A Clinic-randomized Trial of a Clinical Decision Support System to Improve Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals
Phase: NA
Conditions: Smoking
Sponsor: HealthPartners Institute

A Clinic-Randomized Trial of a Clinical Decision Support System to Improve  
Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
Version 9.0 
Protocol 16-069-E 
12Jan2021 
i 
A Clinic Randomized Trial of Clinical Decision 
Support System to Improve Dental Provider 
Delivery of Brief Tobacco Interventions and 
Quitline Referrals 
NIDCR Grant Number: U01 DE026135 
Protocol Number: 16-069-E 
Principal Investigators:  
D Brad Rindal, DDS and Heiko Spallek, DMD, PhD, MSBA 
NIDCR Program Official: Melissa Riddle, PhD 
NIDCR Medical Monitor: Kevin McBryde MD 
Draft or Version Number: 9.0 
12 January 2021 

A Clinic-Randomized Trial of a Clinical Decision Support System to Improve  
Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
Version 9.0 
Protocol 16-069-E 
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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on 
Harmonization 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.  

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Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
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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 Investigators: 
Signed: 
Date: 1/25/2021 
Name: D. Brad Rindal, DDS 
Title: Co-Principal Investigator 
Signed: 
Date: 1/29/2021
Name: Heiko Spallek, DMD, PhD, MSBA 
Title: Co-Principal Investigator 

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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ................................................................................................ II 
SIGNATURE PAGE ................................................................................................................... III 
TABLE OF CONTENTS ............................................................................................................ IV 
LIST OF ABBREVIATIONS ...................................................................................................... VII 
PROTOCOL SUMMARY ......................................................................................................... VIII 
1 
KEY ROLES AND CONTACT INFORMATION ................................................................ XII 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....... 14 
2.1 
Rationale .............................................................................................................. 15 
2.2 
Potential Risks and Benefits ................................................................................. 15 
2.2.1 
Potential Risks .......................................................................................... 15 
2.2.2 
Potential Benefits ...................................................................................... 15 
3 
OBJECTIVES ................................................................................................................... 17 
3.1 
Study Objectives ................................................................................................... 17 
3.2 
Study Outcome Measures .................................................................................... 17 
3.2.1 
Primary Objective ...................................................................................... 17 
3.2.2 
Secondary Objectives ............................................................................... 18 
3.3 
Independent variables and descriptive variables ................................................... 18 
4 
STUDY DESIGN .............................................................................................................. 22 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................. 23 
5.1 
Subject Inclusion Criteria ...................................................................................... 23 
5.2 
Subject Exclusion Criteria ..................................................................................... 23 
5.3 
Strategies for Recruitment and Retention ............................................................. 23 
5.4 
Treatment Assignment Procedures ....................................................................... 24 
5.4.1 
Randomization Procedures ....................................................................... 24 
5.4.2 
Masking Procedures .................................................................................. 25 
5.5 
Subject Withdrawal ............................................................................................... 25 
5.5.1 
Reasons for Withdrawal ............................................................................ 25 
5.5.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention ............................................................................................... 25 
5.6 
Premature Termination or Suspension of Study .................................................... 26 
6 
STUDY INTERVENTION .................................................................................................. 27 
6.1 
Study Behavioral or Social Intervention(s) Description .......................................... 27 
6.2 
Administration of Intervention ................................................................................ 27 
6.3 
Procedures for Training Interventionists and Monitoring the Quality of the 
Provider Behavior Measures ................................................................................. 28 
6.4 
Assessment of Subject Compliance with Study Intervention ................................. 28 
6.5 
Study Procedural Intervention(s) Description ........................................................ 28 
6.6 
Administration of Procedural Intervention .............................................................. 29 
6.7 
Procedures for Training of Clinicians on Procedural Intervention .......................... 29 
6.8 
Assessment of Clinician and/or Subject Compliance with Study Procedural 
Intervention ........................................................................................................... 29 
7 
STUDY SCHEDULE ......................................................................................................... 30 

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7.1 
Screening ............................................................................................................. 30 
7.2 
Enrollment/Baseline .............................................................................................. 30 
7.3 
Intermediate Visits ................................................................................................ 30 
7.4 
Final Study Visit .................................................................................................... 30 
7.5 
Withdrawal Visit .................................................................................................... 30 
7.6 
Unscheduled Visit ................................................................................................. 31 
8 
STUDY PROCEDURES /EVALUATIONS ........................................................................ 32 
8.1 
Study Procedures/Evaluations .............................................................................. 32 
8.2 
Laboratory Procedures/Evaluations ...................................................................... 33 
9 
ASSESSMENT OF SAFETY ............................................................................................ 34 
9.1 
Specification of Safety Parameters ....................................................................... 34 
9.1.1 
Adverse Events ......................................................................................... 34 
9.1.2 
Serious Adverse Events ............................................................................ 34 
9.2 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 35 
9.3 
Characteristics of an Adverse Event ..................................................................... 35 
9.3.1 
Relationship to Study Intervention ............................................................. 35 
9.3.2 
Expectedness of SAEs .............................................................................. 36 
9.3.3 
Severity of Event ....................................................................................... 36 
9.4 
Reporting Procedures ........................................................................................... 36 
9.5 
Halting Rules ........................................................................................................ 37 
10 
STUDY OVERSIGHT ....................................................................................................... 38 
11 
STATISTICAL CONSIDERATIONS .................................................................................. 39 
11.1 
Primary Objective ................................................................................................. 39 
11.2 
Secondary Objectives ........................................................................................... 39 
11.3 
Sample Size Considerations ................................................................................. 39 
11.4 
Planned Interim Analyses (if applicable) ............................................................... 40 
11.4.1 Safety Review ........................................................................................... 40 
11.4.2 Efficacy Review ......................................................................................... 40 
11.5 
Analysis Plan ........................................................................................................ 40 
12 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................. 43 
13 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................ 44 
14 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 46 
14.1 
Ethical Standard ................................................................................................... 46 
14.2 
Institutional Review Board .................................................................................... 46 
14.3 
Informed Consent Process ................................................................................... 46 
14.4 
Exclusion of Women, Minorities, and Children (Special Populations) .................... 46 
14.5 
Subject Confidentiality .......................................................................................... 47 
14.6 
Future Use of Identifiable Data ............................................................................. 47 
15 
DATA HANDLING AND RECORD KEEPING ................................................................... 48 
15.1 
Data Management Responsibilities ....................................................................... 48 
15.2 
Data Capture Methods .......................................................................................... 48 
15.3 
Types of Data ....................................................................................................... 48 
15.4 
Schedule and Content of Reports ......................................................................... 48 
15.5 
Study Records Retention ...................................................................................... 48 

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15.6 
Protocol Deviations ............................................................................................... 48 
16 
PUBLICATION/DATA SHARING POLICY ........................................................................ 50 
17 
LITERATURE REFERENCES .......................................................................................... 51 
SEE PROTOCOL APPENDICES FOR RELEVANT SUPPLEMENTAL MATERIALS. ............... 56 
 

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LIST OF ABBREVIATIONS 
Acronym or 
Abbreviation 
Term 
5As 
Ask, Advise, Assess, Assist, Arrange 
AE 
Adverse Event/Adverse Experience 
AHRQ 
Agency for Healthcare Research & Quality 
BI 
Brief intervention 
CDS 
Clinical Decision Support 
CE 
Continuing Education 
CFR 
Code of Federal Regulations 
CI 
Contextual Inquiry 
DH 
Dental Hygiene (e.g., DH students, DH clinics) 
DHHS 
Department of Health and Human Services 
DTA 
Data Transfer Agreement 
DUA 
Data Use Agreement 
EHR 
Electronic Health Record 
FHIR 
Fast Healthcare Interoperability Resources 
HIT 
Health Information Technology 
HITECH 
Health Information Technology for Economic and Clinical Health Act  
HPI 
HealthPartners Institute 
IOM 
Institute of Medicine 
IRB 
Institutional Review Board 
NIDCR 
National Institute of Dental and Craniofacial Research, NIH, DHHS 
NIH 
National Institutes of Health 
PBRN 
Practice-Based Research Network 
predoc 
Predoctoral (e.g., predoc students, predoc clinics) 
REDCap 
Research Electronic Data Capture 
RT 
Referral to treatment 
SBIRT 
Screening, Brief Intervention, Referral to Treatment 
SRC 
Survey Research Center 
TDQ 
US 
Theoretical Domain Questionnaire 
United States 
 
 
 
 
 
 
 

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Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
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PROTOCOL SUMMARY 
Title:  
A Clinic-Randomized Trial of a Clinical Decision Support 
System to Improve Dental Provider Delivery of Brief 
Tobacco Interventions and Quitline Referrals 
 
Précis: 
Use of clinical decision support (CDS) within electronic health 
record systems (EHR) holds much potential to improve the 
translation of current scientific evidence into clinical practice and 
improve the delivery of optimal, evidence-based, personalized 
treatment. Health care providers have access to evidence-
based guidelines that help patients quit smoking. Translation of 
that knowledge and awareness into daily practice, however, 
remains low.  
This clinic-randomized trial will examine the rate at which dental 
providers deliver a smoking intervention and refer to a quitline 
when their EHR system includes health information technology 
(HIT)-driven CDS compared with providers in control clinics 
without assistance from the CDS. Providers include experienced 
dentists, dental therapists, and dental hygienists in private 
practices and predoctoral and dental hygiene students in dental 
schools. The primary outcome is a binary variable indicating 
whether the provider delivered a brief intervention or referral for 
treatment, as reported by the patient. Additional outcomes 
include patient self-reported actions toward quitting, smoking 
reduction, and smoking cessation. Provider-level barriers, 
facilitators, and potential mechanisms accounting for the effect 
of tobacco CDS will be examined. Using EHRs to translate 
current evidence into dental practice holds much potential yet is 
unrealized in both clinical training and practice. By leveraging 
the dental encounter as an opportunity to deliver smoking 
cessation, we can further decrease smoking rates, leading to 
improved population health.  
 
Objectives: 
Objective 1 (primary): Assess if the CDS increases the 
frequency of BI (Brief Intervention) delivery and/or RT (Referral 
to Treatment) at an index dental visit as compared to treatment 
as usual as reported by patients within 7 days of the index visit. 
  
Objective 2 (secondary): Test the efficacy of the CDS on 
smokers’ initial actions related to cessation (contacting a quitline 
and/or setting a quit date and/or developing a plan to quit and/or 

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starting nicotine replacement or other medication to help quit 
within 7 days) as compared to treatment as usual. 
  
Objective 3 (secondary): Test the efficacy of the CDS on 
smokers’ long term actions related to cessation (quitting 
smoking and/or reducing their smoking within 6 months) as 
compared to treatment as usual.  
 
Objective 4 (exploratory): Identify provider-level barriers and 
facilitators of the effect of the CDS, and test potential mediators 
and moderators of the CDS. 
 
