Preventing Caries in Preschoolers: Testing a Unique Service Delivery Model in American Indian Head Start Programs
Phase: PHASE3
Conditions: Fluoride Varnish and Oral Health Promotion, Usual Care
Sponsor: University of Colorado, Denver

Preventing Caries in Preschoolers:  Testing a Unique Service 
Delivery Model in American Indian Head Start Programs
NIDCR Protocol Number: 09-003E
NIDCR Funding Mechanism: 1U54DE019259-01
Other Identifying Numbers:  
ClinicalTrials.Gov Identifier: NCT01116739
COMIRB: 08-0892
NNHRRB:  NNR-10.268  
 
Principal Investigator:  Patricia Braun, M.D., M.P.H.
NIDCR Program Official: Ruth Nowjack-Raymer, MPH, PhD
NIDCR Medical Monitor:  Holli Hamilton, MD, MPH
Draft or Version Number: 7.0
Day Month Year:  18 Dec 2013 
COMIRB
APPROVED
16-Jan-2016

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
Protocol # 09-003E
18 Dec 2013
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STATEMENT OF COMPLIANCE
The study will be carried out in accordance with Good Clinical Practices (GCP) as required by 
the following
1)  United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46; 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312)
2)  ICH E6; 62 Federal Register 25691 (1997)
3)  NIH Clinical Terms of Award
All key personnel have completed Human Subjects Protection Training.

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
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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/study 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.
Site Investigator:  Patricia Braun, M.D., M.P.H
Signed:
Date:
Name:  Patricia Braun, M.D., M.P.H
Title:  Associate Professor, Department of Pediatrics 
Biology, School of Medicine
University of Colorado Anschutz Medical Campus

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
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TABLE OF CONTENTS
Page
Statement of Compliance ..............................................................................................................2
Signature Page..............................................................................................................................3
Table of Contents ..........................................................................................................................4
List of Abbreviations ......................................................................................................................7
Protocol Summary .........................................................................................................................8
1
Key Roles ...........................................................................................................................12
2
Background Information and Scientific Rationale...............................................................13
2.1
Background Information..........................................................................................13
2.2
Rationale.................................................................................................................15
2.3
Potential Risks and Benefits ...................................................................................16
2.3.1
Potential Risks ............................................................................................16
2.3.2
Known Potential Benefits ............................................................................16
3
Objectives...........................................................................................................................18
3.1
Study Objectives.....................................................................................................18
3.1.1
Primary:.......................................................................................................18
3.1.2
Secondary:..................................................................................................18
3.2
Study Outcome Measures ......................................................................................19
3.2.1
Primary Outcome Measure .........................................................................19
3.2.2
Secondary Outcome Measures...................................................................19
4
Study Design ......................................................................................................................20
4.1
Substudies ..............................................................................................................21
5
Study Enrollment and Withdrawal.......................................................................................22
5.1
Subject Inclusion Criteria ........................................................................................22
5.2
Subject Exclusion Criteria.......................................................................................22
5.3
Treatment Assignment Procedures ........................................................................22
5.3.1
Randomization Procedures.........................................................................22
5.3.2
Masking Procedures ...................................................................................23
5.3.3
Reasons for Withdrawal ..............................................................................23
5.3.4
Handling of Withdrawals .............................................................................23
5.3.5
Termination of Study ...................................................................................23
6
Study Intervention/ Investigational Product ........................................................................25
6.1
Study Product Description ......................................................................................25
6.1.1
Acquisition...................................................................................................25
6.1.2
Formulation, Packaging, and Labeling........................................................25
6.1.3
Product Storage and Stability......................................................................25
6.2
Dosage, Preparation and Administration of Study Intervention/Investigational 
Product....................................................................................................................25
6.3
Modification of Study Intervention/Investigational Product for a Participant ...........27
6.4
Accountability Procedures for the Study Intervention/Investigational Product(s)....27

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6.5
Assessment of Subject Compliance with Study Intervention/Investigational 
Product....................................................................................................................27
6.6
Concomitant Medications/Treatments ....................................................................27
7
Study Schedule...................................................................................................................28
7.1
Screening................................................................................................................28
7.2
Enrollment...............................................................................................................28
7.3
Follow-up Visits for FV............................................................................................28
7.4
Follow-up Safety Contact One Week After FV........................................................29
7.5
Final Study Visit ......................................................................................................29
7.6
Early Termination Visit............................................................................................29
7.7
Unscheduled Visit ...................................................................................................29
8
Study Procedures/Evaluations............................................................................................30
8.1
Clinical Evaluations.................................................................................................30
8.2
Laboratory Evaluations ...........................................................................................30
8.2.1
Clinical Laboratory Evaluations...................................................................30
8.3
Specification of Safety Parameters.........................................................................30
8.4
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters .............................................................................................................30
8.4.1
Adverse Events ...........................................................................................30
8.4.2
Serious Adverse Events (SAEs) and Unanticipated Problems (UPs).........31
8.4.3
Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings .........................................................33
8.5
Reporting Procedures.............................................................................................33
8.5.1
Regulatory Reporting for Studies Conducted Under NIDCR- Sponsored 
IND ..............................................................................................................33
8.5.2
Regulatory Reporting for Studies Not Conducted Under NIDCR- 
Sponsored IND............................................................................................33
8.5.3
Other Adverse Events (if applicable)...........................................................34
8.5.4
Reporting of Pregnancy ..............................................................................34
8.6
Type and Duration of Follow-up of Subjects after Adverse Events.........................34
8.7
Halting Rules...........................................................................................................34
8.8
Safety Oversight .....................................................................................................34
9
Clinical Monitoring ..............................................................................................................35
9.1
Site Monitoring Plan................................................................................................35
10
Statistical Considerations ...................................................................................................36
10.1
Study Hypotheses...................................................................................................36
10.2
Sample Size Considerations...................................................................................36
10.3
Planned Interim Analyses (if applicable).................................................................37
10.3.1 Safety Review .............................................................................................37
10.3.2 Immunogenicity or Efficacy Review ............................................................37
10.4
Final Analysis Plan..................................................................................................38
11
Source Documents and Access to Source Data/Documents .............................................41

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12
Quality Control and Quality Assurance...............................................................................42
13
Ethics/Protection of Human Subjects .................................................................................43
13.1
Ethical Standard......................................................................................................43
13.2
Institutional Review Board ......................................................................................43
13.3
Informed Consent Process .....................................................................................43
13.3.1 Informed Consent/Assent Process (in Case of a Minor).............................44
13.4
Exclusion of Women, Minorities, and Children (Special Populations) ....................44
13.5
Subject Confidentiality ............................................................................................45
13.6
Study Discontinuation .............................................................................................45
13.7
Future Use of Stored Specimens............................................................................45
14
Data Handling and Record Keeping ...................................................................................46
14.1
Data Management Responsibilities ........................................................................46
14.2
Data Capture Methods............................................................................................46
14.3
Types of Data..........................................................................................................47
14.4
Timing/Reports........................................................................................................47
14.5
Study Records Retention........................................................................................47
14.6
Protocol Violations/ Reportable Events...................................................................47
15
Publication Policy................................................................................................................49
16
Literature References .........................................................................................................50
17
APPENDICES.....................................................................................................................52

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
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LIST OF ABBREVIATIONS
ACASI
Audio Computer Assisted Survey Interview
AE
Adverse Event 
AI
American Indian
AI/AN
American Indian/Alaska Native 
BRFQ
Basic Research Factors Questionnaire (referred as ACASI 
survey)
CHRs
Community Health Representatives 
CNOHR
Center for Native Oral Health Research 
COHS
Community Oral Health Specialist
COMIRB
Colorado Multiple Institutional Review Board 
CTCAE
dmfs
Common Terminology Criteria for Adverse Events
Decayed, missing and filled tooth surfaces index (primary)
DSMB
Data and Safety  Monitoring Board
ECC
Early Childhood Caries
FV
Fluoride Varnish 
HIPAA
Health Information Portability and Accountability Act  
HRSA
Health Resources and Services Administration
HS
Head Start
HSCs
Head Start Centers 
IHS
Indian Health Service 
MAR
Missing at Random 
MCAR
Missing Completely at Random 
MNAR
Missing Not at Random 
MOP
Manual of Procedures
NHANES
National Health and Nutrition Examination Survey 
NIDCR
National Institute of Dental and Craniofacial Research
NN
Navajo Nation 
NNHRRB
Navajo Nation Human Research Review Board 
OHP
Oral Health Promotion
PI
Principal Investigator
RDHs
Registered Dental Hygienists 
SA
Specific Aim 
SAE
Serious Adverse Event 
SODM
School of Dental Medicine 
UCD
UP
University of Colorado Anschutz Medical Campus
Unanticipated Problems

