Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings
Phase: NA
Conditions: Opioid Dependence, Addiction, HIV/AIDS, Tuberculosis, Hepatitis
Sponsor: Yale University

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YALE UNIVERSITY
                                  HUMAN INVESTIGATION COMMITTEE
                                     Application to Involve Human Subjects in Biomedical Research
100 FR1 (2015-2) 
SECTION I: ADMINISTRATIVE INFORMATION
Title of Research Project: Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings
Principal Investigator: Sheela Shenoi, MD, 
MPH
Yale Academic Appointment: Associate Professor
Department:  Internal Medicine, AIDS Program
Campus Address:   135 College Street, Suite 323
Campus Phone:  737-6133
Fax: 
Pager: 
E-mail: sheela.shenoi@yale.edu
Protocol Correspondent Name & Address (if different than PI):  Ahsan Ahmad
Campus Phone: 737-6133
Fax: 
E-mail: 
ahsan.ahmad@yale.edu
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. 
See Disclosures and Management of Personal Interests in Human Research 
http://www.yale.edu/hrpp/policies/index.html#COI 
  Yes
X  No
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: 
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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
 Yale-New Haven Hospital—Saint Raphael Campus
 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.
 Clinical Neuroscience Research Unit (CNRU) 
Veterans Affairs Hospital, West Haven
 Other Locations, Specify: 
 International Research Site 
(Specify location(s)): University of Malaya CERIA, 
Kuala Lumpur, Malaysia
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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: 
 Yale University RSC (YU-RSC)
Approval Date:
 Magnetic Resonance Research Center PRC (MRRC-PRC)
Approval Date:
 *Nursing Research Committee
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. 5-9 years 9/1/2016-12/31/2025
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
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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 
  pending
Other (Specify) 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE.
The study is currently listed on ClinicalTrails.gov and is active. 
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.
a. Does your YNHH privilege delineation currently include the specific procedure that you will 
perform?
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b. Will you be using any new equipment or equipment that you have not used in the past for 
this procedure?
 
c. Will a novel approach using existing equipment be applied?
 
