A Study to Evaluate the Accuracy, Usability and Readability of the OraQuick® HIV Self-Test Performed by Observed Intended Users in Canada
Phase: NA
Conditions: HIV Testing, HIV Infections
Sponsor: Unity Health Toronto

 
 
 
A Study to Evaluate the  
Accuracy, Usability and Readability  
of the OraQuick® HIV Self-Test  
Performed by Observed Intended Users 
in Canada 
 
 
 
Protocol Number: REACH – HIV – OraQuick – 2.0 
 
Version: 1.0 
Version Date: 13 July 2021 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 1 of 45 
 
 
PROTOCOL DETAILS 
 
 
 
Study Title: A Study to Evaluate the Accuracy, Usability and Readability of the 
OraQuick® HIV Self-Test Performed by Observed Intended Users in 
Canada. 
Short Study Title: OraQuick HIV Self-Test Study 
Other Study Name:  OraQuick HIVST Study 
Protocol Number: REACH – HIV – OraQuick – 2.0 
Version Number: 1.0 
Version Date: 13-July-2021 
  
 
 
 
 
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 2 of 45 
 
INVESTIGATOR SIGNATURE PAGE 
 
INVESTIGATOR’S AGREEMENT IN ACCORDANCE WITH 
SUBSECTION 81(k) OF THE MEDICAL DEVICES REGULATIONS 
Device Name/Nom de l'instrument: OraQuick ADVANCE®HIV-1/2 Rapid Antibody Test 
Protocol Number/No du Protocole: REACH – HIV– OraQuick– 2.0 
I, Sean Rourke, undertake, as outlined in Subsection 81(k) of the Medical Devices Regulations, 
to: 
(i) conduct the investigational testing in accordance with the protocol: 
A Study to Evaluate the Accuracy, Usability and Readability of the OraQuick® HIV Self- Test 
Performed by Observed Intended Users in Canada 
(ii) inform a patient who is to be diagnosed or treated with the device of the risks and benefits 
associated with its use and obtain the written consent of the patient, 
(iii) not use the device or permit it to be used for any purpose other than the investigational 
testing specified in the protocol, 
(iv) not permit the device to be used by any person other than myself, except under my 
direction, 
(v) in the event of an incident that is related to a failure of the device or a deterioration in its 
effectiveness, or any inadequacy in its labelling or in its directions for use and has lead to the 
death or a serious deterioration in the state of health of a patient, user or other person, or 
could do so were it to recur, report the incident and the circumstances surrounding it to the 
Site Director and the manufacturer or importer of the device, within 72 hours after its 
discovery. 
           
 
  
 
    13-July-2021 
Signature  
 
 
 
 
 
 
Date 
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 3 of 45 
Table of Contents 
 
