Working With HIV Clinics to Adopt Addiction Treatments Using Implementation Facilitation (WHAT-IF?)
Phase: NA
Conditions: Substance-related Disorders
Sponsor: Yale University

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Date Approved:  
6/22/2020 
Study NCT: NCT02907944 
Document: Protocol and SAP 
 

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YALE UNIVERSITY 
 
                                  HUMAN INVESTIGATION COMMITTEE 
 
                                     Application to Involve Human Subjects in Biomedical Research 
100 FR1 (2015-1)  
 
SECTION I: ADMINISTRATIVE INFORMATION 
 
Title of Research Project:  
Working with HIV clinics to adopt addiction treatments using implementation facilitation (WHAT IF?). 
Principal Investigator: 
David Fiellin, MD 
Yale Academic Appointment: 
Professor 
Department: Internal Medicine 
Campus Address:  
367 Cedar Street, Suite 401 A, New Haven, CT 06510 
Campus Phone: 203-737-3347 
Fax:203-737-
3306 
Pager:860-588-
4505 
E-mail: david.fiellin@yale.edu 
Protocol Correspondent Name & Address (if different than PI): 
  
Campus Phone:  
 
E-mail:  
Yale Cancer Center CTO Protocol Correspondent Name & Address (if applicable): 
 
Campus Phone:  
Fax:  
E-mail:  
Business Manager: 
Campus Phone : 
Fax : 
E-mail 
 
 
Investigator Interests: 
Does the principal investigator, or do any research personnel who are responsible for the design, 
conduct or reporting of this project or any of their family members (spouse or dependent child) 
have an incentive or interest, financial or otherwise, that may affect the protection of the human 
subjects involved in this project, the scientific objectivity of the research or its integrity? Note: 
The Principal Investigator (Project Director), upon consideration of the individual’s role and 
degree of independence in carrying out the work, will determine who is responsible for the 
design, conduct, or reporting of the research.  
Faculty Advisor:(required if PI is a student, 
resident, fellow or other trainee)           
 NA 
 
Yale Academic Appointment: 
 
Campus Address:  
 
Campus Phone:  
Fax:  
Pager:  
E-mail:  

Page 3 of 39 
See Disclosures and Management of Personal Interests in Human Research 
http://www.yale.edu/hrpp/policies/index.html#COI  
  Yes  
X No  
 
Do you or does anyone on the research team who is determined by you to be responsible for the 
design, conduct or reporting of this research have any patent (sole right to make, use or sell an 
invention) or copyright (exclusive rights to an original work) interests related to this research 
protocol? 
  Yes  
X No  
 
 
 
If yes to either question above, list names of the investigator or responsible person: 
 
 
The Yale University Principal Investigator, all Yale University co-investigators, and all Yale 
University individuals who are responsible for the design, conduct or reporting of research must 
have a current financial disclosure form on file with the University’s Conflict of Interest Office. 
Yale New Haven Hospital personnel who are listed as co-investigators on a protocol with a Yale 
University Principal Investigator must also have a current financial disclosure form on file with 
the University’s Conflict of Interest Office. If this has not been done, the individual(s) should 
follow this link to the COI Office Website to complete the form:  http://www.yale.edu/coi/   
 
NOTE: The requirement for maintaining a current disclosure form on file with the University’s 
Conflict of Interest Office extends primarily to Yale University and Yale-New Haven Hospital 
personnel.  Whether or not they are required to maintain a disclosure form with the 
University’s Conflict of Interest Office, all investigators and individuals deemed otherwise 
responsible by the PI who are listed on the protocol are required to disclose to the PI any 
interests that are specific to this protocol. 
 
SECTION II: GENERAL INFORMATION 
 
1. Performing Organizations:  Identify the hospital, in-patient or outpatient facility, school or 
other agency that will serve as the location of the research.  Choose all that apply: 
  
a. Internal Location[s] of the Study: 
 Magnetic Resonance Research Center  
 
 Yale University PET Center 
     (MR-TAC)    
 
 
 
 
 YCCI/Church Street Research Unit (CSRU) 
 Yale Cancer Center/Clinical Trials Office (CTO)    
 YCCI/Hospital Research Unit (HRU) 
 Yale Cancer Center/Smilow 
 
 
 YCCI/Keck Laboratories 
 Yale-New Haven Hospital - Nathan Smith Clinic 
 Yale-New Haven Hospital—Saint Raphael Campus – Haelen Center 
 Cancer Data Repository/Tumor Registry 
 Specify Other Yale Location: 
 
 
 
 
 
b. External Location[s]: 
 APT Foundation, Inc. 
 
 
 
 Haskins Laboratories 
 Connecticut Mental Health Center 
 
 John B. Pierce Laboratory, Inc. 

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 Clinical Neuroscience Research Unit (CNRU) 
Veterans Affairs Hospital, West Haven 
 
 Other Locations, Specify:  
 
 
 International Research Site  
(Specify location(s)): 
Immunology Center at Miriam Hospital in Providence, RI; Hartford Hospital’s HIV Clinic in Hartford, 
CT, and SUNY Downstate Medical Center’s HIV clinic in Brooklyn, NY. 
 
c. Additional Required Documents (check all that apply): 
 N/A 
*YCCI-Scientific and Safety Committee (YCCI-SSC)  
Approval Date:  
*Pediatric Protocol Review Committee (PPRC) 
 
Approval Date:  
*YCC Protocol Review Committee (YRC-PRC) 
 
Approval Date: 
 
*Dept. of Veterans Affairs, West Haven VA HSS 
 
Approval Date:  
*Radioactive Drug Research Committee (RDRC) 
 
Approval Date:  
 YNHH-Radiation Safety Committee (YNHH-RSC) 
 
Approval Date:  
 Magnetic Resonance Research Center PRC (MRRC-PRC) 
Approval Date:  
 YSM/YNHH Cancer Data Repository (CaDR)  
 
Approval Date:  
 Dept. of Lab Medicine request for services or specimens form 
 Imaging on YNHH Diagnostic Radiology equipment request form (YDRCTO request) found 
at  http://radiology.yale.edu/research/ClinTrials.aspx) 
*Approval from these committees is required before final HIC approval is granted. See instructions 
for documents required for initial submission and approval of the protocol. Allow sufficient time for 
these requests. Check with the oversight body for their time requirements. 
 
2. Probable Duration of Project: State the expected duration of the project, including all 
follow-up and data analysis activities. 7 years 
 
3. Research Type/Phase: (Check all that apply) 
a. Study Type 
   
 Single Center Study 
   
 Multi-Center Study 
Does the Yale PI serve as the PI of the multi-site study? Yes 
 
No 
 
  
 Coordinating Center/Data Management 
  
 Other:  
 
 
b. Study Phase 
 N/A 
    
 Pilot  
 Phase I 
 Phase II 
 Phase III 
 Phase IV 
    
 Other (Specify)  
 
 
4. Area of Research: (Check all that apply) Note that these are overlapping definitions and 
more than one category may apply to your research protocol. Definitions for the following 
can be found  in the instructions section 4c: 
 Clinical Research: Patient-Oriented 
   
 
 Clinical Research: Outcomes and  
 Clinical Research: Epidemiologic and Behavioral  
                 Health Services 
 Translational Research #1 (“Bench-to-Bedside”)      
 Interdisciplinary Research 
 Translational Research #2 (“Bedside-to-Community”)  
 Community-Based Research 

Page 5 of 39 
 
 
5.   Is this study a clinical trial? Yes 
 
No 
 
NOTE the current ICMJE (International Committee of Medical Journal Editors) definition of a 
clinical trial: “any research study that prospectively assigns human participants or groups of humans 
to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related 
interventions include any intervention used to modify a biomedical or health-related outcome (for 
example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and 
process-of-care changes). Health outcomes include any biomedical or health-related measures 
obtained in patients or participants, including pharmacokinetic measures and adverse events” 
  
If yes, where is it registered? 
  
 
Clinical Trials.gov registry 
 
  
 
Other (Specify)  
 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE. 
 
If this study is registered on clinicaltrials.gov, there is new language in the consent form and compound 
authorization that should be used. 
For more information on registering clinical trials, including whether your trial must be 
registered, see the YCCI webpage, http://ycci.yale.edu/researchers/ors/registerstudy.aspx 
or  contact YCCI at 203.785.3482) 
 
6. Does the Clinical Trials Agreement (CTA) require compliance with ICH GCP (E6)?  
Yes 
 No
 
 
 
7. Will this study have a billable service? A billable service is defined as any service rendered to 
a study subject that, if he/she was not on a study, would normally generate a bill from either 
Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s insurer. The 
service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include 
x-rays, MRIs, CT scans, specimens sent to central labs, or specimens sent to pathology). Notes: 
1. There is no distinction made whether the service is paid for by the subject or their insurance 
(Standard of Care) or by the study’s funding mechanism (Research Sponsored). 2. This generally 
includes new services or orders placed in EPIC for research subjects.  
 
Yes 
 No
 
 If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research 
management system, for Epic to appropriately route research related charges. Please contact 
oncore.support@yale.edu 
8.. Are there any procedures involved in this protocol that will be performed at YNHH or one of 
its affiliated entities?  Yes ___ No X  If Yes, please answer questions a through c and note 
instructions below.  If No, proceed to Section III. 

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a. Does your YNHH privilege delineation currently include the specific procedure that you will 
perform?  N/A 
b. Will you be using any new equipment or equipment that you have not used in the past for 
this procedure? N/A 
  
c. Will a novel approach using existing equipment be applied? N/A 
  
If you answered “no” to question 8a, or "yes" to question 8b or c, please contact the YNHH 
Department of Physician Services (688-2615) for prior approval before commencing with your 
research protocol. 
 
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at 
the HRU, the Principal Investigator and any co-investigators who are physicians or  mid-level 
practitioners (includes PAs, APRNs, psychologists and speech pathologists) who may have direct 
patient contact with patients on YNHH premises must have medical staff appointment and 
appropriate clinical privileges at YNHH. If you are uncertain whether the study personnel meet 
the criteria, please telephone the Physician Services Department at 203-688-2615. By signing 
this protocol as a PI, you attest that you and any co-investigator who may have patient contact 
has a medical staff appointment and appropriate clinical privileges at YNHH. 
 