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.
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SECTION IV:
 PRINCIPAL INVESTIGATOR/FACULTY ADVISOR/ DEPARTMENT CHAIR AGREEMENT
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
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Department Chair’s Assurance Statement
Do you know of any real or apparent institutional conflict of interest (e.g., Yale ownership of a
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
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SECTION V: RESEARCH PLAN
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested. 
AIM 1: To conduct several empiric studies of TB screening and treatment strategies in 
prisoners, including: 
a) Comprehensive TB diagnostic studies, including TB symptoms, chest radiographs, 
tuberculin skin testing (TST), AFB smear, Gene Xpert, and sputum culture to examine best 
practice and alternative strategies for TB screening practices in prisons for HIV+ and HIV- 
prisoners; 
b) A RCT of LTBI prevention strategies among HIV+ and HIV- prisoners with high prevalence 
of HCV using standard 26-week daily isoniazid (26H) vs short-course weekly isoniazid + 
rifapentine (12HR); 
c) A  2-arm preference trial comparing post-release treatment completion in patients on OAT 
(further randomized to MMT vs BPN/NLX) vs no OAT in patients being treated for active 
or latent TB who are transitioning to the community.
AIM 2: To use data from specific aim 1 and publicly available data to conduct agent-based 
modeling for comparative and cost-effectiveness analyses of TB screening and treatment 
strategies among prisoners with and without HIV, incorporating the contribution of LTBI 
and prevalent TB on community transmission post-release.  
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.
Since 2003, Southeast Asia as a region has made major gains in reducing HIV infections and 
related morbidity and mortality by 37%, yet Malaysia is one of 4 countries in the region (all 
had major epidemics concentrated in PWIDs) where HIV mortality grew by >20%.1 Drug 
injection, primarily of heroin, contributes significantly to evolving HIV epidemics, disability 
and mortality.2 Criminalizing drug use rather than expanding risk reduction interventions has 
resulted in increasing imprisonment and concentration of people with HIV and opioid use 
disorders within prisons.3,4 Despite the overlapping and inextricable syndemics of HIV and 
PWIDs, HIV transmission continues unabated.5 Mathematical modeling studies of HIV 
prevention in countries where the HIV epidemic is either concentrated in or is generalizing 
from a PWID-driven epidemic, demonstrate that the combination of high coverage of opioid 
agonist and antiretroviral therapy is the best way to avert new infections,6 irrespective of the 
HIV prevalence among PWIDs.7 Opioid agonist maintenance therapies (OAT), however, are 
the most cost-effective.6 Moreover, prescribing antiretroviral therapy in HIV+ patients 
markedly reduces the development of active TB in patients with latent TB infection (LTBI).8,9 
3. 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.
Study procedures: In the past 5 years, we have documented feasibility with many of the proposed 
procedures in prisons (e.g., TB screening pilot using diverse diagnostic options, implementing 
OAT in prison, prescribing study medications, interviewing participants in private study rooms 
that prison constructed for us with plexiglass doors, using CASI interviews, understanding and 
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quantifying OAT preferences, etc). 10-16 
Part A: All newly admitted prisoners (80-120 on admission days and all 18 years or older) 
undergo a complete assessment, including a brief exam and mandatory rapid HIV test by the 
prison medical unit.  New inmates will be pre-screened, and those who meet eligibility criteria 
will be invited to meet with the research staff and participate in a research study where they will 
be screened for TB (not currently part of standard care).  Inmates interested in participating will 
be invited to have an individual meeting with a research team member to learn more about the 
study.   Those interested in continuing with study activities will undergo informed consent process 
that will cover TB screening diagnostics, study procedures, risks, and benefits.  After obtaining 
informed consent, research staff will administer the following study activities: a brief survey, 
WHO symptom assessment, tuberculin skin testing (TST) with reading after 72 hours, sputum 
induction on 2 consecutive mornings for AFB smear, TB culture (results back 6-8 weeks using the 
BACTEC MGIT 960 liquid culture gold standard), and point-of care (POC) Gene Xpert. Each 
person will have phlebotomy for HBV and HCV Ab, LFTs, and if HIV+, CD4 testing (all of these 
are POC using Alere™). For those with CD4<50, they will undergo POC low-cost, urinary TB-LAM 
lateral flow testing (sensitivity=67%) (Alere™ Determine) to identify disseminated TB.17,18 
Additional demographic, drug use, and TB risks will also be assessed along with prison data 
(release date, previous incarcerations, type of offense). Participants suspected of having active TB 
will then undergo CXR testing. A TB specialist will review all patients and results, ensuring that 
patients with suspected TB initiate treatment. All suspected or confirmed cases active TB cases in 
HIV+ prisoners will have ART initiated after 2 weeks of TB treatment initiation (if CNS TB not 
suspected) if CD4<50 and within 8 weeks for all others. 
For participants with active TB, those remaining in prison after treatment completion (estimated 
n=40-50), research staff will administer the following study activities within 24 months of 
treatment completion: WHO TB symptom assessment, pulmonary function tests (PFTs), point-of 
care (POC) Gene Xpert, and Chest X-ray. Each person will have phlebotomy for C-reactive protein 
(CRP) as well. For patients living with HIV, we will perform CD4 and VL testing. For participants 
who did not have TB, and are still in prison (estimated n=300), research staff will administer 
repeat screening 12-24 months after the first screening: WHO TB symptom screen, POC Gene 
Xpert, AFB Smear, and Chest-X-ray. Each person will also have phlebotomy for CRP. 
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Participants who previously participated in Harapan II Aim 1A who remain in the prison after 12-
24 months with active TB or without active TB will be identified by their remaining sentence in 
prison using administrative data. These participants will be identified by prison officers using their 
study ID, prison ID and names (no patient names will be recorded in the data to protect 
confidentiality). These participants will be brought back to the CERiA clinic inside the prison for a 
pre-screening (to ensure eligibility), and if eligible, will be introduced by a Research Assistant to 
the proposed additional TB screening using the language in the Participant Information 
Sheet/Consent Form. 
After the Research Assistant reads the Participant Information Sheet/Consent Form, the 
participant will be asked if he would like to voluntarily participate in the follow up TB screening. If 
the participant would like to voluntarily participate, he will sign the re-consent form and proceed 
with the follow up screening. If at any time the participant does not want to continue the follow up, 
he may stop with no repercussions.
Additionally, we will review prison logs and health records to determine how many patients are 
diagnosed with TB and HIV, start TB and HIV treatment, and the time to treatment initiation and 
completion (for TB only) among non-study patients to compare with outcomes study patients. We 
will abstract data from prison logs without identifiers and will not interact with incarcerated 
individuals other than the study participants. Additional structural non-patient data pertaining 
to service delivery, implementation of HIV guidelines, and operations in the prison may also be 
collected to compare prison HIV and TB care to national and global guidelines (ex. number of 
medical staff, whether diagnostic or monitoring tools (ex. HIV viral load), medications available 
on the prison formulary, etc) are available.
Eligibility for Part A includes:
 1) Age > 18 years 
2) Malaysian citizen 
3) Prison sentence > 3 months 
4) Absence of active TB within past 2 years of enrollment 
5) Newly admitted prison inmate (<2 days)
6) Able to provide informed consent
Part B:  Prisoners with LTBI from Aim 1 will be asked to participate in Part B.  Our preliminary 
data suggest that >80% of all prisoners have TST+ and 94% of HIV+s and 63% of HIV-s are HCV 
Ab+.10,12,13  We have documented both in a systematic review and using empiric data in Malaysia 
that few prisoners with LTBI receive preventive TB therapy and for those that do, the major factor 
contributing to treatment non-completion is release from prison and hepatotoxicity.19  
Consequently, WHO provides conflicting guidance on TB preventive therapy in prisoners.  In its 
guidelines on managing TB in closed settings, preventive therapy is not recommended, yet in its 
HIV treatment guidelines, long-term isoniazid preventive therapy is recommended, especially if 
TST+. Since these recommendations, a large RCT among non-prisoners compared a once-weekly 
12-week regimen of INH/rifapentine (12HR) to daily 26 weeks of isoniazid preventive therapy 
(IPT: 26H). In terms of TB prevention, efficacy was similar, but patients prescribed short-course 
12HR had higher treatment completion rates (82.1% v.69.0%; p<0.001).20 Since shorter LTBI 
preventive strategies are likely to improve completion, perhaps overturning previous 
recommendations based on the best science. A remaining concern, however, is the high 
prevalence of PWIDs with chronic HCV infection in prison, which might increase hepatotoxicity 
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in a 12HR combination since both isoniazid and rifapentine can damage the liver; CDC is calling 
for studies of 12HR in prisoners, but have not yet funded research. In the absence of studies of 
12HR use in prisoners, it is crucial to assess both completion rates and tolerability (especially 
when high HCV prevalence is present). 
Eligibility for Part B includes:
1)
Meets inclusion criteria for Part A 
2) Has latent TB (HIV+, or TST > 10mm (HIV-)) and no active TB disease
3) >6 months before end of sentence to ensure option for treatment completion
4) AST/ALT <5X ULN, or AST/ALT <3x ULN if TBil >2x ULN
5) Not on a protease inhibitor (drug interaction with rifapentine)
6) No known porphyria
7) Not pregnant (women only).  
Enrolled participants will undergo block stratified randomization, stratifying on four factors: a) 
CD4<350 (if HIV+); b) HCV Ab status; c) ART status; and d) opioid dependence. After 
randomization and allocation to 12HR or 26H, participants will be provided 12HR weekly (12 
weeks) and 26H daily (26 weeks) as directly observed therapy. Every 4 weeks, patients will be 
monitored for AST/ALT, adverse side effects and pregnancy. Premature treatment 
discontinuation will occur for any DAIDS Grade 4 toxicity, patient refusal to continue, or 
pregnancy (women only).  
Study Design: TB Studies
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Legend: LTBI=latent TB infection; H=isoniazid; HP=isoniazid + rifapentine; MMT= methadone 
maintenance treatment; BPN/NLX= buprenorphine/naloxone; OAT=opioid agonist treatment; ART= 
antiretroviral therapy; HCV= hepatitis C virus.
Part C: 
A two-arm preference trial (no MAT, and methadone) of prisoners with opioid use disorders 
who are not or are currently being treated for TB and/or HIV, and are about to transition to the 
community and need to continue their treatment post-release.  Patients may or may not be 
returning to Klang Valley and within 25 km of our research site. We anticipate enrolling 25-
50 participants per arm.
Once consented, study participants will be provided an informed decision-making aid that will 
help them decide if medication-assisted treatment, specifically Methadone, is best for them. 
Participants will also have the option not to enroll in medication-assisted treatment. 
Informed decision-making aid:
Shared decision-making (SDM) is based on the principles of informed consent and patient-
centered care, and involves patients actively partnering with their clinicians to make decisions that 
balance the best evidence for treatment with their personal values and preferences. Such tools 
using validated formal criteria have been developed in a wide variety of clinical contexts (e.g. 
cancer screenings, elective surgery, end-of-life care) to help guide patients in weighting risks, 
benefits and clarifying their values. These tools have demonstrated improved quality of decisions, 
satisfaction and some clinical outcomes. No such SDM tool exists in OUD treatment, and we 
ultimately aim to develop such a tool, pilot and evaluate its effect on clinical outcomes, especially 
in the initiation of and retention in OUD treatment after release from prison. At this time we will 
conduct focus group discussions to assess what baseline concerns, knowledge, and attitude 
participants have towards methadone maintenance therapy (MMT) and buprenorphine /naloxone 
(BPN/NLX). Although BPN/NLX is not new to Malaysia and not yet offered in prison by Ministry 
of Health, we will give a brief overview of BPN/NLX to the participants prior to the group session. 
This group discussion will guide the development of the SDM tool that will be used to help 
prisoners with OUDs decide if MMT is the best option for them.
We will conduct a specialized type of focus group, specifically nominal group technique (NGT), 
in which participants generate responses to a question and also rank the relative importance of 
these responses. Written notes as well as audio recording will be made. Groups will be voluntary 
and anonymous. We will collect demographic information of group participants that will be de-
identified, aggregated and decoupled from any individual responses. Data will be analyzed 
qualitatively for themes as well as quantitatively for frequency of themes and relative rankings 
across all groups. This data will reveal some of the concerns and beliefs that patients have 
regarding MAT on presentation and their relative importance in treatment decision making. 
We will recruit adults with OUDs from CCSC Kerinchi (community MMT site), Ikhlas 
(needle/syringe exchange program) and from Kajang prison. Group sessions will last no longer 
than 1 hour, and will include 6-10 participants per session. Groups will be conducted until a 
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saturation of themes is reached. Participants will undergo informed consent prior to participating, 
and will be compensated 50RM for their time.
 