1. BACKGROUND ........................................................................................................................... 7 
1.1. Summary ................................................................................................................................ 7 
1.2. Device Description ................................................................................................................. 7 
1.3. Clinical Studies of Investigational Device .............................................................................. 8 
1.4. Summary of Known Benefits and Risk of HIV Self-Testing .................................................... 9 
1.5. Study Compliance Statement .............................................................................................. 10 
2. STUDY OBJECTIVES .................................................................................................................. 10 
3. STUDY DESIGN ........................................................................................................................ 10 
3.1. Overall Study Design ............................................................................................................ 10 
3.2. Study Population .................................................................................................................. 12 
3.3. Study Sites ............................................................................................................................ 12 
3.4. Study Description ................................................................................................................. 12 
3.5. Selection and Withdrawal of Participants ........................................................................... 13 
4. STUDY PROCEDURES ............................................................................................................... 15 
4.1 Recruitment ...................................................................................................................... 15 
4.2 Informed Consent ............................................................................................................. 15 
4.3 Enrollment Questionnaire - Review Eligibility Criteria ..................................................... 16 
4.4 Background Data ............................................................................................................... 17 
4.5 Medical History/ Oral Health ............................................................................................ 17 
4.6 Concomitant Medications ................................................................................................. 18 
4.7 Dispensing and Return of the OraQuick® HIV Self-Test Device......................................... 18 
4.8 Participant Self Testing ..................................................................................................... 18 
4.9 Observations and Verification of Participant Self-Testing ................................................ 19 
4.10 Observer’s Interpretation of Study Participant’s Self-Test Result ................................. 20 
4.11 Interpretation of Results – Mock Devices .................................................................... 21 
4.12 Post-Assessment Questions/Label Comprehension .................................................... 21 
4.13 Confirmatory Procedures .............................................................................................. 22 
4.14 Additional Procedures and for Study Participants with Preliminary Positive Self-Test 
Results ............................................................................................................................... 23 
4.15 Additional Procedures for Study Participants with Negative Results ............................ 23 
4.16 Compensation for Study Participants ............................................................................ 23 
5. QUALITY CONTROL AND ASSURANCE ..................................................................................... 23 
5.1 Training ............................................................................................................................. 23 
5.2 Trained Researcher/ Observer Responsibilities ................................................................ 23 
5.3 Study Monitoring .............................................................................................................. 24 
6. DATA ANALYSIS ....................................................................................................................... 24 
6.1. Data Management Processes ........................................................................................ 24 
6.2. Data Reporting ............................................................................................................... 24 
6.3. Primary Analysis ............................................................................................................. 24 
6.4. Secondary Analysis ......................................................................................................... 25 
6.5. Demographics ................................................................................................................ 25 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 4 of 45 
6.6. Error and Failure Rates .................................................................................................. 26 
6.7. Sample Size .................................................................................................................... 26 
7. OBLIGATIONS OF THE INVESTIGATOR .................................................................................... 27 
7.1 Retention of Records ........................................................................................................ 27 
7.2 Device Accountability ....................................................................................................... 27 
7.3 Protocol Amendments ...................................................................................................... 27 
7.4 Protocol Violations and Deviations ................................................................................... 28 
7.5 Adverse Events and Adverse Device Events Reporting .................................................... 28 
7.5.1 Adverse Events ............................................................................................................... 28 
7.6 Severity of Adverse Events ............................................................................................... 29 
7.7 Relationship of Adverse Events to the Device .................................................................. 29 
7.8 Serious Adverse Events (SAE) ........................................................................................... 30 
7.9 Adverse Device Effects (ADE) ............................................................................................ 31 
7.10 Confidentiality of Participant Specimens and Information ........................................... 31 
7.11 Investigator Documentation .......................................................................................... 31 
7.12 Study Termination ......................................................................................................... 32 
8. References .............................................................................................................................. 33 
9. Appendices .............................................................................................................................. 35 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 5 of 45 
STUDY PROTOCOL CONTACTS 
 
OraSure Technologies Inc:  
Name:  
Michele Roehler 
Title:   
Director, Clinical Trials  
Tel: 
 
(484) 353-1658 
Fax: 
 
(610) 332-3425 
Email:  
mroehler@orasure.com   
 
 
Principal Investigator:  
Name:  
Dr. Sean Rourke 
Title:   
Scientist, Li Ka Shing Knowledge Institute, St. Michael’s Hospital 
Professor of Psychiatry, University of Toronto 
Director, CIHR Centre for REACH in HIV/AIDS 
Director, CIHR CBR Collaborative Centre 
Tel: 
 
(416) 878-2779 
Email:  
sean.rourke@utoronto.ca  
 
 
Site Investigators:  
Name:  
Dr. Megan Saunders  
Title:   
Primary Care Physician, Women’s Health in Women’s Hands 
Email:  
megan@whiwh.com 
 
Name:  
Dr. Nina Malayil  
Title:   
Medical Director, Hassle Free Clinic 
Email:  
nina@hasslefreeclinic.org 
 
Name:  
Dr. Réjean Thomas 
Title:   
CEO and Medical Director, Clinique médicale l’Actuel  
Email:  
rejean.thomas@lactuel.ca  
 
Name:  
Dr. Chris Fraser  
Title:   
Medical Director, Cool Aid Community Health Centre 
Email: 
crrfraser@gmail.com  
 
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 6 of 45 
LIST OF ABBREVIATIONS: 
 
