study visit will occur at 24 months after baseline, within 7 days prior to or 31 days after 
the target date.  The final visit will occur sooner than 24 months if a family has moved or 
withdrawn from the study and we conduct the final clinical visit. 
At the final study visit the study staff will:  
• 
Record adverse events as reported by subject or observed by investigator. 
• 
Conduct oral health assessment of the child 
• 
Self-report questionnaire 

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• 
Provide final instructions to subject including how to follow-up of ongoing adverse events 
7.5   Early Termination Visit  
If early termination occurs, we will make a minimum of 5 attempts to contact the caregiver in 
order to complete the oral health clinical assessment and questionnaire.  
7.6 Unscheduled Visit   
An unscheduled visit would be considered to occur if a study subject was in contact with 
a member of the study team regarding oral knowledge, attitudes or practices if the 
contact was not: 1. part of normal texting procedures or 2. related to the occurrence of 
adverse events or unanticipated problems.  All unscheduled visits will be documented 
via a note to file and included in the participants’ research record.   
 
 

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8 STUDY PROCEDURES /EVALUATIONS 
8.1 Study Procedures/Evaluations 
 
Screening Administration:  
 
Trained study staff, usually an RA, will screen individuals for eligibility as described above and in 
Section 5. At screening, all participants will be administered the “AUDIT-C,” which is a 3-item 
alcohol screen (range 0-12) that identifies persons who are hazardous drinkers or have active 
alcohol use disorders (Hodgson et al., 2003).  In men, a score of 4 or more is considered 
positive, and in women a score of 3 or more is considered positive.  For drug misuse screening 
(Smith et al., 2010), we will ask if they have, in the last two weeks, used any of the following 
medicines on their own, without a doctor’s prescription, in greater amounts or longer than 
prescribed (e.g., opioid pain killers (like Vicodin), stimulants, (e.g. Ritalin or Adderall), sedatives 
or tranquilizers (e.g. Valium) or drugs like cocaine or crack, club drugs (e.g. ecstasy), 
hallucinogens (e.g. LSD), heroin, inhalants or solvents (e.g. glue), or methamphetamines (e.g. 
speed).  Participants will answer yes or no to this single question with no further questions about 
which drugs they have used.  Participants who answer ‘yes’ to this single question will not be 
enrolled in the study.  
 
Additionally, participants will be asked to self-report diagnosis of serious mental illness (Bipolar 
Disorder, Mania, Manic-depressive disorder, Schizophrenia, Psychosis).   At screening, all 
participants will be asked “Have you ever been diagnosed with a mental illness?” and if so, 
which ones. If the participant reports that he or she has been diagnosed with one of the mental 
illnesses listed above, they will be excluded. 
 
Study data collected at screening includes documentation of all eligibility and exclusion criteria.   
These data will be recorded using EDC. 
 
Questionnaire Administration:   
 
At baseline, after participants complete the informed consent process, study staff will verbally 
collect contact information and demographic information on the Contact Information eCRF. 
Study staff will enter information directly into REDCAP to ensure that the child, for whom the 
informed consent had been collected, matches the child’s information for the text message 
program (i.e.,  child’s first name, child’s gender, and child’s date of birth.) 
 
All study assessment points include completion of questionnaires by parent participants, to 
assess each of the outcome measures described in Section 3. The participant baseline 
questionnaire will be conducted in person using EDC at the pediatric clinic.  However, when that 
is not possible, participants will have the ability to complete the questionnaire via a secure 
website on their own laptop or other device or via smartphone or over the phone with the study 
team assistance. 

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2 month assessment: a shortened version of the survey, which primarily focuses on collection of 
mediators, will be utilized to assess intervention processes and impact while being sensitive to 
respondent burden and the impact of respondent burden on retention. 
 
4 month assessment: Includes a collection of mediators, secondary outcomes and program 
satisfaction data. 
Oral Health Assessments (Baseline, 12 and 24 months): The OHDC Modified ICDAS protocol 
that was developed as a collaborative effort of the CC and the study PIs will be utilized to collect 
caries outcome data.  This standardized protocol will be used to assess the presence or 
absence of dental caries at the tooth surface level by a trained, calibrated clinical examiner 
blinded to treatment condition.  Dental caries assessment will occur at baseline and then 
annually and in most cases occur at the pediatric clinic.  If the parent cannot bring the child to 
the pediatric clinic, the clinical examiner will utilize a suitable alternative setting to conduct the 
visits, such as the participants’ home.   
 
Referral Procedures  
Referral codes 
• 
1 - There is no visible decay (Regular dental exams are recommended) 
• 
2 - Early dental care is needed (< 5 decayed tooth surfaces) 
• 
3 - Treatment is needed soon (5 or more decayed surfaces) 
• 
4 - Treatment is urgently needed (Pain is reported or infection is present) 
Process for referrals 
A report card indicating each child’s oral health status and need for dental treatment will be 
given to caregivers immediately following the child’s clinical oral health assessment.  The report 
card includes the phone number of the RA and a referral list of local providers to assist the 
caregiver in locating dental treatment for their child.  
For children with a referral code of 4, one week following the oral health assessment, the 
caregiver will be contacted to ensure that treatment was obtained.  If care was not provided, the 
caller will offer to make an appointment for the child. 
Medical Emergency Protocol   
Clinical Examiners will: 
• 
Be equipped with medical emergency kits containing first aid supplies, epi pens, glucose 
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• 
Be Certified in Cardiopulmonary Resuscitation 
• 
Be aware of emergency protocols at each pediatric clinic including emergency exits and 
location of telephones  
Intervention Dose and Engagement:  
 
Agile Health will send regularly scheduled reports which will include data regarding: 
• 
Number of texts sent  
• 
Percent of texts responded to  
• 
Number prompted responses  
• 
Use of program features 
• 
Topics chosen 
• 
Goals set/completed  
• 
Ratings of TMs  and program satisfaction 
 
 
Budget Impact Evaluation:  
 
We will survey IT specialists at all our sites as well as technical experts in industry to estimate 
interface and application costs of two different integration strategies involving the incorporation 
of the OHT intervention into routine clinical care:  1) a fully-automated strategy that involves an 
EHR prompt to providers recommending that they ‘prescribe’ the program to their patients and 
the system automatically enrolls the patient via an EHR to iSMILE  and where a summary is 
returned to the EHR for guidance at future appointments; 2) a more labor intensive strategy but 
less technologically complex approach whereby the provider creates ‘an order’ in the EHR and a 
printout is initiated for the patient and the patient signs themselves up.  Interviews with decision 
makers from our currently targeted sites will be used to explore the barriers and facilitators to 
the intervention implementation and adoption.  
 