Upon making an informed decision using the SDM developed from the focus groups, those that 
choose methadone maintenance treatment (MMT) will initiate 5 mg of methadone, 3-4 months 
prior to release from prison. The dose will increase in 5 mg increments every 7 days (as tolerated) 
until the daily dose is escalated to at least 80 mg or optimal dose before the date of release. Patients 
prescribed MMT will receive medication daily in prison, and will receive their medications weekly 
in form of take-way dosing. MMT will be dispensed at the community research site. All 
participants will be maintained on medication-assisted treatment and will receive follow-up care 
for 6 months after release from prison.
After a baseline assessment, our research assistant (RA) would meet the participant at the prison 
on the day of release to undergo a brief assessment, urine testing and to introduce the patient to 
our community research site to ensure that s/he can find the site after release and take the 
participant home so that our research assistants can know where the person is living/residing.  This 
process will also improve trust between the research staff and the participant.  Thereafter, all 
participants will be seen monthly, where they will undergo urine screening and be assessed for 
alcohol and drug use using timeline follow-back (TLFB), appointments for HIV and/or TB, 
adherence to HIV and/or TB medications, assessments of legal, employment, family issues using 
the Lite version of the Addiction Severity Index (ASI), depressive symptoms, health-related 
quality of life (HRQoL), satisfaction with their treatment. They will also be assessed for diversion 
(and urine testing).
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The primary outcome will be the proportion completing treatment for active or LTBI.  Secondary 
analyses will compare Kaplan Meier curves using Cox proportion hazards and time to 
discontinuation. TB treatment adherence will also be measured using MEMS caps and analyzed 
as we have done previously in TB patients in Ukraine
Eligibility for Part C includes:
1)
Meets inclusion for part A, if possible
2) Opioid dependence 
3) Has LTBI or active TB disease (based on screening in Part A), or no TB
4) Returning to live in Kuala Lumpur/Klang Valley region (within 25 km of Kerinchi research 
site), if possible
5) < 6 months before end of sentence 
6) AST or ALT <5X ULN
7) Not pregnant (women only).  
4. 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
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 
5. Subject Population: Provide a detailed description of the types of human subjects who will 
be recruited into this study.
For Aim 1 (a-c), only prisoners will be recruited. Community-based participants from methadone 
and needle/syringe sites will be recruited solely for the purpose of anonymous focus group 
discussions that will be used to develop the MAT decision making aid.
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Part A:  New intakes from Kajang Prison will be recruited (80-120) per day.  Mandatory HIV 
testing is done on all prisoners.  HIV prevalence is 5%.  All HIV+ prisoners upon entry will be 
approached for informed consent.  For Part B, only prisoners who have >9 months (preferably 
12 months) remaining on their prison sentence will be approached for recruitment. All subjects 
are expected to be Southeast Asians/Pacific Islanders.  While women will represent only 10% of 
the sample, they will be included. The minimum age is 18 years of age, thus children 18-21 years 
old will be eligible for participation.  Currently, only 2% of HIV+ prisoners are between 18-21 
years. For part C, prisoners who have less than 90 days remaining on their prison sentence, but 
more than 90 days of TB treatment remaining will be approached for recruitment. They must be 
at least 18 years old, have latent TB infection defined by TST ≥ 5mm (HIV+), or TST ≥ 10mm 
(HIV-), return to live in Klang Valley (within 25 km of Kerinchi research site), and AST/ALT 
<5X ULN.
Aim 2 will not include Human Subjects. Data analysis only. 
6. 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)
7. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or    
exclusion?
Inclusion and Exclusion Criteria: 
1a: inclusion:

Above 18 years old

Malaysian Citizen

Newly admitted (<2 days)

Able to provide consent

Absence of active TB within 2 years of enrollment

> 3 month prison sentence 
1b inclusion: 

Meets inclusion criteria for part A 

Has latent TB (HIV+, or TST > 10mm (HIV-)) and no active TB disease

>6 months before end of sentence to ensure option for treatment completion
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
AST or ALT <5X ULN, or AST/ALT <3x ULN if TBil >2x ULN

Not on a protease inhibitor (drug interaction with rifapentine)

No known porphyria

Able to provide informed consent 
1c inclusion:

Meets inclusion criteria for Part A, if possible

Opioid dependence 

Hast latent TB (HIV+, or TST > 10 mm (HIV-)), or active TB infection, or no TB

Returning to live in Kuala Lumpur/Klang Valley region (within 25 km of Kerinchi 
research site), if possible

AST/ALT <5X normal 

< 6 months remaining in prison

Able to provide informed consent
Exclusion Criteria:  Pregnant women or women planning to become pregnant will be excluded if 
we implement methadone or buprenorphine during pregnancy, the infant born to the mother is 
highly (>60%) likely to develop an infant abstinence syndrome that is avoidable by not providing 
MMT.  If a woman becomes pregnant during the course of the study, MMT will not be 
discontinued if she is receiving it as withdrawal has resulted in pre-term labor.  For women 
preferring not to be OAT, but who relapse to drug use, entry onto MMT will not be an exclusion 
criteria for remaining in the study. 
 