Abbreviation 
Description 
ACB 
African Caribbean and Black 
AE 
Adverse Event 
ART 
antiretroviral therapy 
CM 
Comparator Method 
EC 
Ethics Committee 
GCP 
Good Clinical Practice 
EIA 
Enzyme Immunoassay 
HIV 
Human Immunodeficiency Virus 
HIVST 
Human Immunodeficiency Virus Self-Test 
ID 
Identification 
IDU 
Injection Drug User 
IFU 
Instructions for Use 
ICH 
International Council for Harmonization 
MSM 
Men who have sex with men 
PID 
Participant Identification  
POC 
Point-of-care 
RA 
Research Assistant 
REB 
Research Ethics Board 
SOP 
Standard Operating Procedure 
UADE 
Unexpected Adverse Device Effect 
US 
United States 
WHO 
World Health Organization 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 7 of 45 
 
1. BACKGROUND 
 Summary 
Oral fluid based self-testing provides another option to increase the uptake of HIV testing. 
Studies have shown that interest and acceptability of self-testing with oral fluid is high.1–
3  
 Despite significant progress made in improving testing rates over time, concern has been 
raised that conventional, public, facility-based testing has several weaknesses, including 
long waiting time, repetitive counselling, the identification of HIV negative people within 
the testing program without a subsequent effective prevention message, poor quality 
control on the part of testers in terms of test administration, and the inability to reach 
key and vulnerable populations.3,4 Self-Testing for HIV (“HIVST”) is an emerging approach 
with the potential to increase the uptake of HIV testing to be high impact, low cost, and 
empowering for those who may not otherwise test, notably in key populations and other 
people at high risk for HIV infection.5 This technological innovation in the healthcare 
industry may be considered a disruptive innovation technology, as it brings to the market 
an innovation that may be affordable, simple, accessible and convenient if successful. 
There is a growing body of supporting evidence showing the acceptability and usability of 
HIVST in various key populations and groups2,5,6 with further plans for evaluations on 
device performance.  
 Device Description   
OraQuick® HIV Self-Test  
OraSure Technologies, Inc. has developed packaging and labeling for use of a variation of 
the OraQuick  ADVANCE® Rapid HIV-1/2 Antibody Test in a self-test environment. This 
product is known as the OraQuick® HIV Self-Test.  It is comprised of the same components 
as the current OraQuick ADVANCE® Rapid HIV 1/2 Antibody Test available in the United 
States. The test is packaged and labeled for consumer use. The OraQuick® HIV Self-Test is 
a single-use, qualitative immunoassay to detect antibodies to Human Immunodeficiency 
Virus Type 1 (HIV-1) and Type 2 (HIV-2) in oral fluid.   
 
The OraQuick® HIV Self-Test is a visually read, qualitative, in vitro lateral flow 
immunoassay for the detection of antibodies to HIV-1 and HIV-2. An oral fluid specimen 
is collected using the flat pad on the test device, followed by the insertion of the test 
device into the vial of developer solution.  
 
The OraQuick® HIV Self-Test package includes a specific, step-by-step instructions and a 
device stand. The actual device and developer vial are not different from the OraQuick 
ADVANCE® Rapid HIV-1/2 Antibody Test (not currently available for commercial use in 
Canada). The difference is in the packaging and labeling which were specifically designed 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 8 of 45 
for consumer use. This packaging, along with the instructions for reading and interpreting 
the results and all accompanying materials, will be used in this study. 
 
 
 
 Clinical Studies of Investigational Device 
 
The OraQuick® HIV Self-Test packaging is the result of a development effort that 
 
incorporated investigator feedback and data collected during clinical investigations of 
 
usability, self-test accuracy, and linkage into care which is licensed under the US FDA.  
 
See additional information for: 
 Approval of OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (June 22, 2004)7  
 Approval of OraQuick In-Home HIV Test (July 3, 2012)8  
 Summary of WHO prequalification assessment for OraQuick HIV 1/2 Self-Test 
(November 2019)9  
 According to a report published by UNITAID in July 2017, an individual’s knowledge of 
 their and their partner’s HIV status is essential to the HIV response. Despite the many 
 benefits of HIV testing, in 2016, approximately 30 per cent of people with HIV globally, 
 (and up to 14% in Canada), remained unaware of their status. Some of the largest gaps in 
testing, prevention and treatment coverage are among men who have sex with men, 
Indigenous communities, people who use drugs, young people and other key populations 
who are often reluctant or unable to access existing services.10,11 Recognizing this, the 
World Health Organization (WHO) recommended that HIVST be offered as an approach 
to complement existing HIV testing approaches, and subsequently released the guidance 
document TSS-1 Human Immunodeficiency Virus (HIV) rapid diagnostic tests for 
professional use and/or self-testing in 2016.12 Since then, HIVST has been scaling up 
rapidly in global settings. 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 9 of 45 
 Summary of Known Benefits and Risk of HIV Self-Testing 
 The potential benefits of an HIV Self-Test include immediate and private test results, 
 which may encourage testing of individuals or high-risk groups who may otherwise 
 refrain from testing due to privacy issues and stigma.  
 