Population: 
• Practitioners. Up to 88 dental hygienists and 88 dentists 
working in up to 22 private practice settings and 360 
predoctoral and 65 dental hygiene students in two dental 
schools will be recruited to the trial. 
• Patients. 720 adult smokers with routine dental visits in 
dental school settings and 720 adult smokers with routine 
dental visits in private practice settings seen by 
practitioners enrolled in the trial are eligible for enrollment 
in order to achieve 430 completed surveys in each 
setting.  
 
Phase: 
Phase 3 clinical trial 
Number of Sites: 
This study will be conducted in up to 14 clinic modules within 
two dental school programs and 22 private practice clinics.  
The School of Dental Medicine at the University of Pittsburgh 
(Pitt) and the Indiana University School of Dentistry (Indiana) 
have been selected as study sites for this project based on their 
emphasis on teaching smoking interventions as part of their 
predoctoral and dental hygiene (predoc/DH) curriculum.  
Up to 22 private-practice clinics having 1-5 dentists and 1-10 
hygienists will be engaged by recruiting volunteers convenience 
sampled from dentists and dental hygienists participating in the 
National Dental PBRN or otherwise recruited through existing 
relationships with HealthPartners, the University of Pittsburgh, 
and Indiana University. 
 
Description of 
The intervention is dental provider exposure to an HIT-driven 

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Intervention: 
CDS tool. The CDS tool generates evidence-based, guideline-
driven provider script sets to assist in the delivery of cessation 
support to smoking patients. A rule-based algorithm 
personalizes the scripts to account for patients’ current smoking 
status and interest in quitting. A user-centered design approach 
underpins the CDS tool design that is expected to be delivered 
in 2 - 5 minutes to remain feasible among the management of 
multiple priorities in the patient encounter. Provider training will 
be composed of two components: 1) Clinical practice guideline 
knowledge (intervention and control clinics) and 2) CDS 
functionality (intervention clinics only). 
Study Duration: 
60 months 
Subject 
Participation 
Duration: 
Patients in dental schools and private practices: 7 months. 
Patient smokers will be surveyed within one week of the index 
dental visit and 6 months +/-1 week after the dental visit to 
assess the delivery of tobacco cessation interventions during 
the dental visit and patient actions related to tobacco use. 
Dental students, dental hygiene students, dentists, and 
hygienists: 21 months. Practitioners will be recruited for up to 15 
months. Upon randomization of respective clinics or clinic 
modules, providers will render usual care in either the CDS-
supported intervention study arm or the control arm for 21 
months.  
Estimated Time to 
Complete 
Enrollment: 
36 months. Initial communication, recruitment, and training of 
providers will occur on a rolling basis over 15 months. Practices 
will have 21 months to see up to 45 eligible and willing patients 
per clinic/clinic module, to complete the provider follow-up 
study, and to have the intervention in place in the clinic/clinic 
module setting long enough to plausibly see an effect. 
 

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Figure 1. Schematic of Study Design 
 

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1 
KEY ROLES AND CONTACT INFORMATION 
Principal 
Investigators:  
D. Brad Rindal, Co-Principal Investigator 
HealthPartners Institute 
8170 33rd Avenue South, MS 23301A, Bloomington, MN, 55425 
Phone: 952-967-75026 Email: Donald.B.Rindal@HealthPartners.com  
Heiko Spallek, DMD, PhD, MSBA, Co-Principal Investigator 
University of Sydney, Faculty of Dentistry  
1 Mons Road, Westmead, NSW, 2145 Australia 
Phone: + 61 439 320 490 Email: heiko.spallek@sydney.edu.au 
 
Medical Monitor: 
Kevin McBryde, MD 
Division of Extramural Research, NIDCR, NIH 
6701 Democracy Blvd, RM:638, Bethesda MD 20892-4878 
Phone: (301) 594-0170 Email: mcbrydekd@mail.nih.gov  
 
NIDCR Program 
Official:  
Melissa Riddle, PhD 
Behavioral and Social Sciences Research Branch, NIDCR, NIH 
6701 Democracy Blvd. RM:650, Bethesda, MD 20892-4878 
Phone: (301) 451-3888 Email: riddleme@mail.nih.gov 
 
Clinical Site 
Investigators: 
 
Jean O’Donnell, BSN, MSN, DMD 
University of Pittsburgh School of Dental Medicine 
Phone: 412-648-8672 Email: jao4@pitt.edu  
Laura Romito, DDS, MS 
Indiana University School of Dentistry 
Phone: 317-278-6210 Email: lromitoc@iu.edu  
Thankam Thyvalikakath, DMD, MDS, PhD 
Indiana University School of Dentistry 
Phone: 317-274-5460 Email: tpt@iu.edu  
Tom Kottke, MD, MSPH 
HealthPartners Institute  
Phone: 651-330-4782 
Email: Thomas.E.Kottke@HealthPartners.Com  
Mark Jurkovich, DDS, BA, MHI 
HealthPartners Institute 
Phone: 952-967-5016 
Email: Mark.W.Jurkovich@HealthPartners.com 
 
 

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Institutions: 
HealthPartners Institute 
8170 33rd Ave. S, MS 23301A, Bloomington, MN, 55425 
University of Pittsburgh School of Dental Medicine 
3501 Terrace St., Pittsburgh, PA 15261 
Indiana University School of Dentistry 
1121 West Michigan St., Indianapolis, IN 46202 
 
 
Other Key Personnel: 
Research Methodology and Analysis Team 
Jeanette Ziegenfuss, PhD (evaluation) 
HealthPartners Institute, Survey Research Center 
Phone: 952-967-5020  
Email: Jeanette.Y.Ziegenfuss@HealthPartners.com  
Steve Asche, MA (analysis) 
HealthPartners Institute 
Phone: 952-967-5018  
Email: Steve.E.Asche@HealthPartners.com  
Tanja Bekhuis, PhD, MS, MLIS, AHIP (methodology)  
TCB Research & Indexing LLC 
1007 Parkview Boulevard, Suite B 
Pittsburgh, PA 15217 
Phone: 570-412-2663  
Email: tanja.bekhuis@tcbinfosci.com  
 
Interoperability Consultant 
John Halamka, MD, MS 
Beth Israel Deaconess Medical Center 
1135 Tremont Street, 6th floor, Boston, MA 02120 
Phone: 617-754-8002 
Email: jhalamka@bidmc.harvard.edu  
 
 
Other staff: 
Emily Durand RDH, Principal Project Manager 
HealthPartners Institute 
Phone: 952-967-7404  
Email: Emily.C.Durand@HealthPartners.com  
Chris Enstad, Project Manager 
HealthPartners Institute  
Phone: 952-967-5007  
Email: Chris.J.Enstad@HealthPartners.com 

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2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
Cigarette smoking is a major modifiable risk factor for adverse health outcomes and a 
major cause of morbidity and mortality (2). Cigarette smoking prevalence among all 
adults ≥18 years has decreased 42.4% since 1965, but declines in current smoking 
prevalence have slowed dramatically, from 20.9% in 2005 to 19.3% in 2010 (3). The 
Healthy People 2010 objective of reducing smoking among adults to ≤12% has not 
been achieved, necessitating new strategies to achieve that goal (4). One of the 3 key 
tobacco use objectives cited is focused on health system changes to increase access, 
affordability, and the use of smoking cessation services and treatments (5). The 
National Commission on Prevention Priorities ranking of clinical preventive services 
identified tobacco-use screening and brief intervention as one of the top 3 most cost-
effective preventive services delivered by health care providers, yet rates of delivery 
remain low (6). 
Evidence-based clinical practice guidelines on smoking cessation for health care 
providers are readily available to clinicians and recommend that different types of 
providers (i.e., physicians, nurses, dentists, psychologists, social workers, cessation 
counselors, and pharmacists) become involved in smoking cessation because, 
collectively, they can enhance abstinence rates(7). Despite this, providers are missing 
opportunities to treat smoking with their patients as recommended (8-10). Limited time 
during the office visit, lack of expertise, and concern about failure (provider self-efficacy) 
are often cited as barriers to providing consistent treatment (11). Similar barriers have 
been identified in the dental setting (12). Previous dissemination and implementation 
research suggests that simply delivering information to providers rarely changes clinical 
practice (13-16) and that “available knowledge is too rarely applied to improve the care 
experience” (17). Passive dissemination of materials, development of clinical guidelines, 
and knowledge generation through professional continuing education (CE) courses 
generally have not been effective in demonstrating an impact on provider behavior and 
clinical outcomes (18-20). Thus, our approach directly activates the provider at the point 
of care by using HIT-driven CDS to generate scripts for provider use that are 
personalized on specific smoking attributes. 
State quitline services could serve a large percentage of US smokers, yet they are 
underutilized. Delivery of services is required in order for quitlines to fulfill their potential 
of improving the health of the US population (21). Increased referral by health care 
providers, including dental providers, may be part of the solution to fully harness this 
potential. Ebbert et al determined that dental providers with limited time and resources 
were able to assist patients who smoke by referring them to a tobacco quitline (22). 
Various strategies to increase smoking cessation activities in the dental office setting 
have been investigated (23-25) and have focused on the delivery of brief interventions 
and quitline referral.  

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2.1 Rationale 
By leveraging the dental encounter as an opportunity to deliver a smoking cessation 
intervention, we will employ an important strategy to decrease smoking rates and 
improve population health. This clinical trial will determine the degree to which the 
deployment of health information technology (HIT)-driven clinical decision support 
(CDS) for smoking interventions in two different dental settings, private practices and 
dental school, will increase cessation assistance by dental providers. Incorporating 
smoking-cessation CDS into the clinical curriculum for dental providers (dentists and 
dental hygienists) can be expected to make smoking cessation counseling part of the 
accepted routine of dental practice because dental providers initially model care the way 
they learned it in school (12, 45, 46). Health care providers have access to evidence-
based guidelines that help patients quit smoking (47, 48). Translation of that knowledge 
and awareness into daily practice, however, remains low (26, 49, 50). CDS that reminds 
and helps providers deliver smoking cessation interventions by providing evidence-
based information during care delivery in a clinically relevant format holds the potential 
to facilitate an evidence-based practice approach (51). 
2.2 Potential Risks and Benefits 
2.2.1 Potential Risks 
Risks to both patients and providers are considered minimal and involve consideration 
of the risk of violation of confidentiality of study data.  
Practitioners. No identifying information on individual provider or student performance 
with respect to the clinical domains addressed in this study or any other aspect of care 
gathered as part of this research project will be made available to leaders or managers 
who make academic, employment, compensation, or disciplinary decisions.  
Patients. Potential risks to patients include the possibility that the intervention may 
provide clinical decision support (CDS) advice to providers on the basis of the national 
evidence-based guidelines, which may be inappropriate for a given individual patient 
and, if applied without further checking the clinical status of a given patient, could lead 
to erroneous therapy, adverse events, disability, or death. However, the clinical 
recommendations are evidence-based and operationalize current national and regional 
standards of care and, therefore, the risk of untoward consequences of such clinical 
actions is considered minimal. Moreover, this potential risk is routinely present in every 
clinical encounter in the health care system. As with any study, additional risks to 
patients include principally the risk of violation of confidentiality. Measures to minimize 
these risks are also discussed below including the use of unique study codes for 
participants, encryption of data for transmission to the Survey Research Center (SRC), 
and compliance with Institutional Review Board (IRB) regulations concerning data 
collection, data analysis, and data storage and destruction. 
2.2.2 Potential Benefits 
No claim is made in communications with participating providers or patients that they 
will derive any personal benefit from participating in this project, however study-

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associated provider actions that support patients efforts to quit or reduce tobacco is 
desired and anticipated. Providers will have no defined benefits from participating in this 
project. However, the CDS designed to encourage smoking cessation conversations in 
the dental setting may familiarize some providers with new information that can improve 
the clinical care they deliver in the present or the future. Patients will have no additional 
direct benefits from participating in this project.  
The proposed intervention will modify two existing EHRs to create recommendations for 
smoking cessation that dentists and dental hygienists can provide for their patients who 
smoke. Smoking has a major impact on health in general, but it also causes periodontal 
disease and oral cancer. We will examine if dental providers with this modified EHR will 
provide more smoking interventions than providers without such an EHR and assess 
the impact of these interventions on smoking cessation, smoking reduction, and quit 
attempts. Any reductions in smoking are likely to improve population health in the 
United States. 

