Sensory Adapted Dental Environments to Enhance Oral Care for Children (SADE-2)
Phase: NA
Conditions: Autism
Sponsor: University of Southern California

Sensory Adapted Dental Environments to Enhance Oral Care for Children 
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SENSORY ADAPTED DENTAL ENVIRONMENTS 
TO ENHANCE ORAL CARE FOR CHILDREN  
(SADE-2 STUDY) 
 
NIDCR Protocol Number: 15-011-E 
NIDCR Grant Number:  DE024978-01 
Principal Investigator:  Sharon A. Cermak, EdD, OTR/L, FAOTA 
NIDCR Program Official:  Elise Rice, PhD 
NIDCR Scientific Project Official: Melissa Riddle, PhD 
NIDCR Medical Monitor: TBN 
Version Number: 5.0 
18 September 2020 
 

Sensory Adapted Dental Environments to Enhance Oral Care for Children 
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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on Harmonisation 
guidelines for Good Clinical Practice (ICH E6), the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46), and the NIDCR Clinical Terms of Award. All 
personnel involved in the conduct of this study have completed human subjects’ protection 
training. 
 

Sensory Adapted Dental Environments to Enhance Oral Care for Children 
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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date:  
 
Name: Sharon A. Cermak, EdD, OTR/L, FAOTA 
 
Title: Principal Investigator 
 
 
 

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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 ............................................................................................................. 9 
1 
KEY ROLES AND CONTACT INFORMATION ................................................................. 12 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....... 15 
2.1 
Rationale .............................................................................................................. 16 
2.2 
Potential Risks and Benefits ................................................................................. 17 
2.2.1 Potential Risks .......................................................................................... 17 
2.2.2 Potential Benefits ...................................................................................... 19 
3 
OBJECTIVES ................................................................................................................... 20 
3.1 
Study Objectives ................................................................................................... 20 
Primary Objective: To compare children’s physiological anxiety (EDA - primary 
outcome) during the dental cleaning in the SADE vs. RDE. .................................. 20 
3.2 
Study Outcome Measures .................................................................................... 20 
3.2.1 Outcome Measures for the Primary Objective ........................................... 20 
3.2.2 Outcome Measures for the Secondary Objectives ..................................... 21 
4 
STUDY DESIGN .............................................................................................................. 25 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................. 26 
5.1 
Subject Inclusion Criteria ...................................................................................... 26 
5.2 
Subject Exclusion Criteria ..................................................................................... 26 
5.3 
Strategies for Recruitment and Retention ............................................................. 27 
5.4 
Treatment Assignment Procedures ....................................................................... 29 
5.4.1 Randomization Procedures (if applicable) ................................................. 29 
5.4.2 Masking Procedures (if applicable) ............................................................ 29 
5.5 
Subject Withdrawal ............................................................................................... 29 
5.5.1 Reasons for Withdrawal ............................................................................ 30 
5.5.2 Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention ............................................................................................... 30 
5.6 
Premature Termination or Suspension of Study .................................................... 30 
6 
STUDY INTERVENTION .................................................................................................. 31 
6.1 
Study Behavioral or Social Intervention(s) Description .......................................... 31 
6.2 
Administration of Intervention ................................................................................ 32 
6.3 
Procedures for Training Interventionists and Monitoring Intervention Fidelity ........ 32 
6.4 
Assessment of Subject Compliance with Study Intervention ................................. 33 
7 
STUDY SCHEDULE ......................................................................................................... 34 
7.1 
Screening ............................................................................................................. 34 
7.2 
Enrollment/Baseline .............................................................................................. 34 
7.3 
Intermediate Visits ................................................................................................ 35 

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7.4 
Final Study Visit .................................................................................................... 38 
7.5 
Withdrawal Visit .................................................................................................... 38 
7.6 
Unscheduled Visit ................................................................................................. 39 
8 
STUDY PROCEDURES/EVALUATIONS ......................................................................... 40 
8.1 
Study Procedures/Evaluations .............................................................................. 40 
9 
ASSESSMENT OF SAFETY ............................................................................................ 42 
9.1 
Specification of Safety Parameters ....................................................................... 42 
9.1.1 Unanticipated Problems ............................................................................ 42 
9.1.2 Adverse Events ......................................................................................... 42 
9.1.3 Serious Adverse Events ............................................................................ 42 
9.2 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 43 
9.3 
Characteristics of an Adverse Event ..................................................................... 43 
9.3.1 Relationship to Study Intervention ............................................................. 43 
9.3.2 Expectedness of SAEs .............................................................................. 43 
9.3.3 Severity of Event ....................................................................................... 44 
9.4 
Reporting Procedures ........................................................................................... 44 
9.4.1 Unanticipated Problem Reporting to IRB and NIDCR ................................ 44 
9.4.2 Serious Adverse Event Reporting to NIDCR.............................................. 45 
9.4.3 Reporting of SAEs and AEs to FDA .......................................................... 45 
9.4.4 Events of Special Interest (if applicable) .................................................... 46 
9.4.5 Reporting of Pregnancy ............................................................................. 46 
9.5 
Halting Rules ........................................................................................................ 46 
10 
STUDY OVERSIGHT ....................................................................................................... 47 
11 
CLINICAL SITE MONITORING ........................................................................................ 48 
12 
STATISTICAL CONSIDERATIONS .................................................................................. 49 
12.1 
Study Hypotheses ................................................................................................. 49 
Primary Objective: To compare children’s physiological anxiety (EDA - primary 
outcome) during the dental cleaning in SADE vs. RDE. ........................................ 49 
12.2 
Sample Size Considerations ................................................................................. 49 
12.3 
Planned Interim Analyses (if applicable) ............................................................... 50 
12.3.1 Safety Review ........................................................................................... 50 
12.3.2 Efficacy Review ......................................................................................... 50 
12.4 
Final Analysis Plan ............................................................................................... 50 
13 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................. 53 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................ 54 
15 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 55 
15.1 
Ethical Standard ................................................................................................... 55 
15.2 
Institutional Review Board .................................................................................... 55 
15.3 
Informed Consent Process ................................................................................... 55 
15.4 
Exclusion of Women, Minorities, and Children (Special Populations) .................... 56 
15.5 
Subject Confidentiality .......................................................................................... 56 
15.6 
Future Use of Stored Specimens and Other Identifiable Data ............................... 57 

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16 
DATA HANDLING AND RECORD KEEPING ................................................................... 58 
16.1 
Data Management Responsibilities ....................................................................... 58 
16.2 
Data Capture Methods .......................................................................................... 58 
16.3 
Types of Data ....................................................................................................... 59 
16.4 
Schedule and Content of Reports ......................................................................... 59 
16.5 
Study Records Retention ...................................................................................... 59 
16.6 
Protocol Deviations ............................................................................................... 59 
17 
PUBLICATION POLICY ................................................................................................... 61 
18 
LITERATURE REFERENCES .......................................................................................... 62 
LIST OF APPENDICES ............................................................................................................ 70 
 

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LIST OF ABBREVIATIONS 
 
ADL 
Activities of Daily Living 
ADOS-2 
Autism Diagnostic Observation Scale, 2nd ed. 
AE 
Adverse Event/Adverse Experience 
ASD 
Autism Spectrum Disorder 
CASI-Anx 
Child and Adolescent Symptom Inventory-4, Anxiety Scale 
CDBRS 
Children’s Dental Behavior Rating Scale 
CHLA 
Children’s Hospital of Los Angeles 
CMP 
Clinical Monitoring Plan 
Co-I 
Co-Investigator 
CRIC 
California Cancer Research Informatics Core  
CRF 
Case Report Form 
CROMS 
Clinical Research Operations and Management Support 
CSOC 
Clinical Study Oversight Committee 
CFSS-DS 
Childhood Fear Survey Schedule, Dental Subscale 
DHHS 
Department of Health and Human Services 
DSSS 
Dental Sensory Sensitivity Scale 
eCRF 
Electronic Case Report Form 
EDA 
Electrodermal activity 
FPS-R 
Faces Pain Scale - Revised 
GCP 
Good Clinical Practice 
GI 
Gingival Index 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
LAUSD 
Los Angeles Unified School District 
MCDASf 
Modified Child Dental Anxiety Scale, faces version 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 
NIDCR 
National Institute of Dental and Craniofacial Research 
NIH 
National Institutes of Health 

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NS-SCR 
Non-Specific Skin Conductance Response (reported as frequency per 
minute) 
OCTOM 
Office of Clinical Trials Operations and Management 
OHI-S 
Oral Hygiene Index - Simplified 
OHRP 
Office for Human Research Protections 
OS-OT 
Occupational Science and Occupational Therapy 
PI 
Principal Investigator 
RDE 
Regular Dental Environment 
SADE 
Sensory Adapted Dental Environment 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SCL 
Skin Conductance Level 
SOP 
Standard Operating Procedure 
SSP 
Short Sensory Profile-2 
 
 
UCEDD 
USC University Center for Excellence in Developmental Disabilities 
UP 
Unanticipated Problem 
US 
United States 
USC 
University of Southern California 
VABS-II 
Vineland Adaptive Behavior Scales, 2nd Edition; Expressive 
Communication Domain 
WASI-II 
Wechsler Abbreviated Scale of Intelligence- second edition 
 
 
 

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PROTOCOL SUMMARY 
 
 
Title: 
Sensory Adapted Dental Environments to Enhance Oral Care for 
Children (SADE-2 Study) 
Précis: 
This study is a randomized clinical trial investigating the efficacy of a 
sensory adapted dental environment (SADE) compared to a 
regular dental environment (RDE) to decrease physiological anxiety, 
distress behavior, perception of pain, and discomfort during a dental 
cleaning in children. The SADE procedure modifies the degree and 
type of visual, auditory, and tactile stimulation that children 
experience during dental cleanings. In this crossover design, the 
SADE will be compared to a RDE in a group of children with 
Autism Spectrum Disorder (ASD) with visits occurring four-six 
months apart. The outcome variables are physiological anxiety as 
measured by electrodermal activity (EDA) and child negative 
responses (distress behavior, perception of pain, sensory 
discomfort) exhibited by the child during dental cleaning visits. 
Analyses will include repeated measures ANCOVA models to 
examine the differences in the within-group factor (environment) in 
the ASD groups. 
Objectives 
1. Primary Objective: To compare children’s physiological anxiety 
(EDA - primary outcome) during the dental cleaning. 
 
2. Secondary Objectives: 
(a) To compare children’s negative behavioral responses 
(behavioral distress, perception of pain, sensory discomfort - 
secondary outcomes) during dental cleanings. 
(b) To test the degree to which physiological anxiety mediates 
the SADE intervention's effects on children's negative 
behavioral responses. 
(c)  To test the degree to which specific child characteristics 
moderate the SADE intervention's effects on children's 
physiological and negative behavioral responses during 
dental cleaning. 
(d)  To compare the SADE intervention to the RDE on quality of 
care, cost-effectiveness, and potential cost savings of dental 
cleaning. 
 
   
Population: 
Participants will be 220 ethnically diverse children with ASD aged 6-
12 years. All children will be Southern California residents. 
Participants will be recruited primarily from Children’s Hospital Los 
Angeles (Dental Clinic, University Center for Excellence in 
Developmental Disabilities, Boone Fetter Clinic, AltaMed General 

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Pediatrics Service) and the Los Angeles Unified School District 
(LAUSD), so the sample in this study will likely over-represent low 
income Hispanic/Latino families who are at high risk for poor oral 
health. Consistent with ASD prevalence statistics, we anticipate a 
ratio of approximately four boys for every girl in the sample.  
 
Phase: 
Clinical Phase II 
Number of Sites: 
One site:  Children’s Hospital of Los Angeles, Dental Clinic 
Description of  
Intervention: 
The SADE intervention consists of physical adaptations to the dental 
cleaning space meant to create a less anxiety-provoking sensory 
experience. Visual, auditory, and tactile stimuli will be altered in the 
SADE. (For more details, see Table 3, Section 6.1.) 
Study Duration: 
Approximately 60 months 
Subject Participation 
Duration: 
Approximately nine-fifteen months per subject 
Estimated Time to 
Complete 
Enrollment: 
40-44 months 
 

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SCHEMATIC OF STUDY DESIGN  
 
Prior to  
Enrollment 
(Day -90 to -1) 
 
 
 
Time Point  
Study Visit 1 
(Day 0) 
 
 
 
 
Time Point  
Study Visit 2 
(Day 1-30) 
 
 
 
 
 
 
 
 
Time Point  
Study Visit 3 
(Day 5-95) 
 
Time Point  
Final Visit 
(Day 125-215) 
 
   
 
 
  
 
 
 
 
 
 
* Complete first dental cleaning (Arm 1- SADE; Arm 2- RDE) 
(Videotape and record EDA throughout dental cleaning, pre- and post-cleaning intraoral photos, OHI-S, 
GI, Plaque Index, Anxiety and Cooperation Scale, Frankl Scale, DSSS, FPS-R) 
 Projection 
Randomize (to order of cleaning) n=180 
Total N=220 children with ASD:  Screen potential subjects by inclusion and 
exclusion criteria; obtain history, document. 
*Arm 1: SADE first 
n=90  
 
Perform baseline assessments (home visit). 
Obtain consent (and assent if appropriate).  
Parent-questionnaire completion: demographics, SSP-2, CFSS-DS, CASI-Anx, etc. If 
appropriate, child-questionnaire completion: CFSS-DS, MCDASf.  
Confirmation of ASD diagnosis (ADOS-2), IQ 
testing (WASI-II). 
*Arm 2: RDE first 
n=90 
 
Final Analyses: Code videotape with 
CDBRS, code EDA variables, # hands 
required, need for restraint, quality of 
cleaning (intraoral photos) 
Arm 1: RDE second 
n=90  
 
Arm 2: SADE second 
n=90 
 

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1 KEY ROLES AND CONTACT INFORMATION 
 
Principal 
Investigator:   
Principal Investigator:   
Sharon A. Cermak, EdD, OTR/L, FAOTA.  
Professor of Occupational Science and Occupational Therapy. 
University of Southern California 
Center for Health Professions (CHP) #133 
Los Angeles, CA 90089  
Phone #: 323-442-2879 (work); 310-433-4131 (mobile) 
Fax #: 323-442-1540 
Email: cermak@usc.edu 
Medical Monitor: 
TBN 
National Institute of Dental and Craniofacial Research 
6701 Democracy Blvd., Room 634, MS 4878 
Bethesda, MD 20892-4878 
 
NIDCR Program 
Officials:   
 
Elise Rice, PhD 
Program Officer 
Behavioral and Social Sciences Research Program 
National Institute of Dental and Craniofacial Research 
6701 Democracy Blvd., MSC 4878 
Bethesda, MD 20892-4878 
Phone: (301) 594-4814 
Email: elise.rice@nih.gov 
 
Melissa Riddle, PhD 
Scientific Project Officer 
Behavioral and Social Sciences Research Branch 
National Institute of Dental and Craniofacial Research 
6701 Democracy Blvd., Room 648, MS 4878 
Bethesda, MD 20892-4878 
Phone: (301) 451-3888 
Fax: (301) 480-8319 
Email: riddleme@mail.nih.gov 
 
Clinical Site 
Investigators: 
José Polido, DDS., MS, (Co-Investigator) 
Chief, Division of Dentistry and Orthodontics at Children’s Hospital 
Los Angeles, Dental Clinic 
4650 Sunset Boulevard, Mail Stop #116 
Los Angeles, CA 90027 
Clinic Phone #: 323-361-2130 
Clinic Fax #: 323-361-1090 
Email: jpolido@chla.usc.edu 
 