 
SECTION III: FUNDING, RESEARCH TEAM AND TRAINING 
 
1. Funding Source: Indicate all of the funding source(s) for this study. Check all boxes that apply. 
Provide information regarding the external funding source.  This information should include 
identification of the agency/sponsor, the funding mechanism (grant or contract), and whether 
the award is pending or has been awarded. Provide the M/C# and Agency name (if grant-
funded).  If the funding source associated with a protocol is “pending” at the time of the 
protocol submission to the HIC (as is the case for most NIH submissions), the PI should note 
“Pending” in the appropriate section of the protocol application, provide the M/C# and 
Agency name (if grant-funded) and further note that University (departmental) funds support 
the research (until such time that an award is made).   
 
 
PI  
Title of Grant 
Name of Funding Source  
Funding 
Funding Mechanism 
 
David Fiellin, 
MD 
Working with HIV 
clinics to adopt 
addiction 
treatments using 
Implementation 
Facilitation 
(WHAT IF?) 
National Institute on Drug 
Abuse 
  Federal 
  State 
  Non Profit 
  Industry 
  Other For 
Profit  
  Other 
 
Grant- R01 DA041067     
Contract#  
Contract Pending 
  Investigator/Department 
Initiated 
  Sponsor Initiated 
  Other, Specify: 
 
 

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IRB Review fees are charged for projects funded by Industry or Other For-Profit Sponsors.  
Provide the Name and Address of the Sponsor Representative to whom the invoice should be 
sent.  Note: the PI’s home department will be billed if this information is not provided. 
 
Send IRB Review Fee Invoice To: 
 
N/A 
  
2. Research Team:  List all members of the research team. Indicate under the affiliation column whether 
the investigators or study personnel are part of the Yale faculty or staff, or part of the faculty or staff 
from a collaborating institution, or are not formally affiliated with any institution. ALL members of 
the research team MUST complete Human Subject Protection Training (HSPT) and Health 
Insurance Portability and Accountability Act (HIPAA) Training before they may be listed on the 
protocol.  See NOTE below. 
 
NOTE: The HIC will remove from the protocol any personnel who have not completed required trainin 
g. A personnel protocol amendment will need to be submitted when training is completed. 
 
 
Name 
Affiliation: Yale/Other 
Institution (Identify) 
 
NetID 
Principal Investigator  
David Fiellin, MD 
Yale University 
Daf7 
Role: Co-Investigator 
Lynn Fiellin, MD 
Yale University 
Les6 
Role: Co-Investigator 
E. Jennifer Edelman, MD 
Yale University 
Eje7 
Role: Co-Investigator 
Jeanette Tetrault, MD 
Yale University 
Tj46 
Role: Co-Investigator 
Philip Chan, MD 
Brown University 
N/A 
Role: Co-Investigator 
Deborah Cornman, PhD 
University of 
Connecticut 
N/A 
Role: Site PI 
Gabriel Rebick, MD 
SUNY Downstate 
Medical Center 
N/A 
Role: Consultant 
Peter Friedmann, MD 
Baystate Medical Center N/A 
Role: Biostatistician 
James Dziura, PhD 
Yale University 
Jdd7 
Role: Biostatistician 
Denise Esserman, PhD 
Yale University 
Dae6 
Role: Systems Analyst 
Laura Simone 
Yale University  
genovese 
Role: Biostatistician 
Tassos Kyriakides, PhD 
Yale University 
Drtk 
Role: Research Coordinator 
 Evangelia Louizos  
Yale University 
 
el244 

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SECTION IV: 
 PRINCIPAL INVESTIGATOR/FACULTY ADVISOR/ DEPARTMENT CHAIR AGREEMENT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Department Chair’s Assurance Statement 
Do you know of any real or apparent institutional conflict of interest (e.g., Yale ownership of a 
As the principal investigator of this research project, I certify that: 
 
The information provided in this application is complete and accurate. 
 
I assume full responsibility for the protection of human subjects and the proper conduct of the 
      research. 
 
Subject safety will be of paramount concern, and every effort will be made to protect subjects’ 
      rights and welfare. 
 
The research will be performed according to ethical principles and in compliance with all federal, 
      state and local laws, as well as institutional regulations and policies regarding the protection of   
      human subjects. 
 
All members of the research team will be kept apprised of research goals. 
 
I will obtain approval for this research study and any subsequent revisions prior to my initiating the 
      study or any change and I will obtain continuing approval of this study prior to the expiration date      
      of any approval period. 
 
I will report to the HIC any serious injuries and/or other unanticipated problems involving risk to 
      participants. 
 
I am in compliance with the requirements set by the University and qualify to serve as the 
      principal investigator of this project or have acquired the appropriate approval from the  
      Dean’s Office or Office of the Provost, or the Human Subject Protection Administrator at 
      Yale-New Haven Hospital, or have a faculty advisor. 
 
I will identify a qualified successor should I cease my role as principal investigator and facilitate a 
smooth transfer of investigator responsibilities. 
 
_____ 
 
 
 
 
 
 
 
 
 
 
 
 
  
PI Name (PRINT) and Signature 
 
 
 
 
Date 
As the faculty advisor of this research project, I certify that: 
 
The information provided in this application is complete and accurate. 
 
This project has scientific value and merit and that the student or trainee investigator has the necessary 
resources to complete the project and achieve the aims. 
 
I will train the student investigator in matters of appropriate research compliance, protection of human 
subjects and proper conduct of research. 
 
The research will be performed according to ethical principles and in compliance with all federal, state 
and local laws, as well as institutional regulations and policies regarding the protection of human subjects. 
 
The student investigator will obtain approval for this research study and any subsequent revisions prior to 
initiating the study or revision and will obtain continuing approval prior to the expiration of any approval 
period. 
 
The student investigator will report to the HIC any serious injuries and/or other unanticipated       
problems involving risk to participants.  
 
I am in compliance with the requirements set forth by the University and qualify to serve as       the faculty 
advisor of this project.  
 
I assume all of the roles and responsibilities of a Principal Investigator even though the student may be 
called a PI. 
 
 
 
 
___________  
______ 
 
 
 
_____ 
    Advisor Name (PRINT) and Signature 
 
 
 
 
Date 
 

Page 9 of 39 
sponsoring company, patents, licensure) associated with this research project? 
 Yes (provide a description of that interest in a separate letter addressed to the HIC.) 
 No 
 
As Chair, do you have any real or apparent protocol-specific conflict of interest between yourself and 
the sponsor of the research project, or its competitor or any interest in any intervention and/or method 
tested in the project that might compromise this research project? 
Yes (provide a description of that interest in a separate letter addressed to the HIC) 
No 
 
I assure the HIC that the principal investigator and all members of the research team are qualified by 
education, training, licensure and/or experience to assume participation in the conduct of this research 
trial. I also assure that the principal investigator has departmental support and sufficient resources to 
conduct this trial appropriately. 
 
   ____________________________  
 
 
 
 
 
 
   Chair Name (PRINT) and Signature   
     
 
 
 Date 
 
   _________________________________ 
   Department 
 
 
YNHH Human Subjects Protection Administrator Assurance Statement 
Required when the study is conducted solely at YNHH by YNHH health care providers. 
 
As Human Subject Protection Administrator (HSPA) for YNHH, I certify that: 
 I have read a copy of the protocol and approve it being conducted at YNHH. 
 I agree to notify the IRB if I am aware of any real or apparent institutional conflict of interest. 
 The principal investigator of this study is qualified to serve as P.I. and has the support of the hospital 
for this research project. 
 
  ______________________________________ 
 
 
 
 
 
 
 
 
    YNHH HSPA Name (PRINT) and Signature         
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 

Page 10 of 39 
SECTION V: RESEARCH PLAN 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  
 
The specific aims with respect to increasing uptake of effective counseling and medications for 
tobacco, alcohol and opioid use disorders (addiction treatments) in four HIV clinics are:  
 
Aim 1. Among key stakeholders, to use quantitative and qualitative (mixed) methods to identify 
the site-specific evidence, context and facilitation-related barriers and facilitators to the 
integration of addiction treatments to help tailor an Implementation Facilitation for each clinic. 
Aim 2. To evaluate the impact of Implementation Facilitation on:  
2a: Organizational readiness to deliver addiction treatments 
2b: Provider readiness to deliver addiction treatments 
2c: Provision of addiction treatments 
2d: Changes in organizational models of care used to deliver addiction treatments  
Aim 3. To evaluate the impact of Implementation Facilitation on ART receipt, viral suppression, 
VACS Index, and retention in HIV care among patients eligible for addiction treatment. 
 
2. Background: Describe the background information that led to the plan for this project. 
Provide references to support the expectation of obtaining useful scientific data. 
 
Why focus on tobacco, alcohol and opioid use disorders? These disorders are prevalent in 
HIV clinics, often co-occur,54 and effective counseling and medication treatments exist.  
 
HIV clinics rarely provide treatment for tobacco, alcohol and opioid use disorders 
While effective addiction treatments exist, their use in HIV clinics is limited for a number of 
reasons at the patient, provider and organizational level.  These include deficiencies in key 
stakeholder motivation, knowledge, prioritization and lack of a systematic approach to screening 
and treatment.54,84,87-89  
 
Integrating addiction treatments into HIV clinics can improve substance use and HIV 
outcomes  
Although there is limited literature on integrated treatment of HIV and substance use disorders in 
HIV clinics, evidence supports this approach.  
 
Models for optimal integration of addiction treatment in HIV clinics may vary by 
organization and substance The implementation of addiction treatment into HIV clinics can be 
achieved using a range of models.92 Using the concept of the medical home,93 different models, 
using the skills of a range of HIV clinic providers such as nurses, social workers, physicians, 
nurse practitioners (NP), physician assistants (PA), pharmacists, and psychologists can support 
the integration of addiction treatment in HIV clinics.94-96 The model that is optimally efficient 
and effective for each clinic may vary based on the substance, organizational, provider and 
patient-level factors. The significance of the Implementation Facilitation strategy (Defined 
below) we will evaluate is that it allows for the models to be developed based on a clinic level 
assessment of facilitators and barriers (formative evaluation) with input from relevant 
stakeholders, and provides flexibility such that models may be tailored depending on the 
substance being addressed, organizational factors, provider comfort, knowledge, skills and 
attitudes and patient input.  