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
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PROTOCOL SUMMARY
Title:
Preventing Caries in Preschoolers:  Testing a Unique Service 
Delivery Model in American Indian Head Start Programs
Phase:
IV
Population:
Children ages 3-6 years in Head Start (HS) Programs in the 
Navajo Nation (NN)
Number of Sites:
3 (Navajo Nation, University of Colorado Anschutz Medical 
Campus, University of California San Francisco)
Study Duration:
The study duration will be 6 years.  This includes 1 year for 
planning, 6 months for each intervention year (1 & 2) for 
recruitment, 3 years for implementation of the interventions: 
baseline and follow-up evaluations, and 1 year for close-out and 
analysis.
Subject Participation 
Duration:
Each participant will be in the study for up to 3 years; 2 years of 
intervention and a third year for follow up measures.
Description of Agent or 
Intervention:
Intervention will include application of fluoride varnish (FV)  
offered) offered 4x a year and oral health promotion (OHP) and 
education for 2 years.
Objectives:
Primary:
1)  To develop, with input from tribal/community members, a 
manualized intervention protocol for an early childhood caries 
(ECC) prevention program to be delivered by specially trained 
community paraprofessionals, called Community Oral Health 
Specialists (COHS)
2)  To implement and evaluate the delivery of FV and OHP 
programs in American Indian (AI) Head Start Centers (HSCs) 
under the following conditions:
Group #1—FV offered 4x a year and OHP for 2 years provided 
by COHS
Group #2— Usual oral health care made available by the IHS 
Dental providers (or other usual providers)
3)  To assess efficacy by comparing decayed, missing, and filled 

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primary tooth surfaces (dmfs) over time between the 2 groups.
Secondary:
1) To assess specific caries patterns 
2) To investigate moderators/mediators of the intervention 
conditions as ascertained via questionnaires on oral health 
knowledge, attitudes, and behaviors
3) To investigate participant utilization of medical and dental 
services for oral health problems and intervention costs, 
intervention savings, net intervention costs, costs/net costs 
per participant, costs/net costs per unit decrease in caries 
associated with each intervention condition
Description of Study 
Design:
The study design will be a cluster randomized design.  HSCs 
within the Navajo Nation (NN) will be stratified by population 
size and randomized within strata to the two groups.  All children 
within the HSC classrooms and a parent/primary caregiver of 
each child will be invited to participate in the intervention 
condition to which the HSC is randomized.  Children will 
participate after informed consent by the parents and after 
informed consent by the participating parent/primary caregiver 
for her/himself.  To be consistent with NIDCR, we will count the 
child and participating parent/primary caregiver dyad as one 
enrolled participant (unit).  Baseline and annual measures of 
dmfs and of dental knowledge, attitudes, and behavior will be 
collected.  Changes in these outcome measures will be 
compared between the two groups.
Estimated Time to 
Complete Enrollment:
6 months for each intervention year (year 1 and year 2)

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
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Schematic of Study Design:
Prior to 
Enrollment
Enlist participation of 52 Classrooms in Head Start Centers and identify potential 
replacement centers for each condition criteria
Randomize Centers
FV at Head Start Centers + Ongoing 
Oral Health Promotion/ Education 
Activities for Head Start children and 
parents-caregivers 
26 Head Start Center Classrooms 
≈520 children [dyad] 
Arm 1 = COHS
3-4 annual parent-caregiver ACASI surveys and Head Start child dental screening
Assessment of Final Study 
Outcome Measures (annual dental 
assessments will measure caries 
increments and severity).
26 Head Start Center Classrooms 
≈520 children [dyad]
Arm 2 = Usual Care
Usual oral health care made 
available by dental providers, 
usually IHS
Individual Parent-Caregiver/Child Enrollment 
Baseline Head Start child dental screenings 
Baseline Parent-Caregiver Survey data collection
Periodic COHS Evaluations

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
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Study Timeline: 

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
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1
KEY ROLES
Individuals:
Program Official:  Ruth Nowjack-Raymer, MPH, PhD 
Title: Program Official
National Institute of Dental and Craniofacial Research 
Address:  6701 Democracy Blvd.
Room 640  Mail Stop 4878
Bethesda, Maryland 20892-4878 
Phone: (301)594-5394 Fax:  
e-mail: Ruth.Nowjack-Raymer@nih.gov
Principal Investigator:  Patricia Braun, M.D., M.P.H
Title: Associate Professor, Department of Pediatrics, School of 
Medicine
Address: University of Colorado Anschutz Medical Campus Denver 
Healttlh and Hospital, 
Eastside Family Health Center
501 28th St. Denver, CO 80205 Phone: 303-436-4694Fax: 303-436-
4665
e-mail: patricia.braun@ucdenver.edu  
Medical Monitor: Holli Hamilton, MD, MPH
Title:  Senior Medical Officer
National Institute of Dental and Craniofacial Research
Address:  6701 Democracy Blvd.
Room 638  Mail Stop 4878
Bethesda, Maryland 20892-4878
Phone: (301)451-3852  Fax: 301-480-8322
Email: hamiltonho@nidcr.nih.gov 
Institutions:
University of Colorado Anschutz Medical Campus
American Indian and Alaska Native Programs
Center for Native Oral Health Research  PI:  Judith Albino, PhD
Address: Nighthorse Campbell Native Health Building - Mail Stop F800
13055 E. 17th Avenue, 3rd Floor
Aurora, CO 80045
Phone:  303-724-0151  Fax:  303-724-1474
e-mail: Judith.albino@ucdenver.edu

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2
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE
2.1
Background Information
Early childhood caries (ECC) is defined as dental caries in the primary teeth of children 
of the ages of 0-6 years.1  Although ECC is largely preventable and the general prevalence of 
this common childhood infection is in decline, marked disparities exist.2-4  The disease levels 
seen in American Indian/Alaska Native (AI/AN) children reflect the most extreme disparities, 
suggesting the need for effective, culturally accepted interventions.5-7  Approaches that combine 
simple clinical procedures such as Fluoride Varnish (FV) with Oral Health Promotion (OHP) 
activities for children and parents/caregivers in a community-based setting appear to offer 
effective and efficient interventions in the prevention of ECC,8-13 yet professional personnel for 
delivery of these services are not always available.  Consequently, alternative provider 
concepts, such as the use of dental therapists as extenders of the current dental care delivery 
system, are increasingly being explored, especially for use in geographically isolated 
communities.14-16  Although the effectiveness of some of these new strategies has not yet been 
fully demonstrated, there is evidence that health outcomes can be enhanced through 
interventions provided by trained paraprofessionals in community settings.17-22  This study will 
test innovative prevention services delivery programs and measure their effects on caries 
incidence in an AI preschool population.
The most recent Indian Health Service (IHS) report cites caries experience rates of 79% 
for AI/AN preschool children, with 68% having untreated dental decay, a prevalence more than 
3 times greater than their non-Native counterparts5, 22 In Navajo Area, dental decay among 
preschool children is severe; with the mean number of decayed, missing and filled tooth 
surfaces (dmfs) for 2-5 year olds reaching 19.0 surfaces,23 the highest in Indian Country.  These 
data suggest that rates of dental decay experienced by AI/AN children today are the highest in 
the U.S., and perhaps the highest in the world.
While substantial evidence exists to document the poor oral health status of these 
children, there have been very few reports of intervention.  Only Bruerd20 has successfully 
demonstrated a community-based intervention to prevent ECC with AI/AN children.  The project 
was funded from 1985-1990 to determine whether community-based health education could 
reduce the prevalence of decay among AI/AN children21.  Twelve pilot Head Start (HS) sites 
received varying levels of OHP training and planned multidisciplinary educational interventions 
for individuals and communities.  For the 12 sites, the average prevalence of decay in the post-
program cohort was 25% less after 4 years; for the 5 sites that continued to implement the 

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program for 4 additional years, the difference was 38%.20  The project did not deliver any direct 
clinical preventive services, and it did not have a controlled design.
Among the clinical interventions to prevent caries in children, the use of fluoride 
demonstrates the strongest evidence base and most predictable success.17  Professional and 
public health measures, including the use of fluoride mouth rinses, gels, dentifrices, and dietary 
supplements, are common means of preventing dental caries.1  These measures are limited in 
scope, however, and benefit primarily those individuals who have financial means and access to 
regular professional oral health care services.  FV is a professionally available topical agent that 
has been employed in the prevention of caries since 1964.  It has been used extensively in 
European countries, and was approved by the FDA in 1991 as a cavity liner and desensitizing 
agent.  Evidence from systematic studies of FV, while far more robust than for other 
professionally applied modalities, remains limited.18  Systematic reviews and meta analyses 
establish mean caries prevention at approximately 33% for primary teeth with the use of FV at 
6-month intervals.9, 19, 23  These recent reviews, paired with the unique and favorable clinical 
characteristics of FV, have prompted the publication of clinical practice recommendations from 
the American Dental Association that support use of FV as the preferred technique for caries 
prevention therapy in children under the age of 6.18
Education programs attempt to increase knowledge, positive attitudes toward oral health 
care, and ensuing behaviors on the part of parents/caregivers about ECC and contributing 
factors.  Parent education efforts may be aimed at influencing behaviors such as promoting 
dental visits, feeding, and/or oral hygiene practices.  While parental educational attainment has 
an inverse relationship with ECC, knowledge alone appears to be insufficient to produce 
behavior change in children or adults.  Systematic review of dental health education literature 
yields very few well-designed intervention studies and insufficient evidence for long term 
behavior change or significant reductions in caries incidence.24
On the basis of treaties, the U.S. government has a trust responsibility to provide health 
care to members of federally recognized tribes—a duty filled by the IHS since 1955.  IHS, 
however, provides care to only about 1.5 million out of 4.1 million who identify themselves as 
AI/AN, and is tremendously underfunded.  This underfunding leads to very limited funding for 
dental health care within the IHS.  Long waits for routine dental visits are common and specialty 
dental services are not provided.25
Community-based health services have sometimes been delivered by specially trained 
paraprofessionals drawn from the community being served, with the implicit logic that members 
of a community are able to better communicate with patients and understand the barriers to 
care.  In AI/AN communities, trained paraprofessionals known as Community Health 
Representatives (CHRs) have extended health care services for many years.  While these 
paraprofessionals have worked successfully to educate clients in such areas as diabetes 