8. How will eligibility be determined, and by whom? 
Eligibility will be determined by the Research Assistants (RAs) hired by the University of 
Malaya – CERIA to work on this study.  An eligibility screening form will be developed into 
REDCap, a data collection and management application that will be used by the local RAs.  
Prior to enrollment, laboratory testing will be completed to ensure normal LFTs and urine 
testing will be completed to ensure that female participants are not pregnant. 
9. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, 
discomforts, or inconveniences associated with subjects participating in the research. 
For Aim 1, it is not anticipated that sensitive questions will be asked that will cause undue 
distress.  For those who become distressed or who are identified to have an underlying 
psychiatric disorder, they will be seen by the Addiction Psychiatrist on this grant.  For the 
prisoners who become distress and the psychiatrist is not IMMEDIATELY available, s/he will be 
referred to the onside prison doctor for evaluation and treatment according to prison protocol.  
During initial consent procedures, they will be fully informed about all parts of the study, 
including the questionnaires, will be asked to read the informed consent form, and will be asked 
whether they would like to participate in the study. They may choose to withdraw from the study 
at any point and decide not to complete the survey.
Clinical Risks Associated with Study Participation:  There are no adverse clinical risks to 
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participating in Aim 2.  For Aim 1, because participants will be taking FDA-approved and 
Malaysian MoH-approved medications, the risks will primarily be for those issues directly 
related to the medications. Specifically for Part B of Aim 1, participants may be at increased risk 
for hepatotoxicity due to the high prevalence of former drug injection and HCV coinfection, 
which might increase the likelihood of liver damage.  Though CDC and WHO do not recommend 
monitoring of LFTs among patients being treated for LTBI, in this case, because of the high 
prevalence of HCV coinfection, we will monitor for adverse side effects in Part B.  The specific 
risks of the two approved medications for treatment of LTBI include:
Rifapentine: The major side effect in RCTs related to this medication is liver inflammation. 
The extent to which patients develop this complication is unknown in patients with HIV/HCV 
coinfection.  
Hepatic Effects: Hepatitic inflammation has been described in patients taking Rifapentine. 
Rifapentine use in patients with abnormal liver function tests and/or liver disease should be 
when considered necessary (e.g., need for treatment of LTBI or active TB) and only with caution 
and close medical supervision. Supervision includes examining for hepatoxicity while examining 
for jaundice. Rifapentine should be discontinued if signs of liver disease develop or worsen (AST 
or ALT >5X ULN, or >3X ULN with symptoms of jaundice, nausea or fatigue,). The risk is 
elevated if administered with other antituberculosis agents (e.g., isoniazid, pyrazinamide) if 
these drugs are used with rifapentine.1
Hyperbilirubinemia (resulting from competition between rifapentine and bilirubin for excretory 
pathways in the liver) possible; such competition has been reported between rifampin and 
bilirubin. An isolated report of moderate increase in bilirubin and/or transaminase 
concentrations is not an indication to interrupt rifapentine therapy; the decision to discontinue 
therapy should be made after repeating the tests, noting trends in the concentrations, and 
considering the patient’s clinical condition.
Clostridium difficile-associated Diarrhea and Colitis: Treatment with anti-infectives, 
including rifamycins, may permit overgrowth of clostridia though this is an extremely rare 
event.  Consider C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-
associated diarrhea and colitis or pseudomembranous colitis) if diarrhea develops and manage 
accordingly with examination of stool and possibly starting empiric metronidazole. Some mild 
cases of CDAD may respond to discontinuance alone. Manage moderate to severe cases with 
fluid, electrolyte, and protein supplements; appropriate anti-infective therapy (e.g., oral 
metronidazole or vancomycin) recommended if colitis is severe.1Agents inhibiting peristalsis 
contraindicated in these patients.
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Interactions
Drug or Test
Interaction
Comments
β-Adrenergic blocking 
agents
Potential increased metabolism of the β-adrenergic 
blocking agent1
Dosage adjustment of the 
β-adrenergic blocking 
agent may be needed1
Antacids
In clinical studies, 
patients were advised to 
take rifapentine 1 hour 
before or 2 hours after 
antacids1
Antiarrhythmic agents 
(disopyramide, 
mexiletine, quinidine, 
tocainide)
Potential increased metabolism of the antiarrhythmic 
agent1
Dosage adjustment of the 
antiarrhythmic agent may 
be needed1
Anticoagulants, oral 
(warfarin)
Potential increased warfarin metabolism1
Adjustment of warfarin 
dosage may be needed1
Anticonvulsants 
(phenytoin)
Potential increased phenytoin metabolism1
Adjustment of phenytoin 
dosage may be needed1
Antifungals, azoles 
(fluconazole, 
itraconazole, 
ketoconazole)
Potential increased metabolism of the antifungal1
Adjustment of antifungal 
dosage may be needed1
Antiretrovirals, HIV 
entry inhibitors
Maraviroc: Concomitant 
use not recommended
Antiretrovirals, HIV 
protease inhibitors (PIs)
Indinavir: Decreased AUC and concentrations of 
indinavir; no effect on pharmacokinetics of rifapentine1
Atazanavir, fosamprenavir, lopinavir, nelfinavir, 
ritonavir, saquinavir: Potential decreased 
concentrations of the PI1
Concomitant use with PIs 
not recommended1 14 a
Manufacturer of 
rifapentine states use with 
extreme caution, if at all, 
in patients receiving PIs1
Antiretrovirals, 
nonnucleoside reverse 
transcriptase inhibitors 
(NNRTIs)
Delavirdine: Potential increased metabolism of the 
NNRTI1
Delavirdine, nevirapine: HIV-infected patients 
receiving a NNRTI who are receiving rifapentine for TB 
may have a higher rate of TB relapse than those treated 
with other rifamycin-based regimens
Concomitant use with 
NNRTIs, with the 
exception of efavirenz, is 
not recommended14 a
Barbiturates
Potential increased metabolism of the barbiturate1
Adjustment of barbiturate 
dosage may be needed1
Benzodiazepines (e.g., 
diazepam)
Potential increased metabolism of the benzodiazepine1
Dosage adjustment of the 
benzodiazepine may be 
needed1
Calcium-channel 
blocking agents 
(diltiazem, nifedipine, 
verapamil)
Potential increased metabolism of the calcium-channel 
blocking agent1
Dosage adjustment of the 
calcium-channel blocking 
agent may be needed1
Cardiac glycosides
Potential increased metabolism of the cardiac glycoside1
Dosage adjustment of the 
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cardiac glycoside may be 
needed1
Chloramphenicol
Potential increased metabolism of chloramphenicol1
Dosage adjustment of 
chloramphenicol may be 
needed1
Clofibrate
Potential increased metabolism of clofibrate1
Dosage adjustment of 
clofibrate may be needed1
Corticosteroids
Potential increased metabolism of the corticosteroid1
Dosage adjustment of the 
corticosteroid may be 
needed1
Dapsone
Potential increased metabolism of dapsone 1
Dosage adjustment of 
dapsone may be needed1
Doxycycline
Potential increased metabolism of doxycycline 1
Dosage adjustment of 
doxycycline may be 
needed1
Erlotinib
Possible decreased erlotinib AUCb
Avoid concomitant use if 
possibleb
Fluoroquinolones (e.g., 
ciprofloxacin)
Potential increased metabolism of ciprofloxacin1
Dosage adjustment of the 
fluoroquinolone may be 
needed1
Estrogens/Progestins
Hormonal contraceptives (oral or other systemic): 
Potential interaction with oral or other systemic 
hormonal contraceptives1
Use nonhormonal 
methods of contraception1
Immunosuppressive 
agents (cyclosporine, 
tacrolimus)
Potential increased metabolism of the 
immunosuppressive agent1
Dosage adjustment of the 
immunosuppressive agent 
may be needed1
Levothyroxine
Potential increased levothyroxine metabolism1
Dosage adjustment of 
levothyroxine may be 
needed1
Macrolides 
(clarithromycin)
Potential increased clarithromycin metabolism1
Dosage adjustment of 
clarithromycin may be 
needed1
Opiate agonists 
(methadone)
Potential increased metabolism of methadone1
Dosage adjustment of 
methadone may be 
needed1
Psychotherapeutic agents 
(amitriptyline, 
haloperidol, 
nortriptyline)
Potential increased metabolism of the 
psychotherapeutic agent1
Dosage adjustment of the 
psychotherapeutic agent 
may be needed1
Quinine
Potential increased metabolism of quinine1
Dosage adjustment of 
quinine may be needed1
Sildenafil
Potential increased sildenafil metabolism1
Dosage adjustment of 
sildenafil may be needed1
Sulfonylurea antidiabetic 
agents
Potential increased metabolism of the sulfonylurea 
agent1
Dosage adjustment of the 
antidiabetic agent may be 
needed1
Theophylline
Potential increased metabolism of theophylline1
Dosage adjustment of 
theophylline may be 
needed1
Tests for serum folate 
Standard microbiologic assays for serum folate and 
Consider using alternative 
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 Concomitant use with HIV protease inhibitors (PIs) or certain HIV entry inhibitors not 
recommended unless there are no other choices because rifapentine decreases the therapeutic 
levels of these medications. Recent data by our group shows that it can be safely administered 
with efavirenz, the most commonly prescribed ART as first line therapy in Malaysia. 
General Precautions
Discoloration of Body Tissues or Fluids
Urine, sweat, sputum, tears, and breast milk may have a red-orange coloration during 
rifapentine therapy.  Soft contact lenses and dentures may become permanently stained. 
Prisoners in Malaysia do not have access to contact lens or dentures. 
Patient Monitoring
In order to avoid excess hepatotoxicity, LFTs will be monitored at baseline.  
Specific Populations
Pregnancy and Lactating
Rifapentine is Category C so pregnant and breast-feeding women will be excluded from 