 

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Leah Stein Duker, PhD, OTR/L (Co-Investigator) 
Research Assistant Professor 
University of Southern California 
Center for Health Professions (CHP) #133 
Los Angeles, CA 90089  
Phone #: 323-442-0371 (work) 
Fax #: 323-442-1540 
Email: lstein@usc.edu 
  
Institutions: 
Clinical site: 
Children’s Hospital Los Angeles, Dental Clinic 
4650 Sunset Boulevard, Mail Stop #116 
Los Angeles, CA 90027 
Contact Person: José Polido (Co-I) 
Clinic Phone #: 323-361-2130 
Clinic Fax #: 323-361-1090 
Email: jpolido@chla.usc.edu 
 
Data processing and analysis sites:  
University of Southern California, Health Sciences Campus 
Center for Health Professions (CHP) #222 
Los Angeles, CA 90089 
Contact Person: Sharon Cermak (PI) or Leah Stein Duker (Co-
Investigator) 
Phone #: 323-442-2879 (Cermak); 323-442-1837 (Stein Duker) 
Fax #: 323-442-1540 
Email: cermak@usc.edu or lstein@usc.edu  
 
University of Southern California, Health Sciences Campus, 
Cancer Research Informatics Core (CRIC) 
Norris Research Tower Lg507 
Los Angeles, CA 90089 
Contact Person: Reed Comire (Database Manager & Director of 
CRIC) 
Phone #: 323-442-7718 
Email: comire_r@med.usc.edu 
 
University of Southern California, Health Sciences Campus, 
Center for Health Professions (CHP) Building (Biostatistics) 
1540 Alcazar Street, CHP 133  
Los Angeles, CA 
Contact person: Cheryl Vigen, PhD (Co-Investigator) 
Phone #: 323-442-2749 
Fax #: 323-442-1540 
Email: vigen@usc.edu 
 
 

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Other Key 
Personnel: 
 
Biostatistician 
Cheryl Vigen (Co-Investigator) 
University of Southern California, Health Sciences Campus, 
Center for Health Professions (CHP) Building (Biostatistics) 
1540 Alcazar Street, CHP 133  
Los Angeles, CA 
Phone #: 323-442-2749 
Fax #: 323-442-1540 
Email: vigen@usc.edu 
 
Database Management 
Reed Comire (Database Manager) 
Cancer Rehabilitation Informatics Core 
University of Southern California, Health Sciences Campus 
Norris Research Tower LG507 
Los Angeles, CA 90089 
Phone #: 323-442-7718 
Email: comire_r@med.usc.edu  
 
Institutional Review Board  
Children’s Hospital Los Angeles, Committee on Clinical 
Investigations 
Mail Stop #23 
Los Angeles, CA 90027 
Contact Person: Dongqing Li (IRB Administrator) 
Phone #: 323-361-6023 
Email: dli@chla.usc.edu  
 
Institutional Review Board 
University of Southern California Health Sciences 
LAC+USC Medical Center 
1200 North State Street 
Los Angeles, CA  90033 
Contact Person: Marie Reyes (IRB Administrator) 
Phone #: 323-276-2225  
Email: marierey@usc.edu  
 

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2 INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
 
This randomized clinical trial, entitled Sensory Adapted Dental Environments to Enhance 
Oral Care for Children (SADE-2 Study), is a follow up of our R34 pilot study, Sensory Adapted 
Dental Environments to Enhance Oral Care for Children with Autism (1R34DE022263-01). We 
propose to examine the efficacy of a sensory adapted dental environment to decrease 
physiological anxiety and negative responses (distress behavior, perception of pain, sensory 
discomfort) in children with autism spectrum disorders (ASD), many of whom have dental 
anxiety and/or sensory over-responsivity. Many of our subjects will have unmet dental needs, 
either from the conditions mentioned above or because our recruiting sources over-represent 
low income, Latino families who are reported to have greater challenges in accessing care. 
Children with disabilities are almost twice as likely to suffer from unmet oral health care 
needs than their peers without disabilities,1 and consequently have an increased risk and 
prevalence of dental disease.2,3  Children with ASD, a condition characterized by impaired 
social-communication and social interaction, and restricted, repetitive patterns of behavior, 
interests or activities,4 represent one such special population at high risk.5,6 In fact, a large 
number of studies indicate that children with ASD exhibit a high incidence of poor oral health, as 
measured by caries prevalence and severity,2,5-9 although there are a small number of 
contradictory studies.10-12 The prevalence of ASD is significantly higher today than in the past, 
estimated in 2014 to be approximately 1 in 68 children in the US.13 Therefore, dentists are 
increasingly likely to encounter children with ASD in their practices. 
 
One factor that may contribute to oral care challenges in children with ASD is sensory 
over-responsivity14 characterized by behavioral responses that are out of proportion to the type 
or amount of stimulation. These responses may include physical withdrawal, vocal outbursts, 
aggressive behaviors, tantrums, or attempts to block incoming stimulation.15,16 Although the 
mechanisms underlying sensory processing disorders are not fully understood,17-20 such 
problems are highly prevalent in the ASD population.21-25 Up to 95% of children with ASD 
demonstrate significantly different sensory behaviors than their TD counterparts, and 61% 
specifically exhibit tactile over-responsivity symptoms as evidenced by difficulty tolerating 
grooming and hygiene tasks.26  
 
Exacerbation of sensory over-responsivity in the dental office can result from exposure 
to bright lights, loud or high-pitched noises, reclining in the dental chair, repeated touch in and 
around the mouth, and the texture, taste, and smell of various oral care products. In a survey of 
196 parents of children with ASD, up to 70% of parents reported that their child experienced 
difficulty with each of these sensory variables in the dental office, with the greatest difficulty 
being instruments in the mouth (70%).27 In this study, almost 50% of parents of children with 
ASD strongly agreed that their child’s sensory over-responsivity made visits to the dentist more 
challenging. Additionally, children with ASD with sensory over-responsivity, compared to 
children with ASD without sensory over-responsivity, exhibited a significantly greater prevalence 
of oral care difficulties in the home and dental office.28 In focus groups that we conducted, 
parents reported reluctance to return to the dentist because of their child’s negative 
experiences. For example, one parent stated that “The first time we took him to the dentist, 
when I heard him screaming for me from the front, I kind of understood how bad this was…there 
was like several people trying to restrain him. They had him in restraints and my wife [in the 
room with him] was in tears…because of that experience we were extremely hesitant to take 
him back.” 

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The proposed SADE-2 intervention modifies the sensory characteristics of the dental 
environment. It does so by altering the degree and type of visual, auditory, and tactile 
stimulation that children experience during dental treatment by reducing the lighting, providing 
soothing sounds, and applying deep pressure input to the child during a dental cleaning. Our 
hypothesis is that these changes will reduce physiological anxiety, negative behavior, pain, and 
sensory discomfort, and enhance cooperation to enable thorough and effective oral care. 
 
The proposed study attempts to replicate and extend Shapiro et al.’s previous work49-51 
with children with developmental disabilities (not including ASD) in Israel, in which a sensory 
adapted dental environment resulted in shorter duration of negative behaviors and greater 
relaxation during treatment as measured by electrodermal activity (EDA), which assesses the 
sympathetic “fight or flight” system. Results from our R34 pilot study examined differences in 
children’s physiological responses in the two intervention conditions (sensory adapted 
environment, SADE, and a regular dental environment, RDE), finding that measures of 
electrodermal activity were lower (i.e. children were more relaxed) in the SADE. When 
examining the behavioral and survey measures, outcomes were in the hypothesized direction 
with primarily small effects (less uncooperative distress behavior, reduced perception of pain, 
and less sensory discomfort in the SADE vs. RDE). However, our R34 study was designed as a 
pilot study and therefore not powered to detect differences between the two dental 
environments. The preliminary positive benefit of the sensory adapted dental environment found 
in children with ASD warrants a large-scale trial to appropriately power the study and enable 
examination of moderating and mediating variables.   
 
In the proposed U01, we will test the effects of the SADE in a larger group of children 
with ASD to examine intervention efficacy and possible mediating and moderating factors. Our 
sample will be ethnically diverse, with more than 50% of the sample underserved, low income 
Latino children. 
 
The development of a modified dental environment may help pediatric dentists, general 
dentists, and dental hygienists reduce common behavioral challenges that occur in treating 
children receiving treatment at the dental office. Because general dentists indicate that behavior 
problems are the greatest barrier treating children with disabilities,52 decreasing children’s 
distress behaviors may increase dentists' willingness to treat children with ASD and other 
children who are difficult to treat, thereby contributing to a reduction in health disparities. 
Treatment may also become more efficient and cost effective. If the child is more cooperative, 
the dentist may be able to complete a more thorough cleaning and better preventive care. 
Safety would also increase as the need for restraint (e.g., protective stabilization provided by a 
papoose board) and/or pharmacological intervention (e.g., nitrous oxide, general anesthesia) 
decreases. Research currently indicates that restraint is utilized with children with ASD 18-33% 
of the time, significantly more than with TD children (1%).27,53 In a survey study conducted by 
our team, 18% of children with ASD without sensory over-responsivity required restraint often or 
almost always for dental care, compared to 38% of children with ASD with reported sensory 
over-responsivity.54 Finally, as ease of cleanings improves, parents may be more likely to bring 
their child to the dentist for routine oral care, which would impact public health.  
 
2.1 
Rationale 
We will be testing a protocol (SADE) that has the potential to change dental clinical 
practice paradigms by altering the degree and type of visual, auditory, and tactile stimulation 
that children experience during dental treatment. Our enhanced environment will reduce the 

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lighting, provide soothing sounds, and apply deep pressure input to the child during a dental 
cleaning. Although the literature clearly documents that sensory over-responsivity is often 
present in children with ASD and our R34 pilot study demonstrated feasibility of clinic-based 
solutions, a randomized clinical trial is now needed to examine our preliminary findings with a 
sufficiently powered study. The SADE draws on (a) the techniques of the Snoezelen, or 
multisensory environmental approach,55-59 and (b) principles of sensory integration theory and 
research.60-61 In both of these approaches, the arrangement and intensity of sensory stimulation 
are modified.59,62  We hypothesize that in the SADE environment, children with ASD will 
have reduced physiological anxiety and negative responses (distress behavior, 
perception of pain, sensory discomfort), allowing for a more efficacious dental cleaning 
visit.  
Because the prevalence of ASD has risen dramatically in recent years,13 it is imperative 
to identify innovative solutions that enable dentists to more readily perform standard clinic-
based procedures for these children. In the proposed study, we will respond to this need by 
attempting to create an environment that prevents or reduces anxiety and negative behaviors 
during oral care in a real life context. Green and Flanagan63 discuss the challenges that stem 
from maladaptive behaviors and emphasize that successful patient management involves 
creating an atmosphere that prevents these behaviors.  
 
2.2 
Potential Risks and Benefits 
 
2.2.1 
Potential Risks 
This study will take the utmost precaution to ensure the welfare of the subjects. This 
study is a conceptual replication and extension of Shapiro et al.’s previous work with children 
with developmental disabilities (other than ASD) in Israel in which no immediate or long-range 
adverse events were reported as a result of the study intervention.49-51 This was verified through 
personal conversation with Dr. Shapiro who was a consultant on the R34 grant. Additionally, in 
our R34 SADE pilot study (n=44 children; n=22 ASD, n=22 typically developing), there were no 
unanticipated problems or adverse events.  
For the current study, risks from dental cleaning using SADE are similar to traditional 
dental visits (e.g., gingival bleeding, mild discomfort). Additional risks related to the study 
include the possibility of: (1) Feeling uncomfortable answering some research-related 
survey questions or being videotaped. Neither of these potential risks were a problem in the 
R34 SADE pilot study; however, if subjects or their parents feel uncomfortable answering some 
questions they may choose to not answer that question. If subjects or their parents feel 
uncomfortable being video-recorded, they can ask the researchers to stop the recording.         
(2) Potential loss of confidentiality. Likewise, this was not a problem in the R34 SADE pilot 
study. This issue will be addressed by strictly identifying video-recordings and accompanying 
surveys by an identification number. All videotapes and surveys will be stored at the University 
of Southern California in a secure file with the understanding that only those persons involved in 
the study will have access to this data. (3) Skin Irritation. We will be using the BIOPAC MP150 
System from BIOPAC Systems, Inc. (Goleta, California) to collect physiological data 
(electrodermal activity) from human subjects. We will be using BIOPAC EL507 electrodes 
(silver-silver chloride electrodes with isotonic gel) placed on the tips of the second and third 
digits of the participant’s non-dominant hand and secured with non-stick medical tape. Sensors 
will be attached using standard laboratory procedures; however, some participants may 
experience skin irritation from the conductance gel used in the sensors. This clears up quickly 

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after the sensors and the gel are removed. We previously utilized this system in our R34 pilot 
study with no reports of injury, skin irritation, or other adverse reactions to the electrodes, gel, or 
tape. Additionally, BIOPAC Systems, Inc. has tested the MP150 System to applicable medical 
device standards, even though, strictly considered, the MP150 is not a medical device. The 
applicable standards for medical safety requirements are determined by IEC 60601-1 and the 
applicable standards for electromagnetic compatibility requirements are determined by IEC 
60601-1-2 (Self-Declaration of Conformity, BIOPAC Systems, Inc., 2011; 
http://www.biopac.com/Corporate.asp?Index=1). (4) EDA fear.  Children may also feel 
uncomfortable having electrodes applied to their fingers. We will minimize children’s discomfort 
by showing the electrodes to the participants as part of a home visit prior to the dental cleaning 
and by providing the children with a social story that shows electrode application. (5) Butterfly 
Vest. There is a possibility that the butterfly vest could inadvertently induce anxiety in our child 
participants. We will address this concern as follows: 
a) The purpose of the butterfly vest is to provide deep touch pressure, which has been 
found by many individuals to be calming and/or relaxing, as described by Temple 
Grandin, an adult with high functioning autism.78 It should also be noted that the butterfly 
vest was not designed to achieve protective stabilization, although we recognize that it 
does so. As such, we will take every precaution taken with protective stabilization 
procedures as described in the Clinical Guidelines for Protective Stabilization for 
Pediatric Dental Patients.79 and adhere to the Guidelines on Behavior Guidance for the 
Pediatric Dental Patient.80 
b) The butterfly vest has been pilot tested fairly extensively in the dental clinic.49,50,81 These 
studies include: (i) our own work with 22 children with ASD and 22 typically developing 
children,81 and (ii) a study by Shapiro et al.50 involving 16 children with developmental 
disability (not ASD) and 16 typically developing children. Among these 76 participants 
who utilized a butterfly vest, only two children were initially apprehensive about using the 
vest. The typically developing child was given the option of not wearing it, but 
nonetheless chose to do so. The child with ASD had recently had a negative experience 
with a papoose board (based on parent report), but later requested the “butterfly hug” 
during the dental cleaning, at which point we closed the wings. Both these reactions 
suggest that the risk of the butterfly vest inducing anxiety or causing traumatization of 
the participant is low. Additionally, in our pilot study, many parents commented informally 
that they really liked the vest and that their child liked the vest, and wondered out loud 
why other dentists didn’t use something similar.   
c) Weighted vests, which also utilize the principle of deep touch pressure (as does the 
butterfly vest), have been used extensively by occupational therapists to treat children 
with sensory processing disorders,82 with a review indicating that side effects and risks 
are minimal.83  
d) The parent is in the dental operatory with the child. Either the parent or the child may 
request discontinuation of any or all components of the intervention at any time during 
the dental cleaning. Additionally, in no instance will children be required to continue with 
the intervention (including use of the butterfly vest) if any serious reaction is noted.  

