Test and Treat TB: A Proof of Concept Trial in South Africa
Phase: NA
Conditions: Tuberculosis
Sponsor: Massachusetts General Hospital

PARTNERS HUMAN RESEARCH COMMITTEE 
PROTOCOL SUMMARY 
Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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Answer all questions accurately and completely in order to provide the PHRC with the relevant 
information to assess the risk-benefit ratio for the study.  Do not leave sections blank. 
 
PRINCIPAL/OVERALL INVESTIGATOR 
Ingrid Bassett, MD, MPH 
 
 
 
PROTOCOL TITLE 
Test and Treat TB: A Proof of Concept Trial in South Africa 
 
 
FUNDING 
National Institute of Allergy and Infectious Diseases 
 
 
VERSION DATE 
5/26/2017 
 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
We will formally evaluate the value of using a rapid TB screening tool, Xpert 
MTB/RIF, on the iThembalabantu Tester, a mobile HIV testing unit operating 
in the peri-urban communities around Durban, South Africa. We will 
compare the Usual Care to a “Test & Treat TB” (T&T TB) approach. T&T TB 
includes: i) Xpert MTB/RIF screening on the mobile unit with rapid receipt of 
test results; ii) expedited TB treatment initiation at the mobile unit; iii) 
monthly SMS appointment reminders; and iv) cashless incentives. In a 2-
arm design, we will compare: 1) T&T TB and 2) Usual care (sample taken at 
mobile unit and sent for testing at a hospital). We propose a proof-of-
concept pilot evaluation to accomplish the following aims:  
 
Aim 1: To establish the feasibility, yield, and clinical impact of a 
“Test & Treat TB” strategy on a mobile HIV screening unit in South 
Africa. 
Hypothesis: Provision of convenient rapid TB test results with expedited 
treatment initiation, combined with SMS reminders, will substantially 
improve rates of TB treatment completion. 
 
Aim 2: To assess the cost and cost-effectiveness of this mobile, 
integrated HIV/TB screening strategy for maximizing linkage to TB 
care and treatment completion. 
Hypothesis: Viewed from a societal perspective, a T&T TB strategy will be 
very cost-effective compared to both expedited testing alone and usual care. 
 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
South Africa has the third highest TB incidence in the world, and HIV-
infected patients in South Africa entering antiretroviral therapy (ART) 
programs have a TB prevalence of 20-25%. TB co-infection is associated 
with a two-fold increased mortality risk and is the leading cause of death. A 
critical barrier to combating TB in HIV-infected individuals has been the 
difficulty in securing a rapid, accurate TB diagnosis.  The delay in TB case 
detection leads to increased morbidity and mortality as well as a longer 
period of infectiousness and increased transmission.  Integrating HIV and TB 
services has been made a priority since ART both reduces the incidence of 
TB dramatically and improves survival.  Interventions that increase efficiency 
of services have improved linkage to and retention in HIV care, and similar 
strategies are needed for TB.  This project addresses that need by 
implementing Xpert at the point of care in the community, outside of 
healthcare facilities, where high-risk individuals may present earlier in the 
course of TB disease.  Bolstered by improvements in ART initiation rates 
through point of care CD4 testing and theoretical framework of the HIV Test 
and Treat approach, we will assess the impact of community-based TB 
diagnosis with Xpert MTB/RIF and expedited treatment initiation on TB 
outcomes, both at the individual level, with this proof-of-concept clinical 
trial, and at the population level using mathematical modeling.   
 
 
RESEARCH DESIGN AND METHODS 
Briefly describe study design and anticipated enrollment, i.e., number of subjects to be enrolled 
by researchers study-wide and by Partners researchers.  Provide a brief summary of the 
eligibility criteria (for example, age range, gender, medical condition).  Include any local site 
restrictions, for example, “Enrollment at Partners will be limited to adults although the sponsor’s 
protocol is open to both children and adults.”
We anticipate 16 months of enrollment to identify 150 TB cases (75/strategy 
* 2 strategies) who will be eligible to meet the study outcomes. All eligible 
adults undergoing HIV or TB testing at the iThembalabantu Tester or with 
the iThembalabantu home testing team will be eligible for enrollment.  All 
subjects who are either HIV-infected or TB symptomatic will be eligible for 
TB screening with Xpert MTB/RIF. 
 