8.2 Laboratory Procedures/Evaluations 
No laboratory procedures or evaluations will be performed as part of this study. 

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9 ASSESSMENT OF SAFETY 
9.1 Specification of Safety Parameters 
Safety monitoring for this study will focus on unanticipated problems involving risks to 
participants, including unanticipated problems that meet the definition of a serious adverse 
event.  
9.1.1 Unanticipated Problems 
Unanticipated problems involving risk to human subjects will be recorded and reported 
throughout the entire study.     
The Office for Human Research Protections (OHRP) considers unanticipated problems involving 
risks to subjects or others to include, in general, any incident, experience, or outcome that 
meets all of the following criteria: 
• 
unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved 
research protocol and informed consent document; and (b) the characteristics of the 
subject population being studied; 
• 
related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• 
suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
9.1.2 Adverse Events 
Adverse events that are plausibly related to the study will be recorded and reported throughout 
the entire study.     
An adverse event is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in the research and  
considered related to the subject’s participation in the research. 
9.1.3 Serious Adverse Events 
Serious adverse events will be recorded and reported throughout the entire study. 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• 
Results in death 
• 
Is life-threatening (places the subject at immediate risk of death from the event as it 
occurred) 

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• 
Results in inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in a persistent or significant disability or incapacity 
• 
Results in a congenital anomaly or birth defect   
• 
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, the event may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
9.2 Time Period and Frequency for Event Assessment and Follow-Up 
AEs, UPs and SAEs will be recorded in the data collection system throughout the study. Events 
will be followed for outcome information until resolution or stabilization. 
9.3 Characteristics of an Adverse Event 
9.3.1 Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are used by the 
Co-PIs: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event onset. 
b. An alternate etiology has been established. 
9.3.2 Expectedness of SAEs 
The study PIs will be responsible for determining whether an SAE is expected or unexpected.  
An adverse event will be considered unexpected if the nature, severity, or frequency of the event 
is not consistent with the risk information previously described for the intervention.   
9.3.3 Severity of Event 
The following scale will be used by the Co-PIs to grade adverse events: 
1. Mild: no intervention required; no impact on activities of daily living (ADL) 

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2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on 
ADL 
3. Severe: significant symptoms requiring invasive intervention; subject seeks medical 
attention, needs major assistance with ADL 
9.4   Reporting Procedures 
9.4.1 Unanticipated Problem Reporting to IRB and NIDCR 
Incidents or events that meet the OHRP criteria for unanticipated problems require the creation 
and completion of an unanticipated problem report form by the Co-PIs.  The report will include 
the following information when reporting an adverse event, or any other incident, experience, or 
outcome as an unanticipated problem to the IRB: 
• 
appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number; 
• 
a detailed description of the adverse event, incident, experience, or outcome;  
• 
an explanation of the basis for determining that the adverse event, incident, experience, 
or outcome represents an unanticipated problem;  
• 
a description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported using 
the following timeline:   
• 
Unanticipated problems that are serious adverse events will be reported to the IRB and 
to NIDCR within 24 hours if death or a life-threatening event or within 72 hours for all 
other serious adverse events.  
• 
Any other unanticipated problem will be reported to the IRB and to NIDCR within 7 days 
of the investigator becoming aware of the problem.  
• 
All unanticipated problems should be reported to appropriate institutional officials (as 
required by an institution’s written reporting procedures).  The IRB will then report to the 
supporting agency head (or designee), and OHRP within one month of the IRB’s receipt 
of the report of the problem from the investigator. 
All unanticipated problems will be reported to NIDCR’s centralized reporting system via Rho 
Product Safety: 
• 
Product Safety Fax Line (US):  1-888-746-3293 
• 
Product Safety Fax Line (International):  919-287-3998 
• 
Product Safety Email:  rho_productsafety@rhoworld.com  

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General questions about SAE reporting can be directed to the Rho Product Safety Help Line 
(available 8:00AM – 5:00PM Eastern Time):   
• 
US:  1-888-746-7231 
• 
International: 919-595-6486 
9.4.2 Serious Adverse Event Reporting to NIDCR 
For any AE meeting the specified Serious Adverse Event criteria, the CO-PIs or their designee 
will submit an SAE form to NIDCR’s centralized safety system via Rho Product Safety. This 
report may be sent by fax or email. Once submitted, Rho Product Safety will send a confirmation 
email to the investigator within 1 business day. The investigator should contact Rho Product 
Safety if this confirmation is not received. This process applies to both initial and follow-up SAE 
reports. 
SAE Reporting Contact Information: 
• 
Product Safety Fax Line (US):  1-888-746-3293 
• 
Product Safety Fax Line (International):  919-287-3998 
• 
Product Safety Email:  rho_productsafety@rhoworld.com  
General questions about SAE reporting can be directed to the Rho Product Safety Help Line 
(available 8:00AM – 5:00PM Eastern Time):   
• 
US:  1-888-746-7231 
• 
International: 919-595-6486 
The study clinician will complete a Serious Adverse Event Form and submit via fax or email 
within the following timelines:   
• 
All deaths and immediately life-threatening events, whether related or unrelated, will be 
recorded on the Serious Adverse Event Form and submitted to Product Safety within 24 
hours of site awareness.  
• 
Serious adverse events other than death and immediately life-threatening events, 
regardless of relationship, will be reported by fax within 72 hours of site awareness.  
All SAEs will be followed until resolution or stabilization.  

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10 STUDY OVERSIGHT 
Study oversight will be under the direction of the study PIs, Dr. Borrelli (lead administrative and 
fiscal PI), Dr. Henshaw, and the NIDCR. The study PIs will have weekly scheduled meetings to 
review study progress and monthly meetings with NIDCR and the DCC.   
In addition to the PI’s responsibility for oversight, study oversight will be under the direction of a 
Data and Safety Monitoring Board (DSMB) composed of members with appropriate clinical, 
statistical, scientific, and ethical expertise. The NIDCR will appoint the Board. The DSMB will 
meet annually to assess safety and efficacy data, study progress, and data integrity for the 
study. If concerns arise, more frequent meetings may be held. The DSMB will operate under the 
rules of an NIDCR-approved charter that will be approved at the organizational meeting of the 
DSMB. The DSMB will provide recommendations to the NIDCR.  

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11 CLINICAL SITE MONITORING 
Clinical site monitoring is conducted to ensure that the rights of human subjects are protected, 
that the study is implemented in accordance with the protocol and/or other operating 
procedures, and that the quality and integrity of study data and data collection methods are 
maintained.  Monitoring for this study will be performed by NIDCR’s Clinical Research 
Operations and Management Support (CROMS) contractor. The monitor will evaluate study 
processes and documentation based on NIDCR standards and the International Conference on 
Harmonisation (ICH), E6: Good Clinical Practice guidelines (GCP). 
Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) 
developed by the CROMS contractor, in collaboration with the NIDCR Office of Clinical Trials 
and Operations Management (OCTOM) and the NIDCR Program Official. The CMP will specify 
the frequency of monitoring, monitoring procedures, the level of clinical site monitoring activities 
(e.g., the percentage of subject data to be reviewed), and the distribution of monitoring reports.  
Some monitoring activities may be performed remotely, while others may take place at the study 
site(s).  Staff from the CROMS contractor will conduct monitoring activities and provide reports 
of the findings and associated action items in accordance with the details described in the CMP.  
Documentation of monitoring activities and findings will be provided to the site study team, the 
study PIs, OCTOM, and the NIDCR. The NIDCR reserves the right to conduct independent 
audits as necessary. 
 