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Despite the fact that the available evidence 
supports the safety of the butterfly vest, we will 
enact the following precautionary strategies: 
a) We will hire a special project consultant with 
expertise in the area of anxiety reactions in 
children to evaluate safety issues pertaining to 
the use of the vest (as well as safety issues 
pertaining to other intervention components). 
b) As in the pilot study, any child or parent will 
have the option of refusing any element of the 
intervention. All refusals will be documented.  
 
Figure 1. The butterfly vest with wings that wrap around (hug) the child. 
c) We will enact a sequential procedure, for each research participant undergoing the 
SADE that consists of: (1) prior to the treatment, explaining each component of the 
intervention (both through a social story and verbally) and getting the child’s assent 
(when able); (2) requiring the research team to monitor any negative reactions to the 
SADE adaptations; and (3) having the dental assistant or dentist remove or minimize 
offending stimuli that emerge during the above steps (or terminate cleaning if 
necessary).  
d) The study will have a data safety monitoring committee (CSOC) which will review all 
adverse events in an effort to ensure the welfare of all research participants.  
e) During the time of the COVID-19 pandemic, participants are at a small risk of contracting 
the virus when they leave their home and come to CHLA. CHLA has launched extensive 
protective measures to prevent the spread of the novel coronavirus and keep patients, 
families and team members safe. 
2.2.2 
Potential Benefits 
Direct benefits for the child participant are two dental cleanings (oral exam, prophylaxis, 
and fluoride application) provided with no out-of-pocket costs. Additionally, scheduling both 
dental visits will occur with a minimal wait time (currently the dental clinic has a wait of 
approximately 8 or more months for scheduling a routine cleaning for a returning or new 
patient). Moreover, dental treatment in the SADE condition may prove more calming to children 
than in the regular dental environment. 
The potential indirect long-term benefits of this study include contributing to knowledge 
of factors that reduce physiological anxiety and negative responses during dental cleanings, and 
help children who are anxious or fearful at the dentist. Findings from this study may contribute to 
safer, more efficient, and less costly treatment for both children with ASD as well as TD children 
with dental anxiety and/or sensory over-responsivity.  

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3 OBJECTIVES 
 
3.1 
Study Objectives 
 
Primary Objective: To compare children’s physiological anxiety (EDA - primary outcome) 
during the dental cleaning in the SADE vs. RDE. 
 
Secondary Objectives: 
a) To compare children’s negative behavioral responses (behavioral distress, perception of 
pain, sensory discomfort - secondary outcomes) during dental cleanings in the SADE vs. 
RDE. 
b) To test the degree to which physiological anxiety mediates the SADE intervention's 
effects on children's negative behavioral responses. 
c) To test the degree to which specific child characteristics moderate the SADE 
intervention's effects on children's physiological and negative behavioral responses 
during dental cleaning.  
d) To compare the SADE intervention to the RDE on quality of care, cost-effectiveness, 
and potential cost savings of dental cleaning. 
 
 
3.2 
Study Outcome Measures  
3.2.1 
Outcome Measures for the Primary Objective 
 
Our primary outcome measure is children’s physiological response measured by EDA during 
the dental cleaning. EDA will be measured using the BIOPAC Systems, Inc. MP150 System. 
This physiological response is caused by sympathetic nervous system activation, which 
increases during stressful or painful situations.64 Sensors will be placed on the child’s fingers 
and EDA recordings will be made immediately prior to and continuously throughout each 
cleaning. Two measures of tonic EDA will be collected: skin conductance level (SCL) and 
frequency of non-specific skin conductance responses (NS-SCR). See Table 1. 
 
 
 
 
 
 
 
 
 

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Table 1. Primary outcome measure of children’s physiological responses for the SADE-2 Study. 
 
Outcome 
measure 
(Completed by) 
Measure & Description 
Type of 
Measure  
(No. of Items) 
When 
Administered 
Specific 
Objective 
Tested 
CRF Name (#) 
Physiological 
Anxiety 
(Researcher-
coded) 
Electrodermal Activity 
(skin conductance level 
and frequency of non-
specific responses) 
assesses level of 
sympathetic nervous 
system activation.  
Psycho-
physiological 
(N/A: scoring 
is continuous 
throughout 
recording) 
Recorded at 
baseline and 
throughout 
both dental 
cleanings. 
1 
Scored EDA Form 
(23) 
 
3.2.2 
Outcome Measures for the Secondary Objectives  
 
Our secondary outcome measures will consist of five behavioral indicators of distress 
(observational coding of behavioral distress from video-recordings, dentist-reported measures of 
child anxiety and cooperation, child self-report of pain, and child self-report of discomfort with 
sensory stimuli), measures of mediating factors, measures of moderating factors, and measures 
of cost-savings and quality of care.  
 
Secondary Objective (a): Negative Behavioral Responses 
Distress Behavior will be measured by video-coding of child’s behavior during the 
cleaning and coded by the researcher using the Children’s Dental Behavior Rating 
Scale, and dentist-report (Frankl Scale and Anxiety and Cooperation Scale). The 
Children’s Dental Behavior Rating Scale (CDBRS) was developed and pilot-tested prior 
to the initiation of our previous R34 pilot study, and was found to have inter-rater 
reliability on children both with and without ASD, K=.97, p<.001.81 The Frankl Scale67 is 
one of the most commonly used rating scales to assess children’s behavior in the dental 
office84 and is universally utilized by both researchers and clinicians.85 The scale has 
high inter-rater reliability and acceptable validity,84 and has been shown to significantly 
correlate with other behavioral indices that are used to assess anxiety and behavior 
during dental treatment.86 The Anxiety and Cooperation Scale87 assesses children’s 
anxiety, fear, and cooperation as rated by dentists and has established reliability and 
validity.88  
 
Perception of Pain will be measured by child self-report utilizing the Faces Pain Scale-
Revised (FPS-R),68 which has established validity and is supported by a high positive 
correlation with a visual analogue scale in children aged 5 to 12 years.68  
 
Discomfort with sensory stimuli will be measured by child self-report utilizing the 
Dental Sensory Sensitivity Scale. This tool was developed and pilot-tested alongside the 
CDBRS, and in our pilot study was sensitive to differences between the SADE and RDE 
in the ASD group (effect size = .69, p<.05).81 
 
 

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Secondary Objective (b): Mediating Factors 
Outcome measures include physiological anxiety (EDA) as a mediator of negative 
behavior (for EDA details see above Section 3.2.1).  
Secondary Objective (c): Moderating Factors 
To test the effect of child characteristics as moderators of SADE, outcome measures will 
include age, autism severity, cognitive ability, sensory sensitivity, and anxiety. 
Secondary Objective (d): Cost-Savings and Quality of Care 
Outcome measures include relative cost of services provided (time to complete 
cleaning, number of staff required, anesthesia required), ascertained by videotaped 
encounters. Efficacy of dental cleaning will be assessed via coded observations of 
plaque index before and after dental cleanings, coded from images captured via 
intraoral camera.  
Table 2. Secondary outcome measures of the SADE-2 Study. 
 
Outcome 
measure 
(Completed by) 
Measure & Description 
Type of 
Measure  
(No. of Items) 
When 
Administered 
Specific 
Objective 
Tested 
CRF Name (#) 
Distress 
Behavior  
(Researcher-
coded from 
video-recording) 
Children’s Dental 
Behavior Rating Scale, 
a psychometrically 
sound tool developed for 
our R34 pilot study that 
assesses overt distress 
behavior.  
Observational: 
Coding of 
video-
recordings  
(5 items, each  
scored the first 
5 minutes of 
prophylaxis) 
Video-
recordings 
occur during 
both dental 
cleanings; 
coding occurs 
at a later time. 
2a 
Children’s Dental 
Behavior Rating 
Scale (22) 
Distress 
Behavior 
(Anxiety and 
Cooperation) 
(Dentist-report) 
Anxiety and Cooperation 
Scale,65 a reliable and 
valid tool for use during 
dental cleaning to 
assess anxiety and 
cooperation.66 
Questionnaire 
(1) 
Immediately 
following both 
dental 
cleanings. 
2a 
Behavioral 
Indices Form (14) 
Distress 
Behavior 
(Uncooperative 
Behavior) 
(Dentist-report) 
Frankl Scale,67 a reliable 
and valid tool for use 
during dental cleaning to 
assess behavior. 
Questionnaire 
(1) 
Immediately 
following both 
dental 
cleanings. 
2a 
Behavioral 
Indices Form (14) 
Perception of 
Pain 
(Child-Report) 
Faces Pain Scale-
Revised,68 a valid tool 
comprised of six faces 
to assess perception 
and intensity of pain. 
Questionnaire 
(1) 
Immediately 
following both 
dental 
cleanings. 
2a 
Faces Pain 
Scale-Revised 
(17) 

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Discomfort with 
Sensory Stimuli 
(Child-Report) 
Dental Sensory 
Sensitivity Scale 
describes the presence 
and magnitude of 
discomfort with different 
sensory stimuli in the 
dental environment.  
Questionnaire 
(6) 
Immediately 
following both 
dental 
cleanings. 
2a 
Dental Sensory 
Sensitivity Scale 
(18) 
Cost-Savings 
(Researcher-
scored) 
Duration of dental 
cleaning, calculated 
from video-recordings 
and notes. 
Observational  
(1) 
Immediately 
following both 
dental 
cleanings. 
2d 
Cost-
Effectiveness & 
Cost-Savings 
Form (21) 
Cost-Savings 
(Researcher-
scored) 
Number of hands 
required for restraint, 
calculated from video-
recordings and notes. 
Observational  
(1) 
Immediately 
following both 
dental 
cleanings. 
2d 
Cost-
Effectiveness & 
Cost-Savings 
Form (21) 
Cost-Savings 
(Researcher-
scored, in 
consultation with 
dentist) 
Need for protective 
stabilization, sedation, 
and/or anesthesia to 
complete cleaning. 
Observational 
(1) 
Immediately 
following both 
dental 
cleanings. 
2d 
Cost-
Effectiveness & 
Cost-Savings 
Form (21) 
Quality of Care 
(Dentist-scored) 
Analysis of oral health 
and plaque before 
cleaning versus after 
cleaning using intra-oral 
photographs 90 
(Rechmann et al., 2014) 
utilizing the Oral Health 
Index-Simplified68 and 
Plaque Index.70  
 
Observational, 
completion of 
OHI-S (12) 
and PIaque 
Index (6) 
based on 
intra-oral 
photographs. 
Intra-oral 
photographs 
taken before 
and after 
dental 
cleaning; 
scoring to be 
completed at a 
later time. 
2d 
Quality of Care 
Recording Form 
(16) 

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Table 3. Child-descriptor variables 
 
Child-
descriptor 
(Completed by) 
Child-descriptor & 
Description 
Type of form 
(No. of Items) 
When 
Administered 
Specific 
Objective 
Tested 
CRF Name (#) 
ASD Diagnosis 
(Psychologist) 
The Autism Diagnostic 
Observation Schedule-2 
(ADOS-2) is used to 
confirm a diagnosis of 
ASD and provides a 
measure of autism 
severity.    
 Observational 
(varies) 
 Visit 2  
2c 
Autism 
Diagnostic 
Observation 
Schedule-2 
 IQ 
(Psychologist) 
Wechsler Abbreviated 
Scale of Intelligence – 
Second Edition provides 
a measure of IQ 
Observational 
(varies) 
Visit 2 
2c 
Wechsler 
Abbreviated 
Scale of 
Intelligence – 
Second Edition 
Short Sensory 
Profile-2  
(Parent) 
Sensory Sensitivity 
Parent 
questionnaire 
(34) 
Visit 1 
2c 
Sensory: Short 
Sensory Profile-2 
(7) 
Dental Anxiety 
(parent) 
Children’s Fear Survey 
Schedule- Dental 
Subscale measures 
dental 
anxiety. 
Parent 
questionnaire 
(15) 
Visit 1 
2c 
Children’s Fear 
Survey Schedule- 
Dental Subscale  
(8) 
General Anxiety 
(parent) 
Child and Adolescent 
Symptom Inventory-4, 
Anxiety Scale 
Parent 
questionnaire 
(21) 
Visit 1 
2c 
Child and 
Adolescent 
Symptom 
Inventory-4, 
Anxiety Scale (6) 
Expressive 
Communication 
Ability 
Vineland Adaptive 
Behavior Scales-II, 
Expressive 
Communication Domain 
Parent 
questionnaire 
(varies) 
Visit 1 
2c 
Vineland 
Adaptive 
Behavior Scales-
II, Expressive 
Communication 
Domain 
Age of child 
(parent) 
Age 
Parent 
questionnaire  
(1) 
Visit 1 
2c 
Family 
information (5) 

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4  STUDY DESIGN 
 
This is a Phase II clinical trial utilizes a randomized cross-over design with two 
conditions at a single-site to test the efficacy of the SADE intervention protocol in reducing 
children’s physiological anxiety and negative responses.  
The Phase II experimental design is overviewed in the Schematic of Study Design 
section of the Clinical Trial Protocol Summary (pg. 11). 
 

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5 STUDY ENROLLMENT AND WITHDRAWAL 
 
The study target sample size is 220 English- and Spanish-speaking children with ASD. We 
anticipate a 4:1 ratio of boys to girls in the ASD group based on current statistics13 (CDC, 2014) 
and consistent with recruitment in our R34 study. Based on our results from our R34 SADE 
study, we anticipate that the ethnic and racial backgrounds of our sample will mirror the general 
population of CHLA patients. Specifically, we expect more than half of individuals to be of 
Hispanic/Latino origin with a preponderance of Caucasian children. 
Based on our R34-funded pilot study, we plan to recruit children with ASD from CHLA Dental 
Clinic. Each week, study staff will review the electronic health records of the list of patients 
scheduled for a dental cleaning in the CHLA Dental Clinic. For those appearing to meet 
inclusion criteria for the study, study staff will contact the parents or guardians and invite 
participation in the study.  
Based on our pilot study, we found that it may be difficult to recruit a sufficient number of 
children with a range of ASD severity. Therefore, for this study we plan to recruit children from 
multiple sites including CHLA (Dental Clinic, USC UCEDD, Boone Fetter Clinic, AltaMed), and 
the Los Angeles Unified School District. See Section 5.3 for greater detail about these sites. 
 
5.1 
Subject Inclusion Criteria 
 
In order to be eligible for the proposed study, all individuals must meet all of the following 
criteria: 
 
Provide signed and dated informed consent (parent permission) and child assent (if 
appropriate) forms. 
 
Willing to comply with all study procedures and be available for the duration of the study. 
 
Male or female, aged 6 through 12 years. 
 
Have an accompanying parent or guardian who speaks English or Spanish. 
 
Live within local commuting distance of CHLA. 
 
Have experienced at least one prior dental cleaning. 
 
Diagnosed with Autism Spectrum Disorder, based on the Autism Diagnostic Observation 
Scale, 2nd ed (ADOS-2)71 as administered by a psychologist from our research team. 
 