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control, smoking cessation, cardiovascular disease prevention, and medication compliance, 
their usefulness in promoting oral health has not been tested.
Head Start (HS) is a comprehensive child development program serving children ages 3-
6 and their families.  This community-based, child-focused program has an overarching goal of 
increasing the social competence of young children in low-income families.  The HS 
Performance Standards mandate the program of services that grantee and delegate agencies 
must maintain; among these are standards supporting the provision of health, including oral 
health, education and services to children and families.26
A pilot study of specially-trained Community Oral Health Specialists (COHS) 
administering FV and OHP in AI children on a Northern Plains reservation was developed and 
implemented in 2001-2005 by the initial Principal Investigator of this study, Dr. David Quissell, to 
reduce ECC in AI children.  The program was funded by a grant from HRSA Office of Rural 
Health Policy (HRSA 4 DIARH0003).  The COHS completed a 160-hour training program that 
included orientation to health and oral health, science and prevention of dental caries, clinical 
procedures, and clinical activities related to screening, varnish application, and referrals.  The 
program was based on home visits. The COHS completed 2,379 visits to 1,263 children.  
Among the children enrolled, about 83% received at least 1 COHS service and more than half 
received 2 or more standard doses of FV. An evaluation of the program was done using dental 
exams at baseline and follow-up, but the evaluation did not have sufficient statistical power to 
demonstrate efficacy of the intervention.
In summary, ECC is a major oral health problem among AI/AN children, and oral health 
funding for these children through the IHS is very limited.  The investigators of this study will 
design an oral health intervention that has the potential of being cost-effective in the AI/AN 
community.  Several elements will be combined together to create an oral health intervention 
that might reduce ECC in AI/AN children.  These elements will include the use of specially 
trained COHS to administer FV and OHP in AI/AN children within HS programs.  The program 
will also undergo a rigorous statistical evaluation.
2.2
Rationale
The hypothesis of this study is that an intensive intervention of specially trained COHS 
administering FV (offered 4x a year) and OHP for 2 years for AI children ages 3-6 in HSCs 
(Group 1) vs. the delivery of usual oral health care made available by the IHS Dental providers 
or other usual providers (Group 2) will reduce the dmfs increment in the Group 1 children when 
compared to the Group 2 children and show improved parent/caregiver dental knowledge, 
attitudes, and behaviors. 

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2.3
Potential Risks and Benefits
2.3.1 Potential Risks
Potential risks include disclosure of confidential information including oral health status, 
extent of oral disease, oral health knowledge, attitudes, and behaviors, and effect mediators or 
moderators.  There is also the potential of psychological distress associated with the oral health 
screening and application of the FV with young children.  Parents/caregivers and children will 
have the opportunity to terminate their involvement in the study at any time.  Study staff will be 
trained in techniques to keep study data confidential.  Patient identifying information will not be 
included in the research databases.  Once data are collected, a research database will be 
created in which data are recorded using research ID numbers.  All data will be stored on 
password-protected network drives, and paper copies of any data or consent forms will be kept 
in locked file cabinets.  
Adverse reactions to the FV are extremely rare; particularly since dispensing of the FV 
and the single unit dosage delivered to each participant will be controlled.  Adverse reactions 
may include temporary change in tooth color27 or potential risk of contact allergy to the 
colophonium resin base if the varnish is applied to ulcerated gingival tissues.  According to the 
FV package insert, edematous swelling has been reported only in rare instances, especially 
following application to extensive surfaces with FV.  Though extremely rare, acute exacerbation 
of asthmatic conditions, or dyspnea, has occurred in asthmatic people.  Nausea can occur in 
patients with known sensitive digestive systems, especially following extensive applications.  
More information is available from the FV MSDS form (Appendix A) attached.  Intervention staff 
will be instructed to monitor children following fluoride application, recognize these adverse 
reactions and respond with prompt referral to the IHS dental clinic.   After attending to urgent or 
emergent needs of the child, intervention staff will contact the study PI immediately to report the 
event and complete reporting requirements.   
2.3.2 Known Potential Benefits
Families in the intervention arm will be provided with toothbrushes and toothpaste 
supplied at regular intervals to meet the needs of all family members throughout the study.  
Families in the usual care arm will also receive toothbrushes and toothpaste after the 
completion of each annual survey.  All participating children will receive a thorough oral health 
screening, a service not always available.  If a child is found to have a dental emergency, e.g., a 
dental abscess, he/she will be immediately referred to the Head Start teacher, who has 
procedures in place for managing medical emergencies.

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The study will provide knowledge to potentially allow for the development and 
implementation of an effective oral health program for the prevention of ECC in rural AI 
populations. 

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3
OBJECTIVES
3.1
Study Objectives
3.1.1 Primary:
3.1.1.1
To develop, with the input from tribal/community members, a 
manualized intervention protocol for an ECC prevention program for 
delivery by specially trained community paraprofessionals, called 
Community Oral Health Specialists (COHS)
3.1.1.2
To implement and evaluate the delivery of FV and OHP programs in 
AI Head Start Centers under the following conditions:
Group 1 - FV (offered 4x a year) and OHP for 2 years by specially trained 
COHS; toothbrushes and toothpaste supplied for entire family 
Group 2 - Usual oral health care made available by their usual dental 
providers, usually IHS; toothbrushes and toothpaste supplied for entire family 
3.1.1.3
To assess efficacy by comparing dmfs over time between the two 
groups
3.1.2 Secondary:
3.1.2.1
To assess specific caries patterns 
3.1.2.2
To investigate moderators/mediators of the intervention conditions as 
ascertained via questionnaires on knowledge, attitudes, and 
behaviors
3.1.2.3
To investigate participant utilization of medical and dental services for 
oral health problems and intervention costs, intervention savings, net 
intervention costs, costs/net costs per participant, costs/net costs per 
unit decrease in caries associated with each intervention condition

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3.2
Study Outcome Measures
3.2.1 Primary Outcome Measure
Decayed, missing, and filled primary tooth surfaces (dmfs) of the children in the study at 
baseline, and annually for 3 years.

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3.2.2 Secondary Outcome Measures
3.2.2.1
Dental caries patterns (anterior, facial/lingual, molar, fissure caries, 
demineralization, etc.) 
3.2.2.2
Variables that may serve as moderators/mediators of the intervention 
conditions as ascertained via questionnaires on knowledge, attitudes, and 
behaviors
3.2.2.3
Participant use of dental and health services for oral health problems, 
program costs associated with each intervention condition, net program 
costs, costs per participant, costs of caries and caries averted 

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4
STUDY DESIGN
This is a multicenter, Phase IV, cluster randomized trial to determine whether an 
intensive intervention of COHS’s administering FV (offered 4x a year) and OHP for 2 years in an 
AI population of children ages 3-6 years in HSCs on the Navajo Reservation vs. usual oral 
health care made available by the IHS dental providers will reduce the dmfs measure in the 
children.  A cluster randomized design was chosen to reduce the potential for contamination 
between the 2 intervention groups.
There are approximately 96 HSC classrooms in the NN (based on 2011-2012 school 
year).  We will stratify HSCs on the basis of population size, and randomly assign the HSC 
classrooms to the 2 arms of the study within the strata.  This will make the number of children in 
each of the 2 arms of the study approximately equal.
The intensive intervention group will have the specially-trained COHS administer FV to 
the children 4x a year and provide OHP to the parents/caregivers and to the children in the HS 
classrooms, for 2 years.  The other randomized group will have usual oral health care made 
available by the IHS Dental providers or other community providers.
Enrollment of HSCs will be done over a period of 6 months (in each year, year 1 and 
year 2).  Upon parental consent of the child and parent/primary caregiver consent for 
her/himself, the HS children from each HSC classroom will be enrolled in the study.  Each 
consented child will participate in the study for up to 3 years.  A baseline assessment of the 
dmfs measure for each child will be done (objective 3.1.1.3 and 3.1.2.1/ outcome 3.2.1 and 
3.2.2.1), and a baseline assessment of the dental knowledge, attitudes, and behaviors of the 
parents/caregivers (objectives 3.1.2.2 and 3.1.2.3/ outcome 3.2.2.2 and 3.2.2.3).  The 
interventions will be administered for 2 years in the Head Start classrooms.  The number of 
interventions a participating child receives will vary with the length of time that the child attends 
the Head Start class.  Annual assessments of the dmfs measure for the children and the dental 
knowledge, attitudes, and behaviors of the parents/caregivers will be made for 3 years.  The 3rd 
annual assessment is included to determine changes in the outcome measures for up to 18 
months after the FV and OHP have ended, to assess the longer term effects of the intervention.
The primary outcome of the study will be changes from baseline in dmfs (dmfs increment 
at two and three years) between the 2 groups.  Secondary outcomes will include possible 
changes in caries patterns, and potential moderators/mediators of treatment effect such as 
parental knowledge, attitudes and behaviors, and the cost of each of the two intervention 
conditions.  
The dmfs measures (objective 3.1.1.3 and 3.1.2.1/ outcome 3.2.1 and 3.2.2.1) will be 
made by oral screening of the children, to be completed by calibrated dental hygienists who will 
visit each HSC in both the COHS intervention (Group 1) and the Usual Care (Group 2) arms.  