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12   STATISTICAL CONSIDERATIONS 
12.1 Study Hypotheses 
Primary hypothesis 1:  Those receiving OHT will have lower 24 month incidence of any new 
caries, compared to those receiving CWT. 
Primary hypothesis 2:  The OHT effect on new caries at 24 months will be mediated through 
Social Cognitive Theory constructs (self-efficacy, motivation, and outcome expectations).  We 
will examine indirect effects of OHT through self-efficacy, motivation, and outcome expectations 
at 2 months, to potentially increased motivation and oral health behavior at 4 months (end of 
intervention) to new caries at 12 and 24 months. We will also examine indirect effects of OHT 
through self-efficacy, motivation, and outcome expectations at 4 months (end of treatment), to 
potentially increased motivation and oral health behavior at 12 months and to new caries at 12 
and 24 months.  
Secondary hypothesis 1: We hypothesize that the total cost of OHT implementation will be more 
cost-effective than standard of care (e.g., oral health anticipatory guidance). 
Secondary hypothesis 2:  Those receiving OHT will have better pediatric oral health behaviors 
(tooth brushing, diet, sugar-sweetened beverages, fluoride toothpaste use, preventive dental 
visits, and oral assessment by parents) at 4 months (end of intervention), 12 months, and 24 
months, compared to those receiving CWT. 
Secondary hypothesis 3: Those receiving OHT will have better oral health behaviors (tooth 
brushing, dental visits), oral health knowledge, and attitudes at 4 months (end of intervention), 
12 months, and 24 months, compared to those receiving CWT. 
Exploratory Analyses:  These analyses will explore whether the effect of OHT vs. CWT on new 
caries at 24 months is greater in subpopulations defined by race/ethnicity, insurance coverage, 
parent education level, child’s prior caries experience, parent depressed mood, and intervention 
dose/engagement. 
12.2 Sample Size Considerations 
Primary sample size considerations focused on primary hypothesis 1, testing for a difference in 
the percentage of children with new caries at 24 months in those randomized to OHT vs. CWT.  
Sample size was calculated for the chi-square test comparing these two independent 
percentages, testing at the two-tailed alpha (Type I error rate) of 0.05 level and achieving 80% 
power (0.20 Type II error rate).   
No interim analyses are planned. 
Power calculations assumed an underlying new caries incidence at 24 months of 23.8% in the 
CWT group vs. 14.3% in the OHT group (corresponding to an odds ratio of 0.53; justification 
given below). 
Based on our experience in the pilot study and our previous studies (e.g., the recently 
completed OHAPH trial), we anticipate examining 70% of enrolled parent/child dyads at 24 

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months.  We do not anticipate missing data other than that due to loss-to-follow-up. We will 
attempt to follow and include all parents in the analysis regardless of their compliance with the 
study protocol and level of engagement with the OHT or CWT intervention (‘intent to treat’). 
Parents lost to follow-up will not be replaced.  Participants, can, however, become ineligible after 
randomization (and not evaluable), for example, if a parent loses custody of the child. 
Participants who become ineligible after randomization will be replaced if the ineligibility occurs 
while the study is still recruiting. If they become ineligible after the study recruitment period, their 
data will not be included in analyses. 
Given the above scenario, an analysis sample of n=600 parent/child dyads (n=300 in each study 
arm) gives 84% power of detecting a significant decrease in caries incidence in the OHT vs. 
CWT group.  This requires an enrollment sample of n=850 (n=425 in each study arm) to account 
for loss-to-follow-up. 
If the underlying incidence of ECC is higher than the assumed 23.8% in the control CWT group, 
we will have greater power of detecting a difference between arms corresponding to an odds 
ratio of 0.53.  For example, for an underlying incidence of ECC in the CWT group of 30%, the 
OR=0.53 corresponds to a difference in incidence of ECC of 18.6% vs 30% and a power of 
90%.  If the underlying incidence of ECC is lower in the CWT group, we will have lower power of 
detecting the OHT effect.  For example, for an underlying incidence of ECC in the CWT group of 
20%, the OR=0.53 corresponds to a difference in incidence of 11.8% vs 20% and a power of 
0.78.  If the underlying intervention effect is weaker than assumed, we will have lower power of 
detecting an effect.  For example, with an incidence of ECC in the CWT group of 23.8% and an 
intervention effect corresponding to an odds ratio of 0.60 (incidence of 15.8% vs 23.8%) power 
would be 69%. 
Power under different incidence levels and intervention effects, analysis samples of n=300 per 
study arm.  The first row corresponds to our primary anticipated effect 
OHT Effect  
Odds Ratio 
ECC Incidence in CWT 
Group 
ECC Incidence in  
OHT Group 
Statistical Power 
0.53 
 
0.53 
0.53 
 
0.60 
0.60 
23.8% 
 
30.0% 
20.0% 
 
23.8% 
30.0% 
14.3% 
 
18.6% 
11.8% 
 
15.8% 
20.4% 
0.84 
 
0.90 
0.79 
 
0.69 
0.77 
 
Justification of the anticipated OHT vs. CWT effects:  Data from the behavioral interventions 
delivered by Kressin et al. (2009) and Weinstein et al. (2004) was used to calculate sample size 
and power because the Kressin oral health data was collected at the largest site in our study 
(BMC) and another pediatric clinic located within a teaching hospital 1 mile away (with a 
population comparable to that at our CHCs). In the study by Kressin, caries incidence in the 
control site was 31.7%; however, participants did not regularly receive fluoride varnish (FV), a 
known preventive measure which reduces caries risk. The application of FV is inconsistent and 
infrequent in our targeted CHCs, but if we conservatively assume that all child participants will 
receive the recommended 4 applications/year, then we can assume that the incidence of caries 

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among controls will be reduced an additional 25% (Weinstein et al, 2004) or from 31.7% to 
23.8%. Kressin et al. (2009) found a 44.2% reduction in caries incidence due to the brief patient 
centered counseling intervention during the pediatric well child visit. If we assume a similar 
effect from the daily text messaging intervention, we would expect a 13.3% incidence of caries 
in the intervention group compared to 23.8% incidence in the control group (accounting for 
possible FV effect). To be slightly more conservative, we can use the 40% reduction in caries 
incidence found by Weinstein et al in his intervention and in the Marinho et al., 2013 Cochrane 
review. This would result in 14.3% caries incidence for the intervention group. In this scenario, 
we would need 300 parent-child dyads at our 24 month follow-up to have an estimated 84% 
power (2 tailed) to detect a 9.5% difference in caries incidence between groups with alpha=0.05 
and according to the standard chi-square test. 
Our second primary hypothesis will examine the mechanism of the OHT effect, examining 
mediation through Social Cognitive Theory constructs of self-efficacy, motivation, and outcome 
expectations. Statistical power for tests of indirect effects of OHT through a mediator will be 
calculated using the joint effects approach; there is 80% power of detecting an indirect effect if 
the power of showing an association between OHT and the mediator, and an association 
between the mediator and 24 month caries incidence, are both 90%.  We have 80% power of 
showing an indirect effect of a continuous mediator if intervention (OHT vs. CWT) explains 2% 
of the mediator (R2=.02), and if a 1 standard deviation increase in the mediator leads to a 30% 
reduction in the odds of caries (an OR=0.70).  This study was powered to detect an OHT effect 
in the overall sample.  Secondary analyses examining whether the OHT effect varies across 
subpopulations defined by race/ethnicity, insurance coverage, maternal education level, or 
child’s prior caries experience will have lower power.  These analyses should therefore be 
considered exploratory.   
12.3 Planned Interim Analyses (if applicable) 
There is minimal risk associated with the interventions and no interim analysis are planned.  
12.3.1   Safety Review 
Safety concerns associated with this study are minimal and there are no plans to halt study 
enrollment in response to a Safety Review. 
12.3.2 Efficacy Review 
There is minimal risk associated with this study.  No interim analyses are planned, and there are 
no plans to halt study enrollment in response to an efficacy review. 
12.4 Final Analysis Plan 
Overview of Analytic Plan:  Primary analyses will focus on the comparison of those assigned to 
OHT vs. CWT on oral health and behavior outcomes using all available data (i.e., restricted to 
those followed) and, following the intent-to-treat principle, randomized subjects will be included 
in the analysis regardless of their compliance with the study protocol and engagement in the 
study interventions.  While no differences between study arms are anticipated due to 
randomization, preliminary analyses will explore differences between arms and variables found 
to differ between groups (at the p<0.10 level) will be adjusted for in analysis.  For dichotomous 
outcome variables (e.g., incidence of any new caries at 24 months; use of fluoride toothpaste) 
analyses will use logistic regression models, with intervention effects reported as odds ratios 