Need an oral cleaning (defined as no oral cleaning within the previous four months). 
o Participants are eligible to be enrolled and complete study Visits 1 and 2 if they 
have had an oral cleaning within the previous four months. However, participants 
will not be eligible to complete Study Visit 3 until a minimum of four months has 
passed following their previous dental cleaning.  
 
5.2 
Subject Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
 
Cleft palate or other oral condition which makes dental care more difficult than usual 
practice. 
 
Prescription of anti-cholinergic drugs (which may alter EDA) (See Appendix M in MOP 
for a list of medications) 
 
Presence of orthodontia (braces). 

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 
Significant motor impairment, such as cerebral palsy. 
 
Any known genetic, endocrine, or metabolic dysfunctions. 
 
Participation in the R34 SADE pilot study. 
 
Any medical condition such as significant cardiac problems that would place the 
individual at increased risk in the study. 
 
5.3 
Strategies for Recruitment and Retention 
 
Recruitment at each site 
CHILDREN’S HOSPITAL LOS ANGELES (CHLA). CHLA will be our main recruitment site and 
is a nonprofit, academic, major pediatric medical center providing healthcare to children 
throughout Los Angeles and surrounding counties. Within CHLA, participants will be recruited 
through several sources: 
CHLA Division of Dentistry and Orthodontics. The Division of Dentistry and Orthodontics, 
aligned with the USC School of Dentistry, provides routine and specialized dental care to 
approximately 3,500 children and adolescents each year, including more than 300 children with 
ASD. Participants with ASD will be recruited from lists of currently scheduled patients; 
recruitment flyers will be posted in the Dental Clinic and dentists will also be asked to distribute 
flyers to appropriate clients who have ASD. These flyers will contain contact information for the 
research staff, enabling parents to contact the research team if they are interested in 
participating in the study. 
 
 
USC Center for Excellence in Developmental Disabilities at CHLA (UCEDD). The USC 
UCEDD, which is part of the CHLA Division of General Pediatrics, is one of more than 65 
university centers in the U.S. focused on training, service, research, and technical assistance for 
people with disabilities and their families. Each year, the UCEDD provides diagnostic and 
intervention services to over 3,000 children with disabilities, including approximately 200 
children with ASD. Recruitment flyers will be posted at the UCEDD and therapists will be asked 
to distribute flyers to clients who have ASD. 
 
Boone Fetter Clinic. The Boone Fetter Clinic at CHLA offers comprehensive services for 
children thought to have autism, neurodevelopmental, or behavioral disorders, offering clinical 
diagnostic and assessment services and serving as a follow-up resource referral for children with 
ASD. Boone Fetter provides diagnostic services to approximately 120 children with ASD each 
year. Recruitment flyers will be posted at the Boone Fetter Clinic and therapists will be asked to 
distribute flyers to clients who have ASD. 
 
AtlaMed General Pediatrics Service. AltaMed, designed to eliminate disparities in health 
care access and outcomes, provides quality health and human services to 16,000 underserved 
Southern California children. Conservatively, 200 of these children are diagnosed with ASD. Dr. 
Robert Jacobs, Director of AltaMed, will assign a pediatrician as a 5% in-kind contribution to this 
U01 study; this pediatrician will identify potential study participants and provide them with 
information about the study. 
 
Participants from previous research studies. Participants will also be recruited from a list 
of children with ASD who have participated in previous research studies at CHLA who have 
consented to be approached about additional research opportunities. These include participants 

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from the Tummy Troubles Study (Grant # 1R21MH089465-01, PI: Levitt). Dr. Marian Williams 
(Co-I) has access to this database of approximately 200 previous participants in research at 
CHLA, including over 100 children with ASD. Dr. Williams will provide these potential study 
participants with information about the study. 
 
LOS ANGELES UNIFIED SCHOOL DISTRICT (LAUSD). In order to ensure that children with a 
wide range of ASD severity are recruited and enrolled in this study, LAUSD will also be a source 
of participant recruitment. LAUSD is the second largest public school system in the United 
States, enrolling over 350,000 students in our targeted age range. Conservatively, we estimate 
that over 2,500 are diagnosed with ASD. These local schools also serve primarily low-income 
Latino children (70%), similar to the demographics at CHLA. Schools within local commuting 
distance of CHLA have been identified, and, with principal approval, recruitment flyers will be 
disseminated to children with ASD. After flyer dissemination, interested parents will be 
responsible for contacting the research team via provided contact information (phone or email) 
for further details of participation.  
 
OCCUPATIONAL THERAPY CLINICS. In order to ensure we reach target enrollment, pediatric 
occupational therapy clinics will also be a source of participant recruitment. Pediatric Therapy 
Network serves over 2,500 children with special needs and provides over 100,000 hours of 
occupational therapy, physical therapy, and speech-language therapy each year as well as 
offering multiple small group programs (e.g., Early Intervention, social skills, augmentative and 
alternative communication, etc.). Therapy West has three facilities in the greater Los Angeles 
area to provide occupational therapy, physical therapy, and/or speech and language therapy, 
treating primarily children with developmental disabilities including Down Syndrome, Cerebral 
Palsy, and Autism Spectrum Disorders.  
 
Retention 
 
To aid in retention of study participants, a series of steps will be taken. Reminder phone calls, 
texts, and/or e-mails for meetings and dental visits will occur (based on stated parent 
preference). Additionally, the first meeting, consisting of the consent process and survey 
completion, will take place at the family home or CHLA, whichever is more convenient for the 
family. Utilizing these strategies in the R34 pilot study, we were able to retain 98% of our 
participants. However, since not all participants will be patients in the CHLA Dental Clinic, we 
expect there may be a larger loss. We have allowed for a loss of 10%, targeting a sample of 165 
participants with complete data from a recruited sample of 220 children with ASD. 
 
Compensation 
 
Families will not incur any out-of-pocket costs for participating in this study. Families’ insurance 
will be billed for one of the two dental visits, and the other visit will be provided free of charge. If 
a participant does not have dental insurance, or if the insurance company denies 
reimbursement, both dental cleanings will be free of charge. Additionally, participants will be 
paid a stipend following each visit to compensate families for their time as for well as parking 
and transportation costs. 
 
The amount and schedule of payments is as follows: 
1. Consent and survey completion visit: $40 following completion of questionnaires 

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2. Administration of ADOS-2 for ASD diagnosis confirmation and IQ test (WASI-II): $40 
following assessment plus $10 parking/transportation 
3. First Dental Cleaning Visit: $40 plus $10 parking/transportation 
4. Second Dental Cleaning Visit: $40 plus $10 parking/transportation (provided only if the  
study’s rideshare option is not used). For our final 25 participants, new CHLA 
procedures that are COVID-19 related are designed to protect the safety of the 
parent/legal guardian and participant. Round-trip rideshare will be available for these 25 
participants. 
Note: To protect the health and safety of patients and staff during the COVID-19 
pandemic, CHLA implemented a new policy that requires participants to take the 
COVID-19 test 72 hours prior to a scheduled dental cleaning visit. This will be scheduled 
by CHLA at no cost to the participant. If the participant wishes, a round-trip rideshare 
(e.g. Lyft) will be available to the participant for this visit. In addition, the participants will 
be provided with a $25 stipend for their time. This additional stipend will be provided at 
the patient’s dental cleaning visit. This process will continue as long as COVID-19 
testing prior to the dental visit is required by CHLA. The study team will follow the most 
current CHLA procedures and guidelines and as changes are made, we will abide by the 
most current CHLA procedures and guidelines. See MOP Appendix P Children’s 
Hospital Los Angeles Pre-procedural COVID-19 Testing and Appendix Q: Children’s 
Hospital Los Angeles COVID-19 Telephone Screening Procedures for additional details 
about the procedures. 
 
Participants tested prior to the pandemic were able to receive a maximum of $190. For the 
remaining participants affected by the CHLA policy during the COVID-19 pandemic, the 
participant will receive a maximum of $215.  
 
5.4 
Treatment Assignment Procedures 
5.4.1 
Randomization Procedures (if applicable) 
Following confirmation of ASD diagnosis (administration of ADOS-2), participants will be 
randomly assigned to the order of treatment, receiving either the Regular Dental Environment 
(RDE) condition or Sensory Adapted Dental Environment (SADE) condition for their first 
cleaning. Because we anticipate different rates of participation between gender and age, 
randomization will be stratified by gender and age (6.0-9.5 years and 9.6-12.11 years) so there 
is a balance in order of treatment between boys and girls and younger and older children in 
each order of environment. Randomization will be performed by our PhD biostatistician following 
a blocked randomization schema for each of the gender-age stratum. We anticipate that the 
largest stratum will be younger boys (~56% of the sample), followed by older boys (24%), 
younger girls (15%), and older girls (6%), thus block sizes will vary so that the study team 
cannot anticipate what the first treatment for a participant will be.   
5.4.2 
Masking Procedures (if applicable) 
For intra-oral photos and analysis of EDA recordings, coders will be blinded to condition (SADE 
vs. RDE). Due to the practicalities of this study and the need to modify dental environments for 
each patient, blinding of treatment condition for patients or dentists is not applicable.  
5.5 
Subject Withdrawal 
 

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Subjects may withdraw voluntarily from the study. The investigator may also terminate a 
subject's participation if the second scheduled dental cleaning cannot be completed within a 
maximum of 8 months following the first dental cleaning (see Section 7.5 for more details). 
 
5.5.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request. 
 
An investigator may terminate a study subject’s participation in the study if: 
 
Any clinical serious adverse event (SAE), laboratory abnormality, or other medical 
condition or situation occurs such that continued participation in the study would not be 
in the best interest of the subject. 
 
The subject meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
 
The subject cannot tolerate electrodes placed on fingertips. 
 
5.5.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
If a study participant voluntarily withdraws from the study, the child will continue to 
receive dental care as usual from his/her personal dentist. If his/her dental care is at CHLA, a 
routine follow-up appointment will be scheduled as appropriate for his/her next dental cleaning 
(e.g., six months following the study-related dental cleaning).  If a subject voluntarily withdraws 
while the study is in the enrollment window, we will replace him/her with another subject; if after 
recruitment and enrollment has closed, no replacement will be made. 
No adverse events or unanticipated problems occurred during our R34 pilot study; however, 
in the event of a serious adverse event or unanticipated problem, as per CHLA’s 
Committee on Clinical Investigations, the investigators and CHLA are not able to offer financial 
compensation or absorb the costs of treatment. If the serious adverse event or unanticipated 
problem is not due to the research protocol and the study is still in the enrollment phase, we will 
replace him/her with another subject. If it occurs after recruitment and enrollment has closed, no 
replacement will be made. 
 
5.6 
Premature Termination or Suspension of Study 
 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification documenting the reason for study suspension or termination will be provided 
by the suspending or terminating party to the investigator, funding agency, and regulatory 
authorities. If the study is prematurely terminated or suspended, the principal investigator will 
promptly inform the IRB and will provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to subjects. 
 
Insufficient adherence to protocol requirements. 
 
Determination of futility. 
 

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6 STUDY INTERVENTION 
 
6.1 
Study Behavioral or Social Intervention(s) Description 
 
This study will investigate the impact of adapting the dental environment on the 
physiological anxiety and negative responses of children with ASD undergoing a dental 
cleaning. Dental cleaning in a sensory adapted environment (SADE) will be compared to usual 
treatment for dental cleaning in a regular dental environment (RDE). 
Dental cleanings in the control condition (RDE) and experimental condition (SADE) will 
take place in a private room in the CHLA Dental Clinic and will each require approximately 15-
45 minutes to complete, and will take place four-six months apart. Every effort will be taken to 
ensure that both cleanings will be performed by the same SADE-trained CHLA pediatric 
dentistry resident and dental assistant. The SADE environment will be set up prior to the child’s 
entrance into the dental room by a member of the research team. 
Table 3 summarizes the specific modifications that comprise the SADE intervention. 
Specifically, visual, auditory, and deep pressure tactile stimuli are altered in an effort to 
maximize relaxation. It should be noted that dentists participating in our R34 pilot study 
indicated that the SADE did not negatively impact their ability to perform the oral cleaning in a 
regular manner. This was also reported by Shapiro et al. (personal communication, February 25, 
2008) who conducted a similar study with children with intellectual and developmental 
disabilities. This will be empirically tested in the proposed study by including a measure of 
quality of care. Additionally, the intervention does not require permanent renovations to the 
dental clinic, as the equipment is portable, requiring approximately 15 minutes to set up or to 
remove. 
 
Table 3. Components of the SADE Intervention. 
 
Visual 
All direct overhead fluorescent lighting and the regular dental overhead lamp 
will be turned off; dark colored “black-out” removable curtains will cover the 
windows in the private dental room. The dentist will wear a head-mounted 
dental lamp directed into the patient’s mouth, reducing bright lights shining into 
the child’s eyes. Slow moving visual color effects (Snoezelen) will shine onto 
the ceiling in the child’s visual field.  
Auditory 
Auditory stimuli will include rhythmic music projected via a Phillips Portable 
Speaker System. Music will be either Dan Gibson’s Exploring Nature with 
Music or similar options. 
Tactile / Deep 
Pressure 
The tactile deep pressure stimulus will consist of a butterfly wrap (a modified 
version of the wrap developed in Israel),49 weighted with a regular pediatric 
dental X-ray vest. The wrap fits around the dental chair and is made of a 
washable material. The “wings” of the butterfly wrap around the child from 
shoulder to ankles, providing a deep “hugging” pressure to produce a calming 
effect.  
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6.2 
Administration of Intervention 
 
The private dental room for the SADE will be prepared by trained research team 
members. Following the set-up of the environment and electrode placement on the study 
participant’s fingers, a three-minute baseline rest period will occur, followed by the dental 
cleaning led by the CHLA resident. In the RDE, the same research team members will video-
record, place electrodes, and obtain EDA recordings, but none of the environmental adaptations 
will be made.  
Each participant will receive a total of two dental cleanings approximately four-six 
months apart. In this crossover design, one cleaning will be in SADE and the other in the RDE. 
The duration of each dental cleaning session will be approximately 15-45 minutes.  
6.3 
Procedures for Training Interventionists and Monitoring Intervention Fidelity 
Dental room set-up. Dr. Leah Stein Duker (Co-I) or her trained designee will be responsible for 
training research team members on the set-up of the private dental room for both the RDE and 
SADE conditions. Two trained research team members will prepare the dental treatment room 
for both conditions, and a checklist will be completed to ensure all equipment has been set-up 
correctly for each condition [Environment Set-Up Fidelity Form (CRF 24) and the Equipment 
Set-Up Checklist (Appendix G)]. 
Dental cleaning sequence of events. Dr. Stein Duker or her trained designee will be responsible 
for training research team members and dental residents about the sequence of events for each 
dental cleaning (e.g., electrode application  rest period  research-related oral hygiene 
assessments  traditional CHLA oral examination  intraoral photographs  prophylaxis   
intraoral photographs   fluoride application   end of study procedures). At each visit a visual 
representation will be taped to the wall by the resident for quick reference (See Appendix C).  
EDA & video equipment set-up, recording, and coding. Dr. Stein Duker or her trained designee 
will be responsible for training research team members on the set-up and use of both the video 
and EDA equipment as well as their coding. Reliability of research team members’ coding of 
EDA recordings and video-recordings will be achieved at a K=.85 using prior recordings from 
the R34 pilot study. Recordings from the U01 will be coded by these reliable team members. 
For quality assurance 25% of EDA codings and 25% of video codings will be compared to 
coding by Dr. Stein Duker. If inadequate reliability is obtained, research team members will 
undergo retraining. This retraining will include practice coding video and/or EDA data side-by-
side with a reliable coder, followed by a retest of reliability (See CRFs 22 and 23 for CDBRS 
and Scored EDA Forms). 
Dental measures. Dr. José Polido (Co-I) will train residents on oral hygiene measures (Oral 
Hygiene Index - Simplified, Plaque Index, Gingival Index) and behavioral measures (Modified 
Anxiety and Cooperation Scale and Frankl Scale) as well as the use of the intraoral camera. Dr. 
Polido or the supervising attending dentist will monitor and check quality of work after the 
resident has completed each dental cleaning.  
ASD diagnosis confirmation. Dr. Marian Williams (Co-I) will either conduct the ADOS-2 
assessment herself or supervise PhD psychology residents who have been trained by formal 
courses offered in conjunction with Western Psychological Services in administration of the 

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Autism Diagnostic Observation Schedule-2 (ADOS-2). Assessments will be videotaped for co-
scoring and training. Dr. Williams will co-score 10% of ADOS-2 assessments using videotapes. 
If a study participant has previously had the ADOS-2 administered at the CHLA UCEDD, we will 
accept the ASD confirmation and study results from that previous assessment.  
 