Inclusion criteria: 
1) Age ≥ 18 years 
2) English or Zulu speaking 
3) Able and willing to give informed consent 
4) Willing to share HIV/TB results with study staff 
5) Access to mobile phone 
6) Willing to attend one of eight local clinics for treatment 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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Exclusion criteria: 
1) Currently taking TB treatment 
 
 
Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects 
enrolled at Partners will not participate in the pharmacokinetic portion of the study.”  Describe 
study endpoints.
Patients waiting to have an HIV or TB test at the mobile unit will be 
approached a bilingual research assistant (English/Zulu) to assess their 
interest in study participation.  The research assistant will go through a short 
screening questionnaire with interested and eligible individuals and collect 
basic demographic information. South African Identification Numbers will be 
collected by the mobile unit staff. Study participants will provide written 
informed consent in their primary language.  As per usual practice, a Tester 
staff member will administer a brief questionnaire regarding prior HIV 
testing history, TB diagnosis and treatment history, TB symptoms, 
hypertension, and diabetes symptoms. The study team collects these 
questionnaires from the Tester staff at the end of the day to record the data. 
Study participants will be asked to provide their mobile phone number and 
the phone number of a friend or family member, as well consent to later 
contact by the study team.  To assist with follow-up, the research assistant 
will record the name of the clinic where the patient anticipates receiving HIV 
and/or TB treatment, in case of a positive HIV test and/or Xpert MTB/RIF 
test.  Patients then undergo rapid HIV testing as per South African protocol, 
and HIV-infected participants will be offered a point of care CD4 count (Alere 
PIMATM Analyzer). Patients can refuse the HIV test and still participate in the 
TB testing portion of the study if they are TB symptomatic.  As per usual 
practice, all HIV-infected subjects will be given a referral letter by mobile 
unit staff detailing next steps for HIV treatment, including locations of 
ART/TB treatment sites. A small group of patients will be recruited through 
iThembalabantu clinic’s home testing team, which works in conjunction with 
a community-based organization in Umlazi to conduct door-to-door testing 
and screening for HIV and TB symptoms. A research assistant and study 
nurse will accompany the home testing team and will assess interest in 
study participation amongst patients who agree to home testing. Patients 
recruited via the home testing team will be subject to the same recruitment, 
study, and follow-up procedures as patients tested directly on the mobile 
unit. 
 
Participants will be randomized into one of two intervention groups: Usual 
Care or T&T TB.  Randomization will be determined by day, stratified by 
mobile sites, in blocks of variable sites.  All patients seen at the mobile unit 
or in the home on a given day will be enrolled in the same strategy to 
simplify logistical considerations and minimize the risk of subjects interacting 
with subjects in another study strategy.   

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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Participants assigned to Usual Care will provide a sputum sample at 
the mobile unit or within their home (if being tested by the home testing 
team) if their TB symptom screen and/or HIV test are positive.  They will not 
undergo Xpert screening on the mobile unit. The sputum sample will be sent 
by the mobile staff to a hospital for TB testing and positive patients will be 
contacted as per usual South African protocol. Sputum samples provided by 
participants assigned to Usual Care who are being tested at home will be 
sent to the district hospital for TB testing. 
HIV-infected or TB symptomatic participants assigned to the T&T TB 
intervention will receive: mobile unit Xpert MTB/RIF screening and an SMS 
stating the test results. If TB-positive, they will have the opportunity to 
receive positive Xpert results at the mobile tester and TB treatment starter 
pack given at the mobile tester. Patients who return to the tester for the 
results will be give 20ZAR of cell phone minutes. Those who are tested by 
the home testing team will not receive Xpert MTB/RIF screening on the 
mobile unit because the Xpert machine is difficult to transport and requires a 
constant power source. Instead, sputum samples will be taken to 
iThembalabantu and the GeneXpert will be run there. Results will be 
available to home-tested patients within 24 hours via SMS. Patients will 
receive monthly SMS reminders for appointments for TB care to improve 
linkage to and retention in clinical care. When a patient makes their first visit 
to a clinic for TB care, he or she will receive 30ZAR of cell phone minutes. 
When study staff verify a patient has finished 6 months of TB treatment, the 
patient will be sent 50ZAR of cell phone minutes by the research project 
manager. 
 
We will assess linkage to TB and/or HIV care for all participants with a 
positive Xpert MTB/RIF test regardless of study arm assignment.  Three 
weeks after the mobile unit or home visit, a research team member will 
contact the TB T&T patient’s specified clinic to ascertain whether the patient 
attended the first TB and/or HIV visit and to obtain the patient’s TB 
registration number. If a patient in the intervention arm did not link to care, 
the team member will call the patient to encourage him or her to seek care. 
For patients in the usual care arm, research staff will determine at three 
weeks whether the patient is TB positive by finding the patient’s test results 
in the National Health Laboratory Services (NHLS) database. For both arms, 
the team member will also contact clinics at six months to assess retention 
in care, using the TB registration number and South African ID number as 
identifiers.  A six-month period permits TB-infected individuals to link to a 
TB clinic and complete TB therapy. 
 