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with 95% confidence intervals.  Count data (e.g., number of new caries at 24 months) will be 
analyzed through Poisson regression models, if the distributional assumptions of the Poisson 
model are met, or negative binomial or zero-inflated models if the outcome distribution better 
meets the assumptions of these models.  Results will be reported as rate ratios with 95% 
confidence intervals.  Continuous variables (e.g., number of tooth brushings per week) will be 
analyzed through mixed effects linear regression models.  Data will also be analyzed by race 
and gender as specified in the Notice of Grant Award, although these analyses will be 
exploratory due to lack of power.  If follow-up falls below the anticipated 70%, primary analyses 
will account for missing data through inverse probability weighting using propensity scores for 
missingness.  If follow-up meets the anticipated 70%, inverse probability weighting may be used 
in sensitivity analyses addressing the impact of missing data.  
The two-tailed alpha 0.05 level will be used to indicate statistical significance. 
Primary aim 1:  We will use logistic regression to compare the incidence of new caries in 
primary dentition (dmfs) over 24 months (no vs. any new caries) in OHT vs. CWT children, 
controlling for age, previous caries, and other relevant variables. Secondary analyses will also 
use logistic regression to compare OHT vs. CWT on the incidence of new caries in permanent 
dentition (DMFS) and mixed dentition (dmfs+DMFS).  Secondary analyses of the number of new 
caries will be conducted using Poisson regression or related methods.  Distributional 
assumptions of Poisson regression will be checked, and negative binomial regression models 
(for over-dispersion) and zero-inflated (negative binomial and Poisson) models (for excess 
zeros) will be considered if appropriate. Given that we are performing oral assessments at three 
time points (baseline, 12 and 24 months), we can also perform a tooth-level analysis of new 
caries in primary and permanent dentition, using mixed effects logistic regression models 
(Gibbons et al., 2010) to account for the multiple observations (teeth) per child. 
 
Primary aim 2:  Our second primary aim is to investigate the mechanisms of the OHT 
intervention effect on caries incidence (mediation analysis).   Mediation analyses will examine 
indirect effects of OHT on caries incidence through constructs from Social Cognitive Theory 
(self-efficacy, motivation, and outcome expectations). We hypothesize that OHT will lead to 
improved self-efficacy, motivation, and outcome expectations, which in turn will be associated 
with better proximal outcomes (increased motivation and oral health behavior) at the end of 
treatment, 4 months.  We further hypothesize that changes in mediators over the course of 
treatment will have a mediational effect on distal outcomes (change in oral health behaviors 
and lower caries incidence at 12 and 24 months). For descriptive analyses of mediation, we 
will take a causal steps approach and test individual mediators, as specified by MacKinnon and 
Fairchild (2007).  Then, we will use the product of coefficients method, using bootstrapped 
confidence intervals (Shrout & Bolger, 2002) to account for the non-normality of the estimated 
indirect effect, which utilizes a multiple mediation model to simultaneously test the effects of 
potential mediators, and enabling the determination of the relative influence of each. We will 
also consider using a counterfactual approach (Valeri & Vanderweele, 2013) although it does 
not allow for time varying effects of mediators, and has not been previously used in oral health 
research like the MacKinnon procedure.  
 
Secondary aims 

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Aim 1.  We will conduct a Budget Impact Analysis (BIA) to assess the financial consequences 
of adoption, diffusion and sustainability of the OHT intervention. BIA will be undertaken from 
the perspective of the budget holder, who makes decisions regarding uptake of interventions. 
To do this, we will follow the best practice guidelines set forth by the International Society for 
Pharmacoeconomics and Outcomes Research (ISPOR) task force (Mauskopf et al., 2007). As 
such, we will identify detailed cost and claims data to assess the cost impact of providing the 
intervention and compare the clinical outcomes of the OHT intervention with the costs of 
achieving those outcomes, and conduct sensitivity analyses to present context specific 
scenarios for different situations (e.g., pediatric clinics that may have a lower/higher proportion 
of Medicaid patients).  Sensitivity analysis will model two different strategies to incorporate the 
OHT intervention into routine clinical care:  1) a fully-automated strategy that involves an EHR 
prompt to providers recommending that they ‘prescribe’ the program to their patients and the 
system automatically enrolls the patient via an EHR to iSMILE  and where a summary is 
returned to the EHR for guidance at future appointments; 2) a more labor intensive strategy but 
less technologically complex approach whereby the provider creates ‘an order’ in the EHR and 
a printout is initiated for the patient and the patient signs themselves up.  We will be able to 
calculate the cost per caries prevented under each scenario. BIA is essential to helping 
potential diffusion targets to form business plans that determine the financial feasibility of the 
OHT intervention. We will survey IT specialists at all our sites as well as technical experts in 
industry to estimate interface and application costs. BIA is a useful approach to help 
stakeholder decision makers decide if this particular intervention is worth creating and 
sustaining beyond grant based startup funding. Policy decision makers will be able to plug in 
and alter assumptions as needed for their situations. We will explore whether or not it is 
possible to assess site specific effects using multilevel modeling (Charns et al., 2012).  
Interviews with decision makers from our currently targeted sites will be used to explore the 
barriers and facilitators to the intervention implementation and adoption. This will help develop 
plans for “implementation spread” to other sites that can be tailored to local requirements and 
needs. 
Aims 2 and 3. We will compare changes in these behaviors over time in OHT vs. CWT using 
mixed effects logistic regression models  (for dichotomous outcomes) and mixed effects linear 
regression models (for continuous outcomes).  Changes in these behaviors from baseline to 2, 
4, 12, and 24 months will be described through odds ratios and 95% confidence intervals for 
logistic models, and slopes for linear models. Differences in changes over time for OHT vs. 
CWT will be tested through group by time interaction terms.   
Aim 4: To identify subpopulations for whom the intervention has the greatest effect, we will 
analyze moderators; e.g., race/ethnicity, insurance coverage, parent educational level, and 
child’s prior caries experience. This aim focuses on moderator effects (also known as effect 
modification) for incident caries over 24 months. We will use logistic regression models with 
multiplicative interaction terms (treatment group x moderator) to compare the efficacy of OHT 
across subpopulations.  
 