treatment.  Specifically, Rifampin administration during the last few weeks of pregnancy can 
cause postnatal hemorrhages in the mother and infant that require treatment with vitamin K. 
Similar effects may occur with rifapentine; appropriate clotting parameters should be evaluated 
if use of rifapentine is considered necessary during the last few weeks of pregnancy.
Specific Drugs and Laboratory Tests that can be affected by Rifapentine
ISONIAZID
Isoniazid (INH) is the recommended treatment for LTBI by the WHO and CDC and is one of the 
commonly used medications worldwide.  Severe and rarely fatal hepatitis associated with INH 
therapy has been reported and may occur or may develop even after many months of treatment. 
The risk of developing hepatitis is age related and increased duration of treatment. Approximate 
case rates by age are: less than 1 per 1,000 for persons under 20 years of age, 3 per 1,000 for 
persons in the 20 to 34 year age group, 12 per 1,000 for persons in the 35 to 49 year age group, 
23 per 1,000 for persons in the 50 to 64 year age group, and 8 per 1,000 for persons over 65 
years of age. The risk of hepatitis is increased with daily consumption of alcohol (alcohol is NOT 
available to Malaysian prisoners). Precise data to provide a fatality rate for isoniazid-related 
hepatitis is not available; however, in a U.S. Public Health Service Surveillance Study of 13,838 
persons taking isoniazid, there were 8 deaths (0.058% or 0.58 cases per 100,000) among 174 
cases of hepatitis (0.012% or 126 cases per 100,000). Thus, drug-induced hepatitis is 
uncommon and mortality is rare. 
Therefore, patients given INH should be carefully monitored and interviewed at monthly 
intervals. For persons 35 and older, in addition to monthly symptom reviews, hepatic enzymes 
and vitamin B12
vitamin B12 are inhibited by therapeutic rifampin 
concentrations; similar effects may occur with 
rifapentine1
assays to determine serum 
folate and vitamin B121
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(specifically, AST and ALT (formerly SGOT and SGPT, respectively)) should be measured prior 
to starting isoniazid therapy and periodically throughout treatment. Usually, enzyme levels 
return to normal despite continuance of medication, but in some cases progressive liver 
dysfunction occurs. Other factors associated with an increased risk of hepatitis include daily use 
of alcohol, chronic liver disease and injection drug use. A recent report suggests an increased 
risk of fatal hepatitis associated with isoniazid among women, particularly black and Hispanic 
women. No blacks or Hispanics will be enrolled. More careful monitoring should be considered 
in these groups, possibly as frequently as monthly. If abnormalities of liver function exceed five 
times the upper limit of normal, discontinuation of INH should be strongly considered. Liver 
function tests are not a substitute for a clinical evaluation at monthly intervals or for the prompt 
assessment of signs or symptoms of adverse reactions occurring between regularly scheduled 
evaluations. Patients should be instructed to immediately report signs or symptoms consistent 
with liver damage or other adverse effects. These include any of the following: unexplained 
anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and 
feet, persistent fatigue, weakness or fever of greater than 3 days duration and/or abdominal 
tenderness, especially right upper quadrant discomfort. If these symptoms appear or if signs 
suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since 
continued use of the drug in these cases has been reported to cause a more severe form of liver 
damage.
Other side effects of INH include minimal drug interactions (none expected with these study 
participants … eg, some antiseizure medications), peripheral neuropathy (obviated because we 
provide pyridoxine), and there are no drug interactions with HIV medications. 
Methadone: Methadone is the current standard of care for treating opioid use disorders in 
Malaysia, and will be provided as part of routine clinical care. The most concerning problem that 
we are likely to encounter is drug interactions with either TB medication (specifically rifampin) 
or HIV medications (for which there are many).  All patients initiating TB or HIV medications 
AFTER being stabilized on MMT will be monitored daily for two weeks for symptoms of opioid 
withdrawal using the Clinical Opioid Withdrawal Scale (COWS). We anticipate, however, that 
most patients will start their TB medications before receiving OAT and precipitating withdrawal 
symptoms will be unlikely. For those already on OAT, MMT doses will be increased by 5mg per 
day for mild symptoms, 10 mg per day for moderate symptoms and 20 mg per day for severe 
withdrawal using the Clinical Opioid Withdrawal Scale (COWS).
Buprenorphine/Naloxone (BPN/NLX):  BPN/NLX, also known by the name SUBOXONE, 
consists of a mixed medication of buprenorphine (BPN) and naloxone (NLX) in a 4:1 ratio by 
mass, respectively. BPN is a μ-opioid receptor partial agonist, which functions by partially 
activating opioid receptors and imitating its effects; however, BPN’s effect plateaus, thus giving 
the user only a minimal effect. NLX is a μ-opioid receptor antagonist with slightly lower affinity 
to opioid receptors than buprenorphine. When administered in combination with BPN, it aids in 
further reducing the partial agonist effect of BPN, especially when such is injected. Together, 
they ameliorate the euphoric and sedative effects of opioids by binding and blocking opioid 
receptors to reduce cravings by inducing a less intense receptor activation. BPN/NLX is FDA 
approved to treat opioid use and alcohol use disorders, and is available for use under the tongue 
or on the inside of the cheek. BPN/NLX has sometimes been a preferred mode of MAT as it has 
a reduced potential for diversion or abuse, can be taken home for daily self-administration and 
has shown increased engagement and retention in community-based treatment. (Malta, et al., 
2019). Additionally, The buprenorphine/naloxone combination tablet (BPN/NLX) was 
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introduced in the Malaysian market in 2006 to reduce potential problems with diversion and 
abuse.  When taken as directed, Naloxone does not interfere with Suboxone’s primary ingredient, 
buprenorphine. The major ingredient in Suboxone, buprenorphine, has undergone in-depth 
studies since 1978, when it was originally introduced as a method of treating opiate addictions. 
Clinical trials sponsored by the National Institute on Drug Abuse have found buprenorphine to 
be effective in: alleviating withdrawal symptoms of opiate drugs, decreasing cravings, reducing 
illict drug use, blocking the effects of other opiates, and retaining patients in treatment programs. 
10. Minimizing Risks: Describe the manner in which the above-mentioned risks will be 
minimized.
Informed Consent: Informed consent will be obtained by the local RAs using an information 
sheet approved by the Medical Ethics Committee of the University of Malaya Medical Centre.  
Participants will also complete a standard consent form for the University of Malaya Medical 
Centre.
Face-to-Face Interviews and surveys/questionnaires: There are minimal risks expected 
from participating in interviews, such as feeling uncomfortable with certain topics being 
discussed. As mentioned previously, all participants for interviews will be reminded that their 
refusal to participate will in no way negatively affect their professional relationship with any of 
the participating agencies or clinics. If participants do feel uncomfortable about certain 
questions asked, subjects will be able to choose not to answer the question that makes them 
uncomfortable. All interviews and consultations will occur in private rooms, to ensure 
confidentiality. All data will be stored in secure locations. Everyone will be told that the meeting 
is confidential.  
Recruitment: Recruitment procedures are designed to reduce the risk of confidentiality loss 
for participants. Patients will not be targeted for recruitment in this study. They will visit 
participating prisons for their routine medical care. They will be reassured that their 
participation is voluntary and confidential.  For participants in Aim 1, recruitment will take 
place in a private prison room. 
Monitoring Adverse Side Effects: 
For patients in Aim 1, Part B (trial of 26H vs 12HR) and Part C (MMT, vs. no MAT), patients will 
be seen monthly clinically for symptoms of hepatitis or neuropathy and LFTs shall be 
monitored.  Anyone whose LFTs increase to >5X ULN, or >3X ULN with symptoms of jaundice, 
nausea or fatigue, will be stopped from receiving medications and LFTs will be monitored 
weekly to ensure that LFTs are decreasing.  Similarly, if patients develop Grade 3 or higher 
peripheral neuropathy, they will be discontinued.  Of note, LFTs will be measured at baseline 
and monthly for 3 months for 12HR and monthly x 6 months for 26H.  
MMT patients will be seen daily for the first month and may have their medications dispensed 
less frequently if they have no evidence of using illicit drugs by self-report or urine testing. 
11. 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.
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a. 
What is the investigator’s assessment of the overall risk level for subjects 
participating in this study? 
b.
If children are involved, what is the investigator’s assessment of the overall risk 
level for the children participating in this study? 
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
Aim 1parts (a-c) requires a DSMB. 
Data and Safety Monitoring Board
We will comprise a full Data and Safety Monitoring Board (DSMB), that will include three 
voting members from colleagues in the field.  The PI on this grant is familiar with the 
implementation of a DSMB; he is currently serving as one of the board members of the 
NIDA Clinical Trials Network studies examining routine HIV testing among drug users.  
The key elements of a DSMB include the following:  
1)
Selecting experts in the field (HIV, TB, Substance abuse) who will serve as members of 
the board.  If funded, we will select two U.S. and one Malaysian experts to serve on the 