Page 11 of 39 
 
Implementation Science and the PARiHS framework can guide efforts to promote the 
uptake of addiction treatment in HIV Clinics  
The field of Implementation Science can promote health care organization change and is gaining 
traction in the fields of HIV and Addiction Medicine.97,98 Implementation Science, defined by 
the National Institute of Health as the study of methods to promote the integration of research 
findings and evidence into healthcare policy and practice,99 provides organized approaches to 
help integrate addiction treatment into HIV clinics.78,100 We will ground the development of our 
Implementation Facilitation in the Promoting Action on Research Implementation in Health 
Services (PARiHS) framework.101 Our proposed research is consistent with a Hybrid Type 3 
effectiveness-implementation study which focuses on simultaneously evaluating the impact of an 
implementation on provider and patient outomes.30  
 
Implementation Facilitation leads to practice change 
Defined as a “process of ‘helping individuals and teams to understand what they need to change 
and how they need to change it in order to apply evidence to practice,’” Implementation 
Facilitation is an effective intervention107 that includes a “deliberate process of interactive 
problem solving and support that occurs in the context of a recognized need for improvement 
and supportive interpersonal relationship.”49 (Table 2)  
 
Research Plan: Summarize the study design and research procedures using non-technical 
language that can be readily understood by someone outside the discipline. Be sure to 
distinguish between standard of care vs. research procedures when applicable, and include 
any flowcharts of visits specifying their individual times and lengths. Describe the setting in 
which the research will take place. 
 
The Working with HIV clinics to adopt Addiction Treatments using Implementation Facilitation 
(WHAT IF?) study will evaluate the impact of Implementation Facilitation on the adoption of 
addiction treatment services in four HIV clinics. We will use a stepped wedge design (See Table 
4). The stepped wedge design is a variation on a cluster randomized clinical trial in which 
participating sites are randomly assigned a time at which the intervention (Implementation 
Facilitation) is begun. The primary comparison is of the change that occurs from the pre-
implementation period to two post-implementation periods, the initial six months (evaluation) 
and the following six months (maintenance). This proposal will consist of three main 
components in each of four clinics: 1) formative evaluation with key stakeholders at each site to 
guide and refine the Implementation Facilitation, 2) conduct of the Implementation 
Facilitation and 3) an evaluation of the impact of the Implementation Facilitation on 
organization and provider-level readiness, provision of addiction treatments, and HIV outcomes.  
 
Intervention Sites  
The sites are the Immunology Center at Miriam Hospital in Providence, RI, , Hartford Hospital’s 
HIV Clinic in Hartford, CT, Haelen Center at Yale-New Haven Hospital, SUNY Downstate 
Medical Center’ HIV clinic in Brooklyn, NY. All sites have conducted research using their 
electronic medical records.144,145,176,177 The diverse sites’ commonalities and differences will 
drive local modifications to the Implementation Facilitation and enrich its generalizability. Table 
3 provides estimates, where known, of the current need for and provision of addiction treatments 

Page 12 of 39 
at the four sites. Currently, approximately 15% of eligible patients are receiving addiction 
treatments.  
 
Table 3. Site Descriptions, Current Need and Provision of Addiction Treatments 
Site 
Miriam 
Immunology 
Center 
Boston 
Medical 
Center 
Hartford 
Hospital 
Downstate 
 
Number of HIV-infected receiving care 
1600 
1200 
500 
1200 
Number with untreated Tobacco Use Disorder 
400 
300 
200 
425 
Number receiving on-site medication for 
tobacco use disorder (bupropion, NRT, 
varenicline) 
140 
Unknown 
75 
110 
Number receiving on-site counseling for tobacco 
use disorder 
Unknown 
Unknown 
50 
7 
Number with untreated Unhealthy Alcohol Use 
100 
200 
75 
240 
Number receiving on-site medication for 
unhealthy alcohol use (naltrexone, acamprosate, 
disulfiram) 
0 
16 
0 
0 
Number receiving on-site counseling for 
unhealthy alcohol use 
Unknown 
16 
0 
100 
Number with untreated Opioid Use Disorder 
80 
100 
80 
100 
Number receiving on-site medication for opioid 
use disorder (buprenorphine, naltrexone) 
32 
50 
0 
4 
Number receiving on-site counseling for opioid 
use disorder 
32 
50 
0 
7 
 
Formative Evaluation (Aim 1) 
 
Overview of Formative Evaluation 
We will conduct a three-stage formative evaluation using mixed-methods178 (qualitative and 
quantitative) to identify evidence, context, and facilitation-related factors impacting the provision 
of addiction treatments and use these data to tailor, refine, monitor and evaluate the effectiveness 
of the Implementation Facilitation. Given that formative evaluation techniques will be used in 
advance, during and following Implementation Facilitation, we will describe the methods in 
detail here and refer back to this section as needed. 
 
Formative evaluation is a widely accepted implementation assessment approach designed to 
identify influences on the development, progress and effectiveness of implementation efforts.109 
To increase use of addiction treatments, we will use this formative evaluation to understand: 1) 
site-specific practices, 2) determinants of these practices, 3) barriers and facilitators to practice 
change, and 4) perspectives regarding Implementation Facilitation. Using the PARiHS 
framework, we will employ a mixed-methods approach with 1) quantitative methods, using the 
Organizational Readiness to Change Assessment (ORCA)105 followed by 2) qualitative methods 
to develop an understanding of evidence, context and facilitation-related factors impacting the 
provision of addiction treatments from the perspectives of diverse stakeholders including 
patients, nurses, social workers, physicians, NPs, PAs, pharmacists, psychologists, clinic 
administrators, payers and clinic directors.  
 
 
 

Page 13 of 39 
Eligibility for Participation in Formative Evaluation: 
Patients: HIV-infected; age >18 years old; meets criteria for lifetime or current tobacco, and/or 
alcohol and/or opioid use disorder regardless of addiction treatment status; able to provide verbal 
informed consent.  
 
Clinic Staff, Administrators: employed at participating HIV clinic for at least six months. 
Payers: employed at an organization or agency that provides funding for medical services for 
HIV-infected individuals for at least 6 months. 
 
Quantitative Data Collection and Analysis 
We will use the ORCA,105 a 77-item instrument based on the PARiHS framework, to evaluate 
evidence, context and facilitation-related factors impacting implementation of addiction 
treatments in each of the four HIV clinics. Baseline ORCA scores will be used to determine 
evidence, context and facilitation-related strengths and weaknesses in organizational readiness to 
implement addiction treatment and to tailor the Implementation Facilitation.  
 
Qualitative Data Collection and Analysis  
We will conduct focus groups with a purposeful sample of key stakeholders at three distinct 
stages of our project: the planning phase, implementation phase and evaluation phase. Purposeful 
sampling is a well-established method in qualitative studies and is designed to identify study 
participants who have direct experience with or knowledge of the phenomenon of interest, in this 
case substance use disorders and addiction treatment. We will ensure appropriate breadth of 
samples with regard to salient characteristics that may influence participant views on the topics 
of interest. We have chosen to use focus groups given their suitability for generating data from 
multiple perspectives regarding the organizational and individual level factors impacting 
complex processes whereby the group interaction is anticipated to stimulate unique ideas.178 We 
will enroll patients, nurses, social workers, physicians, NPs, PAs, pharmacists, psychologists, 
clinic administrators, payers and clinic directors at each site to allow for evaluation of processes 
from multiple perspectives (triangulation). Focus groups will be conducted at each site with 8-10 
patients with past or current tobacco, alcohol and/or opioid use disorders and 8-10 staff members 
and payers, with at least one individual from each of the stakeholder categories. We will conduct 
focus groups until we reach thematic saturation.182  
 
Development of focus group questions: The focus group guides will be informed by the 
PARiHS framework and include “grand tour” questions designed to establish rapport and elicit 
open-ended responses. Probes will be used to understand specific details of those experiences 
and allow for clarification of ideas. We will design and pilot test these guides with patients and 
key informants from the New England HIV Implementation Science Network and refine as 
indicated.  
 
Conduct of focus groups: Dr. Edelman, in conjunction with a trained research assistant, will 
conduct focus groups at each site during year 1 (planning phase), year 2-3 (implementation 
phase) and year 4 (evaluation and maintenance phases). The focus groups will be recorded and 
professionally transcribed for qualitative analysis. Participants will also complete a brief 
anonymous demographic survey. Using directed content analysis,163 we will analyze the data 
with a multi-disciplinary group with experience in qualitative methods, which will include HIV 

Page 14 of 39 
and Addiction Medicine physicians, a HIV Clinic Director, a Clinical Psychologist, and a health 
service researcher. Data will be entered into and organized using Atlas.ti software.  
 
We will share our results with participants (participant confirmation) to ensure that we have 
accurately understood and represented stakeholder’s perspectives and experiences. We will use 
data reduction strategies to sharpen, sort, focus, discard and organize data in a way to draw 
inferences regarding the implementation interventions in place at each facility. We will develop a 
template summary of data at each facility organized by evidence, context and facilitation-related 
factors. Once we have developed that summary for each site, we will create a matrix across all 
sites and respondents to understand the major issues with regard to implementation across sites. 
These data will directly inform the site-specific Implementation Facilitation and be used to 
evaluate the facilitation process and outcomes.  
 
Description of the implementation strategy 
Overview of the Implementation Facilitation (See Table 2) 
Implementation Facilitation will be based on a manualized program developed by Kirchner and 
colleagues106 that has had significant impact on implementing healthcare practices in clinical 
settings. Building on the mixed-methods analysis conducted in Aim 1, we will use the PARiHS 
framework to tailor the Implementation Facilitation for site-specific needs. The facilitators and 
barriers identified by administrators, providers, and patients and will be characterized according 
to the PARiHS sub-elements of patient and clinical experience (communication, knowledgeable 
and empathetic providers), receptive context (resources to provide addiction treatments), and 
culture (value of team-based approach) identified. As described below, PARiHS will be used to 
further explicate and design the Implementation Facilitation, guide the ongoing formative 
evaluation and revise the strategy in an iterative manner to improve implementation success. The 
individual components (Table 2) of Implementation Facilitation are described below. 
 
Table 2. Components of Implementation Facilitation 
 
 
 
 
 
 
 
 
 
 
 
 
Components of Implementation Facilitation 
External facilitator - Dr. Edelman will provide training, coach and mentor local champions, and 
encourage the exchange of ideas within and among sites.  
 