17.  Missing data: We will gather follow-up information and reasons for dropout regardless of 
treatment completion, censoring at the point of loss. We will examine the extent of drop-out, and 
identify characteristics associated with drop-out through logistic regression.  Given drop-out 
does not exceed the expected rate of 30%, primary analyses will be based on available data. 
Secondary analyses will account for missing data and explore the potential impact of drop-out 
on study findings.  We will describe the robustness of our findings with respect to missing data 
using inverse probability weighting.  This approach to handling missing data has two steps: 1) 
develop propensity scores for missing data, which involves using logistic regression to model 
the probability of being followed to the 24 month visit as a function of baseline variables, 
including history of caries; and 2) using the inverse of the propensity scores (predicted 
probabilities from the first step) to serve as weights in our logistic regression model of new 

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primary teeth caries.  Provided the data are missing at random (MAR), that is, the probability of 
missingness can be fully explained by observable data, this approach produces asymptotically 
unbiased estimates. If there is sufficient missing data, and a concern that data may be missing 
not at random, we will also consider pattern mixture models to perform a sensitivity analysis of 
the potential impact of missingness.  
 
 
 
 

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13 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Study staff will maintain appropriate medical and research records for this study, in compliance 
with ICH E6, Section 4.9 and regulatory and institutional requirements for the protection of 
confidentiality of subjects.  Study staff will permit authorized representatives of NIDCR and 
regulatory agencies to examine (and when required by applicable law, to copy) research records 
for the purposes of quality assurance reviews, audits, and evaluation of the study safety, 
progress and data validity.   
Access to source data and documents is controlled through strict physical and electronic 
controls. Staff access permissions will be set according to job description activities. 
Source documents will include informed consent forms completed electronically in REDCap, a 
secure web-based application. Paper consent forms will be available as an alternative as 
necessary. This information will be kept in locked file cabinets, within a locked office within 
GSDM’s research offices at 560 Harrison Avenue and only study staff will have keys. With the 
exception of the data collected through caregiver TMs, the remainder of the source documents 
will be eCRFs.  These include iSMILE screener, iSMILE questionnaire, and caries assessment 
data capture systems, such as REDCAP. The iSMILE specific eCRFs were developed in 
concert with the CC as part of the qualitative and pilot phase.  The eCRFs in CARIN were 
developed by UCSF’s CC and successfully utilized by the Co-PIs during a previous RCT funded 
by the NIDCR (Oral Health Advocates in Public Housing).   
Agile Health (AH) is our technology partner. The AH platform is the primary source of TM data.  
The platform, which is seen through a web-based user interface dashboard, requires 
permissions to access as well as a login.  The dashboard allows our team to monitor incoming 
and outgoing messages in real-time, set personalization without help from a programmer, and 
respond to participant inactivity. The AH platform is HIPAA-compliant, with all PHI / PII data 
encrypted in transit and at rest, and messages are delivered through a secure gateway in an 
encrypted format.  
The iSMILE specific eCRFs for this trial will be housed at the CC. Server racks are bolted to the 
foundation beneath the concrete floor for earthquake preparedness. Physical access is strictly 
controlled. Electronic access is protected with 2 state-of-the-art hardware firewalls, strong 
password protection, and automatic system log-outs. All data are encrypted and backed up onto 
servers daily. Encrypted backup tapes are stored off-site weekly and monthly by a leading 
vendor of storage services (Iron Mountain). Disaster recovery drills will be conducted monthly. 

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14   QUALITY CONTROL AND QUALITY ASSURANCE 
Quality Management is the overall process of establishing and ensuring the quality of 
processes, data, and documentation associated with clinical research activities.  It encompasses 
both quality control (QC), and quality assurance (QA) activities.     
Ultimate responsibility for implementation and maintaining quality assurance and quality control 
systems with written operating procedures to ensure that the trial is conducted and data are 
generated, documented and reported in compliance with the protocol resides with the principal 
investigators of the study.  The project director, CC, and AH will provide regular reports on the 
fidelity and administration of the intervention (listed in section 15.4) to the Co-PIs.  These 
processes are outlined in the study’s Quality Management Plan.   
 
The NIDCR Oral Health Disparities in Children (OHDC) Consortium’s Coordinating Center (CC) 
has developed the Caries and Plaque Screening Examination Training and Calibration for Oral 
Health Disparities in Children Consortium” and annually will conduct in person calibration 
sessions that utilize live patients and adhere to all CP guidelines. All of our clinical examiners 
will attend a calibration session each year and attain competency, based on protocol standards, 
prior to collecting any clinical oral health data. All calibration sessions will follow the protocol 
outlined in “Caries and Plaque Screening Examination Training and Calibration for Oral Health 
Disparities in Children Consortium.”  If for some reason a secondary examiner cannot attend the 
annual CC sessions (for example – a clinical examiner is hired mid-year), he/she will be trained 
and calibrated using the same procedures by the CC, and compared to the Center’s gold 
standard examiner.   
  

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15   ETHICS/PROTECTION OF HUMAN SUBJECTS 
15.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the principles set 
forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, as drafted by the US National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research (April 18, 1979) and codified in 45 CFR Part 
46 and/or the ICH E6.  
15.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the BUMC IRB for review and approval.  Approval of both the protocol and the 
consent form will be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented in the study.   
15.3 Informed Consent Process 
Informed consent is a process that is initiated prior to the individual participating in the study and 
continues throughout study participation.  
Prior to screening, we will obtain brief verbal consent to be screened.  If screening takes place 
over the phone and the participant is eligible, we will retain their data and their identifiable 
contact information and the link between the two.  Thus, we will also request a waiver of 
documentation of consent.  If the screening takes place over the phone and the participant is 
ineligible, we will retain their non-identifiable screening information and destroy their contact 
information and any link between their contact information and screening data. In some cases, 
the baseline survey may be conducted over the phone or via online web link, prior to the 
participant arriving at the clinic. Thus, the waiver of documentation of consent will also be 
needed for this activity.  If the baseline survey is performed at the clinic, the participants will 
complete written informed consent electronically at that time. Paper consent forms will be 
utilized in the event that the electronic consent fails. If the baseline survey is performed over the 
phone, informed consent will be obtained in writing prior to the oral assessment.    
Extensive discussion of risks and possible benefits of study participation will be provided to 
participants and their families, if applicable. A paper copy of the consent form describing in detail 
the study procedures and risks will be given to the participant. Consent forms will be IRB-
approved, and the participant is required to read and review the document or have the 
document read to him or her. The investigator or designee will explain the research study to the 
participant and answer any questions that may arise. Participants will be given the opportunity to 
discuss the study with their surrogates or think about it prior to agreeing to participate. They may 
withdraw consent at any time throughout the course of the study. A copy of the informed 
consent document will be given to participants for their records. The rights and welfare of the 
participants will be protected by emphasizing that the quality of their clinical care or their child’s 
care will not be adversely affected if they decline to participate in this study. 
The consent process will be documented in the research record.   

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Translation of the consent form into Spanish will be reviewed and approved by the IRB for non-
English speaking subjects. The informed consent process will remain the same but will be 
conducted in the subject’s preferred language by study staff who are bilingual in English and 
Spanish.  
At the time of the oral health assessment, the verbal dissent of a child will be honored and those 
activities will not be completed. 
 
RAs, or research study staff members conducting enrollment, will obtain informed consent. All 
informed consent procedures will be done in a private location and all potential participants will 
be given sufficient time to consider their choice to participate or not. 
 
The IRB approved informed consent will be available to potential participants electronically 
through REDCap. The IRB approved informed consent describing in detail the study, including 
both procedures and risks, will be given to the potential participant in their preferred language 
(English or Spanish). The potential participant is required to read and review the informed 
consent document. 
 