 
 
 
For studies involving treatment or diagnosis, provide information about standard of care at 
Partners (e.g., BWH, MGH) and indicate how the study procedures differ from standard care.  
Provide information on available alternative treatments, procedures, or methods of diagnosis.

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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This study will be conducted at the iThembalabantu Tester, which serves a 
peri-urban area in Durban, South Africa. A small group of patients will be 
recruited through iThembalabantu clinic’s home testing team, which works in 
conjunction with a community-based organization in Umlazi to conduct door-
to-door testing and screening for HIV and TB symptoms.  One of the 
intervention groups is Usual Care, and the other strategy (T&T TB) will be 
compared against Usual Care.  These strategies are informed by South 
African Department of Health recommendations. 
 
 
Describe how risks to subjects are minimized, for example, by using procedures which are 
consistent with sound research design and which do not unnecessarily expose subjects to risk or 
by using procedures already being performed on the subject for diagnostic or treatment purposes.
The study team will obtain approval for all study components from not just 
the MGH Institutional Review Board but also from the University of KwaZulu-
Natal (UKZN) Biomedical Research Ethics Committee (Durban ethics board).  
The approval from UKZN will be submitted to the MGH IRB as soon as it is 
received. 
 
Potential risks of participation in this study are minimal to moderate and 
may include stress or anxiety due to new disclosure of HIV status, mild 
discomfort from having sputum induction, breach of confidentiality, and risk 
of untreated TB.  
 
The risk of stress and anxiety due to discussion about HIV, TB, HIV and TB 
screening, and disclosure of HIV status will be minimized by conducting all 
discussions in a private space.  Patients will be informed that their responses 
to questions will in no way affect their care at the mobile unit and that 
subsequent care providers will not have access to their answers.  The 
research assistant will start each interview by reminding respondents that 
they are free to decline to answer any question.  None of the information 
collected through this investigation could affect a subject’s relationship with 
other individuals, such as patient-physician or family relationships, or impact 
the subject’s HIV or TB treatment at other sites. 
 
Study subjects’ privacy will be protected.  As is typical for clinical settings, 
patients will be offered a private place to undergo the baseline questionnaire 
and consent.  Accompanying family members or friends will be asked to wait 
elsewhere.  Any phone conversations after enrollment will be conducted with 
patients only when they are comfortable and can speak freely. SMS 
messages will be specific and informative about the patient’s TB results and 
the subsequent steps in TB care the patient needs to take; a patient’s HIV 
status will never be mentioned in an SMS. TB carries significantly less stigma 
than HIV and to prevent serious misunderstandings and miscommunication 
due to vague messages, SMS messages will be specific to TB. Clear, 
informative messages will also be more helpful to patients because they will 

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Version Date:  June 1, 2005 
 
  
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not be confused by a generalized message. 
 
 
 
 
 
 
 
Risks will also be minimized by handling all research data in a confidential 
manner.  The research office is 
 
 
 sealed with a password-protected electronic 
entrance and does not include patient care areas.  To assure confidentiality, 
each subject will receive a unique identification number.  Research data and 
entry forms will be labeled only with this number.  The research team in 
Durban will maintain a locked file cabinet in the research office accessible 
only to the project manager that connects patient identifiers to unique 
identifiers.  This information will not be available to the Partners-based 
investigators.  Participant confidentiality will be protected through the use of 
study numbers, rather than unique identifiers, at the time of analysis. 
 
Describe explicitly the methods for ensuring the safety of subjects.  Provide objective criteria for 
removing a subject from the study, for example, objective criteria for worsening disease/lack of 
improvement and/or unacceptable adverse events.  The inclusion of objective drop criteria is 
especially important in studies designed with placebo control groups.
 