Local champions - Dr. Edelman will spend the first year of the project working with the local 
site PIs to identify and engage local champions, including physicians, clinic directors, pharmacy 
or nursing leads or local organizational re-design/quality improvement experts. These 
Component 
Description 
External Facilitator 
Outside content expert who assists site 
Local Champion 
Local site stakeholder who promotes change 
Provider Education and Academic Detailing 
Provision of unbiased peer education 
Stakeholder Engagement 
Aligning goals of implementation and those impacted 
Tailor Program to Site 
Addressing site specific needs based on Aim 1 
Performance Monitoring and Feedback 
Assess implementation of screening and treatment efforts 
and inform site of results 
Formative Evaluation 
Quantitative and qualitative determination of impact 
Establish a Learning Collaborative 
Shared learning opportunities tailored to stakeholders 
Program Marketing 
Efforts designed to increase attention to availability of on-
site addiction treatment services 

Page 15 of 39 
individuals, and their current level of involvement in the HIV clinic, will likely vary by site and 
substance. Following the in-person orientation and trainings, Dr. Edelman will provide external 
facilitation including monthly phone meetings for the six months of the Implementation 
Facilitation. The Project Coordinator will take notes during these meetings, capturing 
information on challenges, barriers, facilitators and strategies. This information will be integrated 
into the formative evaluation. 
 
Provider education and academic detailing - Academic detailing involves trained clinician 
consultants visiting other clinicians to share unbiased information about patient assessment and 
treatment with the goal of improving quality of care.106 All providers involved in the 
implementation will have dedicated educational sessions on addiction treatments specifically 
tailored to each provider’s tasks based on the initial formative evaluation and potentially modify, 
remove or add strategies to enhance implementation.  We will address practical issues such as 
efficient use of the electronic medical record, public, private and AIDS Drug Assistance Program 
payment for treatments, and patient monitoring strategies.  We will share protocols for 
integration that have been developed for integration of buprenorphine and naltrexone at the Yale 
HIV clinics and elsewhere. Drs. D. Fiellin, L. Fiellin, Tetrault, and Edelman will be primarily 
responsible for providing the content or identifying local site content experts who can deliver 
interactive training sessions. Training strategies will be based on adult learning theory and 
include didactic presentations on the effectiveness and safety of addiction treatment and skill’s 
based practice sessions. These sessions will focus on 1:1 and small group activities to promote 
the education of providers regarding the use of motivational interviewing, brief interventions, 
addiction counseling and medications. We will focus on frequent brief presentations at provider 
meetings, lectures with meals/refreshments and provide instructional handouts.  
 
Stakeholder engagement will take place at the administrative, provider, and patient level.  
Efforts at increasing engagement will be informed by the focus groups conducted during the 
initial formative evaluation and supported by the efforts of the local champions. This work will 
be informed by the Normalization Process Model183 whereby the external facilitators will work 
to make attention to tobacco, alcohol and opioid use disorders a routine focus of stakeholders 
(e.g. embedded) and processes are developed whereby practices such as routine screening and 
medication use are sustained and routinely monitored. 
 
Tailoring the program to local site will occur as a result of the formative evaluations and will 
be informed by local site PIs and local champions. 
 
Performance monitoring and feedback - This will involve regular assessment of individual 
clinician performance and providing information about that performance.106 We will work with 
clinic directors and other members of the clinic team to identify the optimal outcomes to be 
tracked as well as how often and in what format feedback will be provided based on clinic and 
provider-level data. Outcomes will include the number of screenings performed, prescriptions of 
addiction medications provided or number of sessions of the counseling provided. Dr. Edelman 
in collaboration with Drs. D. and L. Fiellin and Dr. Tetrault will provide additional training or 
educational booster sessions for sites with low implementation and those requesting such 
services. 
 

Page 16 of 39 
Implementation-focused formative evaluation will occur during the implementation and focus 
on the discrepancies between the implementation plan and its operationalization. Examples of 
processes that will be examined include: 1) number and types of educational trainings attended 
by staff, 2) number of staff who view the audit and feedback reports, and 3) number of 
champions that attend facilitation meetings. 
 
Progress-focused formative evaluation meetings, led by Dr. Edelman, will monitor 
achievement of implementation goals and performance targets to identify blocked progress, 
allowing steps to be taken to optimize the intervention. These meetings will focus on barriers and 
strategies to address identified barriers. Non-attendance of site participants will be documented 
and outreach through individual facilitation meetings, calls or emails will be initiated to assess 
for stalled progress and offer assistance.  
 
Interpretive formative evaluation uses the data collected from the other formative evaluations 
and information collected at the end of the project regarding the participant experiences to clarify 
the meaning of successful or failed implementation and to enhance understanding of 
Implementation Facilitation's impact. At the conclusion of the maintenance phase (12 months), 
we will conduct an interpretive evaluation that will assess stakeholder views regarding (a) value 
of each addiction treatment, (b) satisfaction or dissatisfaction with various aspects of 
Implementation Facilitation, (c) reasons for clinic level action or inaction, (d) additional barriers 
and facilitators, and (e) recommendations for further refinements. Information will also assess 
stakeholders’ beliefs regarding Implementation Facilitation’s success and overall ‘‘worth’’.109  
 
A Learning Collaborative will be formed by inviting each of the sites’ local champions, and 
other key stakeholders, to participate in a monthly call to promote shared learning regarding 
issues promoting and hindering implementation of addiction treatment. The local champions and 
key stakeholders will set the agenda and the calls will be facilitated by Dr. Edelman and Dr. 
Fiellin and provide a dedicated time to discuss site-specific updates, challenges and possible 
solutions for implementation of addiction services. Dr. Edelman will make resources, protocol 
templates, materials and presentations available through the New England HIV Implementation 
Science Network and other websites so they will be widely accessible. 
 
Program Marketing will be conducted to promote awareness among patients and providers in 
the clinics of the availability of on-site addiction treatment services. This will include 
dissemination of promotional materials such as “What if? Ask me!” buttons, flyers, pens, pads 
and sticky notes for all clinic staff (Appendix for examples from current studies). The goal of the 
marketing will be to promote screening and treatment. We will emphasize patient motivation in 
this process. While the efficacy of addiction treatment is clear, most research is conducted on 
motivated patients seeking treatment for their addictive disorders. Our experience conducting 
research in HIV clinics and general medical settings demonstrates that patient motivation to 
address their addictive disorder is often very low, especially when their disorder is detected 
during a routine visit for a general medical condition.18,37-39,41 This means that it will be 
imperative for our efforts to increase treatment of addictive disorders in HIV settings to address 
patient motivation. Our “What if? Ask me!” slogan is designed to initiate a motivational 
discussion between patients and providers. The ultimate marketing approach will be tailored to 
the needs of the stakeholders and include direct (e.g. “in-services” to discuss the treatment 

Page 17 of 39 
services and referral processes, flyers) and indirect (e.g. informal conversation) approaches. We 
will distribute a newsletter every six months to provide updates about the “WHAT IF?” program 
across the sites.  
 
Please note that these materials will not be designed until April 2016.  At that time, an 
amendment will be submitted to the IRB for approval.  
 
Evaluating the Effectiveness of the Implementation Facilitation (Aim 2 and Aim 3) 
Overview  
We will use a stepped wedge design (Table 4) to evaluate the effect of the Implementation 
Facilitation on the outcomes. In a stepped wedge design, clinics are randomly assigned to time 
cohorts and then followed prospectively to determine their outcome status. Stepped wedge 
designs are increasingly used to promote the implementation of evidence-based practice and are 
appropriate for evaluating interventions where there is evidence that the intervention is likely to 
be beneficial and when practical considerations require sequential deployment of an 
intervention.50,184 We will have three phases of six-months each: 1) a pre-implementation control 
period, 2) a post-intervention evaluation period, and 3) a maintenance period. The proportion of 
eligible patients in each time period who receive at least one addiction treatment will be assessed 
and the effect of the intervention will be evaluated by comparing pre-implementation to 
evaluation and maintenance periods. This will allow us to assess the short and long-term 
(maintenance) impact of Implementation Facilitation.  
 
Table 4. Overview of clinic phases the stepped wedge study design (IF = Implementation 
Facilitation) 
We will measure a range of implementation variables at baseline, 6 and 12 months (Table 5). 
Using validated instruments before, during and after Implementation Facilitation we will 
examine the impact of Implementation Facilitation on organization readiness, provider readiness, 
treatment provision, models of care and HIV outcomes. For sample size calculation, the primary 
quantitative outcome, assessed six and 12 months after the Implementation Facilitation is 
completed, will be the proportion of eligible individuals receiving addiction treatments from the 
clinic measured using information derived from the electronic medical record. This 
determination will be conducted in a blinded fashion, such that the individual analyzing the 
electronic medical record data will be unaware of the phase (control, evaluation, maintenance) of 
the Implementation Facilitation.50 Secondary quantitative outcomes, assessed at six and 12 
months will be change in organizational readiness measured using the ORCA, change in provider 
readiness to prescribe addiction medications measured using change rulers, and HIV-related 
outcomes. To facilitate data collection, all surveys will be administered to all stakeholders online 
using the survey software, Qualtrics and collected anonymously. 
  