The RA or qualified study staff member will verbally review the informed consent in REDCap 
with the individual to ensure that the potential participant understands the study. The study staff 
member obtaining informed consent will also explain that the parent must consent to their child 
receiving a baseline, 12, and 24 month oral health assessment as part of required study 
enrollment. Additionally, the RA or study staff member obtaining consent will explain that the 
participant will be randomly enrolled into one of two different text message programs, making 
clear that the one that they are assigned to will be determined completely by chance. The RA or 
study staff member obtaining consent will answer any questions that may arise.  
 
For eligible participants screened and enrolled over the phone, participants may either have the 
informed consent procedure done at the time of their clinic appointment, or the informed consent 
will be done prior to their clinic appointment with a waiver of documentation of consent. In the 
latter case, if the participant is willing and able to complete the baseline questionnaire before the 
clinic visit, they will be sent a web link to the questionnaire.  However, participants will not be 
able to access or complete the Baseline questionnaire unless they click “agree” to the consent – 
this will be recorded in REDCap. When they arrive at their clinic appointment, we will obtain 
electronic written informed consent in REDCap at that time. Another scenario is a participant 
who is screened eligible over the phone and would rather complete the baseline questionnaire 
via phone interview, rather than web link. In this case, the research assistant will read the entire 
consent form to the prospective participant and obtain consent to administer the questionnaire 
prior to any study activity. As with the first scenario, when they arrive at the clinic appointment, 
we will obtain electronic written consent in REDCap at that time. These procedures will allow 
participants the option of completing the Baseline measure prior to their clinic appointment, thus 
decreasing participant burden during the clinic visit. It is required that electronic written informed 
consent be collected in REDCap at the time of the in-person baseline oral health assessment.  
 
A copy of all signed informed consent documents will be given to subjects for their records and a 
copy will be retained for the research record. A copy of the electronic informed consent can 
either be e-mailed to the participant, or if preferred, the participant can be given a paper copy of 
the informed consent.  
 

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15.4   Exclusion of Women, Minorities, and Children (Special Populations) 
This study does not exclude women, minorities or children from participating. 
15.5   Subject Confidentiality 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the funding 
agency and their agents.  
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the funding agency. 
Any authorized representatives of the funding agency, including the study monitor, may inspect 
all study documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) for the study subjects. The clinical study 
site will permit access to such records. 
15.6 Future Use of Stored Specimens and Other Identifiable Data 
This study will not be collecting or storing specimens. 
 

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16   DATA HANDLING AND RECORD KEEPING 
The Co-PIs are responsible for ensuring the accuracy, completeness, legibility, and timeliness of 
the data reported.  All source documents should be completed in accordance with the principles 
of good clinical practice in order to ensure accurate interpretation of data as detailed in MOP.  
The Co-PIs will maintain case histories of study subjects, including accurate case report forms 
(CRFs), and all source documentation. 
16.1 Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff under the 
supervision of the Co-PIs.  All source documents and laboratory reports must be reviewed by 
the study team and data entry staff, who will ensure that they are accurate and complete.  
Unanticipated problems and adverse events must be reviewed by the Co-PIs or their designee.  
The CC will provide the study staff with access to the reports listed in section 16.4 that will allow 
the study team to monitor data quality.  
The CC will provide oversight by running reports that show unresolved data discrepancies that 
have not been addressed by the study team.   
16.2 Data Capture Methods 
Data will be collected using several methods. Signed and dated consent forms will be completed 
electronically by the participants through REDCap, a secure, HIPAA-compliant web-based 
application. Paper consent forms will be utilized in the event that electronic capture is 
unsuccessful and will be stored at the BUGSDM offices under secured conditions. Screening 
and questionnaire data will be collected through a secure web-based EDC for direct data entry.  
REDCap will be used to collect data during the oral assessment. For each eCRF, a paper form 
will also be developed and utilized in the rare event that the electronic system is not available.  
All paper forms will be manually entered into the database and the paper forms stored in the 
subjects’ research record.  Data will also be captured through participants’ responses to TMs 
during intervention delivery. Data collected from research participants will be stored in a 
secured, password protected computer file that is separate from identifiers. Any paper data will 
be placed in a locked file cabinet. A file will be maintained that associates the subject name with 
that subject’s study identification number. This file will be kept in a secure, password-protected 
file, separate from the actual study data (e.g. screener and survey data).  
16.3   Types of Data 
Screening and questionnaire data are self-reported from participants and include but are not 
limited to: sociodemographic data; parental oral health knowledge, attitudes, and behaviors; 
psychological mediators/moderators; other health and risk factors; dental utilization data.  This 
data is entered into REDCAP or other electronic data capture software.  Some 
sociodemographic data required for enrollment into the text message system will be collected 
verbally by study staff using a Contact Information eCRF. Study staff will collect participant 
information prior to beginning the self-report baseline questionnaire. Information from 
participants include but are not limited to: child’s first name or nickname; child’s gender; child’s 
date of birth. Study staff will enter data directly into REDCAP or other electronic data capture 
software. Surface level caries data is collected from the children’s oral health assessment 
conducted by the calibrated dental examiner and recorded in REDCAP or other CC approved 

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electronic data capture software. TM  data will include information on caries risk factors, parent 
knowledge, attitude and behaviors.  
 
16.4  Schedule and Content of Reports 
Report Name 
Description/Purpose 
Frequency 
Recipients/ 
Users 
Method for 
Provision  
 
EXAMPLES of reports that will be used by iSMILE 
 
Accrual and 
Attended Visits 
Summary 
The report provides up-to-date, 
pertinent information on the 
UH2/UH3 accrual and attended 
follow-up visits.  
 
The PDF report is produced 
using SAS with data exported 
from the EDC.  
Monthly 
The CC Project 
Manager sends out 
the Accrual And 
Attended Visits 
Summary Report to 
everyone who 
attends the CC-
NIDCR-UH2/UH3 
Project Staff Monthly 
meeting. 
Emailed attachment 
and upload to the 
UH2/UH3 
SharePoint site.  
 
The PDF report is 
produced using SAS 
with data exported 
from the EDC 
system.  
 
Caries Exam 
Report 
 
 
Missing Caries Exams: This 
tab lists participants who have 
an occurred caries exam visit 
but are missing the 
corresponding caries exam.  
 
Study identification numbers 
Missing Surface Data:  This 
tab lists all randomized 
participants who have missing 
tooth surface scores. 
 
Calendar Visit Count:  This 
tab shows the total number of 
caries exams performed during 
each study visit (e.g., baseline, 
12 month, etc.). 
 
Tooth Status Check:  This tab 
shows any participant who has 
a tooth status that has changed 
in an unexpected way from one 
exam to the next observed 
exam.  (e.g. If Tooth 16’s status 
changes from present in the 18-
month visit to unerupted in the 
24-month visit).  
 
For a given participant/visit 
combination, all teeth with 
exceptions are presented in a 
single row.  If a participant 
misses a visit, for example, the 
18 Month visit, but then 
receives an exam at 15 and 21 
Months, then each tooth status 
Monthly 
The CC Project 
Manager sends out 
the Caries Report to 
everyone who 
attends the CC-
NIDCR-Project Staff 
Monthly meeting. 
Emailed attachment 
and upload to the 
UH2/UH3 
SharePoint site.  
 