Subjects will be free to withdraw voluntarily from the study at any time. The 
evaluation team will start each interview by reminding respondents that they 
are free to decline to answer any question they find difficult or 
uncomfortable. To maximize patient safety and public health, subjects in the 
TB T&T arm who have not linked to care at the time of the first follow-up 
assessment (3 weeks after testing) will be considered to have failed to reach 
the secondary study outcome of linkage to care, defined as the first clinic 
visit. Because patients in the usual care arm will receive a call from a local 
TB nurse about their results, we will not have any further contact with 
patients in the usual care arm. We will follow-up on patient outcomes in the 
usual care arm at 9 months by contacting the patient’s self-identified clinic 
and looking up the patient on South Africa national databases. 
In addition, standard protocols to protect the confidentiality of the data will 
be followed. All aggregate data will be securely stored either in locked file 
cabinets or, if in electronic form, on password-protected computers equipped 
with anti-virus software. All subjects will be followed for the duration of the 
study unless they choose to withdraw from the study. 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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FORESEEABLE RISKS AND DISCOMFORTS 
Provide a brief description of any foreseeable risks and discomforts to subjects.  Include those 
related to drugs/devices/procedures being studied and/or administered/performed solely for 
research purposes.  In addition, include psychosocial risks, and risks related to privacy and 
confidentiality.  When applicable, describe risks to a developing fetus or nursing infant.
 
Potential risks of participation in this study are minimal to moderate and 
may include stress or anxiety due to new disclosure of HIV status, mild 
discomfort from having sputum induction, breach of confidentiality, and risk 
of untreated TB. 
 
Stress and anxiety due to disclosure of HIV status: 
Subjects have presented to the iThembalabantu tester or consented to a 
home visit from the iThembalabantu home testing team and agreed to 
undergo an HIV test, and therefore the mild pain from the finger-prick test is 
going to be incurred regardless of the study.  All HIV testing is ultimately 
voluntary, and patients can choose not to test at any time.  The 
questionnaires used for data collection should not cause psychological stress. 
 
We anticipate that some patients who are diagnosed with HIV infection 
during the course of the study will experience additional fear and anxiety in 
dealing with their new diagnosis.  The Tester has trained counselors 
available to discuss test results with patients and has access to an 
appropriate, easily-accessible social work department that has a strong focus 
on HIV-related issues. 
 
Though this anxiety will be faced by many patients, most HIV-infected 
patients will eventually be diagnosed with their disease through the course 
of progressive immunosuppression.  Thus, this anxiety is most likely 
inevitable.  The literature suggests that the improvements in life expectancy 
and quality of life benefits associated with earlier diagnosis and care will 
exceed the transient anxiety associated with the initial diagnosis. 
 
Discomfort of sputum induction for TB testing: 
Patients who agree to TB screening and require sputum induction may 
experience slight irritation from the induction of sputum using hypertonic 
nebulized saline.  The saline is mildly irritating, but rapidly, within minutes, 
will often generate a cough forceful enough to produce a sputum specimen.  
Each induction uses a fresh, single-use tubing for the nebulizer to avoid 
cross-infection.  Sputum collection will follow local infection control practices, 
including collection of sputum in an outdoor area separate from patient 
waiting areas. 
 
Breach of confidentiality: 
It is extremely important that study subjects’ privacy is protected.  As is 
typical for clinical settings, patients will be offered a private place to undergo 

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Version Date:  June 1, 2005 
 
  
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the baseline questionnaire and consent.  Accompanying family members or 
friends will be asked to wait elsewhere.  Participants’ HIV status is kept in a 
locked cabinet in the iThembalabantu research office that will be accessed by 
the research staff to document study subjects’ test results only when no 
patients are present.  All study forms will be kept in locked file drawers, 
available at the South African site.  All aggregate data will be securely stored 
either in locked file cabinets or, if it electronic form, on password-protected 
computers equipped with anti-virus software. 
 
Patients recruited via the home testing team will also be ensured privacy 
during home visits.  The home testing team goes into homes to screen for a 
number of conditions, including HIV, TB, hypertension, and diabetes.  The 
team also inquires about vaccinations in children and assesses if pregnant 
women in the household are in need of antenatal care.  This broad range of 
services helps to ensure that people are not specifically targeted for HIV 
testing.  Additionally, these teams are well-known to the community and 
routinely make home visits, which helps to normalize their presence.  The 
home testing team keeps all patient records confidential and visits all of the 
households in a catchment area to avoid stigmatizing any individual 
household.   
 
Any phone conversations after enrollment will be conducted with patients 
only when they are comfortable and can speak freely. SMS messages will be 
specific to TB and not have any mention of HIV. 
 
Risk of untreated TB for subjects not linked to care: 
Some subjects will get a diagnosis of TB during the course of the study.  To 
maximize patient safety and public health, subjects in the TB T&T arm who 
have not linked to care at the time of the first follow-up assessment (3 
weeks after testing) will be contacted by research staff. Because the South 
African standard of care for TB positive patients involves calling patients, we 
will not contact these patients separately. 
 