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3 
OBJECTIVES 
3.1 Study Objectives 
Objective 1 (primary): Assess if the CDS increases the frequency of delivery of BI (Brief 
Interventions) and/or RT (Referral to Treatment) at an index dental visit as compared to 
treatment as usual as reported by patients within 7 days of the index visit. 
  
Objective 2 (secondary): Test the efficacy of the CDS on smokers’ initial actions related 
to cessation (contacting a quitline and/or setting a quit date and/or developing a plan to 
quit and/or starting nicotine replacement or other medication to help quit within 7 days) 
as compared to treatment as usual. 
  
Objective 3 (secondary): Test the efficacy of the CDS on smokers’ long term actions 
related to cessation (quitting smoking and/or reducing their smoking with 6 months) as 
compared to treatment as usual.  
  
Objective 4 (exploratory): Identify provider-level barriers and facilitators of the effect of 
the CDS, and test potential mediators of the CDS. 
 
3.2 Study Outcome Measures 
The measurement of outcomes for the primary and secondary objectives will be based 
on self-reported data from telephone surveys of dental patients 1-7 days following an 
index dental visit, and 6 months +/- 1 week following the index dental visit. Endpoints 
from patients are based on patient reports about their first observed index visit (not 
subsequent visits), where an index visit is a new or established patient visit where an 
oral evaluation is conducted to determine changes in the patient’s medical and dental 
health status. A detailed description of dependent variables for the primary and 
secondary objectives is shown in Table 1. 
3.2.1 Primary Objective 
 
Aim 1 - Receipt of a brief smoking intervention or referral to a quitline (H1) 
(Objective 1): The dependent variable for H1 (Objective 1) is a binary indicator of 
whether the patient reported that their provider 1) delivered a brief smoking intervention: 
the provider discussed a) developing a quit plan, or b) setting a quit date, or c) using 
medications to help patients quit or d) discussed strategies for quitting, or 2) referral to a 
quitline: a) provided information about how to contact a tobacco quitline, or b) arranged 
for the patient to be contacted by the tobacco quit line, for smoking cessation at the 
index dental visit. This composite variable is satisfied if the patient reports that any of 

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the intervention activities or referral was delivered. This information is obtained from the 
phone survey of patients within 1-7 days of their index dental visit.  
3.2.2 Secondary Objectives 
 
Aim 2 – Smoker’s cessation actions, within one week of visit (H2.1) (Objective 2): 
The dependent variable for H2.1 (Objective 2) is a binary indicator of whether the 
patient reported that they contacted a smoking cessation quitline, set a quit date, 
developed a plan to quit, or starting nicotine replacement or other medication to help 
quit. The CDS is designed to provide a more tailored and targeted message that may 
lead to more tobacco cessation actions by the smoker. This composite variable is 
satisfied if the patient reports that they have done any of these actions within the 1-7 
day period between the index dental visit and date of the first patient survey. This 
information is obtained from the phone survey of patients within 1-7 days of their index 
dental visit.  
Aim 2 - Smoker’s cessation actions, six months after the visit (H2.2) (Objective 3): 
The dependent variable for H2.2 (Objective 3) is a binary indicator of whether the 
patient reported that they quit smoking (stopped smoking for more than one day 
because they were trying to stop smoking), or reduced their smoking use (50% 
reduction in amount smoked at 6 months compared to baseline). This composite 
variable is satisfied if the patient reports that they have done any of these actions within 
the 6 month +/- 1 week period between the index dental visit and date of the second 
patient survey. This information is obtained from the phone survey of patients 6 months 
+/- 1 week after the index dental visit.  
Aim 3 – Barriers, facilitators and mediators of receipt of a brief smoking 
intervention or referral to a quitline (H3.1, H3.2) (Objective 4): 
See the dependent variable for Objective 1.  
3.3 Independent variables and descriptive variables 
A detailed description of independent and descriptive variables is shown in Table 2.  

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Table 1. List of Dependent Variables for Primary and Secondary Objectives 
Variable 
Description 
Data source 
Variable 
type 
Primary objective, dependent variables 
Percentage of visits 
with delivery of 
brief interventions 
and/or referral to 
treatment 
Composite of provider actions 
reported by patient 
Patient baseline 
survey (1-7 
days) 
Binary 
Secondary objectives, dependent variables 
Percentage of 
smokers with initial 
actions related to 
cessation 
Composite of patient-reported actions 
Patient baseline 
survey (1-7 
days) 
Binary 
Percentage of 
smokers with long-
term actions 
related to cessation 
Composite of patient-reported actions 
Patient baseline 
surveys (1-7 
days and 6 
months) 
Binary 
 

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Table 2. List of Independent and Descriptive Variables 
Variable 
Description 
Data source 
Variable 
type 
Study arm 
Primary independent variable. Coded 
as control clinic or clinical decision 
support clinic 
Assigned by 
statistician 
Binary 
Dental school 
system 
Identifier for the dental school source 
of the dental school module 
(Pittsburgh or Indiana) 
Administrative Nominal 
Patient age 
Years 
Patient 
survey (1-7 
days) 
Interval 
Patient sex 
Male or female 
Patient 
survey (1-7 
days) 
Nominal 
Patient race 
Standard categories 
Patient 
survey (1-7 
days) 
Nominal 
Patient ethnicity 
Hispanic or not 
Patient 
survey (1-7 
days) 
Nominal 
Patient education 
Standard categories 
Patient 
survey (1-7 
days) 
Nominal 
Patient income 
<12000, 13000-<25000, 25000-
<50000, 50000-<75000, >=75000 
Patient 
survey (1-7 
days) 
Nominal 
Visit type 
Type of dental visit 
EHR 
Nominal 
Patient smoking 
status 
This used to determine survey 
eligibility, but not final eligibility. 
EHR 
Binary 
Patient smoking 
status 
Used as a descriptive variable and to 
select patients as study eligible and 
analysis eligible 
Patient 
survey (1-7 
days) 
Binary 
Patient amount 
smoked 
Informs script language, functional to 
CDS 
CDS 
Interval 
Patient amount 
cigarettes smoked 
Patient report of amount of cigarettes 
smoked in past 30 days. Descriptive 
variable and covariate. 
Patient 
survey (1-7 
days) and at 
6 months 
Interval 
Variable 
Description 
Data source 
Variable 

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type 
Patient use of 
other tobacco  
Use of cigars, pipes, chewing 
tobacco, e-cigarettes, hookahs, other 
Patient 
survey (1-7 
days) and at 
6 months 
Binary 
Provider age 
Years 
Provider 
survey 
(baseline) 
Interval 
Provider sex 
Male or female 
Provider 
survey 
(baseline) 
Nominal 
Provider race 
Standard categories 
Provider 
survey 
(baseline) 
Nominal 
Provider years in 
practice 
Years 
Provider 
survey 
(baseline) 
Interval 
Provider type 
Dentist or hygienist 
Provider 
survey 
(baseline) 
Nominal 
Provider TDQ 
individual domain 
scores 
Proposed moderators in Aim 3 
(Objective 4) analyses: Theoretical 
Domain Questionnaire individual 
domain scores (10 total) 
Provider 
survey 
(baseline) 
Ordinal 
Change in provider 
self-efficacy TDQ 
individual scores 
from baseline to 6 
months 
Proposed mediators in Aim 3 
(Objective 4) analyses: Self-efficacy 
items from Theoretical Domain 
Questionnaire 
Provider 
survey at 
baseline and 
6 months 
after 
intervention 
Ordinal 
Provider 
satisfaction with 
CDS 
Provider ratings of satisfaction and 
usability of CDS 
Provider 
survey 6 
months after 
intervention 
Ordinal 

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4 
STUDY DESIGN 
The planned study design (see Figure 1) is a group-randomized, controlled, 2-arm trial 
conducted in two settings: predoctoral dental schools and private-practice clinics 
participating in the National Dental PBRN. Fourteen modules (12 predoctoral dental 
school clinic modules, 2 dental hygiene clinic modules) and 22 private practice clinics 
will be separately randomized using covariate-based constrained randomization. 
Balancing covariates to be used in each setting are specified in the Final Statistical 
Analysis Plan.  
Each set of dental school modules and set of clinics will be randomly assigned to one of 
two study arms (CDS or control) using a statistician-prepared randomization table.  All 
consented providers and their patients will be allocated to the study arm to which their 
clinic is assigned. The participants are dentists, dental therapists, dental hygienists, 
dental students, dental hygiene students, and patients.  
Intervention clinics will receive the CDS that will provide clinical practice guideline-
supported, evidence-based, and personalized scripts that are tailored based on 
patients’ self-reported smoking attributes to deliver interventions consistent with the 
standard of care. Control clinics will continue to provide usual care without CDS 
support. Both arms receive a training video on how to incorporate the current tobacco 
cessation guideline. Intervention clinics will receive limited start-up training, 
demonstrating the technical functionality of the CDS. Clinic modules do not overlap and 
there is no integration of dental hygiene student and dental student care delivery. 