6.4 
Assessment of Subject Compliance with Study Intervention  
Dentist Compliance. The Dentist Recording Form [combination of the Oral Health Indices Form 
(See CRF 13) and the Behavioral Indices Form (CRF 14)] will be used to record data as well as 
ensure fidelity to the study protocol. The Oral Health Indices Form includes the Oral Hygiene 
Index – Simplified (OHI-S), Gingival Index (GI), and Plaque Index. The OHI-S, GI, and Plaque 
Index will be completed during the oral examination portion of the dental cleaning; the PIaque 
Index will also be completed by blinded dentists scoring pre-examination and post-examination 
intra-oral photographs. The Behavioral Indices Form includes the Anxiety and Cooperation 
Scale and Frankl Scale and will be completed by the dentist directly following the dental 
cleaning. Additionally, both dental cleanings will be directly observed by research team 
members, and accidental straying from the protocol will be quietly but quickly corrected.  
Participant Compliance. The main measure of participant compliance will be attendance at both 
scheduled visits. To decrease attrition, as was done successfully in our R34 pilot study, we will 
contact participants one day, one week, and two weeks prior to their scheduled appointments 
using the participants’ preferred method of communication (e.g., phone call, email, text). All 
communication attempts will be documented manually on the Call Log Form (CRF 3) and 
tracked. If an appointment is missed, we will make every attempt to reschedule missed 
sessions. 
Researcher Compliance. Prior to leaving USC OS-OT for a scheduled appointment at CHLA, 
the research team will complete the Equipment Fidelity Checklist to ensure all necessary 
equipment is packed for the study protocol. Once at CHLA, the research team will complete the 
Environment Set-Up Fidelity Form (CRF 24) and the Equipment Set-Up Checklist (Appendix G) 
to ensure appropriate set-up of both RDE and SADE conditions. Additionally, a research team 
member will fill out the Visit Completion Form (CRF 25) throughout the dental cleaning to 
ensure all time measurements have been recorded and video-recording has been completed. A 
second team member will complete the EDA Flag Form (CRF 26) to ensure that not only EDA 
has been collected, but marked in real time to designate different dental practices (e.g., 
beginning of oral exam, beginning of prophylaxis, etc.). Following the dentist completion of the 
Dentist Recording Form (Oral Health Indices Form and Behavioral Indices Form; CRFs 13 and 
14), the research team will also visually inspect the forms to ensure that they have been 
accurately and fully completed. 

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7 STUDY SCHEDULE 
 
7.1 
Screening 
 
Screening to Determine Eligibility (Day -90 to -15) 
CHLA Dental Clinic patients/previous research participants only: In order to determine 
initial eligibility, CHLA dental charts and lists of participants in previous research studies will be 
reviewed to identify potential participants. As successfully done for our R34 SADE pilot study, a 
waiver of written or signed consent will be requested from the CHLA IRB for the purposes of 
determining the initial eligibility of participants so we may identify appropriate children to recruit. 
Phone contact (see below for greater detail) will be made to families whose children meet this 
initial eligibility (See inclusion/exclusion criteria above Sections 5.1 and 5.2). 
 
Participants from CHLA (Dental Clinic, UCEDD, Boone Fetter, AltaMed) & LAUSD 
 
CHLA Dental Clinic patients: We will contact the parent/guardian by telephone to tell 
them about the research study (CHLA Dental Clinic patients).  
 
Other CHLA recruitment sites (UCEDD, Boone Fetter, AltaMed), previous research 
subjects who have agreed to be contacted (not those who participated in R34 SADE 
Study), and LAUSD: The parent/guardian will contact the research team responding to 
recruitment brochure/flyer.  
o Following explicit statement of parent/guardian interest in participation, research 
staff member confirms child participant eligibility (meets inclusion criteria, has no 
exclusion criteria traits). 
o Following confirmation of child eligibility, if the parent is still interested in 
participating, an in-person visit is scheduled to conduct the written consent 
process and complete all questionnaires.  
Note. We plan to have a rolling recruitment and enrollment in this study, such that day -30 (for 
example) for one child will likely be different from day -30 for another child. 
7.2 
Enrollment/Baseline 
Enrollment Visit (Visit 1, Day 0) 
 
Further explain study protocol and participant responsibilities in greater detail than that 
discussed on the screening for eligibility phone call. Answer any parent or child 
questions. 
 
Verify inclusion/exclusion criteria. 
 
Obtain and document consent from parent on study consent (parental permission) form. 
Explain and obtain signature from parents on study HIPAA form. 
 
Explain and provide parents with California Bill of Rights. 
 
Obtain and document child assent from child subject on study assent form (if child is 
available and able to complete/understand form). 

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 
Parental completion of the Parent Bilingual Questionnaire to assess the child and 
parent’s bilingual preference (see Appendix N in MOP). 
 
Use the Decision Tree for Accepting Child’s Data as a guideline to determine if the child 
is able to give assent based on the parent report (see Appendix O in MOP). 
 
Parental completion of study questionnaires to obtain demographic information, dental 
history, anxiety, and sensory over-responsivity. (Complete list of measures to be 
completed are listed in the Schedule of Events in Appendix A; see CRFs 5-10, 28: Child 
& Family Information (Demographics), CASI-Anx, SSP-2, SensOR, CFSS-DS, VABS-II 
Expressive Communication Domain, Dental History Form, Dental Care in Children 
Questionnaire) 
 
Child completion of study questionnaires (if able) to obtain information about child 
perception of dental anxiety. (Complete list of measures to be completed are listed in the 
Schedule of Events in Appendix A; see CRFs 11-12: CFSS-DS, MCDASf) 
 
Parents are shown and instructed in the use of the specialized study social story for 
going to the dentist and participating in the SADE study. Parents are informed that the 
social story will be mailed to them with instructions two weeks prior to the child 
participant’s first (and second) dental cleaning. 
 
Parents and children are shown the EDA electrodes and allowed to play with them.  
Note:  This visit (Visit 1) will take place at the participant’s home, or if the family prefers, at 
CHLA, prior to the Autism Diagnostic Confirmation Visit (Visit 2).   
7.3 
Intermediate Visits 
ASD Diagnosis Confirmation and IQ Testing (Visit 2, Day 1 to 270) 
 
At the enrollment visit (Visit 1), parents are informed that their child will need to have the 
ADOS-2 and WASI-II administered at the CHLA UCEDD (parents will also be informed 
of this during the phone screening prior to this visit). Parent contact information will be 
provided to Dr. Marian Williams and her staff at the CHLA UCEDD for scheduling. A 
phone screening process will occur during the scheduling call to determine the 
appropriate ADOS module to be utilized during the ADOS-2 administration. Confirmation 
of ASD diagnosis through ADOS-2 administration is required to continue with visits for 
oral cleaning. If child does not meet the ASD criteria based on the ADOS-2, services or 
treatment at the dental clinic will continue as before but the child will not continue as a 
research participant nor participate in the study’s subsequent visits. If a study participant 
has previously had the ADOS-2 administered at the CHLA UCEDD, we will accept the 
ASD confirmation and study results from that previous assessment. 
 
Child completion of study Assent (if child was not present at Visit 1 and is able to 
complete/understand form)  
 
ASD diagnostic confirmation (Autism Diagnostic Observation Schedule 2) and cognitive 
screen (Wechsler Abbreviated Screening of Intelligence II) administered by Dr. Williams 
or a psychology member of her team. 

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 
All parents/guardians will receive written feedback (by mail) from Dr. Williams or a 
member of her team regarding the general results of the autism and cognitive 
assessments (see Appendix I in MOP) 
 
Following completion of Visit 2, randomization into study condition (RDE vs. SADE) for 
the first dental visit (Visit 3) will occur (see Section 5.4.1 for randomization details). 
**This behavioral assessment (ADOS-II) must be completed and confirm ASD diagnosis 
prior to the continuation of study activities and administration of intervention. 
Intervention Condition 1 (Visit 3, Day 5 to 360) 
 
Obtain and document child assent from child subject on study assent form (if child was 
not present at Visit 1 and is able to complete/understand form). 
 
Child completion of study questionnaires (if child was not present at Visit 1 and is able to 
complete/understand form) to obtain information about child perception of dental anxiety. 
 
Obtain parent-report of current medications of child. 
 
First dental cleaning will occur, based on randomization of participant into RDE vs. 
SADE condition. 
 
Prior to first cleaning, complete Dental Room Set-Up Checklist to ensure fidelity with 
environment. 
 
Dentist will photograph child’s teeth prior to cleaning. 
 
Concurrent with the first dental cleaning, record results of dental cleaning on Oral Health 
Indices Form, complete Visit Completion Form and EDA Flag Form, and collect video-
recording and EDA data. (Complete list of measures to be completed are listed in the 
Schedule of Events in Appendix A; see CRFs 13, 25-26) 
 
Following administration of dental cleaning: 
o Dentist will photograph child’s teeth inside the child’s mouth using an intraoral 
camera. 
o We will obtain dentist’s perception of subject’s behavior throughout the dental 
cleaning [Behavioral Indices Form (Anxiety and Cooperation Scale and Frankl 
Scale); See CRF 14]; complete Usual Dental Care and Planning Form (CRF 15). 
o We will administer child questionnaires (Faces Pain Scale – Revised, Dental 
Sensory Sensitivity Scale, and if in the SADE environment, the Child SADE 
Acceptance Form; See CRFs 17-19).  
o If in the SADE environment, we will administer the Parent SADE Acceptance 
Form (See CRF 20). 
o If, based on the Clinical Examination, the child has any dental needs, the dentist 
will complete the Dental Letter to Parents (Appendix K).  A copy will be given to 
the parent and a copy will be placed in the child’s chart and his/her dental 
findings will be recorded in the child’s e-record if the child is a CHLA dental 
patient. 

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Note-1: Scoring of intra-oral photographs will take place following the dental cleaning at 
CHLA by a trained dentist (CRF 16: Quality of Care Recording Form). Coding of video-
recordings and EDA recordings will occur off-site (at the designated lab space of the 
Health Sciences Campus of the University of Southern California) at a later time. (CRFs 
22-23: Children’s Dental Behavior Rating Scale & Scored EDA Form) 
Note-2: Lighting for the intra-oral photographs is provided by the camera inside the 
mouth and, according to the company representatives, will be comparable in both SADE 
and RDE conditions. 
 
Record and report unanticipated problems as reported by subject/parent or observed by 
investigator/dental staff (See CRF 27: Unanticipated Problem Form). 
Intervention Condition 2 (Visit 4, Day 125-450) 
 
Update parent-report of current medications of child. 
 
Second dental cleaning will occur, based on randomization of participant into RDE vs. 
SADE environment. 
 
Dentist will photograph child’s teeth prior to cleaning. 
 
Concurrent with the second dental cleaning, record results of dental cleaning on Oral 
Health Indices Form, complete Visit Completion Form and EDA Flag Form, and collect 
video-recording and EDA data. (Complete list of measures to be completed are listed in 
the Schedule of Events in Appendix A; see CRFs 13, 25-26) 
 
Following administration of dental cleaning: 
o Dentist will photograph child’s teeth. 
o Obtain dentist’s perception of subject’s behavior throughout the dental cleaning 
[Behavioral Indices Form (Anxiety and Cooperation Scale and Frankl Scale); See 
CRF 14]; complete Usual Dental Care and Planning Form (CRF 15). 
o Administer child questionnaires (Faces Pain Scale – Revised, Dental Sensory 
Sensitivity Scale, and if in the SADE environment, the Child SADE Acceptance 
Form; See CRFs 17-19).  
o If in the SADE environment, we will administer the Parent SADE Acceptance 
Form (See CRF 20). 
o If, based on the Clinical Examination, the child has any dental needs, the dentist 
will complete the Dental Letter to Parents (Appendix K).  A copy will be given to 
the parent and a copy will be placed in the child’s chart and his/her dental 
findings will be recorded in the child’s e-record if the child is a CHLA dental 
patient. 
 
Note-1: Scoring of intra-oral photographs will take place at a later date following the 
dental cleaning at CHLA by a trained dentist (CRF 16: Quality of Care Recording Form). 
Coding of video-recordings and EDA recordings will occur off-site (at the designated lab 
space of the Health Sciences Campus of the University of Southern California) at a later 
time (CRFs 22-23: Children’s Dental Behavior Rating Scale & Scored EDA Form). 

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Note-2: Lighting for the intra-oral photographs is provided by the camera inside the 
mouth and, according to the company representatives, will be comparable in both SADE 
and RDE conditions. 
Note-3: (COVID-19 modifications) At the beginning of the COVID-19 pandemic (March 
2020), all research activities were discontinued. At that time, all participants had been 
recruited and completed Visits 1-3. Twenty-five participants had not completed the final 
visit (second dental cleaning). Once permission to resume research activities is provided 
by USC and CHLA we will adhere to all COVID-19-related guidelines and regulations 
from CHLA and USC. To protect the health and safety of patients and staff during the 
COVID-19 pandemic, CHLA now requires participants take a COVID-19 test 72 hours 
prior to a scheduled dental cleaning visit. This will require an extra visit for our 
participants. Thus, for the remaining 25 participants who will be completing their second 
dental visit, the study team will inform the parent/legal guardian of the COVID-19 test 
(until it is no longer a requirement at CHLA) and the rideshare option for both the 
COVID-19 testing and the dental cleaning visit. The study team will follow the most 
current CHLA procedures and guidelines and as changes are made, we will abide by the 
most current CHLA procedures and guidelines. 
 
Record unanticipated problems as reported by subject/parent or observed by 
investigator/dental staff (See CRF 27: Unanticipated Problem Form). 
 
7.4 
Final Study Visit 
 
Final Study Visit = Visit 4 (125-450 days) 
This study’s final visit will be the second dental cleaning visit at CHLA; there are no special 
procedures or evaluations (other than those noted in Visit 4 above) to be completed after the 
second dental cleaning.  
 