Subjects newly diagnosed with TB in the T&T TB strategy will be given a 
two-week TB treatment starter pack with a label indicating that this is the 
only the start of a longer treatment course, along with extensive counseling 
related to the importance of seeking further care at their clinic, the need for 
at least 6 months of TB treatment, and an SMS reminder near the end of the 
starter pack.  The provision of a weight-based, fixed dose combination 
starter pack is typical practice at the time of new TB diagnosis in non-
Department of Health TB treatment sites in South Africa. 
 
EXPECTED BENEFITS 
Describe both the expected benefits to individual subjects participating in the research and the 
importance of the knowledge that may reasonably be expected to result from the study.  Provide 
a brief, realistic summary of potential benefits to subjects, for example, “It is hoped that the 

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treatment will result in a partial reduction in tumor size in at least 25% of the enrolled subjects.”  
Indicate how the results of the study will benefit future patients with the disease/condition being 
studied and/or society, e.g., through increased knowledge of human physiology or behavior, 
improved safety, or technological advances. 
 
Individual patients in the study, regardless of what strategy to which they 
are assigned, will benefit from their participation by being tested for TB with 
rapid, newly-available tests if they are at high risk of TB (HIV-infected or 
have TB symptoms), which will allow subjects to receive a diagnosis of TB 
more quickly. TB testing can help people get the care that they need and 
help them live longer.  Detection and treatment of TB also has the potential 
benefit of decreasing transmission to others in a patient’s environment.   
 
EQUITABLE SELECTION OF SUBJECTS 
The risks and benefits of the research must be fairly distributed among the populations that stand 
to benefit from it.  No group of persons, for example, men, women, pregnant women, children, 
and minorities, should be categorically excluded from the research without a good scientific or 
ethical reason to do so.  Please provide the basis for concluding that the study population is 
representative of the population that stands to potentially benefit from this research.
 
Subjects for this analysis will be recruited from mobile HIV testing sites in 
and around Umlazi Township in KwaZulu-Natal. A small group of patients will 
be recruited through iThembalabantu clinic’s home testing team. Subjects 
will have presented to these sites voluntarily or agreed to a home visit by 
the iThembalabantu team. All eligible adult patients will be offered 
enrollment. The distribution of gender and age will reflect the current mobile 
testing population. Women known to be pregnant will be encouraged to seek 
care to ensure adequate prenatal care. While HIV infection is an important 
problem in children, analysis of an intervention to improve linkage to HIV 
and TB care for children is beyond the scope of this pilot project. Children 
diagnosed with HIV are aggressively linked to care by study sites by being 
immediately taken to the HIV clinic even without a CD4 cell count, unlike 
adult patients. Additionally, the mobile testing unit does not test children 
under 15 years of age, and those ages 15-17 typically present alone or with 
an informal caretaker who would be unable to provide informed consent 
because they are not the legal health care proxy or guardian according to 
South African policies regarding non-therapeutic research trials.  
 
 
When people who do not speak English are excluded from participation in the research, provide 
the scientific rationale for doing so.  Individuals who do not speak English should not be denied 
participation in research simply because it is inconvenient to translate the consent form in 
different languages and to have an interpreter present.
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
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Individuals who speak either English or Zulu will be eligible for participation 
in this study. 
 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English
          http://healthcare.partners.org/phsirb/nonengco.htm 
 
 
 
RECRUITMENT PROCEDURES 
Explain in detail the specific methodology that will be used to recruit subjects.  Specifically 
address how, when, where and by whom subjects will be identified and approached about 
participation.  Include any specific recruitment methods used to enhance recruitment of women 
and minorities.
All subjects will be recruited from the iThembalabantu mobile HIV testing 
unit operating in the peri-urban communities around Durban. A small group 
of patients will be recruited through iThembalabantu clinic’s home testing 
team, which works in conjunction with a community-based organization in 
Umlazi to conduct door-to-door testing and screening for HIV and TB 
symptoms. The subjects will be approached by a bilingual research assistant 
(English/Zulu) prior to undergoing an HIV test. The research assistant will 
ascertain the patient’s eligibility based on a screening questionnaire, will 
describe the study, answer any questions, and invite the patient to 
participate.  At this contact, conducted in English or Zulu, depending on 
patient preference, the research assistant will describe the risks, benefits, 
and alternatives, including non-participation.  Patients who agree to 
participate and can fully comprehend the study will sign a written consent 
form in their language of choice.  They will then undergo a questionnaire 
prior to HIV testing. 
 