DSMB.  As in other NIDA trials, we will work with NIDA staff to select these individuals.  
Individuals from NIDA will be responsible for the final invitation to participate on the 
Board. During the first six months of the study, while final implementation is being 
conducted, the DSMB will convene to go over their charge, examine the guidance set 
forth by the study team and to question the PI and biostatisticians about pre-defined 
endpoints.  Once these outcomes and stopping rules are defined, the Board will 
reconvene at regularly scheduled times to assess outcomes.  
Defining stopping rules.   For Aim 1, part B, we will be examining completion and 
tolerability of two LTBI prevention strategies. The study is not powered to reduce 
development of active TB, but to establish safety in prisoners who have high prevalence 
of HCV infection.   Tolerability (discontinuation from study medication) will be the 
primary outcome.  All discontinuations will be reviewed by the PI and the team.  Death 
will be brought to the DSMB within 24 hours if medication related (though most deaths 
are related to TB itself).  If the discontinuation rate is 3-fold higher in either group, 
either in the interim analysis when 50% is enrolled or at any time within study 
assessment, the study will be stopped for safety purposes and a press release will be 
made. For Part B, we anticipate a difference between the control group and the two 
intervention groups of about 40%. 
2)
3) Assessment of possible adverse consequences of the various interventions.  No specific 
guidance is available for DSMBs for these kinds of interventions; however, we have 
considerable experience with CHRP, Project PLUS, Project TRUST, Project CONNECT, 
Project BEST and other community research studies to provide a specific plan.  In fact, in 
order to collect information about the “safety” of the intervention, we intend to hire a 
research assistant to gather safety information from three independent sources.  These 
include the weekly study meeting where all active participants are discussed, daily 
conversations with the Health Educators and weekly conversations with the subject 
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comes in for HHRP sessions.  These data are rich and include an impressive amount of 
information to guide an appropriate safety plan for this intervention.  The types of 
information captured below are a number of items that potentially could be an adverse 
event for participation in this study.  The findings from our study will also be reported to 
the DSMB for them to review and provide feedback, and if necessary, halt or refine the 
study.  These include, but are not limited to:
a.
Breaches of confidentiality:  To date, we have had one subject refuse to 
participate in the intervention for fear that someone within his community would 
recognize him coming to the mobile van on a daily basis and therefore be 
identified as being HIV+.  Two others expressed similar concerns a priori, 
however these concerns were dispelled as soon as the subject met the DAART-SP 
who introduced them to the mobile van staff an operation procedures.
b.
Severe adverse events associated with increased adherence to ART or TB 
medications:  It is possible that non-adherent subjects will develop severe 
adverse side effects from properly adhering to a regimen.   Positive Transitions, 
for the subset of subjects who ultimately receive HAART, may have increased 
levels of adherence and therefore more adverse side effects.  We have learned 
from two examples of this type of experience.  One pregnant women developed 
severe drug-related hepatitis while taking her medications properly.  In this case, 
experience with DAART actually improved her outcome because her community 
HIV clinician could only reach this patient through our research program to ask 
her to discontinue her medications.  A second case may have died as a 
consequence of increased adherence to ART.  He initially was quite symptomatic 
and ill from advanced HIV/AIDS with a baseline CD4 = 4.  With time and 
adherence to ART, his CD4 rose and he became asymptomatic and felt better.  He 
began to feel so well that he is believed to have relapsed to drug use (he 
previously felt too poorly to use drugs) and may have overdosed.  Our team 
pursued an autopsy in this case and learned that an opiate overdose was not the 
etiology of his death.  The cause of death is currently unknown.
c.
Assessment of adverse consequences: Several different research staff members 
will assess subjects in both the MMT and IPT interventions.  For those on MMT 
who receive either HAART or TB Treatment, we will monitor for symptoms of 
opioid withdrawal.  Alternatively, we will monitor for overdose in these subjects, 
diversion or drug interactions with MMT.  We would also monitor for breaches of 
confidentiality in PT subjects.  An initial investigation would be undertaken and 
simultaneously reported to the IRB using standard university procedures.
d. Confidentiality of research data:  Breaches of confidentiality regarding research 
data are more difficult to detect.  For that reason, we have in place a number of 
safeguards including double-locked doors, locked file cabinets, confidential and 
dedicated fax machine and double password-protected computers. In accordance 
with federal and university policy, all research personnel are compliant with 
HIPAA training.  If any breach of data confidentiality were detected, we would 
use similarly detailed procedures for report to the PI and IRB simultaneously. 
e.
Complications from MMT:  In this study, we will monitor for adverse consequences in a standard 
way.  First, drug interactions between buprenorphine and HIV antiretrovirals have not been 
extensively evaluated. Efavirenz and nevirapine have been associated with reductions in 
methadone levels, and precipitated clinical withdrawal.  In cases where we can detect symptoms 
of opiate withdrawal, we will increase the methadone dose to treat the symptoms of withdrawal.  
Dr. Altice was the first clinician to report cases of opiate withdrawal among patients receiving 
HAART and methadone and is currently investigating other pharmacokinetic interactions 
between methadone and buprenorphine with antiretroviral drug interactions.  Methadone may 
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result in opiate excess.  Patients are observed daily by the methadone nurse who will refer any 
subject noted to have excess sedation to the physician to assess dosing.  Moreover, we will assess 
drug interaction with methadone and NNRTIs and rifampin through administration of the COWS 
for up to three weeks after any two medications are combined that are known to impact opiate 
levels.  Last, we will recommend that all women use barrier contraceptives to prevent pregnancy.  
For women receiving MMT and who become pregnant, we will continue to monitor them and their 
newborn infant for adverse consequences.  Any such adverse events will be reported to our IRB, 
and when indicated, to the drug manufacturer if a pharmacokinetic drug interaction is identified.  
d. For multi-site studies for which the Yale PI serves as the lead investigator: N/A
i. How will adverse events and unanticipated problems involving risks to subjects or 
others be reported, reviewed and managed?
ii. What provisions are in place for management of interim results?
iii. What will the multi-site process be for protocol modifications?
12. Statistical Considerations: Describe the statistical analyses that support the study design. 
Analytical Plan for Aim 1  
Part A: International guidelines recommend TB screening for prisoners, but they do not offer 
any specific guidance on how to most effectively screen them, especially given restricted budgets 
(especially for prisoners) in resource-constrained settings.  We hypothesize that HIV+ prisoners 
should be prioritized for screening since TB incidence is minimally 10% per year (higher in 
Malaysian prisoners based on our previous pilot data) vs 10% lifetime in HIV-s.  We also 
hypothesize that a number of screening methods are available, but will have differential impact 
on prevalence, incidence and transmission to others (including to prison staff). Precision in the 
estimates will be used for calculations in Aim 2.  All analyses will conform to the STARD 
guidelines for diagnostic accuracy reporting (www.stard-statement.org/). Using standard 
measures for establishing prevalence and incidence of active and LTBI, frequencies will be 
calculated for categorical variables and median with standard deviation (SD) or interquartile 
range (IQR) for continuous variables depending on whether the data were normally distributed 
or not, respectively. Chi square and Student t-tests will compare between Xpert-
negative/culture-positive and Xpert-positive/culture-positive groups. Sensitivity, specificity, 
positive (PPV) and negative (NPV) predictive values of the Xpert and their respective 95% 
confidence intervals (95% CI) will be calculated compared to the results of active TB defined 
using the gold-standard MGIT 960 liquid culture.39,40 For variables identified as being strongly 
collinear with each other (age, duration of drug use and duration of cigarette smoking), final 
models for diagnostic accuracy will be based on the most optimal goodness-of-fit using the 
Akaike Information Criterion (AIC). When combining results from multiple screening tests (e.g., 
symptoms + CXR or symptoms + Gene Xpert), we will examine multiple thresholds using pair 
measures, or Receiver Operator Curves (ROC), where sensitivity and specificity (or even 
predictive values) differ across thresholds.  Such methods provide better discriminative power 
when adjusting the threshold (e.g., varying levels of TB symptoms).41 Using estimates of LTBI of 
84% and active TB 10-15% with a 95% CI and SE=0.025 among a cross-sectional population of 
~4800 HIV+ prisoners, a sample size of 214 HIV+ and 214 HIV- participants would be needed. 
Thus, a sample of 250 HIV- and 250 HIV+ prisoners (N=500) should be more than adequate. 
No loss to follow-up is expected because sentenced prisoners must serve at least 90 days and can 
easily complete screening procedures. 