Upon completion of the second dental cleaning, participants and parents will be informed that 
the study is complete and oral care will return to as it was prior to the study (e.g., continue 
recalls at CHLA every 6 months if CHLA client, or return to other dentist if not a CHLA client) 
with no further compensation or access to the adapted environment. Parents will again be given 
contact information of research team members in the case that they have any questions or want 
to contact the researchers (also located on the signed and dated copy of the consent form). 
Parents will be instructed to contact the research team if any AEs or SAEs occur following Visit 
4. If appropriate, a member of the research team will follow-up via phone call to ensure that any 
AE/SAEs have been resolved. Individual participants will not be informed of study results. 
 
7.5 
Withdrawal Visit 
There will not be a withdrawal visit and no evaluations are specifically required for the final visit 
as the final visit is the second dental cleaning visit (Visit 4 above). 
We will make every attempt to ensure that each child gets two dental cleanings, one in each 
condition (SADE and RDE). Missed appointments will be rescheduled, as many times as 
necessary up to eight months following the child’s first dental cleaning (with participants 
receiving priority scheduling), extra reminders made, and compensation provided to cover 
transportation costs and time. If a child does not complete his/her second cleaning within eight 

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months of his/her first, we will assume that he/she has voluntarily withdrawn and will inform 
parents that their child is no longer eligible to obtain the second dental cleaning, nor is part of 
the study anymore. Parents will also be reminded that there will be no penalty or impact on 
CHLA quality of care as a result of withdrawing or dropping out of the study. 
7.6 
Unscheduled Visit 
If the child requires dental care other than routine cleaning between enrollment and 
completion of the study, he or she may do so at his/her regular dental provider’s office (whether 
that is at CHLA or elsewhere). If an unrelated emergency visit before or between SADE Study 
dental visits occurs, we will record its occurrence and allow the participant to continue to 
participate in the study following review of the reason and outcome of the visit by the principal 
investigator and Co-I, Dr. José Polido. If an unrelated visit occurs between SADE Study visits 
(e.g., treatment of cavities found during Visit 3), we will also record its occurrence and allow the 
participant to continue to participate in the study.  

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8 STUDY PROCEDURES/EVALUATIONS 
 
8.1 
Study Procedures/Evaluations 
Medical History  
Medical history will be obtained from parent-report and will include diagnosis of ASD, list of 
current medications, and a list of any other medical diagnoses. This information will be obtained 
to ensure that the child participant does not meet any of our stated exclusion criteria (e.g., 
genetic, endocrine or metabolic dysfunction; significant motor impairment, cleft palate, taking an 
anticholinergic medication, etc.).  
Prior to Dental Cleanings 
 
Child-Descriptor Assessments. As detailed above (Section 7.2), immediately following 
the consent/assent process parent- and child-report (if child is able) surveys will be completed 
(See CRFs 5-12, 28: Child & Family Information, CASI-Anx, SSP-2, CFSS-DS (parent), VABS-II 
Expressive Communication Domain, Dental History Form, Dental Care in Children 
Questionnaire, CFSS-DS (child), MCDASf), and SensOR. These forms will provide information 
about the child’s sensory processing difficulties, dental anxiety, and previous dental 
experiences. Children with ASD will come to CHLA for an additional visit to confirm ASD 
diagnosis via administration of the ADOS-2 test. At this visit, the psychologist will also 
administer the WASI-II in order to assess child IQ.  
During the Dental Cleanings 
Oral Care-Related Assessments. Consistent with routine practice at CHLA Dental Clinic, 
an oral examination (including assessment of caries, developmental defects, and general oral 
growth and development) will be conducted prior to each of the child’s dental cleanings. The 
dentist will also conduct the Oral Hygiene Index-Simplified, Plaque Index, Gingival Index (OHI-
S, PI, GI; located in Oral Health Indices Form, CRF 13). The first exam will take place at 
approximately the appropriate recall time (e.g., approximately 6 months following the last dental 
cleaning) for the child participant; the second will occur approximately four-six months following 
the first study-related dental visit. Both dental visits will include an oral examination, prophylaxis, 
and fluoride application. 
As part of this study, a dentist blinded to the experimental conditions will also complete 
the Plaque Index from intra-oral photographs taken at the beginning of the cleaning and the end 
of the dental treatment in order to obtain further information about the oral health of the study 
participants. Comparison of pre- vs. post-cleaning PIaque Index scores will be included as a 
quality of care measure. This scoring will take place at a later time (See CRF 16: Quality of Care 
Recording Form). 
Behavioral and Physiological Measures of Distress. Both dental cleanings will be video-
recorded in their entirety, with a focus on the child’s face and on the number of hands being 
used to restrain the child. This information will be video-coded by the research team at a later 
time using the Children’s Dental Behavior Rating Scale (CDBRS) to gather information about 
overt distress behaviors exhibited during the dental cleanings. Additionally, EDA will be 
recorded from the child’s index and middle fingers of his/her non-dominant hand. Electrodes will 
be placed and secured using medical tape, with recordings sent directly to a computer in the 
private dental room via the BIOPAC system. Like the video-recordings, these EDA recordings 
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Immediately Following the Cleanings (at CHLA) 
Dentist. Following the completion of each of the two dental visits, the dentist will take 
additional intra-oral photographs for later scoring of quality of care. He/she will also complete 
the Anxiety and Cooperation Scale and Frankl Scale to report on distress behavior displayed 
during each cleaning (See CRF 14: Behavioral Indices Form). 
Child. Following the completion of each of the two dental visits, the child (if able, and with 
assistance), will report on perception of pain using the Faces Pain Scale – Revised (FPS-R) and 
rank the degree of bother of the sensory stimuli encountered during the dental visit using the 
Dental Sensory Sensitivity Scale (DSSS). Additionally, following the dental visit in the SADE, 
children will be asked five additional questions as part of the Child SADE Acceptance Form to 
elicit information about whether or not they liked/enjoyed the specific adaptations made to the 
environment (See CRFs 17-19). 
Parent. Following the dental visit in the SADE, parents will be asked to complete the 
Parent SADE Acceptance Form to elicit information about how they felt themselves about the 
SADE adaptations and whether or not they perceived that these adaptations helped make their 
child’s experience better (See CRF 20). 
Scoring Occurring at a Later Time (at CHLA or USC) 
 
Dentist-Scoring. At CHLA, a dentist blinded to condition (RDE/SADE) will score the intra-
oral photographs using the PIaque Index. (See CRF 16: Quality of Care Recording Form). The 
rater will be a dental resident who has achieved both inter-rater and intra-rater reliability.  
 
Researcher-Scoring. At USC, a researcher will code video-recordings of the child 
behavior during the cleaning using the training program developed by Dr. Elyse Peterson and 
the study team during the R34 (it is not possible to blind to environment on video-recordings as 
the environment is obvious based on amount of ambient light in the room); this coder will 
achieve inter-rater reliability with Dr. Stein Duker (Co-I) and will change once per year. A 
researcher blinded to environment (RDE/SADE) will score the EDA recordings using the 
BIOPAC program AcqKnowledge; this coder will achieve inter-rater reliability with Dr. Stein 
Duker (Co-I) and will be responsible for EDA analyses for the entirety of the study (See CRFs 
22-23: CDBRS & Scored EDA Forms).   
 

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9 ASSESSMENT OF SAFETY 
9.1 
Specification of Safety Parameters 
Safety monitoring for this study will focus on unanticipated problems involving risks to 
participants, including unanticipated problems that meet the definition of a serious adverse 
event. 
 
Some of the children who participate in this study may experience adverse events that are not 
related to study procedures, but are related to the participants’ diagnosis of Autism Spectrum 
Disorders, and the treatment for these conditions. Such events will not be captured and reported 
for the study, as they will not meet the definition of an unanticipated problem. 
9.1.1 
Unanticipated Problems 
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to subjects or others to include, in general, any incident, experience, or outcome 
that meets all of the following criteria: 
 
unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved 
research protocol and informed consent document; and (b) the characteristics of the 
subject population being studied; 
 
related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
 
suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
9.1.2 
Adverse Events 
An adverse event is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in the research, 
whether or not considered related to the subject’s participation in the research. Adverse events 
related to participants’ ASD diagnosis and related treatment will not be reported in this study, as 
these are not considered Unanticipated Problems. Adverse events, unless serious, will not be 
reported.  
9.1.3 
Serious Adverse Events 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
 
Results in death 
 
Is life-threatening (places the subject at immediate risk of death from the event as it 
occurred) 

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 
Results in inpatient hospitalization or prolongation of existing hospitalization 
 
Results in a persistent or significant disability or incapacity 
 
Results in a congenital anomaly or birth defect   
 
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, the event may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
Adverse Events related to participants’ diagnosis of ASD will not be reported, as these are not 
considered Unanticipated Problems. 
9.2 
Time Period and Frequency for Event Assessment and Follow-Up 
Unanticipated problems will be recorded in the data collection system throughout the study.  
A trained research team member will record all reportable events with start dates occurring any 
time after informed consent is obtained until  30 days (for SAEs) after the last day of study 
participation. At each study visit, the investigator will inquire about the occurrence of UPs, and 
of SAEs not related to participants’ diagnosis of ASD or related treatment, since the last visit. 
Events will be followed for outcome information until resolution or stabilization (See CRFs 27-
29: Unanticipated Problem Form, Serious Adverse Event Form). 
9.3 
Characteristics of an Adverse Event 
9.3.1 
Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are used: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event onset. 
b. An alternate etiology has been established. 
9.3.2 
Expectedness of SAEs 
The NIDCR Medical Monitor and the Study PI will be responsible for determining whether an 
SAE is expected or unexpected.  An adverse event will be considered unexpected if the nature, 

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severity, or frequency of the event is not consistent with the risk information previously 
described for the intervention. 
9.3.3 
Severity of Event 
The following scale will be used to grade adverse events: 
1.  Mild: no intervention required; no impact on activities of daily living (ADL) 
2.  Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on 
ADL 
3. Severe: significant symptoms requiring invasive intervention; subject seeks medical 
attention, needs major assistance with ADL 
9.4 
Reporting Procedures 
9.4.1 
Unanticipated Problem Reporting to IRB and NIDCR 
Incidents or events that meet the OHRP criteria for unanticipated problems require the creation 
and completion of an unanticipated problem report form. As per OHRP recommendation, the 
following information will be included when reporting an adverse event, or any other incident, 
experience, or outcome as an unanticipated problem to the IRB: 
 
appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number; 
 
a detailed description of the adverse event, incident, experience, or outcome;  
 
an explanation of the basis for determining that the adverse event, incident, experience, 
or outcome represents an unanticipated problem;  
 
a description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported using 
the following timeline:   
 
Unanticipated problems that are serious adverse events will be reported to the IRB and 
to NIDCR within 1 week of the investigator becoming aware of the event.  
 
Any other unanticipated problem will be reported to the IRB and to NIDCR within 2 
weeks of the investigator becoming aware of the problem.  
 
All unanticipated problems should be reported to appropriate institutional officials (as 
required by an institution’s written reporting procedures), the supporting agency head (or 
designee), and OHRP within one month of the IRB’s receipt of the report of the problem 
from the investigator. 
All unanticipated problems will be reported to NIDCR’s centralized reporting system via Rho 
Product Safety: 

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 
Product Safety Fax Line (US):  1-888-746-3293 
 
Product Safety Fax Line (International):  919-287-3998 
 
Product Safety Email:  rho_productsafety@rhoworld.com  
General questions about SAE reporting can be directed to the Rho Product Safety Help Line 
(available 8:00AM – 5:00PM Eastern Time):   
 
US:  1-888-746-7231 
 
International: 919-595-6486 
9.4.2 
Serious Adverse Event Reporting to NIDCR 
Any AE meeting the specified Serious Adverse Event criteria will be submitted on an SAE form 
to NIDCR’s centralized safety system via Rho Product Safety. This report may be sent by fax or 
email. Once submitted, Rho Product Safety will send a confirmation email to the investigator 
within 1 business day. The investigator should contact Rho Product Safety if this confirmation is 
not received. This process applies to both initial and follow-up SAE reports. 
SAE Reporting Contact Information:    
 
Product Safety Fax Line (US):  1-888-746-3293 
 
Product Safety Fax Line (International):  919-287-3998 
 
Product Safety Email:  rho_productsafety@rhoworld.com  
General questions about SAE reporting can be directed to the Rho Product Safety Help Line 
(available 8:00AM – 5:00PM Eastern Time):   
 
US:  1-888-746-7231 
 
International: 919-595-6486 
The study clinician will complete a Serious Adverse Event Form and submit via fax or email 
within the following timelines:   
 
All deaths and immediately life-threatening events, whether related or unrelated, will be 
recorded on the Serious Adverse Event Form and submitted to Product Safety within 24 
hours of site awareness.  
 
Serious adverse events other than death and immediately life-threatening events, 
regardless of relationship, will be reported by fax within 72 hours of site awareness.  
All SAEs will be followed until resolution or stabilization.  
9.4.3 
Reporting of SAEs and AEs to FDA 
Not applicable. 

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9.4.4 
Events of Special Interest (if applicable) 
Not applicable. 
9.4.5 
Reporting of Pregnancy 
In the highly unlikely event that a 6-12 year-old is found to be pregnant during the course of the 
study, it will be noted in the database and the subject will be discontinued from the study. 
9.5 
Halting Rules 
Safety findings that would temporarily suspend enrollment and/or study interventions until a 
safety review is convened include SAEs. A safety review will be conducted if there are a large 
number of SAE’s overall, a large number of occurrences of a particular type of SAE, severe 
AEs/reactions, or increased frequency of events.   
Subsequent review of serious, unexpected problems by the Medical Monitor, CSOC, IRB, the 
sponsor(s), or the relevant local regulatory authorities may also result in suspension of 
additional enrollment as well as further trial interventions. 
 

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10 STUDY OVERSIGHT 
In addition to the PI’s responsibility for oversight, study oversight will be under the direction of a 
Clinical Study Oversight Committee (CSOC) composed of members with expertise to oversee 
the study including expertise in autism spectrum disorders, occupational therapy, pediatric 
dentistry, and statistical analysis of clinical trials data. The CSOC will meet to review the clinical 
protocol before study recruitment begins, and then approximately annually to assess 
unanticipated problems, study conduct, and progress.  If major concerns arise, more frequent 
meetings may be held.  The CSOC will operate under the rules of an NIDCR-approved charter 
that will be approved at the organizational meeting of the CSOC. At this time, most data 
elements that the CSOC needs to assess will be clearly defined. The CSOC will provide 
recommendations to the NIDCR. In addition to the CSOC, an internal system for monitoring 
adverse events will be set up in conjunction with the study’s database system. As per NIDCR 
guidelines, members of the CSOC will be appointed by NIDCR.  
  

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

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12 STATISTICAL CONSIDERATIONS 
12.1 
Study Hypotheses    
Primary Objective: To compare children’s physiological anxiety (EDA - primary outcome) 
during the dental cleaning in SADE vs. RDE. 
Hypothesis 1: Children will exhibit less physiological anxiety (SCL and NS-SCR 
frequency) during routine dental care in the SADE condition compared to the RDE. 
 
Secondary Objective 2: To compare children’s negative behavioral responses (behavioral 
distress, perception of pain, sensory discomfort - secondary outcomes) during dental cleanings in 
SADE vs. RDE. 
Hypothesis 2: Children will exhibit fewer negative behavioral responses during routine 
dental care in the SADE condition compared to the RDE. 
 
Secondary Objective 3: To test the degree to which physiological anxiety mediates the SADE 
intervention's effects on children's negative behavioral responses. 
Hypothesis 3: Physiological anxiety mediates the effect of the intervention in 
decreasing child negative behavioral responses.  
 