While many governments offer free testing for HIV in a clinic setting, the ability to self-
test  removes the need for time spent visiting a clinic and waiting for results, particularly 
important where public testing facilities are long distance; many people who make the 
effort  for clinic-based testing often fail to return to receive their test results (both 
positive and negative). Additionally, private HIV testing can reduce the burden for routine 
testing for negative or sero-discordant partners, resulting in more people knowing and 
monitoring their HIV status over time.  
Providing individuals with a tool to test themselves could also lead to earlier diagnosis of 
HIV status, with the potential for earlier medical intervention through both digital health 
technologies/telephone held lines as well as clinic follow-up for confirmatory testing. 
With an earlier diagnosis, individuals are empowered to modify their high-risk behaviours, 
potentially reducing the number of new HIV infections. This empowerment of consumers 
is not only limited to modification of lifestyle decisions, but also in being proactive in their 
health-care decisions. 
The potential risks of an HIV Self-Test include not understanding the limitations of a 
screening test, such as use of the test during the window period of seroconversion, or 
receiving a false positive, false negative, or invalid test result. HIV Self-Tests can be used 
without a counsellor present, with the potential for adverse outcomes if the user obtains 
an unexpected result.  As far as possible, these risks are identified in the HIV Self-Test 
instructions for use (IFU; see Appendix A), with instructions on when not to use the test, 
how to interpret the test result, and what to do next for a positive, negative or invalid 
result. 
Additional risks of HIV Self-Testing include the inability to track individuals for medical 
follow-up, partner notification, and public health reporting. There is also the potential for 
coercive testing and testing by unprepared minors. All of these possible risks are being 
addressed in various forums where experts are developing guidance around HIV Self-
Testing. 
Participants may experience slight temporary discomfort where the gums are swabbed 
during the OraQuick® HIV Self-Test.  
Although every effort to protect participant privacy and confidentiality will be made, it is 
possible that participants' involvement in the study could become known to others, and 
that social harm may result (i.e., because participants could become known as HIV-
infected or at "high risk" for HIV infection).   

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 10 of 45 
 Study Compliance Statement 
 This study will be conducted in compliance with The Canadian Medical Research Council 
 Guideline on the “Code of Ethical Conduct for Research Involving Humans” and according 
 to the general requirements of the International Conference on Harmonisation 
harmonised tripartite guideline E6 (R1): Good Clinical Practice.13    
2. STUDY OBJECTIVES  
The primary objectives of this study will be to:  
1) Evaluate the device performance, i.e. sensitivity and specificity, compared to 
laboratory reference testing  
2) To document if intended users (non-professional “lay users”), can successfully 
perform the steps to use the OraQuick® HIV Self-Test, without product 
familiarization or demonstration (accuracy/usability)  
3) To document if intended users, (non-professional “lay users”), can successfully 
interpret contrived strong positive, weak positive, negative, and a range of invalid 
results (test results interpretation) and  
4) To document if intended users can understand the key messages in the labeling 
(label comprehension). 
3. STUDY DESIGN 
 Overall Study Design 
This is a cross-sectional study that employs both observational and interview-based 
methods.  
A minimum of 900 lay participants (non-healthcare professional and inexperienced in HIV 
self-testing) will read the instructions for use (IFU) and conduct the OraQuick® HIV Self-
Test. They will not be provided any training prior to use of the test. A trained healthcare 
provider or researcher (trained Observer) will watch, and document use of the test and 
independently read the participants self-test result. The participants will then complete a 
questionnaire to share their opinion on usability and label comprehension of this test.  A 
minimum of 400 participants will also be provided five mock devices with different results 
and asked to interpret those results i.e. strong positive; weak positive, negative, invalid 
with no control and no test line, and invalid with no control and a positive test line.14  
All participants will also have a venous blood sample collected for testing of plasma at a 
central laboratory with a 4th generation HIV enzyme immunoassay (EIA) that will serve 
as the Comparator Method (CM). All self-tests will be confirmed using a Canadian 
standard HIV testing algorithm. The sensitivity and specificity of the self-test result will 
be calculated relative to the “clinical truth” of the participants’ HIV status determined by 
the confirmatory test process, where applicable. Participants will be instructed to return 
to the clinic for a follow-up visit, two (2) weeks after self-testing to obtain their 
laboratory test results which will be their official result.  
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 11 of 45 
 