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Questionnaires, known as the Basic Research Factors Questionnaire (BRFQ) or Audio 
Computer Assisted Survey Interview (ACASI) survey, of dental knowledge, attitudes, behaviors 
and service utilization (objectives 3.1.2.2 and 3.1.2.3/ outcome 3.2.2.2 and 3.2.2.3) will be 
completed by the parents/caregivers annually, and the data will be entered into laptop 
computers.  We will follow the families whose children age out of Head Start and make 
arrangements for them to complete the child oral health screening and parent questionnaires at 
a convenient time and location.  All data collected on laptops in the field will be sent first to UCD 
and then uploaded to the central statistical coordinating center.
NIDCR has appointed a Data Safety and Monitoring Board to provide oversight of the 
studies and review of interim analyses for all ECC projects in the consortium. 
A Manual of Procedures (MOP) has been created to detail the conduct and operations of 
the study.  It transforms the study protocol into a guideline that describes all aspects of the 
study’s organization, operational definitions, recruitment, screening, enrollment, randomization, 
intervention, follow-up procedures, data collection methods, data tracking and transfer, case 
report forms (CRFs), and quality control procedures.  
The MOP is a dynamic document that will be updated throughout the study to reflect any 
amendments to the protocol, participant consent forms, CRFs and study procedures.  The MOP 
will be submitted once a year at continuing review unless it requires a change in the protocol.  
At continuing review, tracked changes and a summary of updates to the MOP made throughout 
the year will be submitted.
4.1
Substudies
There will be no substudies.  

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5
STUDY ENROLLMENT AND WITHDRAWAL
5.1
Subject Inclusion Criteria
Once the HSCs on the Navajo reservation are selected for the study, the HSC will be 
randomized to the two intervention groups.   Subject inclusion criteria include:
A)  Children ages 3-6 years at the time of enrollment in the Navajo reservation HSCs and 
having a primary caregiver (preferably parent, or the child’s legal guardian as documented by 
the HSC, but another caregiver such as an aunt or grandmother will not be excluded if he or she 
is the primary caregiver for the child).  A parent or legal guardian must be available to give 
consent for the child to participate in the study.  (Note:  multiple children from the same family 
will not be excluded, provided each child is enrolled in the Navajo Head Start Program.)
B)  American Indian, as defined by the tribe, or children of other races/ethnic groups who are in 
the HS classes on the Navajo reservation (the numbers in this latter group are expected to be 
very small); and
C)  Parent/caregiver able to read, understand, and sign a consent form for his or her own 
participation, and willing and able to follow study procedures and instructions.
5.2
Subject Exclusion Criteria
A child will be excluded if he/she has any of these conditions:
A)  Allergy to any of the components of the FV (for children attending HSCs in Group 1)
B) Ulcerative gingivitis, stomatitis or other conditions resulting in chronically disrupted or irritated 
oral mucosa (for children attending HSCs in Group 1)
C)  Any other conditions or findings that, in the opinion of the investigator, would interfere with or 
preclude participation in the study in either Group 1 or Group 2.
5.3
Treatment Assignment Procedures
5.3.1 Randomization Procedures
A list of Navajo HSCs and the population sizes will be provided to the University of 
Colorado Center for Native Oral Health Research (CNOHR) by the Navajo Nation Head Start 
Program.  The HSCs will be stratified by number of HS classes (1 vs. 2-3) and by Navajo 

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agency (there are 5 agencies), and then the randomization of the HSCs into intervention vs. 
control will be done within those strata.  This will be done to ensure approximately equal sample 
sizes in the intervention and control groups, and approximately an equal number of intervention 
and control participants within each Navajo agency.  A program will be developed to do the 
randomization within each stratum.  Random numbers will be generated, and if the random 
number ends with the digit 0-4, the HSC will be assigned to the control arm and if the random 
number ends with the digit 5-9, the HSC will be assigned to the intervention arm.  
5.3.2 Masking Procedures
The interventions will not be masked in this study.  Group randomization is being 
performed in this study in order to minimize cross-contamination of the intervention conditions.  
Outcome data from the trial will be reviewed centrally by a Data and Safety Monitoring Board for 
the ECC Consortium.  The dental hygienists who screen the children to capture caries 
outcomes annually will be blinded to the intervention condition, and study investigators will be 
masked to the final study outcomes, findings, and results until the study is completed.
5.3.3 Reasons for Withdrawal
Children may be withdrawn from the study if they have an adverse reaction to the FV, or 
any other aspect of the study.  They will also be withdrawn if informed consent is withdrawn by 
the parent/caregiver.
5.3.4 Handling of Withdrawals
If a child withdraws from the study because of an adverse reaction to the FV, it will be 
requested that the child continue in the evaluation but not the treatment part of the study (i.e., 
the annual oral health screening, parent education and child classroom sessions, and 
parent/caregiver questionnaires related to dental knowledge, attitudes, and behavior).  This will 
be done in an attempt to obtain as complete data as possible in follow-up.  Of course, if the 
parent/caregiver wants to withdraw the child from the study entirely, those wishes will be 
honored.
5.3.5 Termination of Study
The study will be terminated in the field after the intervention and subsequent follow-ups 
have been completed and the data are completely cleaned and transferred to the investigator’s 
site.  The study will be terminated at the investigators’ site when all data analyses and study 
manuscripts have been completed.  The central Data and Safety Monitoring Board will be 
monitoring the safety and efficacy data at intervals specified by them throughout the study, and 
they have the authority to terminate the study earlier on the basis of these data reviews.  

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NIDCR, as sponsor, will also be monitoring the study conduct and can recommend termination 
for cause. 

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6
STUDY INTERVENTION/ INVESTIGATIONAL PRODUCT
6.1
Study Product Description
6.1.1 Acquisition
The FV will be purchased from 3M (formerly Omnii Oral Pharmaceuticals).  The FV will 
be shipped to the University of Colorado, School of Dental Medicine and forwarded from there 
to the field office sites.  
6.1.2 Formulation, Packaging, and Labeling
The trade-name of the FV is VANISH; it is a 5% Sodium Fluoride white varnish.  It is 
packaged in 0.5ml unit dose packets and applicator brushes.  The clearly labeled box contains 
1000 sealed unit doses, patient instructions, and dosage stickers to measure quantity 
dispensed.  
6.1.3 Product Storage and Stability
For both intervention conditions, the FV will be labeled and stored in a secure locked 
office, and out of reach of the children.  The FV is a stable agent but is potentially a flammable 
liquid, so it is recommended that it be stored away from heat, acids, and oxidizing agents.  The 
product MSDS does not provide a recommended storage temperature; we will therefore store it 
in a climate-controlled, temperature-monitored area between 10C - 32C.  Handling instructions 
caution that the product is to be kept away from heat, sparks, open flame, pilot lights and other 
sources of ignition; avoid breathing vapors, mists, or spray; use general dilution ventilation 
and/or local exhaust ventilation to control airborne exposures; avoid eye contact; avoid 
prolonged or repeated skin contact; and recommend the washing of hands after handling and 
before eating.  The product’s MSDS is attached to this protocol (Appendix A).
6.2
Dosage, Preparation and Administration of Study 
Intervention/Investigational Product
Only trained study staff will apply the FV to the teeth of the children whose parents have 
consented.  Aseptic procedures and universal precautions will be maintained at all times.  Study 
records and HS child health records will document the application of the FV.  Consistent with 
CDC Advisory Committee on Immunization Practices and standards of pediatric practice, 
COHSs will observe the child(ren) for a minimum of 15 minutes following the fluoride varnish 

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application to observe, resolve, and report any untoward effects.  Parents will be provided with 
post-fluoride instructions each time the FV is administered.
Dosage guidelines include the following:
a.
0.25 mL dosage for children with primary dentition only, or to treat any child requiring 
limited tooth surface or cavity area coverage
b.
0.40 mL dosage for children with mixed dentition who require extensive tooth surface or 
cavity area coverage
c.
0.50 mL dosage for children with permanent dentition who require extensive coverage.
Directions for administration are:
1.
Treatment areas should minimally be “toothbrush” clean; a prophylaxis is not required.
2.
Peel the foil pouch open to expose the VANISH unit-dose package and applicator brush.
3.
Tear off the end of the unit-dose package and dispense the entire contents onto the 
dosing guide.
4.
Use the applicator brush to thoroughly mix VANISH, since the components of all sodium 
fluoride varnishes can separate during storage.  While mixing, keep the material evenly 
distributed inside the inner circle of the dosing guide.
5.
Use the dosing guide to determine the amount of VANISH required.
6.
For best results, excessive saliva is removed by blotting the tooth surfaces with gauze.  
Avoid passing applicator brush through pooled saliva to prevent premature setting on 
bristles.
7.
Paint VANISH evenly to the areas being treated.
8.
Consistent with CDC Advisory Committee on Immunization Practices and standards of 
pediatric practice, the COHSs will observe the child(ren) for a minimum of 15 minutes 
following the fluoride varnish application to observe, resolve, and report any untoward 
effects.  
9.
It is best for the patient to keep VANISH in contact with tooth surfaces as long as 
possible, minimally for 4 hours.  During the treatment period, the patient and the 
parent/caregiver should be instructed to avoid hard foods, brushing teeth, and use of 
products containing alcohol (beverages, oral rinses).  A thorough brushing and flossing 
will remove excess VANISH from tooth surfaces following the treatment period.