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5 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1 Subject Inclusion Criteria 
Dental students and dental hygienists. 3rd and 4th year predoctoral students or 
dental hygiene students enrolled at selected dental schools. 
Private practice dentists and hygienists. General practice dentists or dental 
hygienists practicing at selected private practice clinics 
Adult patients. All consecutive adults (≥ 18 years of age) not yet exposed to the CDS 
and seen in study-enrolled dental school index visits or study-enrolled private-practice 
index visits during the clinic-specific implementation period who are current cigarette 
smokers will be eligible for the study.  
Survey-eligible:  A subset of patients are contacted by the central Survey Research 
Center who provide consent to complete the baseline survey. 
5.2 Subject Exclusion Criteria 
Providers not able or willing to record current tobacco use status in their EHR are not 
eligible. Private practice providers must not be affiliated with the engaged dental 
schools (Indiana University or University of Pittsburgh) in a teaching or clinical position. 
Patient exclusion criteria applied to the usual care post-index encounter telephone 
screening include: (a) patients requesting to opt out of research. 
5.3 Strategies for Recruitment and Retention 
Recruitment and retention of providers: Associated dental hygienists and dentists 
working in private practice settings, and predoctoral and dental hygiene students will be 
recruited to the trial using informational handouts and personal communication with 
study staff. Private practice practitioners will be recruited through existing relationships 
of the National Dental PBRN or the institutions involved in the project. Dental school 
students will be recruited through on-site information sessions conducted by non-
faculty. 
Dental schools: The School of Dental Medicine at the University of Pittsburgh and the 
Indiana University School of Dentistry will recruit student participants through the dental 
school predoctoral and DH clinics. Information sessions hosted by the appropriate 
project staff will be held at each dental school. Information about the study will be 
presented at that time and any potential questions by students will be answered by 
study project management staff with no relationship to the students. Study staff with no 
academic relationship to student providers will administer consent in accordance with 
IRB-approved site-specific procedures.  
Private practices: The study team will recruit private practice clinics through 
relationships established in the National Dental PBRN and prior studies by the 
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who are jointly study staff have relationships with practitioners and can answer 
questions about the study and about participation in research in general, and further 
support the involvement of interested practitioners. No additional National Dental PBRN 
resources will be used. Study staff can use administrative databases and Network 
enrollment questionnaire data to identify eligible private practice settings.  
Provider incentives: Incentives will be provided to students per policy of the school. 
Private practice providers will receive incentives at the completion of the study.  All 
providers will receive a free CE session with a web-based video course on the current 
US Department of Health and Human Services: Treating Tobacco Use and 
Dependence: 2008 Update— Clinical Practice Guideline. 
Recruitment and retention of patients: We anticipate based on administrative data to 
achieve cumulative consecutive patient enrollment across sites to total 1,440 in 8 or 
fewer months (site specific). Patients who have authorized secondary disclosure of their 
information will be securely transferred to HealthPartners. Only study-eligible patients 
will be contacted by the SRC.  Patient contact data and encounter details will be 
reported daily using an EHR system routine (to be programmed by vendor). 
To facilitate surveys, verbal consent will be obtained for patients contacted by phone 
within 7 days of their index visit. Consent and surveys will be conducted centrally by 
SRC professional telephone interviewers trained in human subjects’ protection, HIPAA 
for research and the Responsible Conduct of Research. Patients will be called up to 
eight times at various times of day, including evenings, and days of the week, including 
Saturdays, to maximize recruitment and opportunities for follow-up.  
Patient participants will be provided an incentive after completion of the baseline and 6-
month survey. 
5.4 Treatment Assignment Procedures 
Dental school predoctoral/dental hygiene clinics in Indiana and Pennsylvania, and 
private practice clinics will be randomized. All consented providers and their patients will 
be allocated to the study arm to which their clinic is assigned. 
5.4.1 Randomization Procedures  
Within the predoctoral and dental hygiene clinics, clinic modules will be randomized to 
study arm using covariate-based constrained randomization. Balancing covariates will 
be specified in the final Statistical Analysis Plan. Private practice clinics will be 
randomized to study arm using covariate-based constrained randomization. Balancing 
covariates will include factors that are measurable across all clinics in the recruitment 
pool. Clinic-level factors to be considered include number of patient visits, number of 
smokers, percentage of patients who are smokers, percentage of patients with public-
pay insurance, percentage in specific age groups. The final randomization plan and 
balancing covariates will be described in the final Statistical Analysis Plan.  

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5.4.2 Masking Procedures 
Neither the CDS- nor the control-study arms in dental school and private practice clinics 
will be masked. Study staff will know which clinic assignment, and providers will know 
clinic assignment due to the obvious presence or absence of clinical decision support 
available within the EHR at each clinic. Some protection from bias occurs due to 
patients not being aware that a study is occurring until they are contacted by research 
staff following their index visit. Patients are not made aware of the study arm to which 
their clinic is assigned. However, provider knowledge of study arm could be relayed by 
providers during the dental visit. The Survey Research Center interviewers conducting 
the evaluation interviews will be blind to the patient's clinic assignment. 
5.5 Subject Withdrawal 
Participants may withdraw voluntarily from the study or the investigator may terminate 
participation. 
5.5.1 Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request. 
Patients or providers may wish not to participate due to the perceived impact on their 
time or privacy. Incomplete surveys will be counted as withdrawals.  
5.5.2 Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
 
Patient withdrawal. Within the parameters prescribed by the study protocol, study staff 
will provide support and encouragement to participants in order to minimize withdrawal 
and attrition during the intervention. Every effort will be made to undertake protocol-
specified safety follow-up procedures and capture adverse events (AEs), serious 
adverse events (SAEs), and unanticipated problems (UPs).  
 
Patients may elect to withdraw at any time with no impact on their relationship with their 
provider or the institutions involved on conducting the research. With respect for both 
patients and providers, refusal conversion will not be attempted. Respondents may 
actively or passively refuse to participate in the evaluation surveys. Active refusals will 
not be contacted again by the Survey Research Center. Passive refusals (i.e., a subset 
of non-responders) will only be contacted up to a maximum number of email (providers) 
or telephone (patient) attempts (up to 8) to be respectful of participants and within 
bounds of IRB approval. Withdrawal of providers will be tracked in the provider 
database by the project manager. Withdrawal of patients will be tracked by the SRC 
staff in the centralized study database. 
Withdrawn patients will not be replaced. In the case of patient withdrawal from the 
study, staff will only attempt continued follow-up data collection for patients who are 
withdrawn due to an unanticipated problem (UP). In those cases, only data related to 
the completion of reporting requirements for the UP will be recorded. Patients withdrawn 
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recorded (if known), but will not have any additional study data recorded. Although 
patients withdrawn from the study may continue to receive normal clinical care as 
patients of the participating dentists, additional study data will not be collected from this 
continuing clinical care (except as noted above). 
Practitioner withdrawal. Withdrawn private practices will be replaced with a suitable 
alternate clinic until the time of randomization ensuring covariate balance remains intact. 
 
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. If the study is prematurely 
terminated or suspended, the principal investigator will promptly inform the IRB and will 
provide the reason(s) for suspension or termination. 
Circumstances that may warrant termination include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to subjects. 
• Insufficient adherence to protocol requirements. 
• Data that are not sufficiently complete and/or evaluable.  
• Determination of futility. 
 

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6 
STUDY INTERVENTION 
6.1 Study Behavioral or Social Intervention(s) Description 
A user-centered design of the CDS tool is supported by prior multi-method approaches 
of the study team which have explored tobacco cessation activities and EHR workflows 
among dentists and dental hygienists. Each patient-specific index visit for the study is 
defined as the first encounter during the clinic-specific implementation period when the 
enrolled provider updates that patient’s smoking status in the CDS application, cueing 
contact by the Survey Research Center (SRC). Additional subsequent dental visits may 
include additional CDS updates by the provider, but these encounters do not result in 
additional SRC contacts until the 6 month patient survey.  
Prior research supports CDS that should not interrupt the providers’ usual approach to 
history taking. Thus a user-centered approach to activation of the CDS will allow for a 
seamless integration into a variety of practitioner workflows (e.g., dental hygienists’ 
versus dentists’ workflow) and visit types. This integration will enable providers to 
engage the CDS whenever a tobacco cessation is relevant to the patient encounter. Our 
prior work has shown the merit of this approach (64).  
Provider scripts and patient educational materials are based on the current clinical 
practice guideline endorsed by a consortium of eight Federal Government and nonprofit 
organizations, AHRQ’s evidence-based guidance materials for healthcare providers, 
and materials available to patients from http://smokefree.gov/. Script flow is based on 
the 5As model (Ask, Advise, Assess, Assist, Arrange). Supportive motivational 
intervention messaging is provided for patients not ready to make a quit attempt now. 
6.2 Administration of Intervention 
The EHR vendors will modify their respective EHR products to integrate the CDS. After 
pilot testing, this modified EHR product will be installed in all study and control clinic 
environments and exposed to consented dental providers (dentists, dental students, 
dental hygiene students).  
In the context of the familiar EHR environment, providers in the intervention arm will be 
exposed to the CDS. Assessment of the patients’ reported daily use, previous quit 
attempts, and interest in quitting drives a CDS rule-based algorithm that displays 
personalized scripts for that patient. Using the scripts as a jumping off point, the 
provider is free to adapt the messaging using best clinical judgment and according to 
patients’ individual needs and preferences as well as risk factors for oral disease (see 
Section 6.3 on observational monitoring of fidelity for details about evaluating 
standardization of the delivery of the scripts as intended per the clinical guideline). The 
provider selects scripts and patient resources that were “delivered.” Using this 
information, the tool creates an automated “smart note” to efficiently document the 
activities for reference in guiding future encounters, as well as for compliance with 
record keeping requirements. 

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6.3 Procedures for Training Interventionists and Monitoring the Quality of the 
Provider Behavior Measures 
 
Procedures for Training Interventionists Providers in private practices in both the 
intervention and control clinics will participate in a video-cast professional CE course 
(approximately 30 minutes) on how to implement the current tobacco cessation 
guideline, specifically in dental practice. The two dental schools participating in this 
study place a high priority on comprehensive guideline-driven tobacco education. All 
students are exposed to tobacco cessation training in their curriculum, however it 
occurs early in the didactic curriculum, so students will also view the video-cast thus 
standardizing, as much as is practical, their most recent knowledge with practicing 
providers. All intervention clinics will receive basic training on the functionality of the 
CDS tool in the form of a video-cast and an interactive session with a project manager 
who has clinical training experience. 
 
Monitoring Provider Behavior Measures Utilizing Clinic Observations 
The outcome measure for Objective 1 relies on patient reporting of the provider actions 
during the clinical encounter.  This measure has the potential for inaccurate recall by the 
patient.  To address this concern we will conduct observations on a subset of the clinical 
encounters, recording the actions of the provider. These results will be compared to the 
patient reported results in order to determine the degree of recall bias.  The number of 
observations will be determined after assessing agreement of the two measurements. 
 