 
Flowchart representation of the overall process from recruitment through 
Confirmatory testing: 
 
 
 
Participant returns for confirmatory (offical) test results 2 weeks later (Appendix H)
Participant opt-in for the Mock Result Interpretation portion of the study (Appendix G)
Observer  interviews participant with self test questionnaire (Appendix F) 
Participant performs Self-Test and interprets result (Appendix D & E)
Participant given Self-Test package
Observer instructs Participant on study process (not testing process)
Participant sent into clinical room with site Observer 
Participant brought into private room for venous blood collection (confirmatory lab test) 
Enrolment (Appendix C)
Registration and confirmation of Eligibility (Appendix C)
Administer Informed Consent (Appendix B)
Subject Recruitment

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 12 of 45 
 
 Study Population 
In this study, eligible participants will be those eighteen (18) years or older, of any race 
or gender.  The population will be comprised of a minimum of 900 participants with 
unknown HIV status (never tested or last known HIV negative test must be a minimum 
of 3 months prior), including 400 participants at risk for HIV infection e.g. injection drug 
users (IDU), men who have sex with men (MSM), etc. These participants will be 
recruited from geographically distinct study sites to represent an ethnic, genetic and HIV 
risk diverse  population across Canada.14 
 Study Sites 
The study will be in up to seven (7) sites across Canada, along with regions utilizing their 
provincial laboratories, where available. These sites will include clinics that provide 
services to individuals from high-risk populations such as IDUs, MSM, and members of the 
African, Caribbean and Black (ACB) and Indigenous communities. This will ensure that we 
reach our quota of high-risk persons.14 All study procedures will be conducted under the 
supervision of the local site principal investigator or his/her designee.   
Note: The study sites will follow all appropriate safety requirements that are in place 
during entire study conduct, to ensure the safety of all participants and the healthcare 
providers. This will include the use of any appropriate personal protective equipment 
(PPE), as recommended by each provincial jurisdiction. 
 Study Description 
Usability 
 The self-test portion of the study will be performed on consenting persons 
 (referred to as participants) and will include recruitment of participants who have 
 consented to be tested for HIV as per the test procedures outlined. 
 The participant will be evaluated for the self-test process success or difficulty by a silent, 
non-interacting trained healthcare professional / researcher (Observer) in the same room. 
Overall processes include self-test Usability (observation to determine if participants 
perform all critical steps correctly), Results Interpretation (confirmation by observer to 
determine if participant interprets test results correctly), and Label Comprehension 
(questionnaire to determine that the participant is aware of test limitations and what to 
do following the test result). Successful completion of these tasks will be evaluated as a 
percentage of the overall process, with all critical errors identified.   
Each participant will obtain an oral fluid specimen and perform the test, including result 
interpretation, according to only those materials provided with the OraQuick® HIV Self-
Test (e.g. instructions for use). 
Each self-test will be observed by trained healthcare professional/ researcher (referred to 
as Observers). The Observer does not tutor or interact with the participant conducting 
the self-test but notes errors and other observations about the participant.  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 13 of 45 
The Observer also interprets the test result, immediately after the participant and within 
the validated reading time stated in the instructions for use and records the result 
separately. 
 All participants will have a venous blood sample taken (typically from the forearm; up to 
7mls or about 1.5 tablespoons) and sent to a local provincial laboratory for HIV EIA testing. 
The laboratory portion of the study will conduct Comparator Method (“CM”) testing on 
plasma from venous blood samples collected from study participants  
with 
Health 
Canada licensed HIV-1/HIV-2 combination antigen/antibody test that is in routine use in 
the participating local laboratories. Results of all laboratory testing will be shared with the 
intended use sites since the lab test will serve as the standard of care test.  
 Sites will be using their local lab or arrange to have samples sent to a lab that uses the 
 same comparator assay. 
 Results from the lay user OraQuick® HIV Self-Test will be compared to the laboratory 
 HIV EIA testing.     
 Subsequent care decisions will be based solely on the results of the study site’s standard 
of care test, not on the OraQuick® HIV Self-Test result. 
Readability  
 Participants will also be provided five (5) mock devices with different results and asked to 
 interpret those results. These responses will document whether intended users, (non-
 professional and inexperienced in HIV self-testing), can successfully interpret contrived 
 strong positive, weak positive, negative and a range of invalid results. 
 The participants will then complete a questionnaire (see Appendix G) to share their 
opinion on usability of this test.   
 Selection and Withdrawal of Participants  
3.5.1. Inclusion/Exclusion Criteria  
Participant’s eligibility to enroll will be based upon inclusion and exclusion criteria and the 
signing of informed consent.  The requirements for inclusion/exclusion are as follows: 
 Inclusion Criteria  
 