Part B: In CDC’s original non-inferiority trial of 26H v 12HR, treatment completion differed 
significantly (67.0% v 82.1%); however, there were no HIV+s (and therefore no ART prescribed) 
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and HCV infection was <3%. Therefore tolerability for a longer exposure to 26H may decrease 
completion further. We will compare the proportion completing TB preventive therapy (no 
adverse side effects) for the two groups and control for any confounders that may differ after 
randomization. Using an alpha=0.05 and power=0.8 and a 20% difference (most conservative), 
we would need 118 per arm. We hypothesize, however, that 26H will be tolerated even less based 
on studies of IPT hepatoxicity in a RCT of isoniazid in prisoners (21% in with HCV)42 and HCV+ 
patients (correlated with longer IPT exposure).43-45 Thus, even increasing the difference in 
treatment completion to 20% (still conservative), the sample size would need to be 164. Thus, 
we will conservatively enroll 177 per arm or 354 patients total. We will analyze the data two 
ways, including ITT as a difference in proportion of treatment completion used in RCTs. In 
order to discern factors associated with differences in treatment completion, we will treat the 
entire recruited sample as a cohort and using Cox regression, examine time to treatment 
discontinuation between the two groups using Cox Proportion Hazards as well as examine the 
independent factors associated with treatment discontinuation (e.g., being on ART, HCV status, 
baseline AST/ALT, CD4 strata, etc). 
Part C: Eligibility will be having no TB disease, TB disease or LTBI, on TB medications that 
must be completed after release, and meet pre-incarceration DSM-V criteria for opioid 
dependence. We will compare a control group of prisoners choosing no OAT and compare them 
to OAT patients. Even though we anticipate 15-20% attrition, we will count missing=failure to 
be conservative and will censor the data based on the mid-point between the last and the missed 
visit.  The primary outcome will be the proportion completing treatment for active or LTBI.  
Secondary analyses will compare Kaplan Meier curves using Cox proportion hazards and time to 
discontinuation. TB treatment adherence will also be measured using MEMS caps and analyzed 
as we have done previously in TB patients in Ukraine. 
For the FGDs, data will be analyzed qualitatively for themes as well as quantitatively for 
frequency of themes and relative rankings across all groups. This data will reveal some of the 
concerns and beliefs that patients have regarding MAT on presentation and their relative 
importance in treatment decision making.
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.
A.  DRUGS, BIOLOGICS and RADIOTRACERS
1. Identification of Drug, Biologic or Radiotracer: What is (are) the name(s) of the drug(s) 
biologic(s) or radiotracer(s) being used? Identify whether FDA approval has been granted and for what 
indication(s). 
Rifapentine and Isoniazid.  Both are approved by the FDA.  
Methadone is an FDA-approved medicine currently in Malaysia, and standard of care in Prison
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B.  DEVICES
1.      Are there any investigational devices used or investigational procedures performed at Yale-
New Haven Hospital (YNHH) (e.g., in the YNHH Operating Room or YNHH Heart and 
Vascular Center)?  ☐Yes   ☒No    If Yes, please be aware of the following requirements:
NOT APPLICABLE
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__80-120 per day will be recruited; 
300-375 will be enrolled in parts b & c_
b.    If this is a multi-site study, give the total number of subjects targeted across all 
sites__N/A_ 
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): Information sessions
3.  Recruitment Procedures: 
a.
Describe how potential subjects will be identified.
AIM 1: 
Part A: Recruitment will take place among all new prison intakes as noted above.  Informed consent 
procedures will occur in our private room in the prison medical unit with a closed door but plexiglass 
window so that we can assure the prison staff that security regulations are not being breached.  The 
risks and benefits of the study will be described.  The risks are minimal and include phlebotomy of 30cc 
of blood (2 tbsp), chest radiograph (minimal radiation exposure) and expectoration of sputum.
Part B: Among those in Part A who have LTBI and who otherwise meet eligibility criteria, they will 
undergo informed consent in the private research room at the prison with a plexiglass door in a similar 
manner as done for Part A. 
Part C: Among those in Part A who have LTBI or active TB, 6 months or less remaining in prison and 
who otherwise meet eligibility criteria, they will undergo informed consent in the private research room 
at the prison with a plexiglass door in a similar manner as done for Part A. 
Participants in Parts A and B will NOT be compensated for ANY research activities while within the 
prison.  This is done to avoid any real or perceived level of coercion.  Participants in Part C, however, 
will receive mobile flip phones, with calling minutes added every month of follow-up.  The mobile 
phones will be used to communicate with participants to facilitate scheduling follow-up appointments 
post-prison release.  Participants who already have their own personal mobile phone prior to prison 
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release can use their personal devices and will still be offered to have minutes added to their phone 
each month.  To thank participants for participating in our study they will be offered the option to keep 
the mobile phone at the end of the study or receive the monetary equivalent of the mobile phone (RM50 
or ~16.67).
AIM 2:  No human subjects will be used.  
b.
Describe how potential subjects are contacted. 
Subjects will be contacted in the prison and asked if they would like to learn more about the 
project. 
c.
Who is recruiting potential subjects? 
Part A:  New intakes from Kajang Prison will be recruited daily.  Mandatory HIV testing is 
done on all prisoners.  HIV prevalence is 5%.  All prisoners that meet pre-screening eligibility and 
who are interested in participating in the study will be approached for informed consent.  For Part 
B, only prisoners who have >6 months (preferably 12 months) remaining on their prison sentence 
will be approached for recruitment. For Part C, prisoners who have less than 6 months remaining 
on their prison sentence will be approached for treatment.
Subjects will be recruited by local research assistants. 
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 
 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 
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 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?  N/A – HIPAA is not applicable. 
 Yes, all subjects
 Yes, some of the subjects
 No
If yes, describe the nature of this relationship.
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.)
The research will be conducted in Malaysia where HIPAA does not apply.  
Choose one: 
☐ For entire study 
☒ 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;
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.
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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
HIPPA not relevant to international studies. 
8. 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. 
Informed Consent: Patients in Aim 1 will undergo informed consent as we have done in all of 
our previous HIV and TB studies. Our previous experience has been high (near 100%) for 
participating in TB screening studies.  Of note, HIV testing is mandatory for prisoners and their 
status will already be known.  The Prisons Department has provided our team with dedicated 
research space for both our HIV and TB studies, including well-ventilated rooms for conducting 
interviews.  Each room has a large plexiglass window built into the door so that prisoners can 
enter the room with research staff and a prison guard can watch, but not hear the any informed 
consent procedures nor receipt of any interview data. Research assistants who are NOT 
employed by the prison will perform all informed consent procedures. Any Information or 
advertising information sheets will be approved by the IRBs at both Yale and the University of 
Malaya. All participants will be reminded that their refusal to participate will in no way 
negatively affect their relationship with the prison officials, the prison health system or any 
participating medical sites in the community either during the conduct of the research or into 
the future.  For Aim 1B, 1C and the FGD an information sheet and separate consent document 
approved by the University of Malaya Medical Center will be used to consent the inmates.  
9. 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. 
The study interviewers are trained in interviewing and will assess the subject’s understanding 
through verbal responses and non-verbal cues. Interviewers will ask open ended questions while 
introducing the details of the study to the subject such as “Can you tell me what you understood 
from our discussion?” or “What should you do if you want to stop participating in this study?” 
and will use IRB approved consent forms during informed consent procedure. If the interviewer 
determines that the subject does not fully comprehend the study purpose and his or her role as a 
participant, the subject will not be consented and will not be eligible for the study. 
10. 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. 
An Information Sheet and separate consent form, approved by the University of Malaya Medical 
Center, will be used for each eligible participant. 
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11. 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. 
All documents including data collection instruments and informed consent forms will be 
translated into Bahasa Malaysia and administered by research assistants who speak the language.  
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 
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. 
12. 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
   