6.4 Assessment of Subject Compliance with Study Intervention 
The HPI data center will generate reporting tools summarizing patient response rates. 
These reports will be provided to the study team and reviewed monthly to determine the 
need for additional training. This report will be reviewed monthly by the study team and 
by the Medical Monitor as needed.  
6.5 Study Procedural Intervention(s) Description 
A user-centered design of the CDS tool is supported by prior multi-method approaches 
of the study team (52) which have explored tobacco cessation activities and EHR 
workflows among dentists and dental hygienists. Based on this preliminary work and 
responses to a survey of National Dental PBRN members from across the US, the CDS 
will be designed to target specific index visits (D0140. Limited oral evaluation; D0150. 
Comprehensive Oral Evaluation) when it is expected the dentist and/or dental hygienist 
will routinely update the patient’s medical history and smoking status. In the intervention 
clinics the CDS will be activated when the tobacco status is updated. A flexible 
approach to accessing the tool will allow for adaptability to a variety of practitioner 
workflows and visit types and will enable providers to engage the CDS when relevant to 
the patient encounter.  

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Provider scripts and patient educational materials are based on the current Clinical 
Practice Guideline sponsored by a consortium of eight Federal Government and 
nonprofit organizations (55), AHRQ’s evidence-based guidance materials for healthcare 
providers (56), and materials available to patients from http://smokefree.gov/. Script flow 
is based on the 5As model (Ask, Advise, Assess, Assist, and Arrange). Supportive 
motivational intervention messaging (57) is provided for patients not ready to make a 
quit attempt now. 
Figure 1 of the Visualization Appendix (Appendix E) illustrates the three parts of the 
CDS as it appears within the providers’ EHRs. The provider asks a few tobacco 
questions about smoking status as part of a health history update that triggers the CDS. 
The interventions delivered by the provider are customized based on the smokers’ 
responses to baseline questions. The provider elects which personalized scripts and 
patient resources to deliver in the patient encounter by checking the boxes provided. 
Using this information, the tool creates an automated “smart note” to efficiently 
document the activities and for use in follow-up during future encounters with the 
patient. This figure also illustrates the CDS functionality which generates unique script 
sets based on the patient’s smoking status (i.e., reported daily use), previous quit 
attempts, and interest in quitting.  
6.6 Administration of Procedural Intervention 
See study Manual of Procedures (MOP) for this detail. 
6.7 Procedures for Training of Clinicians on Procedural Intervention 
See site-specific training materials (MOP appendix) for this detail. 
6.8 Assessment of Clinician and/or Subject Compliance with Study Procedural 
Intervention 
See study MOP monitoring plan for this detail as well as Section 14 on quality control 
and quality assurance. 
 

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7 
STUDY SCHEDULE 
7.1 Screening 
Providers: To ensure students meet inclusion criteria, they will attend a lunch and learn 
session at which time informed screening, recruitment, and consent procedures will be 
completed with study staff who do not have a relationship with the students (e.g., no 
academic oversight).  
Patients: Providers will routinely assess patients for tobacco status. Patients who have 
authorized secondary disclosure of their information will be securely transferred to 
HealthPartners.  Only study-eligible patients will be contacted by the SRC.   
7.2 Enrollment/Baseline 
Provider baseline enrollment: Providers in private practices may be enrolled in 
dentist/dental therapist/dental hygienist, as appropriate, since care is delivered as a 
team. Dental and dental hygiene students will be enrolled as individuals nested within 
clinic modules that are anticipated to be static for the duration of the study period. Upon 
enrollment, providers and student providers will be invited to complete the baseline 
survey. 
Patient baseline enrollment: Study enrollment and all follow-up data are driven by the 
index visit. A system-generated, study specific-encounter ID will ensure patients are 
only contacted at baseline one time, even if intermediate dental encounters occur and 
their tobacco status is updated again.  
7.3 Intermediate Visits 
Patient intermediate visits: Not applicable. Patients may return for non-study related 
dental visits. These visits will not alter the timeline of the baseline or 6-month follow-up 
surveys 
Provider intermediate visits: Not applicable. Providers are surveyed at baseline and 
after 6 months of study participation. 
7.4 Final Study Visit 
Patient final visits: The final patient contact consists of the SRC-administered 6-month 
survey conducted by phone and tracked in the central REDCap database. 
Provider final visits: The final provider visit consists of the 6-month survey 
administered electronically and tracked in the central REDCap database. 
7.5 Withdrawal Visit 
Patient withdrawal: Patients may withdraw at any dental visit within the study period. 
This will be relayed by the dental provider and tracked by the project manager or SRC 
staff such that follow-up is discontinued. This option will be addressed with providers in 

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training. Patients may also withdraw while in contact with SRC staff. This will not affect 
nor be communicated to providers, practices, or schools. 
Practice withdrawal: Up to 4 back-up private practices will be recruited to 
accommodate clinic-level withdrawal. Withdrawn private practices will be replaced with 
a suitable alternate clinic to ensure clinic randomization remains intact.  
7.6 Unscheduled Visit 
No unscheduled intervention-related visits are anticipated. Unscheduled contact may 
occur with the study manager whose contact information will be provided (e.g., patients 
seeking clarification about incentive payment). This is common and typical in practice-
based research which takes a customer-service based approach to ensuring 
participants have comfort with and ease of accessibility to the researchers. 

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8 
STUDY PROCEDURES /EVALUATIONS 
8.1 Study Procedures/Evaluations 
Patient Survey procedures: Patient contact data will be sent to the HPI Survey 
Research Center in keeping with HIPPA authorization procedures and Data Use 
Agreements approved by the respective sites. In the period between 1-7 days after the 
index dental visit, a baseline survey will be attempted with each patient. Call attempts 
continue until either a survey is completed or a patient indicates that they do not want to 
participate. The outcome disposition of each call attempt is recorded by the interviewer 
in the centralized study database to ensure accurate calculation of contact, response, 
cooperation and refusal rates. Upon successful contact with a patient, interviews will be 
conducted with willing participants in a standardized manner utilizing the IRB approved 
script and survey questions and responses. Refusal conversion is not attempted. Any 
study-related patient questions are fielded using a study Frequently Asked Questions 
document. Survey responses are recorded by the interviewer in real-time in the 
centralized study database. Interviewers are monitored for script adherence, accuracy 
of data entry and study knowledge by SRC staff. 
Patients that complete a baseline survey become due for a follow-up survey six months 
after the index visit. In order to maximize response rates, the SRC will begin calling 
these patients one-week before the six-month mark. Up to eight call attempts will be 
made in the two-week window spanning the six-month mark. Call attempts, survey 
administration and documentation follow the same procedure as the baseline survey. 
Survey questions vary slightly between the baseline and six-month surveys as indicated 
in the Survey Item Grid (Appendix K). 
Interviews will be conducted in English and Spanish. The IRB approved script and 
questionnaire will be translated, back-translated and reconciled by a professional 
translation firm. Spanish-speaking trained telephone interviewers, employed by the 
SRC, will attempt survey completion with Spanish-speaking patients. All interviewers 
work onsite in a central location. In addition to completion of training in practices of 
standardized telephone interviewing for research, all interviewers are trained in HIPAA 
and the responsible conduct of research through CITI. 
Provider survey procedures: Upon enrollment in the study, providers will receive their 
baseline survey. Private practice providers will be asked to complete and return theirs 
by the completion of the training session. Student providers will be invited to complete 
theirs in the lunch and learn session where the study is introduced. Survey responses 
will be collected separately from any identifiers (e.g., provider ID) needed to connect 
provider data to clinic level data for the purposes of analysis. Six-month surveys (90 
days -30/+90 days) will be provided and collected confidentially by the project staff at 
the respective sites. HealthPartners project managers will deliver and obtain surveys 
from the private practice settings. Baseline and 6-month surveys will be marked with a 
common study ID.  

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8.2 Laboratory Procedures/Evaluations 
No laboratory procedures are anticipated in this trial. 

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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 (SAE). 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: 
(1) Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB-
approved research protocol and informed consent document; and (b) the characteristics 
of the subject population being studied; 
(2) Related or possibly related to 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 
(3) 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. 
9.1.1 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. 
9.1.2 Serious Adverse Events 
An SAE is one that meets one or more of the following criteria: 
(1) Results in death 
(2) Is life-threatening (places the subject at immediate risk of death from the event as it 
occurred) 
(3) Results in inpatient hospitalization or prolongation of existing hospitalization 
(4) Results in a persistent or significant disability or incapacity 
(5) Results in a congenital anomaly or birth defect 

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(6) 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 patient and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 
9.2 Time Period and Frequency for Event Assessment and Follow-Up 
Unanticipated problems will be recorded in the data collection system throughout the 
study. The PI will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after 
the last day of study participation. Since there are no routine research contacts with 
patients aside from the surveys after the index visit and 6 month survey, we will train 
providers to solicit and record information about potential AEs. The study coordinator 
will solicit information from clinicians monthly through electronic communications. 
Events will be followed by the Study Coordinator for outcome information until the event 
has resolution or stabilization. Patients will also be referred to their dental or medical 
provider as appropriate for management and resolution. 
9.3 Characteristics of an Adverse Event 
9.3.1 Relationship to Study Intervention 
All adverse events will have their relationship to study intervention or study participation 
assessed and documented in the patient research record and will be included in 
summary reporting to the IRB and the Medical Monitor. Evaluation of relatedness will 
consider etiologies such as natural history of the underlying disease, concurrent illness, 
concomitant therapy, study-related procedures, accidents, and other external factors. 
To assess relationship of an event to study intervention, the following guidelines are 
used for this study: 
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. 

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9.3.2 Expectedness of SAEs 
The NIDCR Medical Monitor and the Study PIs will be responsible for determining 
whether an SAE is expected or unexpected.  An adverse event will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the 
risk information previously described for the intervention.   
9.3.3 Severity of Event 
The following scale will be used 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. 
This will be recorded in the subject’s research record and in summary reports of the 
study. 
9.4 Reporting Procedures 
Incidents or events that meet the OHRP criteria for unanticipated problems require the 
creation and completion of an unanticipated problem report form. OHRP recommends 
that investigators include the following information when reporting an AE, or any other 
incident, experience, or outcome as an unanticipated problem to the IRB:  
(1) Appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number.  
(2) A detailed description of the AE, incident, experience, or outcome.  
(3) An explanation of the basis for determining that the AE, incident, experience, or 
outcome represents an unanticipated problem.  
(4) 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:  
(1) Unanticipated problems that are SAEs will be reported to the IRB and to NIDCR 
within one week of the investigator becoming aware of the event.  
(2) Any other unanticipated problem will be reported to the IRB and to NIDCR within two 
weeks of the investigator becoming aware of the problem.  
(3) All unanticipated problems will be reported to appropriate institutional officials (as 
required by an institution’s written reporting procedures), the supporting agency head 

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(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:  
(1) Product Safety Fax Line (US): 1-888-746-3293  
(2) Product Safety Fax Line (International): 919-287-3998  
(3) 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):  
(1) US: 1-888-746-7231  
(2) International: 919-595-6486 
9.5 Halting Rules 
Halting rules are not expected to be applicable for this trial involving CDS-supported 
usual care. 