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6.3
Modification of Study Intervention/Investigational Product for a 
Participant
No modifications of the FV will be made.
6.4
Accountability Procedures for the Study 
Intervention/Investigational Product(s)
Study staff involved in the delivery of the FV will be required to sign out the inventory 
prior to use.  The field office will maintain records of FV units in the inventory and signed out to 
the study personnel.  Lot numbers and expiration dates of the product will also be tracked.  
Unopened packages and expired fluoride varnish will be returned to the NNFO, where 
investigators will determine the method of disposal.
6.5
Assessment of Subject Compliance with Study 
Intervention/Investigational Product
Records of the FV applications and post application observation will be kept for each 
child in the COHS intervention group as a record of compliance with the intervention.  A copy of 
this information will be placed in the child’s Head Start Health Record.  Data will be collected on 
the dental service utilization of each child in the study at the time of the annual ACASI survey 
measures completed by parents (objectives 3.1.2.2 and 3.1.2.3/ outcome 3.2.2.2 and 3.2.2.3).  
6.6
Concomitant Medications/Treatments
Children taking fluoride supplements should discontinue the use of the supplements for 
2-3 days following each FV application.

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7
STUDY SCHEDULE
7.1
Screening 
Children and parents will be screened for entry into the study according to inclusion/ 
exclusion criteria at the time of enrollment.  
7.2
Enrollment
Once the HS programs that will participate in the two treatment arms have been 
identified, study staff will travel to each participating site and host sessions for teachers, staff 
and parents to explain the program and begin obtaining informed consent from parents.  Upon 
obtaining informed consent from a parent/legal guardian, the child will be enrolled in the study, 
along with his/her parent/primary caregiver, who also will provide informed consent.  A baseline 
oral health screening will be completed, along with the ACASI survey completed by the 
parents/caregivers regarding demographic information about the children, health history, and 
the parents’/caregivers’ dental knowledge, attitudes, and behaviors.  Toothbrushes and 
toothpaste will be given, enough for each family member in the household.  
Prior to the varnish dates, under normal and usual conditions, notices will be sent home 
with children notifying parents of the upcoming varnish date(s) for the COHS intervention group.  
The notice will state the date(s) that the COHS will be administering FV in the HS classroom.  
7.3
Follow-up Visits for FV 
The applications of FV for HS children and OHP will be delivered in the HSCs by the 
COHS (Group 1).  FV will be offered 4x a year for 2 years to children in the classroom on the 
scheduled day; multiple attempts will be made to provide FV to children not in the classroom on 
the scheduled day.  Group 2 participants will receive usual oral health care made available by 
the IHS Dental providers (or other dental providers outside the reservation). 
Annual dmfs measure of the children, and parent ACASI survey to collect dental 
knowledge, attitudes, and behaviors will take place annually for 3 years.  We will follow the 
families whose children age out of Head Start and make arrangements for them to complete the 
child oral health screening and parent ACASI survey at a convenient time and location.  All 
annual follow-up assessments will be done as near as possible to the anniversary of the 
previous year’s oral health screening at that HSC, with the goal of completing them within a 
month either side of that date.  

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7.4
Follow-up Safety Contact One Week After FV
The COHS will contact the parent/caregiver of each child who received FV 3-10 
business days after administration to inquire if the child had any adverse reaction, and/or 
required any unscheduled (urgent or emergent) health care consultation or visit.  If the child had 
a reaction or required a health care consultation or visit, information regarding the encounter will 
be documented on the adverse event form and the PI will be notified.
7.5
Final Study Visit
The final study visit will be the third year follow-up evaluations of the children and the 
final parent/caregiver questionnaires.
7.6
Early Termination Visit
No early termination visits are anticipated.
7.7
Unscheduled Visit 
No unscheduled visits are anticipated.

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8
STUDY PROCEDURES/EVALUATIONS
8.1
Clinical Evaluations
All children in the study will be provided an oral health screening at baseline and 
annually thereafter for 3 years (up to 4 screenings total).  The oral health screening will collect 
dmfs measures (objective 3.1.1.3 and 3.1.2.1/ outcome 3.2.1 and 3.2.2.1) of the children, to be 
completed by calibrated dental hygienists who will visit each HSC in both the COHS intervention 
(Group 1) and usual care (Group 2) arms.  Procedures for the oral health screening will be 
followed according to the protocol of the Caries Outcome Work Group of the ECC consortium.  
The Caries Outcome Work Group will develop an SOP for the oral health screenings, which will 
be attached to this protocol.  The criteria for the determination of dmfs measures according to 
Drury, et al.28 will be used.  These criteria include the counting of both non-cavitated and 
cavitated carious lesions.  
8.2
Laboratory Evaluations
8.2.1 Clinical Laboratory Evaluations
There will be no clinical laboratory evaluations in the study. 
8.3
Specification of Safety Parameters
Safety parameters will include any serious adverse events (SAEs) or any unanticipated 
problems involving risk (UPs) that occur with general participation in the COHS program.  
Adverse events related to the topical application of FV will be collected for 3-10 days following 
each application (refer to section 7.4).
8.4
Methods and Timing for Assessing, Recording, and Analyzing 
Safety Parameters
8.4.1 Adverse Events
ICH E6 defines an adverse event (AE) as any untoward medical occurrence in a patient 
or clinical investigation subject administered a pharmaceutical product regardless of its causal 
relationship to the study treatment.  An AE can therefore be any unfavorable and unintended 
sign, symptom, or disease temporarily associated with the use of medicinal (investigational) 
product including anaphylaxis, oral discomfort, or oral disfigurement.  In this study, due to the 

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anticipated low risk of the intervention, AEs that do not meet the reporting criteria parameters for 
medically attended events, SAEs or UPs will not be collected. 
All medically attended, or medically treated AEs, or circumstances where parent or 
guardian contacted health care provider for advice regarding AE for this time period will be 
reported on an AE form.  This would exclude an upset stomach or runny nose that required no 
treatment or health care provider contact in addition to bumps and bruises treated at home.  
Medically attended events will be captured in a 3-10 day window after FV administration.  SAEs 
and UPs will be captured throughout the study period.
All AEs will be graded for severity and relationship to the study product.  Severity may be 
graded based on the following scale: mild, moderate, severe, life-threatening, death (CTCAE 
criteria:  http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
Relationship to Study Products:  The clinician’s assessment of an AE’s relationship to the test 
article will be a part of the documentation process, but it will not be a factor in determining what 
is or is not reported.  If there is any doubt as to whether a clinical observation is an AE, the 
event will be reported.  All AEs will have their relationship to the study product assessed using 
the terms:  associated or not associated.  In a clinical trial, the study product must always be 
suspected.  To help assess the relationship of the AE to the study product, the following 
guidelines will be used:
1.
Expected (Associated) Adverse Event:  An adverse event that is consistent in the nature 
or severity with the applicable product information (e.g., Investigator Brochure)
2.
Unexpected (Not Associated) Adverse Event:  An adverse reaction, the nature of 
severity of which is not consistent with the applicable product information
The subject with a medically attended AE will be contacted by the PI and/ or the study 
doctor/dentist via telephone  ortelephone or in person for a safety follow-up within one week 
after FV administration and documentation of the AE.  Information will be collected on any 
medically attended visits for cause.
8.4.2 Serious Adverse Events (SAEs) and Unanticipated Problems (UPs) 
A serious adverse event (SAE) is an AE that, in the view of the investigator or sponsor, 
results in any of the following outcomes:
1.
Death
2.
Life-threatening event 

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◦
The decision is based on the investigator’s opinion. Must place the subject at 
immediate risk of death. Example: Anaphylaxis.  An adverse event that, had it 
occurred in a more severe form, might have caused death 
3.
An event requiring inpatient hospitalization or prolongation of existing hospitalization.  
This excludes any planned hospitalizations for elective procedures that are not related to 
study participation.
4.
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions
5.
A congenital anomaly/birth defect subsequent to the administration of the agent
6.
An important medical event that may not result in death, be life-threatening, or require 
hospitalization, but may be considered serious that, based upon appropriate medical 
judgment, may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed above
Note on inpatient hospitalization and prolongation of hospitalization:  Subject must be 
hospitalized for more than 24 hours.  Going to the hospital for observation does not meet 
the definition of hospitalization.  Emergency room visits that do not result in an 
admission to the hospital should be evaluated for one of the other serious outcomes 
(e.g. life-threatening, required intervention to prevent permanent damage; other serious 
medically important event). 
All related SAEs occurring at any time during the 2-year treatment and additional year of 
follow-up will be reported to NIDCR via the CROMS contractor, as well as to COMIRB and 
NNHRRB within 72 hours of receipt of information about the SAE.  All SAEs will be recorded on 
the appropriate SAE CRF, be followed through to resolution or stabilization by a study clinician, 
and be reviewed and evaluated by a study clinician.
An unanticipated problem involving risks to the subjects or to others (UP).  This 
would be any incident, experience, or outcome that meets all of the following criteria:
1.
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;
2.
Related or possibly related to a subject’s participation in the research; and 
3.
Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) related to the research than was 
previously known or recognized.