The Excel report is 
produced by SAS 
with data exported 
from the EDC 
system.  
 
 
 

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transition between 15 and 21 
Months will be analyzed.  
Status transitions that are 
expected or unchanged are not 
shown in this tab. 
 
Surface Status Check:  This 
tab shows any 
participant/surface combination 
whose surface status has 
changed in an unexpected way 
from one visit to the next.  (e.g. 
If Tooth 51’s lingual surface 
status changes from 
fillingNonAmalgam in the 21-
month visit to sound in the 24-
month visit).  Status transitions 
that are expected or unchanged 
are not shown in this tab. 
 
 
Surface Agreement Overall:  
This tab contains a complete 
mapping of surface status 
changes from one exam to the 
next consecutive, occurred 
exam.  (e.g. the surface status 
of a tooth changes from decay 
Cavitated to missing Caries).  
The earlier status is shown in 
the rows, whereas the latter 
status is shown in the columns.  
Perfect agreement, in a 
hypothetical scenario where no 
status changes occur, would be 
indicated by all non zero counts 
along the diagonal, and all off-
diagonal counts equal to zero. 
 
Surface Agreement Overall 2:  
This tab shows the Test of 
Symmetry in the overall surface 
agreement.  This tab can be 
ignored for routine operational 
purposes.   
 
Surface Agreement Overall 3:  
This tab gives some additional 
Kappa statistics.  This tab can 
be ignored for routine 
operational purposes. 
 
Surface Agreement, Same 
Examiner:  This tab presents 
output similar to that of the 
Overall Surface Agreement tab, 
except that only the exams 
conducted by the same 
examiner are presented.  So, if 
a Baseline and 3 Month exam 

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were conducted by Examiner 
#1, and the 6 Month exam was 
conducted by Examiner #2, and 
the 9 and 12 Month exams 
were conducted by Examiner 
#1, then only the Baseline-3 
Month pair, and the 9-12 Month 
pair data would be shown.  All 
mixed-examiner consecutive 
combinations are not included 
in these totals. 
 
Surface Agreement, Same 
Examiner 2:  This tab shows 
the Test of Symmetry in the 
overall surface agreement.  
This tab can be ignored for 
routine operational purposes. 
 
Surface Agreement, 
Reversals:  This tab uses a 
subset of the data in the 
Surface Agreement Overall tab.  
Only those surface transitions 
that represent an unlikely 
transition, e.g., from Missing to 
Sound, are represented here.  
The cell counts in this tab are 
identical to the cell counts in the 
Overall tab. 
 
Missed And 
Occurred Out Of 
Window 
Deviations 
The Missed And Occurred Out 
Of Window Deviations report 
provides statistics on the 
Deviation Types and Off Study 
participants for the protocol.   
 
The report also provides data 
on non-deviations, such as 
occurred visits, planned visits, 
and Off-Study data, and is 
provided in this document, 
rather than as a separate 
document, to minimize the 
number of separate reports. 
 
Monthly 
The CC Project 
Manager sends out 
the Missed And 
Occurred Out Of 
Window Deviations 
Report to everyone 
who attends the CC-
NIDCR-Project Staff 
Monthly meeting. 
Emailed attachment 
and upload to the 
UH2/UH3 
SharePoint site.  
 
The Excel report is 
produced by SAS 
with data exported 
from the EDC 
system.  
 
 Non-Visit Timing 
Deviations 
The Non-Visit Timing 
Deviations report provides 
statistics on the Deviation 
Types and Off Study 
participants for the protocol.   
 
 
Monthly 
The CC Project 
Manager sends out 
the Non-Visit Timing 
Deviations Report to 
everyone who 
attends the CC-
NIDCR-Project Staff 
Monthly meeting. 
Emailed attachment 
and upload to the 
UH2/UH3 
SharePoint site.  
 
The Excel report is 
produced by SAS 
with data exported 
from the EDC 
system.  
 

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Participant-report 
questionnaire 
Check 
This report provides an 
accounting of all the 
questionnaire forms.  If there 
are any errors on any of the 
forms (in completed, queried, or 
validated status), they will be 
listed in this report by Form and 
also in Summaries by Month, 
Form, Visit, and Participant. 
Monthly 
The CC Project 
Manager sends out 
the Questionnaire 
Check Report to the 
study PI and Project 
Manager 
Emailed attachment 
and upload to the 
UH2/UH3 
SharePoint site.  
 
The Excel report is 
produced by SAS 
with data exported 
from the EDC 
system. 
 
DSMB Report 
This contents of this report will 
be determined by the NIDCR 
and DSMB members after 
DSMB is constituted 
To be 
determined 
by NIDCR 
CC creates report 
draft in collaboration 
with Co-PIs 
Emailed attachment 
and upload to the 
UH2/UH3 
SharePoint site.  
 
The Excel report is 
produced by SAS 
with data exported 
from the EDC 
system.  
 
 
Examples of Custom, On-Demand Reports that iSMILE will use for project monitoring 
 
Accrual Tracking 
This report lists accrual totals 
stratified by site, language and 
index versus additional child.   
 
It also lists the individual 
participants consented stratified 
by site and child type (Index v 
Additional).  
 
For each ID, the linked 
(“related” on the report)IDs, 
consent date, language of 
consent, off study date, and 
date entered into REDCAP is 
provided.   
 
Accrual totals include both On 
Study and Off Study 
participants.   
 
The report also provides a 
check of the EDCs to make 
sure that the information there 
is complete. 
As Needed 
Project Staff – can 
run as needed 
Automated report 
Accrual Summary 
By Month And Site 
The report lists total accrual 
stratified by site and month.   
 
It has distinct sections that 
include Index children, 
Cumulative Index children,  
 
Accrual totals include both on 
study and off study participants.   
 
As Needed 
Project Staff – can 
run as needed 
Automated report 

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The report also shows 
cumulative accrual. 
 
Participant 
Contact Listing 
This report lists the following 
information for every study 
identification number -- Child’s 
Date of Birth, Child’s Name, 
Address, Primary Caregiver’s 
Name, Primary Phone Number, 
Alternative Phone Number, 
Email Address, Study Site, and 
the Consent Language.  
 
The Participant Contact Listing 
report also enables searching 
for the participant ID based on 
demographic information.  
Usually the last four digits of the 
phone that called are used to 
identify what study ID is linked 
to that number.  
 
The report pulls info from 
participants who are enrolled in 
the study.   
 
Participants who have left the 
study will not show up on this 
report. 
Daily 
Project Staff – can 
run as needed 
Automated report 
Participants Off 
Study 
The top half of the report 
provides statistics on the 
number and proportion of 
participants Off Study stratified 
by arm, site, off-study reason, 
and month.  
 
The bottom half of the report 
lists all the participants that 
have been taken Off-Study and 
includes the following 
information for each participant:  
study ID, Off-Study Date, On 
Study Date, Days on study, 
Study Site, Arm, Off-Study 
Reason, and Explanation. 
 
Monthly 
Project Staff – can 
run as needed 
Automated report 
Staff Assignments 
The Staff Assignments report is 
used for a variety of purposes, 
most commonly to see 
information on staff 
assignments including study 
IDs assigned and sites 
assigned.  
 
As Needed 
Project Staff – can 
run as needed 
Automated report 
Eligibility 
Summary 
The Eligibility Summary report 
provides statistics on the 
questions that make up the 
Eligibility Questionnaire. 
 