Provide details of remuneration, when applicable.  Even when subjects may derive medical 
benefit from participation, it is often the case that extra hospital visits, meals at the hospital, 
parking fees or other inconveniences will result in additional out-of-pocket expenses related to 
study participation.  Investigators may wish to consider providing reimbursement for such 
expenses when funding is available
 
Participants randomized to the intervention arm can receive a small 
cashless incentive of up to 100 ZAR (equivalent to 9 US dollars) of cell 
phone minutes. TB-positive patients can receive 20 ZAR for picking up 
their results at the mobile unit, 30 ZAR for linking to care at a clinic, and 
50 ZAR for completing TB treatment. 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
          http://healthcare.partners.org/phsirb/recruit.htm

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          Guidelines for Advertisements for Recruiting Subjects
          http://healthcare.partners.org/phsirb/advert.htm
 
          Remuneration for Research Subjects
          http://healthcare.partners.org/phsirb/remun.htm
 
 
CONSENT PROCEDURES 
Explain in detail how, when, where, and by whom consent is obtained, and the timing of consent 
(i.e., how long subjects will be given to consider participation).  For most studies involving more 
than minimal risk and all studies involving investigational drugs/devices, a licensed physician 
investigator must obtain informed consent.  When subjects are to be enrolled from among the 
investigators’ own patients, describe how the potential for coercion will be avoided.
Most subjects will be recruited from the iThembalabantu mobile HIV testing 
unit operating in the peri-urban communities around Durban. A small group 
of patients will be recruited through iThembalabantu clinic’s home testing 
team, which works in conjunction with a community-based organization in 
Umlazi to conduct door-to-door testing and screening for HIV and TB 
symptoms. The subjects will be approached by a bilingual research assistant 
(English/Zulu) prior to undergoing an HIV or TB test. The research assistant 
will ascertain the patient’s eligiblity based on a screening questionnaire, will 
describe the study, answer any questions, and invite the patient to 
participate.  At this contact, conducted in English or Zulu, depending on 
patient preference, the research assistant will describe the risks, benefits, 
and alternatives, including non-participation.  Patients who agree to 
participate and can fully comprehend the study will sign a written consent 
form in their language of choice.  They will then undergo a questionnaire 
prior to HIV or TB testing.  As is typical for clinical settings, patients will be 
offered a private place to undergo the baseline questionnaire and consent.  
Accompanying family members or friends will be asked to wait elsewhere.  
 
Patients will be informed that their responses to questions will in no way 
affect their care at the mobile unit and that subsequent care providers will 
not have access to their answers.  The research assistant will start each 
interview by reminding respondents that they are free to decline to answer 
any question.  None of the information collected through this investigation 
could affect a subject’s relationship with other individuals, such as patient-
physician or family relationships, or impact the subject’s HIV or TB 
treatment at other sites. 
 
The mobile testing unit moves from place to place without a publicly 
available schedule.  Therefore, patients presenting for HIV or TB testing on 
any given day will not be aware of the research study in advance, and they 
will not have an extended amount of time in which to make the decision to 
participate. 

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NOTE: When subjects are unable to give consent due to age (minors) or impaired decision-
making capacity, complete the forms for Research Involving Children as Subjects of Research 
and/or Research Involving Individuals with Impaired Decision-making Capacity, available on 
the New Submissions page on the PHRC website: 
http://healthcare.partners.org/phsirb/newapp.htm#Newapp
 
For guidance, refer to the following Partners policy: 
          Informed Consent of Research Subjects
          http://healthcare.partners.org/phsirb/infcons.htm
 
 
 
DATA AND SAFETY MONITORING 
Describe the plan for monitoring the data to ensure the safety of subjects.  The plan should 
include a brief description of (1) the safety and/or efficacy data that will be reviewed; (2) the 
planned frequency of review; and (3) who will be responsible for this review and for determining 
whether the research should be altered or stopped.  Include a brief description of any stopping 
rules for the study, when appropriate.  Depending upon the risk, size and complexity of the 
study, the investigator, an expert group, an independent Data and Safety Monitoring Board 
(DSMB) or others might be assigned primary responsibility for this monitoring activity.        
 
NOTE: Regardless of data and safety monitoring plans by the sponsor or others, the principal 
investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects 
under his/her care. 
 