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An unanticipated problem may be an SAE and meet the reporting requirements of an 
SAE, or a UP may not manifest any criteria of an SAE and would therefore require reporting to 
the IRBs only, as per IRB requirements.    All UPs occurring at any time during the 2-year 
treatment and additional year of follow-up will be reported.  
8.4.3 Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings
Laboratory tests will not be performed in this study.  If a dental emergency is found in a 
study child (e.g., a dental abscess), the child will be referred to the Head Start teacher, who has 
procedures in place for managing medical emergencies.
8.5
Reporting Procedures
8.5.1 Regulatory Reporting for Studies Conducted Under NIDCR- 
Sponsored IND
This study will not be conducted under an IND.
8.5.2 Regulatory Reporting for Studies Not Conducted Under NIDCR- 
Sponsored IND
All SAEs and UPs will be reported by the field staff to the study PI within 24 hours of 
receipt of the information in the field.  The study PI will report all SAEs to NIDCR via the 
CROMS contractor, within 72 hours of receipt of information about the SAE.  The CROMS 
contractor will notify the DCC.
All SAE forms and UP forms should be sent to:
Safety Fax Line:  888.746.3293 or 919-287-3998, or
Product Safety Email:  rho-productsafety@rhoworld.com
For information regarding SAEs, sites can contact the SAE Hotline for guidance:
Safety Hot Line:  888.746.7231 or 919.595.6486
Unanticipated problems must be reported to the appropriate IRB per their requirements.
All medically attended events, SAEs and UPs will also be reported in each annual 
statistical progress report that is sent to the DSMB.

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8.5.3 Other Adverse Events (if applicable)
Adverse events as defined in Section 8.4.1 of protocol occurring during the 3-10 
days after each FV application will be recorded on the appropriate case report form and 
followed to resolution as noted in Section 8.6.
8.5.4 Reporting of Pregnancy
Not applicable
8.6
Type and Duration of Follow-up of Subjects after Adverse 
Events
Children who have a medically attended AE as defined in Sections 8.4.1-8.4.2 of the 
protocol will be followed weekly by the PI and/or study dentist until the AE resolves or stabilizes.  
This might include visits to the HSC or home visits by study staff.  If the AE does not resolve 
within one month, the child will be referred to their usual medical or dental care provider as 
appropriate.  If the need is/becomes urgent, immediate referral will be made.
8.7
Halting Rules
The frequency of AEs meeting criteria defined in protocol Section 8.4.1 in this study is 
expected to be very small.  If the number of SAEs is large, or of a particular type, NIDCR and 
the Data and Safety Monitoring Board may consider temporarily suspending enrollment and/or 
the FV interventions until a safety review is convened.  The objective of the safety review would 
be to make a decision on whether the study should continue per protocol, proceed with caution, 
be further investigated, be discontinued, or be modified and then continued.
8.8
Safety Oversight 
NIDCR has appointed a Data and Safety Monitoring Board, which will review data from 
all of the studies in the ECC consortium.  The conduct of the DSMB and rules regarding how 
often the Board will meet have been described in the DSMB Charter for the study.

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9
CLINICAL MONITORING
9.1
Site Monitoring Plan
Site monitoring will be conducted to ensure that human subject protection, study 
procedures, study intervention administration, and data collection processes are of high quality 
and meet sponsor, GCP/ICH, and regulatory guidelines, and that the study is conducted in 
accordance with the protocol and sponsor SOPs.  NIDCR, the sponsoring agency, or its 
designee will develop a site monitoring plan and conduct site monitoring visits as described in 
the site monitoring plan.
Site visits will be made at standard intervals as defined by NIDCR and may be made 
more frequently as directed by NIDCR.  Monitoring visits will include, but are not limited to, 
review of regulatory files, accountability records, case report forms, informed consent forms, 
medical and laboratory reports, and protocol compliance.  Study monitors will meet with 
investigators to discuss any problems and actions to be taken and document visit findings and 
discussions.
A separate monitoring plan document will be developed by the DSMB and the sponsor 
to describe who will conduct the monitoring, at what frequency monitoring will be done, and 
what level of detail monitoring will be conducted.

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10
STATISTICAL CONSIDERATIONS
10.1 Study Hypotheses
The hypothesis of this study is that intensive intervention of specially trained COHS 
delivering fluoride varnish 4x a year and ongoing oral health promotion activities for 2 years to 
preschool children and families through Navajo Nation Head Start centers (Group 1) vs. the 
delivery of usual care (Group 2) will reduce the decayed missing and filled tooth surfaces 
increment in the Group 1 children when compared to the Group 2 children, and show improved 
parent/caregiver dental knowledge, attitudes, and behaviors.  The dmfs measure is the primary 
outcome of the study on which sample size will be based. 
10.2 Sample Size Considerations
Sample size is based upon the following assumptions:
1.
The primary outcome measure is dmfs, measured at baseline and annually for three 
years after the beginning of the intervention when the HS children ages 3-5 at enrollment 
(or possibly 6, depending on the timing of enrollment) will be ages 6-8 (or possibly 9).
2.
The test statistic used is the t-test for 2 independent samples, with an inflation factor for 
the cluster randomized design.29, 30
3.
The null hypothesis is no difference in the mean dmfs between the 2 randomized groups 
2 years and 3 years after the beginning of the intervention when the children are 5-7 6-8 
(or possibly 9) years old.  The alternative hypothesis is that there is a difference.
4.
Type I error rate will be set at 0.05
5.
Type II error rate will be set at 0.20 (Power = 0.80)
6.
From the 1999 IHS oral health survey 5, the average dmfs for AI children ages 5-7 was 
18.55.  It was also observed that Navajo children tended to have dmfs measures about 
30% higher than the national average for all AI children.  Therefore, it was assumed that 
the average dmfs for Navajo children ages 5-7 will be about 24 under conditions of usual 
care, with a standard deviation of about 24.  We also assumed a 40% reduction in this 
average dmfs measure for group 1.
7.
Based on the experience of other studies the Centers for American Indian and Alaska 
Native Health have conducted with AI communities, a 70% retention rate was assumed.

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8.
If subjects drop out of the study due to adverse effects or other reasons, we will ask 
them to continue in the follow-up even if treatment is discontinued, so that we can 
perform an “intention to treat” analysis.  The “intention to treat” analysis will be the 
primary analysis of the study.
9.
We also assumed an average HS class size of about 20 children and an intraclass 
correlation of about 0.045, considered to be an appropriate intraclass correlation.31 
On the basis of the assumptions above, we calculate a need to randomize 52 HSC 
classrooms, or about 26 HSC classrooms in group 1 and 26 HSC classrooms in group 2.  This 
means that we will need to enroll about 1040 children, or 520 children in group 1 and 520 
children in group 2.  Sample size calculations are shown in the table in Appendix B.
10.3 Planned Interim Analyses (if applicable)
Planned interim analyses will be established by the Data and Safety Monitoring Board 
appointed by NIDCR.  Our planned sample size will be adjusted after the DSMB decides on 
their policy with regard to interim analyses.
10.3.1 Safety Review
SAEs will be reported to NIDCR Medical Monitor by the CROMS contractor within 24 
hours of their receipt by the contractor.   If the number, frequency, or character of the SAEs or 
UPs is unexpected, the investigator, NIDCR and/or the DSMB can call for a safety review (see 
section 8.7).  AEs will be reported to the DSMB routinely in the semi-annual statistical progress 
report. 
10.3.2 Immunogenicity or Efficacy Review
Not applicable.