Participants considered eligible for inclusion are those who: 
1. Are 18 years of age and older 
2. Are able to speak / read / write English or French 
3. Have presented for voluntary testing for HIV infection in the clinic or community 
based setting  
4. Are willing to participate in the study site’s standard of care HIV counselling and 
testing program and receive the study site’s standard of care test results 
5. Are willing to be a participant in the study 
6. Are able to provide informed consent i.e. understands and signs the informed 
consent form  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 14 of 45 
7. Are able to complete the required testing on the allocated testing day 
8. Are willing to provide the necessary oral fluid and venipuncture blood for use in 
the study protocol testing methods. 
9. Are of unknown HIV status (last HIV negative test must be a minimum of 3 
months prior) 
 
Exclusion Criteria  
Participants considered ineligible for participation in the study are those who meet any of 
the following exclusion criteria: 
1. Do not meet all the inclusion criteria 
2. Are known HIV positive 
3. Are on antiretroviral therapy (ART) or anti-HIV medications for the treatment of 
HIV, either as pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP) 
or experimental vaccine 
4. Have any experience or have ever conducted a rapid diagnostic self-test for HIV 
or any other infectious disease 
5. Are currently participating in a concurrent trial of HIV self-tests 
6. Are investigator site employees or immediate family members of sponsor or 
investigator site employee 
7. Are a practicing medical healthcare professional (doctor, nurse or HIV counsellor 
that performs HIV testing with Rapid Tests) 
8. Any condition which, in the opinion of the Observer, would make the participant 
unsuitable or unsafe for enrolment or could interfere with the completion of the 
assessment and questionnaire etc. or bias the outcome, e.g. being unable to see / 
read by forgetting to bring reading glasses, being intoxicated, acute sickness, 
visibly distressed. 
 
3.5.2. Withdrawal of Participants  
 Participants may withdraw from study participation at any time.  The Observer will 
 attempt to acquire all study related information and document the reason for 
 withdrawal.  Information and data collected up to the time of participant’s 
 withdrawal from the study may be used without identifying any personal 
 information, consistent with the informed consent signed for enrollment, unless 
the participant provides a written request to limit the use and sharing of their 
study data. 
Investigator(s) may separately determine if participation by any subject in this 
study should be limited or be withdrawn.  The investigator may close the study 
prematurely for any reasons including administrative decisions.   
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 15 of 45 
4. STUDY PROCEDURES 
4.1 Recruitment 
 
Participants will be recruited from up to seven (7) geographically distinct Canadian 
sites. Prospective participants will be representative of the Canadian HIV testing 
population, including a minimum of 400 participants at risk for HIV infection (e.g. 
IDU, MSM, etc.). 
 
Recruitment of participants will be done through i) clinic and community-based   
recruitment - after strategic planning and relevant research, the co-investigators 
will identify active HIV testing clinics and institutions that have an appropriate 
participant base, ii) word-of-mouth recruitment - participants will be encouraged 
to tell others about the study and iii) various media channels.  
 
Once participants have been identified through recruitment, they will be 
approached, informed about the study and the role they will play in the study 
procedure. These participants must consent to be tested for HIV as per the study 
site’s standard of care procedures before enrolling in the study. These sites will 
direct all investigative and administrative functions for the study. The participating 
sites must have the ability to comply with all local government requirements for 
HIV testing and reporting. 
  