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10 STUDY OVERSIGHT 
Medical Monitor. In addition to the Grant PI’s (GPI) and Study PI’s (SPI) responsibility 
for oversight, external study oversight will be involve Medical Monitor Oversight 
Reporting. This oversight includes submission of a Medical Monitor Oversight Report to 
NIDCR at 6 month intervals, beginning approximately 6 months after enrollment begins 
until data collection is completed. 
 

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11 STATISTICAL CONSIDERATIONS 
11.1 Primary Objective 
Aim 1: Assess the impact of tobacco CDS on the frequency of provider-delivered brief 
smoking interventions or referral to a quitline for smoking cessation treatment.  
Hypothesis 1.1 (Objective 1): Smokers seen in dental clinics using CDS will be 
more likely to report that their provider delivered a brief smoking intervention or 
referral to a quitline for smoking cessation at their index encounter than smokers 
seen in clinics without CDS. 
11.2 Secondary Objectives 
 
Aim 2: Assess the impact of tobacco CDS on smokers’ cessation and reduction actions. 
Hypothesis 2.1 (Objective 2): Smokers seen in dental clinics using CDS will be 
more likely to report contacting a quitline, setting a quit date, developing a plan to 
quit or starting nicotine replacement or other medication to help quit within 7 days 
of their index encounter than smokers seen in clinics without CDS. 
Hypothesis 2.2 (Objective 3): Smokers seen in dental clinics using CDS will be 
more likely to report quitting smoking, or reducing their smoking within 6 months 
of their index encounter than smokers seen in clinics without CDS. 
 
11.3 Sample Size Considerations 
Sample size justification for aim 1 Primary objective): 
Dental schools: Based on data extracted from an administrative review of dental visits 
in 2013 in the two dental school settings, there are 2,800 visits by smokers (by an 
estimated 2,660 smokers) in a 12-month period in the 14 study dental clinics. A total of 
720 smokers will be approached to participate in the study over an 8-month recruitment 
period. Based on an expected 60% response rate to the 7-day survey of smokers, it is 
anticipated that 430 patient surveys (215/study arm) will be completed. In our prior 
study (see section 1.1.2) found that 15-20% of patients in control clinics reported 
receiving a brief smoking intervention in the dental clinic. The expectation for the 
endpoint for H1.1 (Objective 1) of receiving a smoking cessation intervention or quitline 
referral in this study is set at the lower end of that expectation at 15%. The actual 
sample size of n=430 is reduced to an effective sample size of 230-320 for the power 
analysis to reflect clinic-level ICCs for receiving a smoking intervention, which ranged 
from an ICC of 0.01-0.025 for specific intervention endpoints in the prior CATI study. 
With a sample of 430 patient surveys and a clinic-level ICC for the endpoint of 0.01-
0.025, this study will have 80% power (alpha=0.05, two-sided, R2 with other 
covariates=0.1) to detect a difference in the H1.1 (Objective 1) endpoint of 15% for 
patients in control clinics compared to 29%-31% (reflecting ICC of 0.01-0.025) for 
patients in CDS clinics (delta=14%-16%).  

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Private practices: There are an estimated 1,475 visits by smokers (by an estimated 
1,328 smokers) in a 12-month period in 16 randomly selected study private practice 
clinics, based on surveys of National Dental PBRN private practices. We will initially 
recruit 22 practices with the expectation that 20 will remain involved in the study. Patient 
and sample size calculations are based on 20 private practice clinics. A total of 720 
smokers will be approached to participate in the study over an 8-month recruitment 
period for each clinic. It is assumed that the 60% response rate to the 7-day survey of 
smokers and ICCs for the endpoint will be the same in this setting as described above 
for dental schools at 0.01-0.025. It is expected that a lower percentage of smokers in 
control clinics in this setting will report receiving a brief smoking intervention than in the 
control dental school setting described above, with an expected rate half that of the 
dental schools to arrive at 7% in control clinics. The actual sample size of n=430 is 
reduced to an effective sample size of 288-364 for the power analysis to reflect clinic-
level ICCs for receiving a smoking intervention. With these assumptions, this study will 
have 80% power (alpha=0.05, two-sided, R2 with other covariates=0.1) to detect a 
difference in the H1.1 (Objective 1) endpoint of 7% for patients in control clinics 
compared to 17%-19% for patients in CDS clinics (delta=10%-12%). 
 
All power analysis was conducted with Pass v11(58) with the goal of adequately 
powering the primary objective. An interim analysis is planned for review by the Medical 
Monitor if requested. This analysis will be descriptive and will not alter the course of the 
study. No adjustment is made to alpha for this interim analysis. 
 
11.4 Planned Interim Analyses (if applicable) 
11.4.1 Safety Review 
We do not expect any safety events because this is a minimal risk intervention. 
However, the safety review plan will include quarterly reports of patient accrual, 
enrollment, follow-up, and provider use of CDS.  
11.4.2 Efficacy Review 
One interim efficacy analysis on short-term outcomes in aims 1 (Objective 1) and 2 
(Objective 2) will be conducted when half of the baseline surveys have been conducted. 
This analysis will be conducted for review by the Medical Monitor and will be descriptive 
(no statistical testing). There is no initial plan to stop the study early due to futility or 
exceptional efficacy. Because this is a minimal risk study, it is unlikely that there would 
be a rationale for stopping the study due to adverse events. However, the Medical 
Monitor will ultimately make decisions regarding the need for stopping rules.  
11.5 Analysis Plan 
Overview. This group-randomized trial will randomize up to 14 dental school modules 
and up to 22 private dentistry practices to receive or not receive tobacco clinical 
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participating dental schools. A larger number (22) of private practice clinics are included 
to increase power and balance study arms on key characteristics, both large concerns 
in a group-randomized design. Also, it is expected that only 20 of 22 clinics will remain 
in the study. Primary outcomes are obtained from patient surveys and consist of 
composites reflecting patient reports of actions taken by the dental provider and patient 
reports of their own actions regarding smoking cessation. Because of the numerous 
differences in the dental school and private practice settings and the interest in testing 
generalizability of the intervention in both settings, all analyses are conducted 
separately within each setting. Sample size justifications and power calculations are 
estimated separately within setting to ensure adequate data within each setting to 
address the primary aims. Sample size determinations are based on needs for the 
primary objective. Secondary objectives, secondary analyses, and subgroup analyses 
are exploratory and do not determine sample size calculations. A final Statistical 
Analysis Plan will provide detail on the specific fixed and random effects to be included 
in each model, as well as relevant covariates. 
Analysis plan for aims 1 (Objective 1, primary) and 2 (Objectives 2,3, secondary). 
Hypothesis 1.1 (Objective 1) posits that patients seen at clinics randomly assigned to 
the tobacco CDS intervention will be more likely to report that their provider offered a 
brief smoking intervention or referral to a tobacco cessation quitline than patients seen 
at clinics with CDS. Hypothesis 2.1 (Objective 2) posits that patients seen at clinics 
randomly assigned to the tobacco CDS intervention rather than control clinics will be 
more likely to report that they have engaged in short-term activities towards cessation of 
contacting a quitline, setting a quit date, starting nicotine replacement or other 
medications to quit, or developing a quit plan. Hypothesis 2.2 (Objective 3) posits that 
patients seen at clinics randomly assigned to the tobacco CDS intervention will be more 
likely to report that they have engaged in cessation activities of quitting smoking for one 
day or longer or reducing smoking use. Because clinics are the unit of randomization 
and the outcome varies at the level of the patient, generalized linear mixed model 
regression with a logit link and binomial error distribution will be used to test the effect of 
the intervention on the binary endpoints of Objectives, 1, 2, 3.  Adjustment for 
imbalances across intervention arms for relevant patient-level characteristics will be 
consideredThe analytic approach described above will be conducted separately in the 
dental school setting and the private practice setting.  
If the count of dental school modules or private practice clinics having completed patient 
surveys is fewer than 10, or if the mean number of completed patient surveys per 
randomized unit (dental school module or private practice clinic) is less than 15, an 
alternative primary analytic strategy will be conducted. This strategy will emphasize 
descriptive statistics and comparisons across clusters of within-cluster summaries 
rather than inferential tests of differences by study arm. Specifically, the count and 
proportion will be reported within each dental school module or private practice clinic for 
the Objective 1 endpoint: patient report that within 7 days their provider offered a brief 
smoking intervention or referral to a tobacco cessation quitline, Objective 2 endpoint: 
patient report within 7 days that they engaged in short-term activites towards cessation 
or contacted a quitline, and Objective 3 endpoint: patient report at 6 months that they 
have engaged in cessation activities of quitting smoking for one day or longer or 

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reducing smoking use. Proportions and exact (Clopper-Pearson) confidence intervals 
will be computed and plotted by clinic, grouped by study arm. Beyond the grouping or 
stratification of results by study arm, no other stratification or adjustment will be 
conducted.  
The inferential portion of the alternative analytic strategy will be made secondary due to 
concerns about biased standard errors (and resulting confidence intervals and p-values) 
in cluster-randomized studies with a small count of clusters, or few members within 
each cluster (McNeish & Harring, 2017). However, the planned generalized linear mixed 
model regression described above will still be used to provide the estimate of the fixed 
intervention effect (Maas & Hox, 2005) for Objectives 1, 2, and 3. The standard error 
and p-value for the fixed intervention effect are likely more biased and will be reported 
but viewed with caution. Due to the small sample size and smaller number of events for 
Objectives 1, 2 and 3, no further covariate adjustment will be considered in these 
models. The resulting generalized linear mixed models (logit link, binomial error 
distribution) will thus consist of a binary endpoint for the specific objective predicted by a 
fixed effect for study arm, and a random effect for dental school module or private 
practice clinic. The sample size in this alternative analytic strategy won’t allow for 
adjustment or imputation to address missing surveys or survey items.  
The analytic sample for Objectives 1 and 2 consists of patients who have completed 
constituent items for endpoint composites for Objectives 1 or 2 in the survey completed 
within 7 days of the index date. Study arm for each patient is based on randomization of 
the linked dental school module or clinic at which the patient was seen. The analytic 
sample for Objective 3 consists of patients who have completed constituent items for 
endpoint composite used in Objective 3 in the survey completed at 6 months following 
the index date. Study arm for each patient is based on randomization of the linked 
dental school module or clinic at which the patient was seen.  
Handling of missing data in primary aims 1 (Objective 1) and 2 (Objectives 2, 3) 
Endpoints for aims 1-3 (Objectives 1-4) are binary indicators from patient surveys. Since 
the only patients consented for the study are those who complete a baseline survey, it is 
expected that missing data for the endpoints for H1.1 (Objective 1), H2.1 (Objective 2), 
H3.1 (Objective 4), H3.2 (Objective 4) will be rare. The endpoint for H2.2 (Objective 3) is 
binary and will be missing for the estimated 30% not completing the 6 month survey or 
those who leave the endpoint survey items blank. The approach for handling missing 
data will depend on the expected mechanism of missingness. Approaches to be 
considered include conditioning the analysis on characteristic predictive of missing data, 
and multiple imputation (MI) procedures to accurately estimate parameters across 
multiply imputed data sets. 
 