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10.4 Final Analysis Plan
The primary outcome measure will be the difference between groups 1 and 2 on the 
changes in mean dmfs between baseline and 2-year and 3-year follow-up.  Descriptive statistics 
will be examined first to yield important information about the most appropriate analysis 
strategies.  If the change scores for dmfs are not normally distributed, a log transformation can 
be made, or a non-parametric test can be used.  Longitudinal methods of analysis will be used 
to examine these repeated, correlated observations within subjects over time.32, 33  Other 
models such as negative binomial regression, mixture models such as ZIP and ZINB will be 
considered.  
Exploratory analyses will first be done to evaluate the trends in the data to determine the 
most appropriate mean and covariance structures for the data.  Graphical displays will be used 
to assess the mean structure for modeling fixed effects, including scatter plots of the response 
variable versus time, plots of individual subject profiles, plots of mean profiles, and smooth 
curve fits to the data.  Simple plots of individual subject profiles (dmfs over time) can be very 
revealing and show whether there is heteroscedasticity in the data (fanning of the curves with 
time).
Linear mixed models will be used because they can incorporate both fixed and random 
(subject-specific) effects and permit different covariance structures.  A typical example (“random 
regression”) allows each subject an individual time trend, and treatment effects may cause 
differences in slope over time.  The within-subjects autocorrelation is assumed to be due to 
these individual trends, on top of which is superimposed independent measurement errors.  
When analyzing randomized trials, it is assumed that the responses are the values that occur 
after randomization, because they are influenced by treatment.  Thus, it is customary in such 
trials to consider the baseline value as a covariate, rather than as a response variable.  The 
randomization of subjects in groups or clusters (i.e., HSCs) can also be accounted for in the 
mixed model with a random effect for group.
Two important considerations in fitting mixed models are determining covariance and 
mean structures for the data.  We will first define the covariance structure; many forms are 
available, depending on the correlations in the data.  Little, et al.,34 provide a useful article on 
modeling the covariance structure for longitudinal data by using the MIXED procedure in SAS 
software.  Once a suitable covariance structure has been determined, an appropriate mean 
structure can be determined.
Missing or incomplete data are a common problem in randomized clinical trials where 
the outcome is measured longitudinally.  Here, exploratory analyses will be done first to 
determine if the missing observations are missing completely at random (MCAR), missing at 
random (MAR), or missing not at random (MNAR) and whether multiple imputation should be 
done, or modeling of the non-response.  Complete case analysis will be the primary analysis, 

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since available data analysis with mixed models only assumes MAR (Molenberghs).  As a 
secondary analysis multiple imputation or modeling of the non-response mechanism will be 
done to include those cases without complete data.
The secondary outcomes will include caries patterns, cost analyses and the array of 
information representing knowledge, attitudes, and behaviors of parents that may serve as 
mediating and moderating variables.  Caries patterns will be analyzed by looking at the different 
dmfs components and the specific teeth involved.  
Cost-effectiveness analysis is used to compare costs of alternative interventions for a 
similar health outcome.  Results are presented as a cost-effectiveness (or CE) ratio of the 
intervention net cost (intervention costs minus savings) per health outcome such as 
improvement in quality-adjusted life years (QOL). For this proposal, intervention cost and net 
cost estimates will be used to construct cost indicators such as the cost/net cost per child 
served and, if the program is found to be effective, the cost/net cost per unit decrease in caries. 
Such indicators are sometimes referred to as preliminary CE ratios for 2 reasons. First, the 
ratios measure the cost for a process-outcome or a health-outcome such as caries rather than 
QOL.  Second, we will estimate only short-term net intervention costs, not long-term costs that 
may result with improvements in oral health behaviors and practices overtime. 
We will document all costs associated with the intervention from two perspectives, that 
of the provider and that of society, which includes both provider and participant direct and 
indirect intervention costs.  Costs include direct dental and medical costs; other direct costs 
(e.g., costs for travel to obtain services), and indirect costs (e.g., costs associated with patient 
time spent for a dental visit, time spent off work).  Intervention costs from the provider 
perspective include direct costs for all stages of program implementation (adapting the 
intervention for use in this population, service implementation, and service provision), excluding 
research costs.  They include costs of any additional dental services study participants incurred 
as a result of the intervention (e.g., utilization of preventive dental services).  Participant 
intervention costs (e.g., time and travel costs) will also be accounted for.  We will assess 
intervention savings by estimating averted treatment costs due to a reduction in ECC using 
parent-reported data on children’s use of dental and medical services for oral health problems, 
time spent obtaining services, and travel costs.35-38  Standardized price data will be used to 
value service utilization, non-clinical intervention costs, travel costs, and time costs.
Provider and participant intervention cost will be summed to calculate total intervention 
costs.  Short-term net costs will be obtained by subtracting intervention savings from the total 
intervention costs.  We will compare the intervention costs and net costs incurred in groups 1 
and 2, and preliminary cost-effectiveness ratios (e.g., the cost per participant and cost per 
averted cary).  We will examine the influence of demographic and clinical characteristics on the 
cost findings.  Finally, we will conduct sensitivity analyses to evaluate the inherent uncertainty of 

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assumptions concerning costs on the findings.  The sensitivity analyses will include univariate 
analyses and second-order Monte Carlo sensitivity analyses.39
In a series of secondary analyses, hierarchical models will be constructed wherein 
potential mediators and moderators such as parental knowledge, attitudes and behaviors, are 
added to the primary outcome model to assess the degree to which these factors explain the 
relationship between intervention conditions and dmfs changes.  For instance, a sequence 
might be as follows:  1) intervention condition; 2) intervention condition + sociodemographics; 
and 3) intervention condition + sociodemographics + mediators.  Using the approach 
recommended by Hosmer and Lemeshow,40 we will first assess the bivariable relationships of 
each variable with dmfs.  Only those variables with a bivariable relationship at p<=0.25 will be 
included in these final models.
The potential of specific variables to have moderating effects will be assessed through 
the use of interaction terms; for instance, we might find that those with high levels of chronic 
stress in their lives are less likely to incorporate the important health behaviors that the COHS 
encourage into their everyday lives.

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11
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Study records will be maintained for each child and parent/caregiver enrolled in the 
study.  Source documents include all paper and electronic data files collected at the child/family 
level such as: informed consent forms, oral health screening results, delivery of fluoride varnish; 
attendance records of the children and parents/caregivers at OHP encounters; parent/caregiver 
questionnaires assessing dental knowledge, attitudes, and behaviors; use of dental and medical 
services for oral health problems; intervention costs; and records of the activities of the COHS.
There will also be source documents collected at the HSC level.  These will include 
characteristics of the HSC, FV inventory records, and OHP activities at the HSC-level.
Source documents will be maintained in locked file boxes during data collection periods 
and subsequently transferred to a locked file cabinet at the RC2 NN field office.  After annual 
enrollment is complete, participant consent forms will be transported to UCD for long term 
storage in accordance with HIPAA regulations. 

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12
QUALITY CONTROL AND QUALITY ASSURANCE
Ultimate responsibility for implementation and maintaining quality assurance and quality 
control systems with written standard 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 investigator of the intervention trial.  The project coordinator and field coordinator 
will provide regular reports on the fidelity and administration of the intervention to the PI.
The Center for Native Oral Health Research (CNOHR) also has responsibility for monitoring 
progress via monthly meetings to review and evaluate the performance of the intervention trial.  
Their role is to ensure that the intervention trial conducted and data generated are in 
compliance with the protocols, good clinical practices and the applicable regulatory 
requirements.  The CNOHR’s internal governance groups (Executive Committee, CNOHR 
Coordinating Committee) meet monthly to ensure the intervention trial is meeting objectives and 
to consider all aspects of the project for oversight, feedback and suggestions enhancing future 
progress along with monitoring of expenditures and cost allocations as the project progresses.  
Their oversight includes verification that the PI has secured appropriate agreements from all 
involved parties, has adequately secured the data/documents and reports and all protocols and 
standard operating procedures have been followed and quality assurance and quality control of 
the data, its reliability and assessment have been appropriately recorded, maintained and 
evaluated during the intervention trial.  CNOHR members of the statistics and data coordinating 
center will work closely with the leadership and staff of the intervention trial to provide statistical, 
data management, programming, methodological and electronic communications support.  They 
will also have oversight responsibility to ensure compliance of the intervention trial with the 
protocols, the accuracy and completeness of the documents, reports, notes, etc. and quality 
management of overall intervention program.  
CNOHR Community Advisory Committee, a 6-member committee representing tribal 
governments and health organizations and other community organizations participating in the 
CHOHR research activities, will meet at least once annually to review progress of the 
intervention trial and its impact/benefit on the communities being served. 

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13
ETHICS/PROTECTION OF HUMAN SUBJECTS
13.1 Ethical Standard
The PI 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 of the U.S. 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; 62 Federal Regulations 25691 (1997).
13.2 Institutional Review Board
This protocol, the associated informed consent documents, recruitment and retention 
materials, forms, and COHS curriculum and intervention materials for this study will be reviewed 
and approved as required by the University of Colorado Multiple Institutional Review Board 
(COMIRB) and the Navajo Nation Human Research Review Board (NNHRRB) prior to the start 
of the study.  Any amendments to the protocol or consent or recruitment materials will also be 
approved by these committees before implementation.
13.3 Informed Consent Process
Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continuing throughout the individual’s study participation.  Extensive 
discussion of risks and benefits of the FV and of participation in the study will be provided to the 
children and their families.  Consent forms describing in detail the FV and OHP, study duration 
and procedures, and risks and benefits will be given to the parents/caregivers and written 
documentation of informed consent will be required prior to starting the study.  Consent forms 
will be reviewed and approved by all of the committees listed in section 13.2.  Upon the 
parents/caregivers’ reviewing the informed consent document, the investigators will explain the 
study to the children and parents/caregivers and answer any questions that may arise.  Parents 
or legal guardians will sign the informed consent for the children and parents/caregivers will sign 
the informed consent document for their own participation prior to any procedures being done 
specifically for the study.  The children and parents/caregivers will have the opportunity to 
discuss the study with family members and think about it prior to agreeing to participate.  The 
subjects may withdraw consent at any time throughout the course of the trial without 