 
 
 
 
Clinic 1 Control Control 
Control 
Control 
IF 
Evaluation  
Maintenance 
Clinic 2 Control Control 
Control 
IF 
Evaluation 
Maintenance Maintenance 
Clinic 3 Control Control 
IF 
Evaluation 
Maintenance Maintenance Maintenance 
Clinic 4 Control 
IF 
Evaluation Maintenance Maintenance Maintenance Maintenance 

Page 18 of 39 
 
 
 
Table 5. Summary of Study Assessments  
Assessment 
Data 
Source 
Baseline 
Control 
6 months 
Evaluation 
12 months 
Maintenance 
Organizational Readiness to 
Change Assessment 
Provider and 
Organizational 
representatives 
X 
X 
X 
Change Rulers for each 
medication and counseling 
intervention 
Provider and 
Organizational 
representatives 
X 
X 
X 
Conduct of screening for 
each condition 
Electronic Medical 
Record 
X 
X 
X 
Use of each medication and 
counseling intervention 
Electronic Medical 
Record 
X 
X 
X 
Patient demographic 
information 
Electronic Medical 
Record 
X 
X 
X 
Receipt of antiretroviral 
therapy 
Electronic Medical 
Record 
X 
X 
X 
Tobacco, Alcohol and 
Opioid Use Disorders 
Electronic Medical 
Record 
X 
X 
X 
Psychiatric Diagnoses 
Electronic Medical 
Record 
X 
X 
X 
Clinic Visits 
Electronic Medical 
Record 
X 
X 
X 
Laboratory values 
Electronic Medical 
Record 
X 
X 
X 
Receipt of benzodiazepines 
Electronic Medical 
Record 
 
 
X 
Receipt of COVID-19 
screening and COVID-19 
diagnosis 
Electronic Medical 
Record 
 
 
X 
 
Adequacy of sample size  
Based on prior work,78,79,106,107 we anticipate that Implementation Facilitation will increase the 
proportion of eligible patients provided addiction treatment by the clinics from a baseline of 15% 
of eligible patients (Table 3) to 26% during the evaluation phase and 33% during the 
maintenance phase. This reflects an 11% absolute increase (75% relative increase) during the 
evaluation phase and a 19% absolute increase (125% relative increase) during the maintenance 
phase. A parallel group design, unadjusted for clustering and repeated measures would require a 
sample size of 592 (296 in each the control and intervention arms) to detect the estimated effect 
size (15% control vs. 26% intervention; power 90% and Type I error (alpha) of 0.05). We used 
the formula of Woertman et al. to incorporate the effect of the stepped wedge design.184 It was 
assumed that each clinic would provide a minimum of 300 addiction treatment eligible patients 
(n). In addition, the following assumptions were used, intracluster correlation, ρ = 0.01, number 
of steps, k = 4, number of baseline measurements, b=1, number of measurements taken after each 

Page 19 of 39 
step, t=1. With the above assumptions, the derived DESW = 0.63, thus yielding an adjusted 
sample size of 375 across the 4 clinics. This yields a sample size for the initial evaluation phase 
of 94 patients per clinic who are eligible for addiction treatment (tobacco, alcohol or opioid use 
disorder). Three primary time points will be used, control (six months) evaluation (six months) 
and maintenance (six months). Given we will have adequate power to detect a difference of a 
11% increase in the provision of addiction treatments in the evaluation phase, we will be 
adequately powered for the 19% increase anticipated during the maintenance phase and for the 
other quantitative analyses proposed in Aims 2 and 3. This sample size estimated above is based 
on a ‘cross-sectional’ design. Even if the population in the clinics/clusters is assumed to be a 
stable ‘cohort’, the power will likely be more than sufficient due to within-patient correlation. 
 
Pre-implementation and serial assessments  
Organizational Readiness: We will use the ORCA to measure factors impacting the provision 
of addiction treatments. This 15-minute survey is based on the PARiHS framework and asks the 
respondent to rate local factors related to evidence, context and facilitation on a 5-point Likert 
scale from strongly disagree to strongly agree. Facilitation questions will be omitted from the 
pre-implementation assessment since this part of the intervention and will not have taken place.  
 
Provider Readiness: We will use change rulers, among appropriate providers, for each of the 
medications and counseling to assess readiness to provide each medication and counseling 
intervention.185 The change rulers will independently assess, on a 0-10 scale each provider’s: 1) 
confidence to prescribe/provide the intervention, 2) readiness to prescribe/provide the 
intervention and 3) commitment to prescribe/provide the intervention. Stage of change 
assessments have been validated and have been used in the field of addiction and mental health 
to assess readiness to adopt evidence-based treatments.186-189 
 
Addiction Treatment Eligibility: We will work with each site to incorporate screening for 
smoking and use of the AUDIT-C,190 NIAAA single question screen or NIDA-MED ASISST191. 
The NIDA-MED ASISST and NIAAA screen have good operating characteristics for both 
alcohol and drug use disorders in medical settings.192-194 We will use electronic medical records 
to identify addiction treatment eligible patients based on ICD-9 diagnoses for current (or in 
remission, at risk for relapse) substance use disorders, positive NIDA-MED ASISST or for 
tobacco - smoking 5 or more cigarettes/day and alcohol - AUDIT-C > 3, positive NIAAA screen.  
 
Provision of Addiction Treatments: We will use the electronic medical record to identify 
prescriptions for each of the target medications in the surveillance period. We will use CPT 
codes to determine whether specific counseling therapies were provided.  
 
3. Genetic Testing    N/A 
 
A. Describe 
i. the types of future research to be conducted using the materials, specifying if 
immortalization of cell lines, whole exome or genome sequencing, genome wide 
association studies, or animal studies are planned 
ii. the plan for the collection of material or the conditions under which material will 
be received 

Page 20 of 39 
iii. the types of information about the donor/individual contributors that will be 
entered into a database 
iv. the methods to uphold confidentiality 
 
B. What are the conditions or procedures for sharing of materials and/or distributing for 
future research projects? 
C. Is widespread sharing of materials planned? 
D. When and under what conditions will materials be stripped of all identifiers? 
E. Can donor-subjects withdraw their materials at any time, and/or withdraw the identifiers 
that connect them to their materials? 
i. How will requests to withdraw materials be handled (e.g., material no longer 
identified: that is, anonymized) or material destroyed)? 
 
F. Describe the provisions for protection of participant privacy 
G. Describe the methods for the security of storage and sharing of materials  
 
 
4. Subject Population: Provide a detailed description of the types of human subjects who will 
be recruited into this study. 
 
Participants for patient focus groups will be an estimated 24-30 HIV-infected men and women 
with a history of tobacco, alcohol or opioid use disorder who receive care in one of the three 
HIV clinics.  These individuals will participate in focus groups to determine their perspective 
on the optimal ways to integrate treatment for tobacco, alcohol and opioid use disorders into 
HIV clinics. We will also enroll an estimated 240 staff (clinicians and administrators) across 
the four sites to participate in focus groups and complete on-line quantitative assessments. 
 
 
5. Subject classification: Check off all classifications of subjects that will be specifically 
recruited for enrollment in the research project. Will subjects who may require additional 
safeguards or other considerations be enrolled in the study? If so, identify the population of 
subjects requiring special safeguards and provide a justification for their involvement. 
 
 Children 
 
 
 Healthy  
 
Fetal material, placenta, or dead fetus 
 Non-English Speaking 
 Prisoners  
 Economically disadvantaged persons 
 Decisionally Impaired 
 Employees  
 Pregnant women and/or fetuses 
 Yale Students  
 
Females of childbearing potential 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as 
potential subjects? 
 Yes  
 No (If yes, see Instructions section VII #4 for further 
requirements) 
 
 
6. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or    
exclusion? 
 Patient inclusion criteria:  

Page 21 of 39 
1. HIV-infected 
2. Receiving HIV care in the index clinic 
3. Age >18 years old 
4. Meets criteria for lifetime or current tobacco, alcohol and/or opioid use disorder 
regardless of addiction treatment status 
5. Able to provide verbal informed consent 
 
     
     Staff inclusion criteria:  
1. Employed at participating HIV clinic for at least 6 months 
2. Able to provide verbal informed consent.   
 
Payer inclusion criteria: 
1. Employed at an organization or agency that provides funding for medical services for 
HIV-infected individuals for at least 6 months. 
2. Able to provide verbal informed consent.   
 
 
  Exclusion criteria:  Unable to provide verbal informed consent 
 
7. How will eligibility be determined, and by whom?  
 
Patients, Staff and Payers: 
Local Research Assistants will recruit patients, staff and payers from their HIV clinical care 
sites and determine eligibility.   
 
8. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, 
discomforts, or inconveniences associated with subjects participating in the research.  
 
Risk to subjects is minimal as the intervention proposed is consistent with quality improvement 
efforts and all analyses will be performed with attention to privacy and security.  The participants 
in the focus groups will be provided with an information sheet outlining the purpose of the study 
and their ability to opt out at any time.  The Site PI or Research Assistant will obtain informed 
consent from site staff participating in the focus group interviews. The rating scales and 
questionnaires are all non-invasive, and should also add no risks to subjects, as our past 
experience indicates. 
 
9. Minimizing Risks: Describe the manner in which the above-mentioned risks will be 
minimized. 
 
Numerous steps will be taken to protect confidentiality. In addition, a Certificate of 
Confidentiality has been obtained from NIDA to protect information collected from patients 
during the conduct of the focus groups. This certificate will protect the confidentiality of all 
patient level data by this study. 
 
Recruitment and informed consent: 
There are three aspects to the study: 

Page 22 of 39 
 
I. 
Focus Groups with patients, clinic staff and payers  
II. 
Online survey based on the measure ORCA – clinic leadership staff and providers  
III. 
Patient Outcomes: Evaluation of intervention on patient level outcomes using patient-
level data from the electronic medical records 
 
 
 
I. Focus Groups 
Local Research Assistants will recruit patients from their HIV clinical care sites to participate in 
focus groups.  If they are interested, participants will be asked to come to a private office where 
they will meet with a Research Assistant who will describe the study in more detail, determine 
interest in participating, and assess potential eligibility.  After fully informing participants about 
the study and answering any questions, the Research Assistant will obtain verbal informed 
consent. 
 
There may be a perceived risk among HIV clinic staff that participation in this research may 
impact their employment status in a negative way.  To address this concern, we will work with 
the HIV clinics to provide staff assurances that their participation in the research will in no way 
affect their employment status either positively or negatively.  Surveys and focus groups will be 
voluntary, and participants will be free to skip any questions they do not wish to answer.  
Information collected for research purposes will not become part of staff’s personnel records.  
The informed consent for the HIV clinic staff form will outline these assurances.  For the 
recording of the focus group sessions, participants will be made aware during the informed 
consent process they will be digitally recorded and, for patients, that the nature of these sessions 
will involve participants speaking about information regarding their health status, smoking, 
alcohol use, and opioid use, HIV status, and medical history.   
 
Audio recordings will be stored on a password protected computer.  The research team and the 
professional transcriptionists will use the Yale Secure Transfer File website to send recordings 
and transcripts.  Identifying information from any of the participants in the formative evaluations 
will be kept separately from any forms on which they record information. References to 
identifying information will be eliminated from the written transcript of the interview in 
preparation for analysis of qualitative data. Names and any other identifying information 
collected on evaluation forms, meeting minutes, or field notes and document reviews will be 
eliminated in preparation for analysis of these records. These precautions are expected to be 
completely effective in eliminating risks to confidentiality. 
 
Recorded sessions:  Participants will be made aware during the informed consent process that 
focus groups will be digitally recorded.  However, participants will be instructed to avoid using 
names and the recordings will be coded by randomly generated group numbers to protect 
participant confidentiality.  Participants will be given the option to have their information 
redacted from transcripts.  The transcripts will be reviewed by Dr. Edelman or the Research 
Coordinator and all personally identifying information will be removed prior to analysis. All 
appropriate actions will be taken by staff members to minimize the risks associated with loss of 
confidentiality.  Audio files will be coded by number and will be erased. 