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

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13 QUALITY CONTROL AND QUALITY ASSURANCE 
Quality Management Plan: The following is a summary of the quality management 
activities that are planned for each key study activity:  
Patient Screening and Enrollment:  
Proper screening relies on usual care clinical and administrative EHR data. Follow-up 
training as need will be conducted for cause or at the request of the providers involved. 
See Protocol Section 6.10 for detail on how this will be assessed.  
Site project managers will be a resource for the EHR managers, vendors, providers and 
site staff to ask questions during the phases of patient screening and enrollment. The 
HPI project manager will keep a log of questions and issues encountered and solutions 
across sites. This will ensure consistency of solutions to problems encountered by 
providers. The Study Team will also use the log to create a regularly updated 
‘Frequently Asked Questions’ document that will be available to all sites. Quality 
assurance queries implemented by the vendors and EHR managers to ensure quality 
data reaches the HPI data store will be developed in the pilot testing phases of the 
project. Quality management processes and periodic reporting will be continued until all 
patient and provider follow-up is complete.  
Data Collection:  
Metrics. All data will be reviewed for completeness and entered electronically within the 
centralized study database, Accuracy and completeness of the data is maximized 
through alerts and pop-ups if the data is inconsistent or not entered. 
Protocol Deviations. All deviations from protocol will be captured, documented, 
reviewed and addressed on an ongoing basis to insure integrity of the data. 
Monitoring Quality Assurance. Co-Investigator leaders will regularly meet with their 
site’s study staff to discuss study progress and problem solve. The purpose of these 
meetings is to focus on the day-to-day operations of the project and to assure that all 
necessary tasks are completed in a timely fashion and strictly according to study 
protocol. Monthly meetings will include all co-investigators and will address scientific 
issues, including refinement of conceptual models, strategies to streamline and deploy 
the interventions efficiently and effectively, and strategies to maximize both recruitment 
and retention of study subjects, as well as methods to assure uniformity and fidelity to 
intervention protocols and data collection. 
In collaboration with the Survey Research Center and HPI programmer, the HPI project 
manager and study statistician will develop and provide to the study team and NIDCR 
regular reports related to subject accrual and data quality to assess the progress of the 
clinical study, any relevant safety data, and critical efficacy endpoints and provide 
recommendations to NIDCR.  
Data Analysis and Interpretation. All data analyses for presentations and publications 
will be verified by a “secondary” programmer/statistician for 1) validity of statistical 

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programming to correspondence with interpretation, and 2) correct and appropriate 
analytic results (output) presented in presentation and/or publication. 

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14 ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1 Ethical Standard 
The investigators 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.  
14.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all subject materials 
will be reviewed by the IRB s at the respective involved sites. Approval of both the 
protocol and the consent forms must be obtained before any provider or patient is 
enrolled. Any amendment to the protocol will require review and approval by the IRB 
before the changes are implemented in the study.  
14.3 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 
providers and patients  
Providers: Consent forms will be mailed and/or emailed or presented in person to 
potentially eligible providers with contact information provided to allow the prospective 
subjects to ask questions. Signed provider consents will be obtained and stored by the 
site-specific project managers per local IRB requirements as well as requirements by 
the funder. 
Patients: Verbal consent will be obtained for patients surveyed by phone by trained 
HealthPartners Survey Research Center staff. 
14.4 Exclusion of Women, Minorities, and Children (Special Populations) 
Racial and ethnic minorities will be included in the study at least proportional to the 
composition in the sites’ patient populations. Individuals of any sex or racial/ethnic 
group may participate.  Patients 18 years of age and older will be included in this study. 
See the Planned Enrollment Table for estimates of the inclusion of racial and ethnic 
minorities across all sites.  
If needed, HealthPartners’ Survey Research Center can conduct surveys with 
monolingual Spanish speakers. Other languages can be accommodated if the need 
justifies the expansion of Survey Research Center staff. 
Other minority groups and special populations are included in this study unless a 
cognitive or communication disorder prevents completion of the patient telephone 
consent and survey.  

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14.5 Subject Confidentiality 
Figures 3 of the Visualization Appendix E shows the data flow of the CDS outlining the 
protective measures to secure patient and provider confidentiality based on a need-to-
know principle. Confidentiality will be ensured by assigning an arbitrary and unique 
subject identification number to each participant. All electronic study data will be 
maintained in a computerized database residing on a username and password 
protected-access fileserver to which only the researchers involved in the study will have 
access. Access privileges will be role-dependent. A crosswalk table linking this code 
number to a provider and a patient medical record number will be destroyed within 12 
months after completion of analyses needed to test study hypotheses. The documented 
informed consent procedure for providers and student providers will be reviewed in 
advance, approved, and monitored on an ongoing basis by the 3 participating IRBs. All 
study related paper documents containing individually identifiable information will be 
maintained in locked file cabinets within the respective sites secure physically secured 
research offices. 
All recruitment will be conducted in compliance with applicable federal and state laws. 
Recruitment processes and materials will be approved by each institution’s Institutional 
Review Board (IRB). Each site will oversee the participant protections at each site, 
which will include compliance with HIPAA regulations.  
14.6 Future Use of Identifiable Data 
No protected health information (PHI) data will be included in the analytical dataset. 
Data will be stored within a secure folder on the research server with limited access to 
project team members for the required timeframe. This study does not involve 
specimens or genetic testing.  
 

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15 DATA HANDLING AND RECORD KEEPING 
15.1 Data Management Responsibilities 
The investigators in the study will be responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported.  
15.2 Data Capture Methods 
Data Collection. There are four main data instruments for the study: 1. The patient 
baseline telephone survey conducted 1-7 days after the index dental encounter, 2. The 
patient 6-month post-baseline telephone survey, 3. The provider survey conducted both 
pre- and post-implementation, and 4. The instrument used to monitor general 
adherence to the use of the CDS tool as intended.  
Screening. Demographic and tobacco status information verified at the time of the 
encounter will be used for determining patient eligibility  
CDS Data. Tobacco assessment details and documentation of use of SBIRT scripts and 
patient resources used by providers will be collected electronically at the point of care 
through a secure web application.  
Data collection and accurate documentation will be the responsibility of all study staff 
under the supervision of Dr. Brad Rindal and Dr. Heiko Spallek, the co-PIs. 
Unanticipated problems and adverse events will be reviewed by the investigator or 
designee. 
15.3 Types of Data 
All provider- and patient-reported outcome measure data will be stored in the secure 
centralized study database.  
15.4 Schedule and Content of Reports 
Reports to monitor enrollment rate, adverse events, outcomes, and study conduct will 
be generated regularly using the centralized study database and discussed at the site 
meetings, all-investigator meetings and reported to the Medical Monitor and program 
official as requested.  
15.5 Study Records Retention 
Study records will be maintained for at least three years from the date that the grant 
federal financial report (FFR) is submitted to the NIH. No records will be destroyed 
without the written consent of the sponsor, if applicable. It is the responsibility of the 
sponsor to inform the investigator when these documents no longer need to be retained. 
15.6 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 

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part of the subject, the investigator, or study staff. As a result of deviations, corrective 
actions that address the non-compliance issue have been developed by the study staff 
and will be 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 addressed in study subject source documents and 
promptly reported to NIDCR and the local IRB, according to their requirements. 
 

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16 PUBLICATION/DATA SHARING POLICY 
Each participating site must execute a data use or data transfer agreement (DUA or 
DTA) and seek IRB approval at their local site. These steps will ensure that all de-
identified data being shared for analysis will be protected. Identifiable data will not be 
reused, and the de-identified data set will be transferred via a secure file share or 
encrypted email. 

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17 LITERATURE REFERENCES 
1. 
Rindal DB, Rush WA, Schleyer TK, Kirshner M, Boyle RG, Thoele MJ, et al. 
Computer-assisted guidance for dental office tobacco-cessation counseling: A 
randomized controlled trial. American Journal of Preventive Medicine 2013;44(3):260-
64. 
2. 
Prevention CfDCa. How tobacco smoke causes disease: the biology and 
behavioral basis smoking-attributable disease: a report of the Surgeon General. A 
Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human 
Services; 2010. 
3. 
Vital signs: current cigarette smoking among adults aged ≥18 years--United 
States, 2005-2010. MMWR Morb Mortal Wkly Rep 2011;60(35):1207-1212. 
4. 
Services USDoHaH. Healthy People 2010. Washington DC: U.S. Department of 
Health and Human Services.; 2000. 
5. 
HealthyPeople.gov. Tobacco Use. In: Promotion OoDPaH, editor. 
6. 
Maciosek MV, Coffield AB, Edwards NM, Flottemesch TJ, Goodman MJ, Solberg 
LI. Priorities among effective clinical preventive services: results of a systematic review 
and analysis. Am J Prev Med 2006;31(1):52-61. 
7. 
Fiore M, Jaen C, Baker T, al e. Treating tobacco use and dependence: 2008 
Update Clinical Practice Guideline. In: Services USDoHaH, editor. Rockville, MD: Public 
Health Service; 2008. 
8. 
Conroy MB, Majchrzak NE, Regan S, Silverman CB, Schneider LI, Rigotti NA. 
The association between patient-reported receipt of tobacco intervention at a primary 
care visit and smokers' satisfaction with their health care. Nicotine Tob Res 2005;7 
Suppl 1:S29-34. 
9. 
Ferketich AK, Khan Y, Wewers ME. Are physicians asking about tobacco use 
and assisting with cessation? Results from the 2001-2004 national ambulatory medical 
care survey (NAMCS). Prev Med 2006;43(6):472-6. 
10. 
Quinn VP, Stevens VJ, Hollis JF, Rigotti NA, Solberg LI, Gordon N, et al. 
Tobacco-cessation services and patient satisfaction in nine nonprofit HMOs. Am J Prev 
Med 2005;29(2):77-84. 
11. 
Shroeder SA. What to do with a patient who smokes. JAMA 2005;294(4):482-
487. 
12. 
Rindal DB, Rush WA, Boyle RG. Clinical inertia in dentistry: a review of the 
phenomenon. J Contemp Dent Pract 2008;9(1):113-21. 
13. 
Avorn J, Fischer M. 'Bench to behavior': translating comparative effectiveness 
research into improved clinical practice. Health Aff (Millwood) 2010;29(10):1891-900. 
14. 
Schectman JM, Schroth WS, Verme D, Voss JD. Randomized controlled trial of 
education and feedback for implementation of guidelines for acute low back pain. J Gen 
Intern Med 2003;18(10):773-80. 