A Data Safety and Monitoring Board (DSMB) will be developed, which will 
consist of three independent reviewers, including a statistician, an expert in 
HIV/TB, and a clinician.  The DSMB will meet once every six months by 
conference call.  The Principal Investigator will prepare material for the 
DSMB to review and will not be present for part of the DSMB meeting.  The 
DSMB will be provided with reports of adverse events as they occur, and the 
Chair of the DSMB has the responsibility of calling an ad hoc meeting if the 
type or frequency of serious adverse events is of concerns.  The DSMB may 
request additional information from the Principal Investigator at any time in 
the course of its review of the study.  The DSMB will ensure documentation 
of informed consent and review confidentiality procedures.  A report will be 
provided to the Principal Investigator, the University of KwaZulu-Natal Ethics 
Committee, and the Partners Human Research Committee.   The DSMB will 
cease meeting after enrollment concludes. 
 
Data monitoring and quality assurance will be done on an ongoing basis.  A 
project coordinator and data coordinator will monitor study data every 
month to ensure the accuracy and completeness of consent forms and other 
study questionnaires.  In order to ensure patient safety, data and safety 

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monitoring will include review of all adverse events, enrollment, and protocol 
deviations, in addition to review of any interim analyses to ensure 
confidentiality is maintained.  Field staff will be responsible for reporting 
adverse events, including breach of patient confidentiality, to the project 
coordinator, local Co-Investigator, and the Principal Investigator.   
 
Adverse events and unanticipated problems that occur during the conduct of 
the study, after study completion, or after subject withdrawal or completion 
will be submitted within 5 working days/7calendar days of the date that the 
Principal Investigator first becomes aware of the problem, as per the 
Partners Human Research Committee’s policy. 
 
Describe the plan to be followed by the Principal Investigator/study staff for review of adverse 
events experienced by subjects under his/her care, and when applicable, for review of sponsor 
safety reports and DSMB reports.  Describe the plan for reporting adverse events to the sponsor 
and the Partners’ IRB and, when applicable, for submitting sponsor safety reports and DSMB 
reports to the Partners’ IRBs.  When the investigator is also the sponsor of the IND/IDE, include 
the plan for reporting of adverse events to the FDA and, when applicable, to investigators at 
other sites.   
 
NOTE: In addition to the adverse event reporting requirements of the sponsor, the principal 
investigator must follow the Partners Human Research Committee guidelines for Adverse Event 
Reporting
Data monitoring and quality assurance will be done on an ongoing basis.  A 
project coordinator and data coordinator will monitor study data every 
month to ensure the accuracy and completeness of consent forms and other 
study questionnaires.  In order to ensure patient safety, data and safety 
monitoring will include review of all adverse events, enrollment, and protocol 
deviations, in addition to review of any interim analyses to ensure 
confidentiality is maintained.  Field staff will be responsible for reporting 
adverse events, including breach of patient confidentiality, to the project 
coordinator, local Co-Investigator, and the Principal Investigator.   
 
The DSMB will be provided with reports of adverse events as they occur, and 
the Chair of the DSMB has the responsibility of calling an ad hoc meeting if 
the type or frequency of serious adverse events is of concerns.  The DSMB 
may request additional information from the Principal Investigator at any 
time in the course of its review of the study.  The DSMB will ensure 
documentation of informed consent and review confidentiality procedures.  A 
report will be provided to the Principal Investigator, the University of 
KwaZulu-Natal Ethics Committee, and the Partners Human Research 
Committee.   
 
 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
14 
MONITORING AND QUALITY ASSURANCE 
Describe the plan to be followed by the principal investigator/study staff to monitor and assure 
the validity and integrity of the data and adherence to the IRB-approved protocol.  Specify who 
will be responsible for monitoring, and the planned frequency of monitoring.  For example, 
specify who will review the accuracy and completeness of case report form entries, source 
documents, and informed consent.   
 
NOTE: Regardless of monitoring plans by the sponsor or others, the principal investigator is 
ultimately responsible for ensuring that the study is conducted at his/her investigative site in 
accordance with the IRB-approved protocol, and applicable regulations and requirements of the 
IRB.
 
Data monitoring and quality assurance will be done on an ongoing basis.  A 
project coordinator and data coordinator will monitor study data every 
month to ensure the accuracy and completeness of consent forms and other 
study questionnaires.  In order to ensure patient safety, data and safety 
monitoring will include review of all adverse events, enrollment, and protocol 
deviations, in addition to review of any interim analyses to ensure 
confidentiality is maintained.  Field staff will be responsible for reporting 
adverse events, including breach of patient confidentiality, to the project 
coordinator, local Co-Investigator, and the Principal Investigator.   
 