Page 23 of 39 
 
II. Online Survey 
Survey data:  Information obtained from sites will include descriptive information and research 
assessments.  Access to this information will be limited to study staff. Analytic datasets will be 
created with study identification codes. There will be an online consent for participants. 
 
 
 
III. Patient Outcomes 
Electronic medical record data: We will only collect aggregate and de-identified data from the 
electronic medical record. Any potentially individual identifiable health information will be 
protected in accordance with the Health Insurance Portability and Accountability Act (HIPAA) 
of 1996. All research personnel will be trained on Institutional Review Board (IRB) and HIPAA 
procedures.  
 
In Case of Injury: If a participant is injured as a direct result of participation in this study, 
treatment will be provided.  The participant and/or his or her insurance carrier will be expected 
to pay the costs of this treatment. No additional financial compensation for injury or lost wages 
is available.  Participants will not waive their legal rights by participating in this study.  
 
 
10. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan 
(DSMP) based on the investigator’s risk assessment stated below. (Note: the HIC will make 
the final determination of the risk to subjects.) For more information, see the Instructions, 
page 24. 
 
a.  
What is the investigator’s assessment of the overall risk level for subjects 
participating in this study? Minimal 
b. 
If children are involved, what is the investigator’s assessment of the overall risk 
level for the children participating in this study? N/A 
c. 
Include an appropriate Data and Safety Monitoring Plan. Examples of DSMPs are   
 available here http://www.yale.edu/hrpp/forms-templates/biomedical.html  for 
i. Minimal risk 
ii. Greater than minimal 
 
Data and Safety Monitoring Plan: 
The risk of loss of privacy is minimal. Measures in place to prevent the loss of privacy include 
password protection on data files and computer workstations.  
Below we detail the data center architecture, backup strategies, and physical data storage that 
will support the protection of our data. 
 
Data Monitoring and Storage: 
We are planning to use a Web-based computer system for data collection, monitoring and 
reporting.  This system has proven to be very efficient and reliable in clinical trials being 
conducted by our research team.  The core of this system consists of a database hosted on a 
network of secure servers that are capable of collecting and storing data using Web based 
applications that are accessed by the remote users via standard Internet browsers. The Web based 

Page 24 of 39 
data system is designed to fulfill strict requirements of a clinical trial regarding data collection, 
monitoring, and reporting from the recruitment of participants to the delivery of data sets suitable 
for statistical analyses at the end of the trial.  The system meets the highest security and 
reliability standards.  All connections to the systems are secured and encrypted and only 
authorized users are able to access the system. All data is stored in encrypted files, and multiple 
backups of the system and all data are maintained. 
Data and safety monitoring procedures in this study include computerized data collection and 
monitoring systems and an organizational structure of clearly defined tasks assigned to all 
research and clinical personnel involved in the conduct of this study. The computerized data 
collection and monitoring system consists of a database system that records research activities, 
completion of scheduled assessments, and delivers computerized versions of most of research 
instruments used in this study. Research assistants use this database to monitor and schedule 
activities and to administer study assessments. Data entry of non-computerized assessments is 
accomplished by using specialized data entry software (such as, SPSS Data Entry or Microsoft 
Access Data base) facilitating efficient data entry and allowing elimination of out-of range 
values and double entry of data for detection of key punch errors. 
 
The organizational structure used to ensure quality of data in this project include: 1) extensive 
training and close supervision of research assistants in data collection; 2) preliminary review of 
all data for completeness and coding errors by data manager/analyst; and 3) utilization of error-
checking statistical procedures. 
 
Experienced data manager/analysts and the PI supervise data procedures. The research team will 
meet weekly to review the overall progress of the study.  All error corrections are fully 
documented in the research records of the study. All research personnel are required to 
participate in and document training in protection of human subjects and the responsible conduct 
of scientific research. Procedures for training and supervision of Research Assistants, and 
transcriptionists have been developed as part of our previous and current studies. Initial training 
utilizes intensive seminars on all of the research instruments, after which the coordinator 
observes the trainer administer the assessments and co-rates the assessments. Subsequently, the 
coordinator will conduct the assessments and make the ratings with the trainer present for a 
minimum of five full assessments and until complete agreement is obtained. During the study, 
the Yale-based Research Coordinator will review all survey assessments and provide feedback 
on the completeness, accuracy or errors forms. Continued supervision and training on all 
instruments is provided on a regular basis to insure continued reliability of the assessments. 
 
d. For multi-site studies for which the Yale PI serves as the lead investigator: 
i. How will adverse events and unanticipated problems involving risks to subjects or 
others be reported, reviewed and managed? 
 
All adverse events are reported using the Yale Institutional Review Board (IRB) standard template 
for reporting adverse events.  The Yale Principal Investigator (PI) reviews all adverse events, 
classifies the attribution of adverse events (e.g., definitely, probably, possibly related; unlikely or 
unrelated) and grades the severity of the event, utilizing the FDA’s definition of serious adverse 
events, on a 6-point scale (0=no adverse event or within normal limit; 1=mild; 2=moderate; 
3=severe; 4=life-threatening; 5=fatal).  Serious, definitely protocol related adverse events will be 

Page 25 of 39 
reported immediately to the IRB and to NIDA.  Adverse events will be reported in summary form 
at least annually to the IRB.  The summary will include the number of subjects enrolled and a 
summary of graded adverse events to date, using the chart format included in the Yale University 
DSMP template.  The PI will evaluate all adverse events and determine whether the event affects 
the Risk/Benefit ratio of the study and whether modifications to the protocol (e.g., Risks to 
Subjects) or consent form (e.g., Risks and Inconveniences) are required.   
 
 
ii. What provisions are in place for management of interim results? 
 
         No interim analyses will be performed. 
 
iii. What will the multi-site process be for protocol modifications? 
 
There will be one protocol document and each participating institution will utilize 
that document.  The Yale PI is responsible for the coordination of the approval of 
the protocol as well as its subsequent amendments and will be responsible to ensure 
that the sites are using the correct version of the protocol.  The Yale PI will collect 
and maintain copies of all IRB approvals from each site and will collect and review 
conflicts of interest declarations made by the Site PIs. 
 
11. Statistical Considerations: Describe the statistical analyses that support the study design.  
 
General considerations: This is a stepped wedge randomized trial to evaluate the impact of 
Implementation Facilitation. Randomization and data analysis will be conducted by Drs. Dziura, 
Kyriakides and the Yale Center for Analytic Sciences (YCAS). All analyses will be carried out 
using SAS v9.3 (SAS Institute, Cary, NC) and an alpha level of 0.05 will be used to establish 
statistical significance. 
 
Interim monitoring: Interim monitoring will focus on adherence to protocol, completeness of 
data retrieval from each clinics electronic medical record, and uptake of the Implementation 
Facilitation. A set of monitoring tables will be generated by YCAS for this purpose. No interim 
looks for efficacy are planned. 
 
Analysis for Aim 2a, 2b, and 2c: Number (percent) will be used to present data from 
categorical variables. Continuous variable data will be presented as means (+/- SD) and those 
with a non-normal distribution will be characterized using medians (interquartile range). 
Differences across the clinics will be assessed using appropriate parametric or non-parametric 
techniques. The provision of addiction treatments among those eligible (Aim 2c) will be 
expressed as a percentage and the distribution of results in the control (unexposed) periods will 
be compared with those in the evaluation (exposed) and maintenance (exposed) periods. 
Characteristics of patients and clinics will be shown by randomization status in each step of the 
design. We will conduct similar analyses for the measures of organizational and provider 
readiness (Aims 2a, 2b) where the dependent variable will be expressed as continuous measures 
(ORCA score and change rulers). Based on the PARiHS, we hypothesize that stakeholder scores 
on the ORCA subscales including clinical experiences, patient preferences, leadership culture 

Page 26 of 39 
and measurement will mediate the proportion of patients receiving addiction treatment. We will 
test the relationship among this outcome and these mediators. To test the significance of the 
mediation effect, which is called the indirect effect, we will calculate Sobel's test for each 
proposed mediator. We will use an intent-to-treat approach (i.e. cluster analysis will be done) 
according to the time clinics were intended to cross over from control to Implementation 
Facilitation. A linear mixed model will be used, adjusting for calendar time (a potential 
confounder due to its association with both exposure to the intervention and outcome), with a 
random effect for clinic, a fixed effect for each step and allowing for repeated measures for 
patients in the clinics. Since the population of the clinics participating in the proposed trial will 
be rather stable, thus rendering this a cohort stepped wedge design, an additional random effect 
for patients in each clinic will be introduced.  
 
Analysis for Aim 2d: To determine the impact of Implementation Facilitation on models of care 
we will describe the extent to which the provision of treatment for each substance is coordinated 
(facilitated by the HIV clinic), co-located (provided in the clinic) or integrated (provided by the 
primary HIV provider) by clinic. We will track changes in these models of care from the control 
period to the evaluation and maintenance periods. 
 
Analysis for Aim 3: These analyses will be restricted to patients diagnosed with a tobacco, 
alcohol or opioid use disorder. ART receipt will be defined as at least 180 days of three 
concurrent antiretroviral agents in the 6-month interval based on prescriptions in the electronic 
medical record. Viral suppression, will be defined as HIV RNA <200 copies/mL at last test 
closest to the time of data extraction, consistent with Department of Health and Human Services 
(DHHS) guidelines. Although current limits of detection are lower, this cutoff allows for low-
level “blips” that have no clinical significance. The VACS Index will be evaluated based on most 
recent values at the time of data extraction. VACS Index score will be treated as a continuous 
variable. Retention in HIV care, per DHHS guidelines uses a 24-month measurement period. It is 
defined as at least one HIV medical care visit in each 6-month period, with a minimum of 60 
days between the first medical visit in the prior 6-month period and the last medical visit in the 
subsequent 6-month period. This measure has good agreement with the Institute of Medicine 
indicator for retention in care and is an independent predictor of mortality. We will evaluate 
whether patients have had at least 1 visit in the 6-month period prior to time of data extraction. 
These analyses will be adjusted for demographics (age, gender), and presence of psychiatric 
diagnosis (anxiety, major depression, severe mental illness). We will use descriptive statistics to 
characterize addiction treatment eligible patients overall and by substance at baseline and 
examine changes at each interval. We will then examine each of these HIV-related outcomes at 
the 6-month intervals of control, evaluation and maintenance phases based on the provision of 
addiction treatment. We will determine the association between provision of addiction treatment, 
including benzodiazepines and outcomes with the MIXED models procedure repeated measures 
and generalized estimating equations (GEE) to account for repeated measures for dichotomous 
outcomes. We will adjust for fixed demographics, substance use disorder and psychiatric 
diagnoses. We will describe the association with odds ratios and 95% confidence intervals. For 
continuous outcomes, we will use multivariable linear regression with GEE with similar 
adjustment.  
 