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
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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? 
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.  
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 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? 
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?   
       
b. How will the research data be collected, recorded and stored? 
AIM 1: For Parts (A-C), all interview data will be recorded using a PC tablet and uploaded 
directly into REDCap, a data collection system using wireless internet (available within our 
prison research offices).  All clinical data will be returned to the prison clinic and to the research 
staff and recorded directly in the participant database.  All study interviews, done through 
REDCap, will be recorded without personal identifiers and only the PIs, study coordinator, and 
data managers will have access to the Link File to study number and identifiers.  Uploaded data 
will go directly into the REDCap database.  The data will be cleaned by the Data Management 
team.  
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?
Do all portable devices contain encryption software? 
 Yes   
 No
         If no, see http://hipaa.yale.edu/guidance/policy.html
All research staff members have undertaken Human Subjects’ training and know the importance 
of maintaining confidentiality of the participants’ information. Staff members refer to study 
subjects by study number to maintain their privacy. All data and study instruments which are 
recorded by study number only are maintained in secure password-protected computers and 
locked cabinets at Ceria at the University of Malaya and at the Yale AIDS program.
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.
The data will be stored in the manner noted above for at least seven years after completion of the 
study. Storage will be without individual identifiers. These data will be analyzed so that the 
findings can contribute to scientific literature that could be used to develop effective 
interventions for prisoners with LTBI or active TB disease. 
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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) 
The Principal Investigator and research staff will have access to collected data.
g. If appropriate, has a Certificate of Confidentiality been obtained? The research is covered by 
a CoC since it is NIH-funded.
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. 
We plan to report any infectious disease we identify (eg, HIV, TB) to the local authorities in 
accordance with the local reporting requirements. 
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.) 
The benefits for AIM 1 are numerous. For Part A, identifying the optimal TB screening strategy 
for prisoners, will guide prison care worldwide, but especially in LMICs.  For Part B, the 
potential benefits are that we may identify that providing a SHORT-COURSE 
INH/RIFAPENTINE (12HR) course results in INCREASED LTBI completion rates and 
LOWER or even SIMILAR toxicity.  As such, it would greatly improve LTBI treatment 
strategies for HIV+ prisoners who are at profoundly high risk for developing active TB. For Part 
C, the benefits of participating in this study include being better informed about available 
medication-assisted treatment options, receiving a medication-assisted treatment of their choice 
to manage their opioid use disorder, and receiving healthcare for TB management.
         SECTION X: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS
1.     Alternatives: What other alternatives are available to the study subjects outside of the research?
The alternative to participation in the study is non-participation. Subjects who do not wish to 
participate in this study may obtain healthcare, drug treatment, and other services through 
standard means in the prison. 
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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. 
Participants in Parts A , B and C will NOT be compensated for ANY research activities while within 
the prison.  This is done to avoid any real or perceived level of coercion.  Participants in Part C, 
however, will be paid for their time for research interviews post-release only (RM50 or ~$16.67 
per interview).  This amount is intended to cover their time and transportation costs to attend the 
interview. 
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.     
Participants will not have any costs associated with this research.
4.
In Case of Injury: This section is required for any research involving more than minimal risk.
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? 
Any possible adverse drug experiences will be referred to and evaluated by a licensed clinician at 
the prison. If needed, the subject will be referred to an infectious disease specialist for treatment.  
Costs for treatment will be the same as the cost for any other treatment provided at the prison.   
In cases when the prison clinicians cannot be contacted, the client will be assessed and treated 
with backup from the site Co-I who is a medical doctor. 
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