Secondary Objective 4: To test the degree to which specific child characteristics moderate the 
SADE intervention's effects on children's physiological and negative behavioral responses 
during dental cleaning.  
Hypothesis 4: The magnitude of physiological and negative behavioral response 
change in the SADE, relative to the RDE, will be greater in children with ASD with 
increased sensory over-responsivity, high dental anxiety, greater ASD severity, lower IQ, 
and/or younger age.  
 
Secondary Objective 5: To compare the SADE intervention to the RDE on quality of care, 
cost-effectiveness, and potential cost savings of dental cleaning. 
Hypothesis 5a: The SADE intervention, compared to the RDE, is cost-effective and 
results in decreased overall costs. 
Hypothesis 5b: The SADE intervention, compared to the RDE, results in improved 
quality of care as evidenced by thoroughness of dental cleaning.  
12.2 
Sample Size Considerations 
 
The R34 pilot study provided estimates of effect size used for sample size calculations, which 
ranged greatly across measures for children with ASD. Figure 1 shows the N required to detect 
a difference between dental environments based on the results from the pilot study. As these 
effect sizes were typically smaller than those found by Shapiro et al.,50-51 they represent a more 
conservative estimate of sample size, and have the benefit of being specific to the population 
and measures proposed here. Sample size estimates were computed to detect the effect of the 
repeated measurement environment for outcomes specified in the primary objective, with EDA 
being the primary outcome (Hyp 1) and distress behavior, perception of pain, and sensory 
discomfort secondary, with 1– =0.80 and 
=0.025 (Hyp 2). In the R34 pilot study, the effect 
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1). The effect size of the environment difference for sensory discomfort and pain intensity were 
large (d’s = 0.69 and 0.62, respectively), while distress behavior measure effects were small 
(d’s ranging from 0.11 to 0.23), likely due to the restricted range of answers in those measures. 
Attrition in the pilot data was extremely low (2%), however the more conservative attrition 
estimate of 10% was used for these calculations. Thus we will recruit 220 children with ASD, 
anticipating having repeated measures on 165. This N will allow for the detection of a within 
group change attributable to environment of Cohen’s d = 0.22. Figure 1 shows the estimated 
sample size, including the effect sizes from the R34; as indicated, our target sample size, after 
attrition, should have sufficient power to detect differences in our primary outcome.   
 
Figure 1. Sample size estimates based on ASD participants of R34 Pilot and Feasibility Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.3 
Planned Interim Analyses (if applicable) 
Not applicable.  
12.3.1 
Safety Review 
Not applicable. This is a low risk study and safety will be monitored by research team members, 
the PI, IRB and the CSOC. For the current study, risks from dental cleaning using SADE are 
similar to traditional dental visits (e.g., gingival bleeding, mild discomfort). For a full list of 
potential risks, see Section 2.2.1.   
12.3.2 
Efficacy Review 
There are no interim analyses planned for this trial. Efficacy of the primary factor of environment 
will be determined as defined in the final analysis plan.   
12.4 
Final Analysis Plan 
Descriptive statistics will be performed for all variables of interest to describe the participant 
population at baseline, including attrition rate and missing data, to compare those randomized to 
SADE first vs. those randomized to RDE first. We anticipate a low attrition rate (~10%) and will 
impute missing data for intent-to-treat analyses using Markov Chain Monte Carlo (MCMC) 

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imputation with multiple values imputer for each missing value averaged for an estimation for 
analyses. Bivariate associations between outcomes (physiological anxiety and children’s 
negative behavioral responses), environment (SADE or RDE), and covariates (age, gender, 
order of visit, autism severity, IQ, and sensory sensitivity) will be described. The primary 
objective of determining difference between dental environments will be tested using intent-to-
treat models examining the within-subject factor of dental environment (SADE vs RDE) using 
repeated measures ANCOVA for each outcome. A priori covariates include age (continuous), 
randomized order of visit, gender, and temperature. Other participant characteristics that are 
unbalanced between order of visits will be included as covariates ad hoc.  
The secondary objective of examining the mediating effect of physiologic response on 
behavioral outcomes will be tested by first examining the bivariate relationships between EDA 
and behavioral outcomes, and then adding EDA estimates (SCL and NS-SCR) to models of 
dental environment difference on behavioral outcomes, and examining the change in the within 
group coefficients. A change in coefficient >15% will be considered evidence of mediation. 
While we have several outcomes, we specify only one mediator, thus we will apply a rational 
approach to examination of multiple outcomes, and will assess the fidelity of our study by 
estimating effect sizes (Cohen’s d) of the dental environment before and after the mediation 
factors are assessed to confirm that statistical results were supported by clinical relevance of 
findings. If physiological anxiety does mediate the environment’s effect on negative behavioral 
responses, we anticipate that the anticipated effect of environment will be eliminated once we 
add in EDA to the models specified in Hypothesis 2. Analyses will be performed using SPSS 
(v.22); a priori two-sided  = 0.05. 
 
Primary Objective: Hypothesis 1 
The primary objective is to test the effect of the environment (SADE vs RDE) on physiological 
anxiety. Hypothesis 1 specifies an effect of environment on the outcome, thus the main effect of 
interest will be B1, the dental environment.  
 
Hyp 1: EDA = B0 + B1*Environment + Covariates 
 
Secondary Objective 2: Hypothesis 2 
The secondary objective explores further outcomes and mechanisms of the group differences. 
Hypothesis 2 is analogous to those in the primary aim and have the same coefficients of 
interest. However, there are multiple, secondary outcomes including behavioral distress, 
perception of pain, and sensory discomfort). As noted above, we will apply a rational approach 
to examination of multiple outcomes and will assess effect sizes of the coefficients, in addition to 
the statistical significance. 
 
Hyp 2: Negative behavior  = B0 + B1*Environment + Covariates 
 
Secondary Objective 3: Hypothesis 3 
Hypothesis 3 seeks to test the degree to which physiological anxiety mediates the effect of the 
SADE intervention’s impact on negative behavior. To test this hypothesis, we will add to the 
model for Hypothesis 2 above and look at the change in the coefficient and effect size of B1 as 
well as the effect of EDA (B2) on negative behavior.  
 
Hyp 3: Negative behavior = B0 + B1*Environment + B2*EDA + Covariates 
 

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Secondary Objective 4: Hypotheses 4a & 4b 
Hypothesis 4 seeks to determine whether there is a moderating effect of EDA and negative 
behavior variables on the impact of the environment. It is anticipated that there is greater benefit 
of the SADE intervention for ASD children with greater ASD severity, decreased IQ, increased 
sensory over-responsivity, higher dental anxiety, and/or younger age.  These models are 
exploratory and will be assessed initial with each moderator alone. Then a stepwise regression 
model will be built to see if there are moderators that are more important than others. The 
previously described associations will assist us in determining if there is a risk of collinearity 
amongst the variables.  
 
Hyp 4: EDA or Negative behavior = B0 + B1*Environment + B2*Moderators + 
B3*(Environment*Moderators) + Covariates 
 
Secondary Objective 5: Hypotheses 5a & 5b 
Hypotheses 5a and 5b are similar, examining the environment difference on the costs and 
quality of care. The general model is presented below. Quality of care will be determined by 
scoring of pre- vs. post- intra-oral photographs on the OHI-S and PIaque Index measures. 
Health care costs are defined as personnel time burden, including direct costs of the 
intervention (e.g., training, materials, overhead, and direct patient care). The cost-effectiveness 
of the SADE intervention will be represented in the form of an incremental cost-effectiveness 
ratio of the cost (C) relative to the quality of care (E): (CSADE – CRDE)/(ESADE – ERDE).  
 
Hyp 5: Cost or Quality = B0 + B1*Environment  
 
These models are paired and will involve paired t-tests or non-parametric corollary for 
continuous outcomes if the outcome is normal or non-normally distributed, respectively. For 
dichotomous outcomes (e.g., need for sedation), McNemar’s test will be used to examined 
differences in need for the paired observations. 
 
Cost Effectiveness Analysis. In assessment of medical interventions, cost-effectiveness 
evaluations become increasingly relevant.72 Using this evaluation approach and the 
comparative intervention RDE as the reference standard, the cost-effectiveness of the SADE 
intervention will be represented in the form of an incremental cost-effectiveness ratio as: (C1 - 
C0)/(E1 - E0), where the subscript 1 refers to the SADE intervention arm and the subscript 0 
refers to the RDE comparative arm. C1 represents the average net cost of implementing the 
intervention; C0 represents the average net cost of the RDE comparative arm; E1 represents the 
quality of care associated with the SADE intervention; and E0 represents the quality of care 
associated with RDE. We will consider alternative effectiveness outcomes.  
 
We will use alternative measures of effectiveness in conducting our economic evaluation of the 
intervention. We will also combine several of the effectiveness scales into a measure of dental 
performance using structural equations models with unobservable dental health status as a 
latent variable in a multiple indicators, multiple causes framework.73 In this approach, all 
structural measures of dental treatment including patient functional status and patient outcome 
measures will be used as health status indicators, whereas clinical, environmental, and 
background characteristics will serve as causal factors in explaining dental health status 
changes. We will compute confidence intervals for the cost-effectiveness ratios using 
bootstrapping and develop cost-effectiveness acceptance curves.74 

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13 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
The study staff will maintain appropriate medical and research records for this study, in 
compliance with ICH E6, Section 4.9 and regulatory and institutional requirements for the 
protection of confidentiality of subjects.  Study staff will permit authorized representatives of 
NIDCR and regulatory agencies to examine (and when required by applicable law, to copy) 
research records for the purposes of quality assurance reviews, audits, and evaluation of the 
study safety, progress and data validity.   

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14 QUALITY CONTROL AND QUALITY ASSURANCE 
This study has a comprehensive manual of procedures (MOP), including standard operating 
procedures (SOP) for each study-related task.  
The research team will meet every other week to review structure and processes, identify any 
errors, and determine ways to prevent future errors. Dr. Leah Stein Duker (Co-I), who is 
responsible for implementation of staff training and quality assurance, will meet with the PI and 
Project Specialist on alternate weeks, and as needed in the interim times. When errors occur, 
we will consider the following: Are there adequate written procedures? Were the procedures 
followed? Was training done? Was it adequate? Is work being monitored? Are individual roles 
and responsibilities clear and defined? Clarifications and additions will be made as needed. 
All hard-copy documents will be visually checked by a member of the research team after 
completion and again prior to filing to ensure 100% completion of forms. All forms (parent-, 
child-, dentist-, and researcher-report forms) will be entered into our database and visually data 
checked to ensure quality and accuracy of data reporting; if there are more than 4-6 errors per 
1,000 entries, we will re-train data entry staff and check the subsequent 1,000 entries. If again 
there are more than 4-6 errors per 1,000 entries we will switch to double data entry in the Café 
Database. Additionally, 25% of all video-recordings and EDA recordings will be double-coded to 
ensure proper inter-rater reliability and adherence to scoring protocols.  
Dr. Leah Stein Duker (Co-I) will be responsible for addressing quality assurance issues by 
asking detailed questions of research members collecting data and visually inspecting one of 
every 10 child’s forms. Quality assurance/quality control tasks regarding data entry will include 
visual data checking by one independent research assistant. Following a noted discrepancy, the 
Project Coordinator, Research Assistant (OTD Resident), PhD Student, Project Specialist, or 
Dr. Stein Duker will check the source document to resolve disagreement, determine how the 
error was made (e.g., mis-entry, illegible handwriting, etc), and the correct data will be input into 
the Café database. Dr. Stein Duker will then review data entry processes with the data entry 
research team member who entered the data incorrectly, ensuring that no questions or 
confusion exists in regard to his/her job responsibilities. 
All training will be conducted by Dr. Stein Duker. Staff will complete mock administrations of all 
forms, including consent and assent. Video-recording training will occur on-site at CHLA 
regarding camera placement and goals of recordings. Video-recording coding training (how to 
code the CDBRS) will occur at USC. The training video will be viewed, questions will be asked 
of Dr. Stein Duker, and a minimum of 10 videos will be viewed and scored, ensuring inter-rater 
reliability with Dr. Stein Duker, with a minimum of 85% agreement. Training in the use of 
electrodermal equipment will include practice set-up and recording of volunteer students and 
other research team members. Training to understand psychophysiological concepts and 
administer and score EDA recordings will include five hour-long lectures and one hour-long 
laboratory activity by Dr. Dawson (Co-investigator and EDA expert) followed by practice scoring, 
supervised by Dr. Stein Duker. At least 10 recordings coded independently by the team member 
with a minimum of 85% agreement with Dr. Stein Duker will be required, ensuring inter-rater 
reliability on this measure. Dr. Stein Duker will also train all data entry staff on the use of the 
SADE database in the Café system, originally created for the R34 and modified for the U01.   

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15 ETHICS/PROTECTION OF HUMAN SUBJECTS 
 
15.1 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the principles set 
forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, as drafted by the US National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research (April 18, 1979) and codified in 45 CFR Part 
46 and/or the ICH E6; 62 Federal Regulations 25691 (1997).  
 
15.2 
Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IRB for review and approval. Approval of the protocol, consent form, and 
assent form will be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented in the study.   
Note. This study will obtain dual approval, as done in the R34 Pilot Study, from Children’s 
Hospital Los Angeles IRB (the Committee on Clinical Investigations) as well as the University of 
Southern California’s IRB (Health Sciences Review Board). 
 
15.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout study participation. Extensive discussion of risks and possible 
benefits of study participation will be provided to subjects and their families, if applicable. A 
consent form describing in detail the study procedures and risks will be given to the subject. 
Consent forms will be IRB-approved, and the subject will be required to read and review the 
document or have the document read to him or her. The investigator or designee will explain the 
research study to the subject and answer any questions that may arise. In order to assure that 
the subject understands, the investigator will ask the subject to verbally summarize what they 
are going to do. The subject will sign the informed consent document prior to any study-related 
assessments or procedures. Subjects will be given the opportunity to discuss the study with 
their surrogates or think about it prior to agreeing to participate. They may withdraw consent at 
any time throughout the course of the study. The rights and welfare of the subjects will be 
protected by emphasizing to them that the quality of their clinical care will not be adversely 
affected if they decline to participate in this study. 
Study assent forms will be used for children with ASD when appropriate. The study will be 
verbally described to the child and the child subject will be provided with a simplified form 
(assent) providing the details of the study intervention, study procedures, and potential risks. In 
order to assure that the child understands, the investigator will ask the child to verbally 
summarize what they are going to do. The child will then sign and date the assent. For those 
subjects who are unable to give assent based on their cognitive abilities, the subject will be 
informed about the trial to the extent compatible with the subject’s understanding. 
The original signed and dated consent/assent forms will be retained by the study staff. However, 
a second original of each form will be given to subjects for their records, and a copy of each 
form will be placed in the child’s CHLA dental chart.  