Page 27 of 39 
Plan for Missing Data: Several strategies will be imposed to accommodate the likelihood that 
missing data will occur during this study. Prevention is the most obvious and effective manner to 
control bias and loss of power from missing data. We will follow the intent to treat principle, 
requiring follow-up of all clinics randomized regardless of the treatment received. Timely data 
entry combined with quarterly missing data reports will trigger protocols for tracking and 
obtaining missing data. Despite these efforts it is reasonable to assume missing data will occur. 
Our primary analysis is valid under the assumption that missing data is missing at random 
(MAR). We will evaluate the plausibility of this assumption by determining the extent of missing 
data and use logistic regression to identify factors associated with missing data. We will conduct 
sensitivity analysis using pattern-mixture and selection models under missing not at random 
(MNAR) assumptions to examine the robustness of conclusions of the primary analysis to 
missing data. 
 
SECTION VI: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND 
DEVICES 
 
 
If this section (or one of its parts, A or B) is not applicable, state N/A and delete the rest of the 
section.    
 
N/A  
SECTION VII: RECRUITMENT/CONSENT AND ASSENT PROCEDURES  
 
1. Targeted Enrollment: Give the number of subjects: 
a.   targeted for enrollment at Yale for this protocol_25 
b.    If this is a multi-site study, give the total number of subjects targeted across all 
sites_270__  
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
 
 Flyers 
 
 
 
 
 Internet/Web Postings 
 
 
 Radio 
 Posters  
 
 
 
 Mass E-mail Solicitation  
 
 Telephone 
 Letter 
 
 
 
  
 Departmental/Center Website 
 
 Television 
 Medical Record Review  
 
 Departmental/Center Research Boards 
 Newspaper 
 Departmental/Center Newsletters 
 Web-Based Clinical Trial Registries 
 
  YCCI Recruitment database 
 
 Clinicaltrials.gov Registry (do not send materials to HIC) 
 Other (describe): 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified. 
 
I. Focus Groups:  
Local Research Assistants will work with the Site PIs and providers to identify patients, staff  
and payers for the focus groups from their HIV clinical care sites. 
II. Online Survey: 
Local Research Assistants will work with the Site PIs to identify clinic leadership staff and 
providers. 
III. Patient Outcomes:  

Page 28 of 39 
To assess the impact of the Implementation Facilitation, patients will not be directly recruited.  
We will use electronic medical records at each site to evaluate the effectiveness of the 
implementation facilitation strategy on patient level outcomes.  
 
b. Describe how potential subjects are contacted.  
       
I. Focus Groups: 
Local Research Assistants, Site PIs and providers will approach potential subjects for 
participation in focus groups.   
 
II. Online Survey: 
Yale research staff and local site PIs will contact clinic leadership staff and providers for surveys 
using emails. 
III. Patient Outcomes: 
Patients will not be directly recruited as we will rely on data available through the electronic 
medical record collected as part of routine care.  
 
c. Who is recruiting potential subjects?  
 
 
I. Focus Groups: 
Local Research Assistants, Site PIs and providers will recruit potential subjects for participation 
in focus groups.   
II. Online Survey: 
Yale research staff and local site PIs will recruit clinic leadership staff and providers for surveys 
using emails. 
III. Patient Outcomes: 
N/a 
 
4. Screening Procedures 
a. Will email or telephone correspondence be used to screen potential subjects for 
eligibility prior to the potential subject coming to the research office? 
 Yes  
 No 
b.  If yes, identify below all health information to be collected as part of screening and 
check off any of the following HIPAA identifiers to be collected and retained by the 
research team during this screening process.  
 
HEALTH INFORMATION TO BE COLLECTED: 
HIPAA identifiers:  
 Names  
 All geographic subdivisions smaller than a State, including: street address, city, county, precinct, zip codes and their 
equivalent geocodes, except for the initial three digits of a zip code if, according to the current publicly-available data from 
the Bureau of the Census: (1) the geographic unit formed by combining all zip codes with the same three initial digits contains 
more than 20,000 people, and (2) the initial three digits of a zip code for all such geographic units containing 20,000 or fewer 
people is changed to 000.  
  Telephone numbers 
 Fax numbers  
 E-mail addresses 
 Social Security numbers  
 Medical record numbers 
 Health plan beneficiary numbers  

Page 29 of 39 
 Account numbers  
  All elements of dates (except year) for dates related to an individual, including: birth date, admission date, discharge 
date, date of death, all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages 
and elements may be aggregated into a single category of age 90 or older  
 Certificate/license numbers  
 Vehicle identifiers and serial numbers, including license plate numbers  
 Device identifiers and serial numbers  
 Web Universal Resource Locators (URLs)  
 Internet Protocol (IP) address numbers  
 Biometric identifiers, including finger and voice prints  
 Full face photographic images and any comparable images  
 Any other unique identifying numbers, characteristics, or codes  
 
 
5. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical 
relationship with any potential subject?  
 Yes, all subjects 
 Yes, some of the subjects 
 No 
 
If yes, describe the nature of this relationship. 
 
The Yale investigators may have a clinical relationship with subject potential subjects who participate 
in the piloting of interview guides for the focus groups.  The local Site PI’s may have a clinical 
relationship with a potential subject.  
 
6. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization 
for either the entire study, or for recruitment purposes only.  Note: if you are collecting PHI as part of 
a phone or email screen, you must request a HIPAA waiver for recruitment purposes.) 
 
Choose one:  
☒ For entire study (Patient outcomes component only, see below) 
☐ For recruitment purposes only  
☐ For inclusion of non-English speaking subject if short form is being used 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for 
use/disclosure of this data; 
ii. If requesting a waiver of signed authorization, describe why it would be 
impracticable to obtain the subject’s signed authorization for use/disclosure of this 
data; 
I. Focus Groups:  No personally identifying information will be collected; therefore, no HIPPA 
form is required. 
 
II. Online Survey:  No personally identifying information will be collected therefore, no HIPPA 
form is required. 
 

Page 30 of 39 
III. Patient Outcomes: Electronic medical record data will be collected in aggregate and de-
identified when possible.  A HIPPA waiver is requested.   
 
By signing this protocol application, the investigator assures that the protected 
health information for which a Waiver of Authorization has been requested will not 
be reused or disclosed to any person or entity other than those listed in this 
application, except as required by law, for authorized oversight of this research 
study, or as specifically approved for use in another study by an IRB. 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale 
HIPAA-Covered entity must be accounted for in the “accounting for disclosures log”, by subject 
name, purpose, date, recipients, and a description of information provided.  Logs are to be 
forwarded to the Deputy HIPAA Privacy Officer. 
 
7. Required HIPAA Authorization: If the research involves the creation, use or disclosure of 
protected health information (PHI), separate subject authorization is required under the 
HIPAA Privacy Rule. Indicate which of the following forms are being provided: 
 
  
 Compound Consent and Authorization form 
 
  
 HIPAA Research Authorization Form 
 
 
8. Consent Personnel: List the names of all members of the research team who will be obtaining 
consent/assent.  
 
David Fiellin, MD 
Lynn Fiellin, MD 
E. Jennifer Edelman, MD 
Jeanette Tetrault, MD 
Philip Chan, MD 
Deborah Cornman, PhD 
Gabriel Rebick, MD 
Evangelia Louizos 
Michael Virata, MD 
Research Assistants to be hired 
 
 
9. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will 
be obtained, including parental permission or surrogate permission and the steps taken to ensure 
subjects’ independent decision-making.  
 
I. Focus Groups: 
The Site PI or Research Assistant will obtain informed consent from patients and site staff 
participating in the focus group interviews. Participants will be asked to come to a private office 
where they will meet with a Research Assistant who will describe the study in more detail, 
determine interest in participating, and assess potential eligibility.  After fully informing 
participants about the study and answering any questions, the Research Assistant will obtain 
verbal consent. 

Page 31 of 39 
 
II. Online Survey: 
Yale research staff and local site PIs will contact clinic leadership staff and providers for surveys 
using emails and participants will consent to the study online before taking the survey. 
 
III. Patient Outcomes: 
Patients will not be directly approached; a waiver is requested. 
 
10. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the 
personnel obtaining consent will assess the potential subject’s ability and capacity to consent to the 
research being proposed.  
 
All research personnel are required to participate in and document training in protection of 
human subjects and the responsible conduct of scientific research, including assessment of a 
potential subject’s capacity to consent to the study. 
 
11. Documentation of Consent/Assent: Specify the documents that will be used during the 
consent/assent process. Copies of all documents should be appended to the protocol, in the same 
format that they will be given to subjects.  
 
I. Focus Groups: 
A verbal informed consent will be used for focus groups.   
II. Online Survey: 
An online informed consent will be used for survey data. 
III. Patient Outcomes: 
Electronic Medical Records will be used; therefore, is a waiver of informed consent is requested.  
 
12. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for 
research involving non-English speaking subjects. If enrollment of these subjects is anticipated, 
translated copies of all consent materials must be submitted for approval prior to use.  
 
N/A 
 
 
12(a) As a limited alternative to the above requirement, will you use the short form* for 
consenting process if you unexpectedly encounter a non-English speaking individual interested 
in study participation and the translation of the long form is not possible prior to intended 
enrollment?  
YES ☐  NO ☐ 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same 
language, then the full consent form should be translated into that language for use the next time 
a subject speaking that language is to be enrolled. 
 
Several translated short form templates are found on our website 
at:  http://www.yale.edu/hrpp/forms-templates/biomedical.html. If the translation of the short 

Page 32 of 39 
form is not available on our website, then the translated short form needs to be submitted to the 
IRB office for approval via amendment prior to enrolling the subject. Please review the 
guidance and presentation on use of the short form available on the HRPP website. 
 
If using a short form without a translated HIPAA Research Authorization Form, please 
request a HIPAA waiver in the section above.  
 