A Clinic-Randomized Trial of a Clinical Decision Support System to Improve  
Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
Version 9.0 
Protocol 16-069-E 
12Jan2021 
 
52 
15. 
Rohrbach LA, Grana R, Sussman S, Valente TW. Type II translation: transporting 
prevention interventions from research to real-world settings. Eval Health Prof 
2006;29(3):302-33. 
16. 
Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a 
systematic review of rigorous evaluations. Lancet 1993;342(8883):1317-22. 
17. 
Institute of Medicine. Best Care at Lower Cost: The Path to Continuously 
Learning Health Care in America: Institute of Medicine; 2012. 
18. 
Bandura A. Perceived Self-Efficacy in the Exercise of Control Over AIDS 
Infection. Evaluation and Program Planning 1990;13. 
19. 
Coates TJ, Stall RD, Catania JA, Kegeles SM. Behavioral factors in the spread of 
HIV infection. AIDS 1988;2 Suppl 1:S239-46. 
20. 
Farmer AP, Legare F, Turcot L, Grimshaw J, Harvey E, McGowan JL, et al. 
Printed educational materials: effects on professional practice and health care 
outcomes. Cochrane Database Syst Rev 2008(3):CD004398. 
21. 
Keller PA, Feltracco A, Bailey LA, Li Z, Niederdeppe J, Baker TB, et al. Changes 
in tobacco quitlines in the United States, 2005-2006. Prev Chronic Dis 2010;7(2):A36. 
22. 
Ebbert JO, Carr AB, Patten CA, Morris RA, Schroeder DR. Tobacco use quitline 
enrollment through dental practices: a pilot study. J Am Dent Assoc 2007;138(5):595-
601. 
23. 
Shelley D, Anno J, Tseng TY, Calip G, Wedeles J, Lloyd M, et al. Implementing 
tobacco use treatment guidelines in public health dental clinics in New York City. J Dent 
Educ 2011;75(4):527-33. 
24. 
Houston TK, Richman JS, Ray MN, Allison JJ, Gilbert GH, Shewchuk RM, et al. 
Internet delivered support for tobacco control in dental practice: randomized controlled 
trial. J Med Internet Res 2008;10(5):e38. 
25. 
Little SJ, Hollis JF, Fellows JL, Snyder JJ, Dickerson JF. Implementing a tobacco 
assisted referral program in dental practices. J Public Health Dent 2009;69(3):149-55. 
26. 
Babor TF, McRee BG, Kassebaum PA, Grimaldi PL, Ahmed K, Bray J. 
Screening, Brief Intervention, and Referral to Treatment (SBIRT): toward a public health 
approach to the management of substance abuse. Subst Abus 2007;28(3):7-30. 
27. 
Romito L, Budyn C, Oklak MA, Gotlib J, Eckert GJ. Tobacco use and health risks 
in two dental clinic populations: Implementation and evaluation of a brief targeted 
intervention. Gen Dent 2012;60(5):e326-34. 
28. 
Gilbert GH, Richman JS, Qvist V, Pihlstrom DJ, Foy PJ, Gordan VV. Change in 
stated clinical practice associated with participation in the Dental Practice-Based 
Research Network. Gen Dent 2010;58(6):520-8. 
29. 
Lenz BK. Beliefs, knowledge, and self-efficacy of nursing students regarding 
tobacco cessation. Am J Prev Med 2008;35(6 Suppl):S494-500. 
30. 
Schleyer TK, Song M, Gilbert GH, Rindal DB, Fellows JL, Gordan VV, et al. 
Electronic dental record use and clinical information management patterns among 

A Clinic-Randomized Trial of a Clinical Decision Support System to Improve  
Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
Version 9.0 
Protocol 16-069-E 
12Jan2021 
 
53 
practitioner-investigators in the Dental Practice-Based Research Network. Journal of 
American Dental Association 2013;144(1). 
31. 
Velly AM, Schiffman EL, Rindal DB, Cunha-Cruz J, Gilbert GH, Lehmann M, et 
al. The Feasibility of a clinical trial of pain related to temporomandibular muscle and 
joint disorders: The results of a survey from the collaboration on Networked Dental and 
Oral Research Dental Pracitice-Based Research Networks. Journal of American Dental 
Association 2013;144(1):e1. 
32. 
Nixdorf DR, Law AS, Look JO, Rindal DB, Durand EU, Kang W, et al. Large-
scale clinical endodontic research in the national dental practice-based research 
network: study overview and methods. J Endod 2012;38(11):1470-8. 
33. 
Gilbert GH, Richman J.S., Gordan V. V., Rindal D.B., Fellows J.L., Benjamin 
P.L., Wallace-Dawson M., Williams O.D. the DPBRN Collaborative Group. Lessons 
learned during the conduct of clinical studies in The Dental PBRN. Journal of Dental 
Education 2011;75(4). 
34. 
Carr AB, Ebbert JO. Interventions for tobacco cessation in the dental setting. 
Cochrane Database Syst Rev 2006(1):CD005084. 
35. 
Havlicek D, Stafne E, Pronk NP. Tobacco cessation interventions in dental 
networks: a practice-based evaluation of the impact of education on provider 
knowledge, referrals, and pharmacotherapy use. Prev Chronic Dis 2006;3(3):A96. 
36. 
Kottke TE, Brad Rindal D, Rush WA, Asche SE, Enstad CJ. Persistence of 
smoking-cessation decision support use in a dental practice. Am J Prev Med 
2015;48(6):722-8. 
37. 
ADA. 2010 Technology and Social Media Survey; 2010. 
38. 
Atkinson JC, Zeller GG, Shah C. Electronic patient records for dental school 
clinics: more than paperless systems. J Dent Educ 2002;66(5):634-42. 
39. 
Blumenthal D, Tavenner M. The "meaningful use" regulation for electronic health 
records. N Engl J Med 2010;363(6):501-4. 
40. 
Boyle RG, Solberg LI, Fiore M. Use of electronic health records to support 
smoking cessation (Review). Cockrane Database of Systematic Reviews 2011(12). 
41. 
HIT. JASON Task Force Report - Argonaut Project. In; 2014. 
42. 
Corporation JTM. A Robust Health Data Infrastructure. McLean, VA: AHRQ; 
2014. Report No.: 14-0041-EF. 
43. 
HealthIT.gov. Nationwide Health Information Network (NwHIN) Power Team. 
44. 
Technology PsCoAoSa. Report to the President and Congress. Designing a 
Digital Future: Federally Funded Research and Development in Networking and 
Information Technology; 2010. 
45. 
Kao RT. The challenges of transferring evidence-based dentistry into practice. J 
Evid Based Dent Pract 2006;6(1):125-8. 

A Clinic-Randomized Trial of a Clinical Decision Support System to Improve  
Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
Version 9.0 
Protocol 16-069-E 
12Jan2021 
 
54 
46. 
Spallek H, Song M, Polk DE, Bekhuis T, Frantsve-Hawley J, Aravamudhan K. 
Barriers to implementing evidence-based clinical guidelines: a survey of early adopters. 
J Evid Based Dent Pract 2010;10(4):195-206. 
47. 
Fiore M, Bailey, WC, Cohen, SJ,. Treating tobacco use and dependence: a 
clinical practice guideline. Rockville, MD: US Dept. of Health and Human Services; 
2000. 
48. 
Services UDoHaH. Treating Tobacco Use and Dependence - 2008 Update: 
Corrections and Additions to the Public Health Service (PHS) Clinical Practice 
Guideline. In: Services PH, editor. Rockville, md: AHRQ; 2008. 
49. 
Grimshaw JM, Thomas RE, MacLennan G, Fraser C, Ramsay CR, Vale L, et al. 
Effectiveness and efficiency of guideline dissemination and implementation strategies. 
Health Technol Assess 2004;8(6):iii-iv, 1-72. 
50. 
Walker AE, Grimshaw J, Johnston M, Pitts N, Steen N, Eccles M. PRIME--
PRocess modelling in ImpleMEntation research: selecting a theoretical basis for 
interventions to change clinical practice. BMC Health Serv Res 2003;3(1):22. 
51. 
Bright TJ, Wong A, Dhurjati R, Bristow E, Bastian L, Coeytaux RR, et al. Effect of 
clinical decision-support systems: a systematic review. Ann Intern Med 2012;157(1):29-
43. 
52. 
Thyvalikakath T, Durand E, Spallek H, Enstad C, Asche SE, Rindal DB, et al. 
Dental hygienists' usage of tobacco-cessation decision support tools in practice: A 
qualitative study. International Journal of Evidence-Based Practice for the Dental 
Hygienist. 2015;1(1):57-65  
53. 
Rush WA, Schleyer TK, Kirshner M, Boyle R, Thoele MJ, Lenton PA, et al. 
Integrating tobacco dependence counseling into electronic dental records: a multi-
method approach. J Dent Educ 2014;78(1):31-9. 
54. 
Irwin JY, Torres-Urquidy MH, Schleyer T, Monaco V. A preliminary model of work 
during initial examination and treatment planning appointments. Br Dent J 
2009;206(1):E1; discussion 24-5. 
55. 
AHRQ. Treating Tobacco Use and Dependence. In. Rockville, MD; 2013. 
56. 
AHRQ. Helping Smokers Quit. A Guide for Clinicians. In; 2014. 
57. 
AHRQ. Patients Not Ready to Make a Quit Attenpt Now (the "5 R's"). In; 2012. 
58. 
Hintze J. PASS 11, LLC (using). In. Kaysville, Utah; 2011. 
59. 
MacKinnon DP. Introduction to Statistical Mediation Analysis (Multivariate 
Appplications Series): Taylor & Francis; 2008. 
60. 
MacKinnon DP, Fairchild AJ, Fritz MS. Mediation analysis. Annu Rev Psychol 
2007;58:593-614. 
61. 
Ma J, Akhtar-Danesh N, Dolovich L, Thabane L, investigators tC. Imputation 
strategies for missing binary outcomes in cluster randomized trials. BMC Medical 
Research Methodology 2011;11(1):18. 

A Clinic-Randomized Trial of a Clinical Decision Support System to Improve  
Dental Provider Delivery of Brief Tobacco Interventions and Quitline Referrals 
Version 9.0 
Protocol 16-069-E 
12Jan2021 
 
55 
62. 
Hennrikus D, Rindal DB, Boyle RG, Stafne E, Lazovich D, Lando HA. How well 
does the health history form identify adolescent smokers? J Am Dent Assoc 
2005;136(8):1113-20. 
63. 
Lando HA, Hennrikus D, Boyle RG, Lazovich D, Stafne E, Rindal DB. Promoting 
tobacco abstinence among older adolescents in dental clinics. J Smoking Cessation 
2007;2(1):23-30. 
64. 
Thyvalikakath TP, Durand EU, Spallek HS, Enstad CJ, Asche SE, Rindal DB, 
Rush WA. Dental Hygienists’ Usage of Tobacco-Cessation Decision Support Tools in 
Practice: A Qualitative Study. International Journal of Evidence-Based Practice for the 
Dental Hygienist 2015; 1(1):17-18.  
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SUPPLEMENTAL MATERIALS 
These documents are relevant to the protocol, but they are not considered part of the 
protocol. They are stored and modified separately. As such, modifications to these 
documents do not require protocol amendments. 
See Protocol Appendices for relevant supplemental materials.