 
For guidance, refer to the following Partners policies: 
          Data and Safety Monitoring Plans and Quality Assurance
          http://healthcare.partners.org/phsirb/guidance.htm#13
 
          Reporting Unanticipated Problems (including Adverse Events)
          http://healthcare.partners.org/phsirb/guidance.htm#7
 
 
 
PRIVACY AND CONFIDENTIALITY 
Describe methods used to protect the privacy of subjects and maintain confidentiality of data 
collected.  This typically includes such practices as substituting codes for names and/or medical 
record numbers; removing face sheets or other identifiers from completed 
surveys/questionnaires; proper disposal of printed computer data; limited access to study data; 
use of password-protected computer databases; training for research staff on the importance of 
confidentiality of data, and storing research records in a secure location.   
 
NOTE: Additional measures, such as obtaining a Certificate of Confidentiality, should be 
considered and are strongly encouraged when the research involves the collection of sensitive 
data, such as sexual, criminal or illegal behaviors.
 
All study sites have internet access and the capacity to enter computerized 
data.  The Partners-based investigators will work closely with the South 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
15 
African team on all data collection and management systems.  Trained 
research assistants will record participant responses on paper data forms.  
Data collection forms will be scanned and uploaded weekly.  Original forms 
will be kept in a locked cabinet in a locked office.  The research office is 
 
password-protected electronic entrance and does not include patient care 
areas.  Screening and enrollment data will be entered locally by dedicated, 
trained staff into a web-based study tracking system, which will be 
constructed and maintained by the Partners-based team.  All data 
transmissions will be encrypted.  Local workstations and networks are 
password-protected and restricted to use by study personnel only.  
 
Adherence to confidentiality measures will be overseen on site by the study 
project manager.  All data will be collected by the South African team, and 
each participant will receive unique study ID number. Research data and 
entry forms will be labeled only with this number.  The research team in 
Durban will maintain a locked file cabinet in the research office accessible 
only to the project manager that connects patient identifiers to unique 
identifiers.  This information will not be available to the Partners-based 
investigators who will have access only to data stripped of patient identifiers. 
Participant confidentiality will be protected through the use of study 
numbers, rather than unique identifiers, at the time of analysis. 
 
The risk of stress and anxiety due to discussion about HIV, TB, HIV and TB 
screening, and disclosure of HIV status will be minimized by conducting all 
discussions in a private space.  Patients will be informed that their responses 
to questions will in no way affect their care at the mobile unit and that 
subsequent care providers will not have access to their answers.  The 
research assistant will start each interview by reminding respondents that 
they are free to decline to answer any question.  None of the information 
collected through this investigation could affect a subject’s relationship with 
other individuals, such as patient-physician or family relationships, or impact 
the subject’s HIV or TB treatment at other sites. 
 
Study subjects’ privacy will be protected.  As is typical for clinical settings, 
patients will be offered a private place to undergo the baseline questionnaire 
and consent.  Accompanying family members or friends will be asked to wait 
elsewhere.  Any phone conversations after enrollment will be conducted with 
patients only when they are comfortable and can speak freely. SMS 
messages will be specific to TB and not have any mention of HIV. 
 
 
SENDING SPECIMENS/DATA TO RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
Specimens or data collected by Partners investigators will be sent to research collaborators 
outside Partners, indicate to whom specimens/data will be sent, what information will be sent, 

Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  June 1, 2005 
 
  
16 
and whether the specimens/data will contain identifiers that could be used by the outside 
collaborators to link the specimens/data to individual subjects.
  
No data will be collected by Partners investigators as part of this study.  All 
data will be collected by the South African team. 
 
Specifically address whether specimens/data will be stored at collaborating sites outside 
Partners for future use not described in the protocol.  Include whether subjects can withdraw 
their specimens/data, and how they would do so.  When appropriate, submit documentation of 
IRB approval from the recipient institution.
 
All data will be collected by collaborators in South Africa. Specimens used for 
Xpert MTB/RIF screening will be disposed of appropriately. Specimens used 
in the validation process will be sent to the National Health Laboratory 
Service (NHLS) for microscopy and culture. Specimens will not be stored.  
 
RECEIVING SPECIMENS/DATA FROM RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
When specimens or data collected by research collaborators outside Partners will be sent to 
Partners investigators, indicate from where the specimens/data will be obtained and whether the 
specimens/data will contain identifiers that could be used by Partners investigators to link the 
specimens/data to individual subjects.  When appropriate, submit documentation of IRB 
approval and a copy of the IRB-approved consent form from the institution where the 
specimens/data were collected.
 
The research team in Durban will collect and maintain the study data, and 
the Partners-based investigators will only have access to data stripped of 
patient identifiers, which will be sent by encrypted transfers.  The South 
Africa-based project manager will be the only individual will access to the 
locked file cabinet containing the linkages to patient identifiers.