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Additionally, as this study will recruit both English- and Spanish-speaking families, 
professionally translated consent and assent documents will be available to parents and child. 
Additionally, appropriate study team members who are fluent in Spanish, will conduct the 
consent and assent procedures.  
The consent process will be documented in the clinical and research record. The NIDCR 
Informed Consent and Assent Documentation Checklist will be reviewed to be sure all aspects 
are included in the Consent (see Appendix L in MOP). The two documents, “Documenting the 
Consent Process” and “Suggestions for Consenting/Assenting Research Subjects/Participants” 
will be used as training tools and serve as a reminder of the tasks associated with adequate 
consent practices and documentation.   
15.4 
Exclusion of Women, Minorities, and Children (Special Populations) 
Our study excludes children younger than 6.0 years and older than 12.11 years, as well as 
participants (parents) who do not fluently speak English or Spanish. 
Age. Research indicates that younger age is associated with the presence of uncooperative 
behaviors in the dental operatory in children with ASD.75-77 Additionally, this project provides a 
conceptual replication and extension of Shapiro et al.’s previous work50-51 with children with 
developmental disabilities (other than ASD) in Israel; in this study a similar age-range was used. 
Language. Participants will be recruited primarily from CHLA and LAUSD, which provides 
services to an ethnically diverse population, with approximately 60-70% Hispanic/Latino. 
Therefore, we anticipate that the majority of our sample will be either English- or Spanish-
speaking. Additionally, some of the tools we will be using have only been validated in English 
and Spanish.  
15.5 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the sponsor(s) 
and their agents. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to any study information relating to subjects. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. Only the Principal Investigator, Dr. Leah Stein Duker (Co-I and responsible for 
training and quality assurance), the Project Specialist, and members of the research staff 
collecting or participating in data entry will have access to study records (e.g., forms, video-
recordings, EDA recordings, etc.). No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the Principal 
Investigator.  
The study monitor, representatives of the NIDCR, and IRB representatives may inspect all study 
documents and records required to be maintained by the investigator, including but not limited 
to, all CRFs, video-recordings, intra-oral photographs, and EDA recordings for the study 
subjects. The study site (office containing CRF, etc. storage, not CHLA where intervention is 
performed) will permit access to such records.  
 

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15.6 
Future Use of Stored Specimens and Other Identifiable Data 
 
The consent form will include, as one of its stipulations, the agreement to have the child’s oral 
cleaning and ADOS assessment videotaped. Assurances related to secure storage of data will 
be provided. As video-recordings will be utilized for coding training purposes, the recording itself 
will not be de-identified (children may be called by their first name by the dental professional or 
parent during the oral cleaning or by the psychologist during the ADOS and child’s face will be 
seen in videos), but video files will only be named via identification number. EDA recordings and 
intra-oral photographs will likewise be named via identification number. 
All video data, electrodermal data, photographs, completed documents, questionnaires, and 
CRFs will be personally transported to USC in a privately owned vehicle by a research team 
member immediately following collection at CHLA. Electronic data (video-recordings, EDA 
recordings, and intra-oral photographs) will be transferred onto a secure server in the Division of 
Occupational Science and Occupational Therapy where it will be password protected so that 
only members of the research team may access it. The primary server is backed up twice a day 
in California as well as replicated to a remote site in Arizona once a night. Primary back-ups are 
retained for 31 days, at which point a monthly tape back-up is made. Additional back-up copies 
will be kept on an external hard drive that will be stored in a locked cabinet in the Principal 
Investigator’s office.  
The hard-copy documents (completed ADOS assessments, questionnaires, and CRFs) will be 
kept in a locked file cabinet in Lucía Floríndez’s (Bilingual Project Coordinator) office. The key to 
the identification code will be stored in a locked file in Dr. Sharon Cermak’s personal office. 
Hard-copy documents, video- and EDA recordings, and intra-oral photographs will be stored for 
six years following the completion of the study.  
Additionally, as part of the consent form, parent(s) and children (if able) will have the option to 
have the child participant’s dental cleaning video utilized in publications and/or professional 
conferences. When the results of the research are published or discussed at conferences no 
information will be included that would reveal any participant’s identity; however, the child’s face 
may be viewed with permission from the parent. 
Genetic testing will not be performed. 
Per CHLA’s new policy that is related to COVID-19, new procedures were implemented to 
protect the safety of the participant and parent/legal guardian. A nasopharyngeal swab is 
collected during the COVID-19 testing at the COVID-19 Testing Clinic at CHLA and will be 
labeled, bagged, and sent to their lab. The management of the sample is at CHLA and not USC. 
The study team will follow the CHLA guidelines and requirements until notified that CHLA has 
discontinued the process.  
 

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16 DATA HANDLING AND RECORD KEEPING 
The investigators are responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. All source documents should be completed in a neat, legible 
manner to ensure accurate interpretation of data. The investigators will maintain adequate case 
histories of study subjects, including accurate case report forms (CRFs), and source 
documentation.  
Data will be retained for a minimum of six years following closure of the study; identifiers will be 
destroyed at the end of the study. Data will only be shared with members of our research team. 
Video and electrodermal data will be stored on a secure server in the Division of Occupational 
Science and Occupational Therapy where it will be password protected so that only members of 
the research team may access it. The primary server is backed up twice a day in California as 
well as replicated to the remote site once a night (in Arizona); primary back-ups are retained for 
31 days, at which point a monthly tape back-up is taken. After the completion of the study, back-
up copies will be kept on an external hard drive that will be stored in a locked cabinet in the 
Principal Investigator’s office. After the completion of the study, original documents, including 
questionnaires and data collection sheets, will also be kept in a locked cabinet in Dr. Stein 
Duker’s (Co-I) or Dr. Cermak’s (PI) office. Original hard copies of our consent, assent, and 
HIPAA documents will be kept in a locked, secure cabinet in the Principal Investigator’s office.  
16.1 
Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff under the 
supervision of the investigator. All source documents and CRFs must be reviewed by the study 
team and data entry staff, who will ensure that they are accurate and complete. Unanticipated 
problems and adverse events must be reviewed by the Principal Investigator.   
All data will be entered into a database (Café) created for our R34 Pilot study and updated for 
our U01 study. This database was developed and programmed by the University of Southern 
California Cancer Research Informatics Core (CRIC). All data will be entered by trained 
members of our research team, and data will be exported by our statistician, Dr. Cheryl Vigen 
(Co-I); the role of CRIC as our data coordinating center will be adding new forms and updating 
existing forms, troubleshooting if any questions and/or problems arise using the Café database 
throughout our study and summary reports delivered every other month. 
16.2 
Data Capture Methods 
All data collected, with the exception of video-recordings, EDA recordings, and intraoral 
photographs will be paper documents. Video-recordings, EDA recordings, and intraoral 
photographs will be electronic in nature. Paper documents will be entered into our secure and 
password-protected database (Café) by trained research assistants; data entries will be visually 
checked by a second trained research assistant, ensuring accuracy and quality control of data 
entry. The original copies of these paper forms will be securely stored in a locked cabinet in 
CHP 222-W. All consent and assent forms will also be stored in a locked cabinet in the PI’s 
office (CHP 222-V). 
Video- and EDA recordings and intra-oral photographs will be transferred to a secure computer 
server that is backed-up nightly and is accessible to only those with the correct security 
clearance and password; original files (e.g., the camera recording stored on the camera) will 

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then be deleted. After these recordings are scored and recorded onto the appropriate CRF, the 
scored data will also be entered into our Café Database system.  
Data entry of paper forms will occur within 8 weeks following the visit; visual data checking will 
occur by two months. Entry of data that requires coding and/or double coding prior to database 
entry (e.g., CDBRS score from video-recordings, SCL/NS-SCR data from EDA data; oral 
hygiene measures from intra-oral photographs) will occur within six months of the visit. Data will 
be continuously entered into our database throughout the study, but will undergo batched 
processing following the locking of the database when study activities are completed. 
Data will be centralized. All data will be collected either at the subject’s home (child-descriptor 
assessments) or at CHLA (ASD diagnosis confirmation, IQ assessment, dental cleaning 
assessments). However, all system components (research staff, clerical staff, software 
applications, servers, locked cabinets, etc.) will be located at SADE-dedicated space in the USC 
Division of OS-OT located on the Health Sciences Campus.  
16.3 
Types of Data 
Data collected will include descriptive data of the participants and outcome measure data. 
Descriptive data characterizing the participants will include questionnaire responses from 
parents and children. Outcome measure data will include questionnaire responses from children 
and dental professionals, oral health indices, physiological recordings from children, and video-
recordings of children undergoing dental cleanings (See CRFs 5-23 for a list of all child-
descriptor and outcome measures; see Appendix A for Schedule of Events).  
As our intervention modifies the dental environment and does not change the traditional dental 
cleaning protocol, we will question parents and dental professionals regarding adverse events 
and serious adverse events as our safety data collection. This will occur prior to and following 
each dental visit, and information will be stored in the same secure Café database as our other 
data. 
16.4 
Schedule and Content of Reports 
Reports to monitor enrollment will occur monthly and will include a de-identified list of children 
as well as their gender, race, ethnicity, and age. This will be generated and maintained by Ms. 
Annie Hong, Project Specialist. 
Reports for study progress will occur two times per year and will contain preliminary descriptive 
analyses of all child-descriptor variables; these will be conducted by our statistician, Dr. Vigen 
(Co-I). 
The database will be locked by the Café database CRIC administrator prior to data export by 
our statistician for final data analysis.  
16.5 
Study Records Retention 
Study records will be maintained for at least six years from the date that the grant federal 
financial report (FFR) is submitted to the NIH. 
16.6 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical 
Practice, or Manual of Procedures requirements. The noncompliance may be on the part of the 

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subject, the investigator, or study staff. As a result of deviations, corrective actions are to be 
developed by the study staff and implemented promptly. 
These practices are consistent with investigator and sponsor obligations in ICH E6: 
 
Compliance with Protocol, Sections 4.5.1, 4.5.2, 4.5.3, and 4.5.4 
 
Quality Assurance and Quality Control, Section 5.1.1 
 
Noncompliance, Sections 5.20.1 and 5.20.2 
All deviations from the protocol will be addressed in study subject source documents and 
promptly reported to NIDCR and the local IRB, according to their requirements.   

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17 PUBLICATION POLICY 
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final 
peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. 
Study results will be made available as soon as possible. Final peer-reviewed journal 
manuscripts that arise from NIH funds will be submitted to the digital archive PubMed Central 
immediately upon acceptance for publication. The MyNCBI’s My Bibliography feature will be 
used to monitor Public Access Compliance. 
The Principal Investigator will inform the NIDCR Project Officer of manuscripts and 
presentations prior to publication. All publications and presentations will be shared with NIDCR. 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted 
a clinical trials registration policy as a condition for publication. The ICMJE defines a clinical trial 
as any research project that prospectively assigns human subjects to intervention or concurrent 
comparison or control groups to study the cause-and-effect relationship between a medical 
intervention and a health outcome. Medical interventions include drugs, surgical procedures, 
devices, behavioral treatments, process-of-care changes, and the like. Health outcomes include 
any biomedical or health-related measures obtained in patients or participants, including 
pharmacokinetic measures and adverse events. The ICMJE policy requires that all clinical trials 
be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the 
National Library of Medicine. Other biomedical journals are considering adopting similar 
policies. For interventional clinical trials performed under NIDCR grants and cooperative 
agreements, it is the grantee’s responsibility to register the trial in an acceptable registry, so the 
research results may be considered for publication in ICMJE member journals. The ICMJE does 
not review specific studies to determine whether registration is necessary; instead, the 
committee recommends that researchers who have questions about the need to register on the 
site of registration, or consult the editorial office of the journal in which they wish to publish. 
U.S. Public Law 110-85 (Food and Drug Administration Amendments Act of 2007 or FDAAA), 
Title VIII, Section 801 mandates that a "responsible party" (i.e., the sponsor or designated 
principal investigator) register and report results of certain "applicable clinical trials."  
This study will follow USC guidelines in regard to developing publication procedures to resolve 
authorship issues.  

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18 LITERATURE REFERENCES 
 
1. 
Silver, E.J. & Stein, R.E.K. (2001). Access to care, unmet health needs, and poverty 
status among children with and without chronic conditions. Ambulatory Pediatrics,1, 314-
320.  
 
2. 
DeMattei, R., Cuvo, A., & Maurizio, S. (2007). Oral assessment of children with autism 
spectrum disorder. Journal of Dental Hygiene, 81, 65-76.  
 
3. 
Seirawan, H., Schneiderman, J., Greene, V., & Mulligan, R. (2008). Interdisciplinary 
approach to oral health for persons with developmental disabilities. Special Care in 
Dentistry, 28, 43-52. 
 
4. 
American Psychiatric Association (2013). Diagnostic and statistical manual of mental 
disorders (5th ed.).. Arlington, VA: American Psychiatric Publishing.   
 
5. 
Kopycka-Kedzierawski, D.T., & Auinger, P. (2008). Dental needs and status of autistic 
children: Results from the national survey of children’s health. Pediatric Dentistry, 30, 
54-58. 
 
6. 
Marshall, J., Sheller, B., & Mancl, L. (2010). Caries-risk assessment and caries status of 
children with autism. Pediatric Dentistry, 32, 69-75. 
 
7. 
Child and Adolescent Health Measurement Initiative (2011). National survey of children 
with special health care needs 200-10 [Online data set]. Retrieved from 
http://www.childhealthdata.org/browse/survey?s=1 
 
8. 
Jaber, M. A. (2011). Dental caries experience, oral health status and treatment needs of 
dental patients with autism. Journal of Applied Oral Science, 19(3), 212-217. 
 
9. 
Klein, U., & Nowak, A. (1999). Characteristics of patients with autistic disorder (AD) 
presenting for dental treatment: A survey and chart review. Special Care in Dentistry, 19, 
200-207. 
 
10. 
Fahlvik-Planefeldt, C. & Herrstrom, P. (2001). Dental care of autistic children within the 
non-specialized Public Dental Service. Swedish Dental Journal, 25, 113-118.  
 
11. 
Loo, C.Y., Graham, R.M., and Hughes, C.V. (2008). The caries experience and behavior 
of dental patients with autism spectrum disorder. Journal of the American Dental 
Association, 139, 1518-1524. 
 
12. 
Morinushi, T., Ueda, C., Tanaka, C., (2001). Autistic children: experience and severity of 
dental caries between 1980 and 1995 in Kagoshima City, Japan. Journal of Clinical 
Pediatric Dentistry, 25(4), 323-328. 
 

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13. 
Centers for Disease Control and Prevention (2014). Autism spectrum disorders: Data 
and statistics. Retrieved from http://www.cdc.gov/ncbddd/autism/data.html. 
 
14. 
U.S. Department of Health and Human Services, National Institute of Dental and 
Craniofacial Research (2014). Practical oral care for people with autism (NIH Publication 
No. 04-5190). Retrieved from 
http://www.nidcr.nih.gov/OralHealth/Topics/DevelopmentalDisabilities/PracticalOr
alCarePeopleAutism.htm 
 
15. 
Miller-Kuhaneck, H. (2008). Going to the Dentist. Sensory Processing Disorder 
Foundation. Retrieved from http://www.spdfoundation.net/library/dentist.html.  
 
16. 
Tomcheck, S. D. (2010). Sensory processing in individuals with an autism spectrum 
disorder. Autism: A comprehensive occupational therapy approach, 135-161. 
 
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LIST OF APPENDICES 
 
Appendix A: Schedule of Events 
 
Appendix B: Case Report Forms 
 
Appendix C: Visual Representation of Dental Cleaning Sequence of Events 
 
Appendix D: Pictures of SADE Set-Up from R34 Pilot Study 
 
Appendix E: Pictures of R34 Pilot Study “Butterfly” 
 
Appendix F: Equipment Checklist 
 
Appendix G: Equipment Set-Up Checklist