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jeopardizing any entitlements that they have with regard to the HS program or to the IHS dental 
clinics.  A copy of the informed consent document will be given to the parents/caregivers for 
their records.  The original of the informed consent form will be kept in locked files in the study’s 
field office until the completion of enrollment.  An electronic copy will also be sent to the Study 
Coordinator at the UCD investigators’ site.  Upon completion of each annual enrollment period, 
the original consent forms will be transported by study staff to the UCD offices for secure 
storage.  The rights and welfare of the subjects will be protected by emphasizing to them that 
the quality of their dental care will not be adversely affected if they decline to participate in the 
study.
13.3.1 Informed Consent/Assent Process (in Case of a Minor)
Parents/legal guardians will be asked to provide consent for their children (by definition 
younger than 7 at enrollment), whether or not they themselves will participate in the study 
activities. The parent/legal guardian will be advised about procedures in the relevant arm of the 
study and informed that they may discontinue the child’s participation at any time, including any 
time that they may sense that their child wishes to discontinue.
A parent age 15 or older who has not her or himself attained the age of majority and 
wishes his/her HS child to be enrolled in the study may provide consent for that child without 
further documentation (COMIRB instructions for Attachment H).  Time and care will be taken to 
assure that underage parents understand their and their children’s roles.
A parent age 15 or older who has not her or himself attained the age of majority and 
does not provide documented proof of emancipation granted by state or tribal authority must, 
however, obtain his or her own parent’s consent to participate in the study as parent/caregiver.  
The underage parent’s assent to participate in the study her or himself will be documented on 
the consent form; the same consent form will be used to document the full informed consent of 
her or his parent. 
13.4 Exclusion of Women, Minorities, and Children (Special 
Populations)
No special populations will be excluded.

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13.5 Subject Confidentiality
Subject confidentiality is strictly held in trust by the participating investigators, their staff, 
and the sponsor (NIDCR) and their agents.  This confidentiality covers the clinical information 
and the data on dental knowledge, attitudes, and behaviors of participating subjects.  The 
subjects’ identities will be held in records in locked cabinets at the field office.  Each subject will 
be given a study ID, which will be used in all research databases.  .
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 sponsor and the NN.
The study monitor or other authorized representatives of the sponsor may inspect all 
documents and records required to be maintained by the investigator, including but not limited 
to, medical, dental (office, clinic, or hospital) and pharmacy records for the subjects in this study. 
The clinical study site will permit access to such records, upon approval by the NN.
13.6 Study Discontinuation
In the event that the study is discontinued, the study subjects will be referred to their 
usual dental care provider for further treatment with FV or other dental treatment.
13.7 Future Use of Stored Specimens
Not applicable.

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14
DATA HANDLING AND RECORD KEEPING 
14.1 Data Management Responsibilities
Only study personnel at the UCD field office site, UCD Denver and the University of 
California San Francisco (UCSF) data coordinating center will have access to the data.  The PI 
is responsible to ensure the accuracy, completeness, legibility, and timeliness of the data 
reported.  All source documents will be completed in a neat, legible manner to ensure accurate 
interpretation of data.  Any data given to the Navajo Nation upon conclusion of the study or the 
NNHRRB will be de-identified prior to transfer and then delivered to the Navajo Nation Data 
Resource Center.
14.2 Data Capture Methods
Data will be collected using several methods.  Consent forms, documentation of 
informed consent forms, enrollment forms, Head Start Center data, program intervention and 
cost forms, safety forms and protocol deviation forms will be completed on paper forms.  During 
the enrollment period, consent forms will be stored in locked file cabinets in the NN field office 
(NNFO).  Upon completion of each annual enrollment period, the original consent forms will be 
transported by study staff to the UCD offices for secure storage.  All other original paper data 
forms will be stored in a locked filing cabinet at the NNFO.    
Original copies of the completed paper data forms will be stored in a locked filing cabinet at the 
NNFO.  Paper data forms will be scanned and archived to the UCD secure server.  The data 
manager and study staff at UCD & NNFO will enter the relevant data items from these forms for 
transfer to the UCSF DCC.  Participants will be identified using a participant ID number only.  
No identifying participant information will be sent to the DCC.  
Survey Questionnaires are collected annually via Audio Computer Assisted Survey 
Instrument (ACASI).  Caries data are collected annually using the Caries Research Instrument 
(CARIN); a graphical user interface for electronically recording and storing dmfs data.  Data 
collected electronically (ACASI, CARIN and Access databases) will be backed up to encrypted 
flash drives and stored securely during data collection.  These data will be sent to UCD via VPN 
connection after each data collection session.  After the data are checked for completeness, the 
data will be uploaded via secure ftp by the UCD data manager to the UCSF DCC.
The data transferred to the UCSF DCC will undergo audits for valid characters, valid 
ranges, and pre-specified consistencies between fields.  Potential errors in the data will be 
transmitted back to the UCD data manager for resolution.  The UCD data manager will work 

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with study staff to rectify any potential errors.  Necessary changes to the data will be made and 
transferred by the UCD data manager to the UCSF DCC.
14.3 Types of Data
Data stored in paper format include consent and HIPAA documents, and program 
evaluation forms.  Electronic data include information as part of the primary and secondary 
outcome measures of the study; demographic information, questionnaires related to dental 
knowledge, attitudes, beliefs, and practices, child use of dental and medical service for oral 
health problems, parent time and travel costs associated with the intervention and obtaining 
services; and program intervention costs.
14.4 Timing/Reports
After initially obtaining informed consent from the parents and baseline oral health 
screenings (dmfs measurements) and questionnaires, the COHS interventions with 
parents/caregivers continue for 2 years with follow up evaluation after the third year.  COHS will 
provide classroom activities for children 4 times per year and parent/caregiver events 3 times 
per year (in addition to the first parent/caregiver kick-off session, which will include both children 
and parents/caregivers).  All children will be provided annual oral health screenings at baseline 
and for 3 years.  Demographic information and questionnaires relating to dental knowledge, 
attitudes, beliefs and practices will take place at baseline and annually for 3 years.  Program 
intervention and cost data will be compiled semi-annually.
14.5 Study Records Retention
Any data given to the Navajo Nation or the NNHRRB will be de-identified prior to transfer 
and then delivered to the Navajo Nation Data Resource Center.  All paper study records will be 
destroyed 7 years after IRB acknowledgement of study closure in accordance with HIPAA 
regulations.  Electronic study records will be securely archived at the UCD Centers for American 
Indian and Alaska Native Health (CAIANH).
14.6 Protocol Violations/ Reportable Events
Protocol Violations are defined as an accidental or unintentional change to the approved 
protocol that harmed participants or others or that indicates participants or others may 
be at increased risk of harm.  Protocol violations will be tabulated and reported to the Data 
Coordinating Center and the IRBs of record for the study.  Examples of protocol violations 
include but are not limited to:  

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
Ineligible participant entered into the study.

An actual unforeseen harmful or unfavorable occurrence to participants or others that 
relates to the research protocol

Complaint of a participant when the complaint indicates unexpected risks or cannot 
be resolved by the research team

A problem involving data collection, data storage, privacy or confidentiality. 

Non-compliance by the PI or research team.

Any other problem that caused a risk to the participants or others.
Protocol violations resulting in SAEs or UPs will be reported as described in sections 8.4 
and 8.5.

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15
PUBLICATION POLICY
Following completion of the study, the investigators are expected to publish the results of 
this research in various scientific journals.  The investigators will register this intervention trial in 
an acceptable registry such as ClinicalTrials.gov and in addition the PI will submit all journal 
articles that arise from this intervention trial to the digital archive PubMed Central as required by 
NIH.
Within one year of commencing implementation of the study, the investigators will 
develop a publication plan that will detail, for each planned manuscript, the title and content of 
the manuscript, the writing committee, the priority of the manuscript, and a timeline.  The 
investigators will review the publication plan quarterly to evaluate the progress of each 
manuscript.  Statistical analyses will be performed by the statisticians according to the priorities 
of each manuscript.
In addition, the Navajo Nation Human Research Review Board requires that all proposed 
manuscripts for publication will be submitted as a complete manuscript in an approved 
publishable format to the review board for distribution to the NNHRRB with a cover sheet for 
comments and vote.  The Cover Vote/Comment Sheet will be returned to the assigned staff and 
tallied for voting purposes.  All comments will be forwarded to the PI to be included in the 
revision of the manuscript and upon revised manuscript submittal, the Board shall render a final 
vote.  A period of one month is given to the Board members to review proposed manuscripts.  
Upon approval by the Board, the PI/Author shall receive an approval letter with conditions.  
Upon publication, the PI is requested to submit three copies of the publication to the Navajo 
Division of Health.  One copy is filed, another is given to the partnering program and the other is 
reserved for the Navajo Nation Data Resource Center.  Any data given to the Navajo Nation or 
the NNHRRB will be de-identified prior to transfer and then delivered to the Navajo Nation Data 
Resource Center.
NIDCR is represented on the CNOHR Executive Committee and will receive draft 
manuscripts as submitted for publication and a copy of each manuscript as soon as it is officially 
“in press.”

Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
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Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
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Protocol Title:  Preventing Caries in Preschoolers: Testing a Unique
Service Delivery Model in American Indian Head Start Programs
Version 7.0
Protocol # 09-003E
18 Dec 2013
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APPENDICES
Appendix A:  Material Safety Data Sheet Omni 5% Sodium Fluoride Varnish
Appendix B:  Sample Size Calculations
Appendix C:  Consent Forms
Appendix D:  Caries Outcome Work Group Standard of Practice