 
 
 
 
(Note to HIC:  This section is repeated for each of the 3 aspects of the study, 13a, 13b, 13c) 
 
13a. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed 
consent, or a full waiver of consent, depending on the study. If you will request either a waiver 
of consent, or a waiver of signed consent for this study, complete the appropriate section below.   
 
I. Focus Groups: 
Requesting a waiver of signed consent; a verbal informed consent will be used. 
 
 
 Not Requesting a consent waiver  
 
 Requesting a waiver of signed consent 
       
 Requesting a full waiver of consent 
    
 
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6) 
 Requesting a waiver of signed consent for Recruitment/Screening only  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
 
OR 
 
c. Does the research activity pose greater than minimal risk?  
 Yes If you answered yes, stop. A waiver cannot be granted.  Please note: 
Recruitment/screening is generally a minimal risk research activity   
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
 Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.) 

Page 33 of 39 
 
  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
 
OR 
 
c. Does the research pose greater than minimal risk? 
 Yes If you answered yes, stop. A 
waiver cannot be granted.    
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
  
 B. Full waiver of consent: (No consent from subjects will be obtained for the activity.)  
 Requesting a waiver of consent for Recruitment/Screening only  
a. Does the research activity pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity  
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
 Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.) 
 
  
 
If requesting a full waiver of consent, please address the following: 
 
 
  
a. Does the research pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted.   
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date  
 
13b. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed 
consent, or a full waiver of consent, depending on the study. If you will request either a 
waiver of consent, or a waiver of signed consent for this study, complete the appropriate section 
below.   
 
 Not Requesting a consent waiver  
 
 Requesting a waiver of signed consent 
       
 Requesting a full waiver of consent 
 

Page 34 of 39 
II. Online Survey: 
Requesting a waiver of signed consent; an online informed consent will be used. 
 
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6) 
 Requesting a waiver of signed consent for Recruitment/Screening only  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
OR 
 
c. Does the research activity pose greater than minimal risk?  
 Yes If you answered yes, stop. A waiver cannot be granted.  Please note: 
Recruitment/screening is generally a minimal risk research activity   
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
 Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.) 
 
  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
OR 
 
c. Does the research pose greater than minimal risk? 
 Yes If you answered yes, stop. A 
waiver cannot be granted.    
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
  
 B. Full waiver of consent: (No consent from subjects will be obtained for the activity.)  
 
 Requesting a waiver of consent for Recruitment/Screening only  
a. Does the research activity pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity  
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  

Page 35 of 39 
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
 Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.) 
 
 
  
 
If requesting a full waiver of consent, please address the following: 
 
 
  
a. Does the research pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted.   
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
13c. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed 
consent, or a full waiver of consent, depending on the study. If you will request either a 
waiver of consent, or a waiver of signed consent for this study, complete the appropriate section 
below.   
 
III. Patient Outcomes: 
Electronic Medical Records will be used; there is a waiver of consent. 
 
 
 Not Requesting a consent waiver  
 
 Requesting a waiver of signed consent 
       
 Requesting a full waiver of consent 
    
 
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6) 
 Requesting a waiver of signed consent for Recruitment/Screening only  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
 
OR 
 
c. Does the research activity pose greater than minimal risk?  
 Yes If you answered yes, stop. A waiver cannot be granted.  Please note: 
Recruitment/screening is generally a minimal risk research activity   
 No  
AND 

Page 36 of 39 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
 Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.) 
 
  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
 
 
OR 
 
c. Does the research pose greater than minimal risk? 
 Yes If you answered yes, stop. A 
waiver cannot be granted.    
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
  
 B. Full waiver of consent: (No consent from subjects will be obtained for the activity.)  
 Requesting a waiver of consent for Recruitment/Screening only  
a. Does the research activity pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity  
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
 
 Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.) 
 
  
 
If requesting a full waiver of consent, please address the following: 
 
 
  
a. Does the research pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted.   
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver? It is not     
                         feasible to obtain consent from all participants. 
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date? N/A 
 

Page 37 of 39 
 
SECTION VIII: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
a.    What protected health information (medical information along with the HIPAA identifiers) 
about subjects will be collected and used for the research?    
        
Electronic medical record data: We will only collect aggregate and de-identified data from the 
electronic medical record. Any potentially individual identifiable health information will be 
protected in accordance with the Health Insurance Portability and Accountability Act (HIPAA) of 
1996. All research personnel will be trained on Institutional Review Board (IRB) and HIPAA 
procedures. 
 
b. How will the research data be collected, recorded and stored?  
Recorded sessions:  Participants will be made aware during the informed consent process that 
focus groups will be digitally recorded.  However, participants will be instructed to avoid using 
names and the recordings will be coded by randomly generated group numbers to protect 
participant confidentiality.  Participants will be given the option to have their information 
redacted from transcripts.  The transcripts will be reviewed by Dr. Edelman or the Research 
Coordinator and all personally identifying information will be removed prior to analysis. All 
appropriate actions will be taken by staff members to minimize the risks associated with loss of 
confidentiality.  Audio files will be coded by number and will be erased. Audio recordings will 
be stored on a password protected computer.  The research team and the professional 
transcriptionists will use the Yale Secure Transfer File website to send recordings and 
transcripts.   
 
Survey information:  Information obtained from sites will include descriptive information and 
research assessments.  Access to this information will be limited to study staff. Analytic datasets 
will be created with study identification codes.  
 
Electronic medical record data: We will only collect aggregate and de-identified data from the 
electronic medical record. Any potentially individual identifiable health information will be 
protected in accordance with the Health Insurance Portability and Accountability Act (HIPAA) of 
1996.  
 
c.    How will the digital data be stored? 
 CD  
 DVD  
 Flash Drive  
 Portable Hard    
       Drive  
 Secured Server  
 Laptop Computer  
 Desktop Computer  
 Other 
d.    What methods and procedures will be used to safeguard the confidentiality and security of     
the identifiable study data and the storage media indicated above during and after the subject’s 
participation in the study? 
 
We are planning to use a Web-based computer system for data collection, monitoring and 
reporting.  This system has proven to be very efficient and reliable in clinical trials being 
conducted by our research team.  The core of this system consists of a database hosted on a 
network of secure servers that are capable of collecting and storing data using Web based 
applications that are accessed by the remote users via standard Internet browsers. The Web 

Page 38 of 39 
based data system is designed to fulfill strict requirements of a clinical trial regarding data 
collection, monitoring, and reporting from the recruitment of participants to the delivery of 
data sets suitable for statistical analyses at the end of the trial.  The system meets the highest 
security and reliability standards.  All connections to the systems are secured and encrypted 
and only authorized users are able to access the system. All data is stored in encrypted files, 
and multiple backups of the system and all data are maintained. 
Identifying information from any of the participants in the formative evaluations will be kept 
separately from any forms on which they record information. References to identifying 
information will be eliminated from the written transcript of the interview in preparation for 
analysis of qualitative data. Names and any other identifying information collected on 
evaluation forms, meeting minutes, or field notes and document reviews will be eliminated in 
preparation for analysis of these records. These precautions are expected to be completely 
effective in eliminating risks to confidentiality. 
 
Information obtained from sites will include descriptive information and research 
assessments.  Access to this information will be limited to study staff. Analytic datasets will 
be created with study identification codes. 
 
Do all portable devices contain encryption software? 
 Yes   
 No 
         If no, see http://hipaa.yale.edu/guidance/policy.html 
  
e. What will be done with the data when the research is completed? Are there plans to destroy     
the identifiable data? If yes, describe how, by whom and when identifiers will be destroyed. If 
no, describe how the data and/or identifiers will be secured. 
 
Upon completion of the study, all computerized subject datasets will be stored in a password-
protected study computer, to which only the PI, investigators and study personnel will have access.  
All paper files with subject information will remain in locked files in the study office of the PI, 
until they are destroyed, after all analyses are complete. 
 
f.   Who will have access to the protected health information (such as the research sponsor, the  
investigator, the research staff, all research monitors, FDA, Yale Cancer Center Data and Safety 
Monitoring Committee (DSMC), SSC, etc.)? (please distinguish between PHI and de-identified 
data)  
 
During an audit or program evaluation, representatives from the Yale Human Investigation 
Committee and from the National Institutes of Health may have access to subject data, but will 
strictly follow rules of confidentiality.   
 
g.   If appropriate, has a Certificate of Confidentiality been obtained?  
 
We have obtained a Certificate of Confidentiality from the National Institute on Drug Abuse. 
 
h.   Are any of the study procedures likely to yield information subject to mandatory reporting   
requirements? (e.g. HIV testing – reporting of communicable diseases; parent interview -incidents 
of child abuse, elderly abuse, etc.). Please verify to whom such instances will need to be reported.  

Page 39 of 39 
 
No. 
 
SECTION IX: POTENTIAL BENEFITS 
 
 
Potential Benefits: Identify any benefits that may be reasonably expected to result from the 
research, either to the subject(s) or to society at large. (Payment of subjects is not considered a 
benefit in this context of the risk benefit assessment.)  
 
         Participants and the HIV clinics will gain from their feedback from the academic detailing, 
provider education, stakeholder engagement, program tailoring, performance monitoring and 
feedback, formative evaluation, learning collaborative, and program marketing. Participants and 
others may eventually benefit from the scientific knowledge that may be gained from this work.  
 
 
         SECTION X: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 
 
1.     Alternatives: What other alternatives are available to the study subjects outside of the research? 
 
Potential study subjects have the freedom to refuse participation in the focus groups. 
2.  
Payments for Participation (Economic Considerations): Describe any payments that will be 
made to subjects, the amount and schedule of payments, and the conditions for receiving this 
compensation.  
          
 
Patients will be compensated $25 for their participation in focus groups.  As allowed by local 
institutional policies, clinic providers, administrators and payers will be compensated $50 for 
their participation. 
 
 
3. 
Costs for Participation (Economic Considerations): Clearly describe the subject’s costs 
associated with participation in the research, and the interventions or procedures of the study that 
will be provided at no cost to subjects.      
 
 
There are no costs to the subjects to participate in this research.   
 
4. 
In Case of Injury: This section is required for any research involving more than minimal risk. 
N/A 
 
a.     Will medical treatment be available if research-related injury occurs?  
 
b.     Where and from whom may treatment be obtained?  
 
c.     Are there any limits to the treatment being provided?  
 
d.     Who will pay for this treatment?  
 
e.     How will the medical treatment be accessed by subjects?