 
As Needed 
Project Staff – can 
run as needed 
Automated report 

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Enrollment 
Verification 
The Enrollment Verification 
report checks to make sure 
participants are eligible for the 
study and correctly entered.   
 
Bi-weekly 
Project Staff – can 
run as needed 
Automated report 
Missing 
Demographics 
Data By 
Participant 
This report identifies 
participants that are missing 
demographics data. 
 
The following information is 
provided.  The participant’s 
study ID, who the consent was 
verified by (initials), The date 
that Consent was signed, The 
participant’s status (e.g. On 
Treatment).   
 
Then an ‘x’ appears in the table 
under whatever Demographics 
information is missing for a 
particular study ID. 
 
Bi-weekly 
Project Staff – can 
run as needed 
Automated report 
Missing 
Enrollment Data 
By Participant 
The Missing Enrollment Data 
By Participant Table report 
identifies when any of the 
following enrollment data are 
missing:  
 
Consent: Consent Form, 
Signed Date, Version Date, 
Approved Date, Expiration 
Date.  
Eligibility: Form Version (this is 
automatic), Verified By, Status 
Date, Eligibility Status, eligibility 
questions 
On Study: Seq. No., On Study 
Date, Study Site, Subject Staff 
assignments. 
Treatment Tab: Step code 
(automatic), arm code, on arm 
date. 
 
If one of the above is missing, 
the report will list the study ID 
and list a ‘x’ in the column for 
the information that is missing. 
Bi-weekly 
Project Staff – can 
run as needed 
Automated report 
Participant Phone 
Number Check 
The Participant Phone Number 
Check report checks to make 
sure the participant child and 
caregiver’s telephone numbers 
match. 
Daily 
Project Staff – can 
run as needed 
Automated report 
Call Records 
The Call Records report is used 
to identify participants who have 
not been contacted as our 
procedures outlined. 
Weekly 
Project Staff – can 
run as needed 
Automated report 
Form 
Discrepancies 
The Form Discrepancies report 
can be used in two ways. 
 
Weekly 
Project Staff – can 
run as needed 
Automated report 

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1) The report can be run by the 
Project Assistant and used to 
see if they have any pending 
queries that need to be 
answered. 
 
2) The report can be run without 
checking the box to “show only 
forms with no response”.   
 
a) This version of the report 
includes forms that are in any 
status but have not yet been 
validated.   
 
b) It will also include study IDs 
that are showing up because a 
piece of data was entered that 
was outside the range.   Both 
field and section level queries. 
Staff Visit 
Schedule 
The Staff Visit Schedule report 
is used by the Project Assistant 
to find out what visits they have 
coming up each week. 
Weekly 
Project Staff – can 
run as needed 
Automated report 
 
Data Closeout and Database lock: 
In conjunction with the PIs, the CC will perform continuous data QC during the data collection 
phase of the project. These processes will identify and ameliorate almost all correctable 
database errors, on an ongoing basis. In addition, the following closure checks will be 
implemented: 
 
• Check that the project database and export database are consistent with the 
specifications in the project data dictionary 
 
• Determine the status of each subject entered (i.e., excluded, completed, withdrawn, lost to 
follow-up, etc.) 
 
• Check for value formatting problems in database exports 
 
 
Steps for locking the database: 
The PIs will work with the CC and the clinical site monitoring contractor (Rho) to help 
coordinate site monitoring and study close-out visits and resolve any identified issues, as 
appropriate. 
 
Following collection of all data, additional data processing will be required, e.g., longitudinal 
coding of dental examination data, creation of psychosocial scale scores.  In conjunction with 
that data processing, additional QA/QC checks will be made, which may result in identification 

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of a small number of additional database errors; any such errors will be corrected by the CC 
data manager, with the assistance of the study team, as appropriate. Following PI 
concurrence, the database will be locked. 
 
When locking the database, the CC will ensure a full backup is completed and stored on the 
CC secure drive in a project-specific folder accessible to the CC Directors, or their designated 
alternate. The CC secure drive is a secure network drive behind the UCSF firewall that 
requires password-protected, role assignable access, and includes instantaneous local back-
up with version control and daily offsite back- up. All study team user rights will be removed 
from the corresponding EDC system(s). Once the database is locked, access to the export 
files will be ‘read only’ and password protected. 
 
An encrypted copy of the final data set will be electronically transmitted to the ), The file will 
be ‘read only’ and strong password protected.

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Statistician or PI(s) confirms the data has been received either via email or faxed receipt, 
the password will be given via a second e-mail. 
 
16.5  Study Records Retention 
All paper documents will be stored in locked secured cabinets at GSDM’s research offices at 
560 Harrison Avenue in Boston, Massachusetts.   
The primary databases will reside on a secured server, accessible to appropriate BU GSDM 
staff, Agile Health Staff and at the central Data Coordinating Center at UCSF.   
All study records and computer files will be retained for at least 3 years after the final financial 
report for the UH3 award is submitted to the NIH or the final study manuscript is published, 
whichever is later. At each 3 year interval, the necessity of keeping the study records and 
computer files longer will be reviewed and decided upon. 
 
16.6   Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or Good Clinical 
Practice (GCP) requirements. The noncompliance may be either on the part of the subject, the 
investigator, or the study site staff. As a result of deviations, corrective actions will be developed 
and implemented promptly as determined by the IRB.  
These practices are consistent with ICH E6: 
4.5 
Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
Quality Assurance and Quality Control, section 5.1.1 
5.20 
Noncompliance, sections 5.20.1, and 5.20.2. 
It is the responsibility of the Principal Investigators to use continuous vigilance to identify and 
report deviations within 5 working days of identification of the protocol deviation, or within 5 
working days of the scheduled protocol-required activity.  All deviations must be reported to the 
BUMC IRB per their guidelines and promptly reported to the NIDCR Program Official. The CC 
will provide a facility to log protocol deviations. PIs will be responsible for reporting Reportable 
PDs (including SDs) and UPs directly to their institutional IRB(s) within the specified IRB 
timeframe 
All study staff will have weekly reviews with their supervisor to identify compliance to protocol 
details. Any and all study related meetings will also dedicate time to review the possibility of 
identifying any protocol deviations. Protocol deviations will be sent to the BUMC IRB per their 
guidelines. The PI/study staff will be responsible for knowing and adhering to the IRB 
requirements. 
All deviations from the protocol will be addressed in study subject source documents.  A 
completed copy of the NIDCR Protocol Deviation Form will be maintained in the regulatory file, 
as well as in the subject’s source document.   

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17   PUBLICATION/DATA SHARING POLICY 
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final 
peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. 
Data from this study will be shared in accordance with the NIH Data Sharing Policy. 
https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm  
The National Institutes of Health (NIH) has issued a policy to promote broad and responsible 
dissemination of information from NIH-funded clinical trials through ClinicalTrials.gov. The policy 
establishes the expectation that all investigators conducting clinical trials funded in whole or in 
part by the NIH will ensure that these trials are registered at ClinicalTrials.gov, and that results 
information of these trials is submitted to ClinicalTrials.gov. Please see 
https://www.federalregister.gov/documents/2016/09/21/2016-22379/nih-policy-on-the-
dissemination-of-nih-funded-clinical-trial-information. 

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18   LITERATURE REFERENCES 
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SUPPLEMENTAL MATERIALS 
None at this time.