It is anticipated that the target population for this study will include a mix of high-
risk and low-risk populations. The total study population will include a minimum 
of 900 participants whose HIV status is unknown. All 900 participants will be 
assessed for usability and label comprehension and 400 from the 900 participants 
enrolled will be asked to participate in a results interpretation study using pre-
made devices that will mimic the different test results that might be observed.  
 
 
Study numbers for each of the study objectives were not computed. They were 
determined to meet compliance requirements from the Health Canada Guidance 
Document: Guidance for Manufacturers pf Human Immunodeficiency Virus (HIV) 
Rapid Diagnostic Tests (RDTs) for use at the point of Care of for Self-Testing.14 
4.2 Informed Consent 
 
Informed Consent will be obtained from individuals before they are allowed to 
participate in the trial. The Informed Consent form will be reviewed and approved 
by a Research Ethics Board (REB) or Ethics Committee (EC). The principal 
investigator or his/her designated staff will provide the Informed Consent for 
participation in this study to the participant, explain the nature of the study and 
sample collection procedures, and answer any questions that might arise. The 
Informed Consent will contain general information about the study (see Appendix 
B).   

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 16 of 45 
Participants will be consented prior to conducting any study-related procedures. 
Participants will be encouraged to ask questions to ensure the entire process is 
clearly understood. Study participants will be instructed that they may reject the 
specimen collection procedure and withdraw from the study at any time. 
Participants must agree to and submit their Informed Consent form prior to formal 
enrolment into the study. The informed consent will be offered after verbal 
explanation of the study procedures in English/French. The Informed Consent will 
have the appropriate signature lines that need to be filled out to complete the 
Informed Consent process, facilitating enrollment. 
 
4.3 Enrollment Questionnaire - Review Eligibility Criteria 
Participants providing informed consent and meeting inclusion criteria may be 
eligible to participate in the study. Participants will be administered an Enrolment   
           Questionnaire to ascertain successful qualification for enrolment (Appendix C). The 
questionnaire clearly outlines the inclusion and exclusion criteria. If participants 
satisfy all the inclusion criteria and none of the exclusion criteria, eligibility for 
enrolment can be confirmed. All participants evaluated for participation in this 
study will be assigned a unique participant identification number (PID number). 
Enrolment questionnaires will capture information such as PID Number, Age, 
Nationality 
and 
Employment 
status. 
Participants 
that 
do 
not 
satisfy 
inclusion/exclusion criteria are documented and reported as exclusions. In addition, 
the reason for the enrolment failure will also be recorded.  
The PID number will also be considered the Participant Number, following the 
format below: 
 AA = Study name 
 BB = Province of Investigational Site; example ON for Ontario, QC for Quebec. 
 CC = Investigational site number identifier 
 DDD = Sequential sample identifier, starting at 001 for all participants  
For example, Self-Test-Ontario-Site#1-Participant#1: ST-ON-01-001:  
 
Multiple copies of pre-printed labels with the PID Number will be provided to the 
study site facility.  These labels will be placed on the forms and whole blood samples. 
 
                     The enrollment questionnaire will gather the following demographic information:    
 Age  
 Ethnicity  
 Gender 
 Experience with HIV testing 
 HIV Status/Risk 
 Language capabilities 
 Visual Status (glasses/contacts) 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 17 of 45 
4.4 Background Data 
For all study participants meeting inclusion/exclusion criteria, background data to 
be collected will include:   
 Experience with HIV testing  
 Date of last HIV test (approx.) 
 Highest education level achieved (None, Primary, Secondary /High 
School, College/University or Higher)  
 Language capabilities  
 Employment status (employed/unemployed) 
 Visual status (use of reading glasses) 
 Reading/writing impairment 
4.5 Medical History/ Oral Health 
For all study participants meeting inclusion / exclusion criteria, their self-reported 
medical history will be obtained and documented.  In addition to any self-reported 
medical conditions, specific medical conditions will be queried, in particular the 
study participant’s HIV status.  Data to be documented will include: 
 
Medical History - Participants may choose to report their medical history; this will 
be documented and archived for statistical review.  Information may include: 
 
 Self-reported HIV status. 
o Unknown, never tested 
o Unknown, previously tested negative at least three (3) months 
prior.  The date and location of testing along with the type of test 
is to be recorded, if known. 
o HIV positive.  (If yes, the exclusion criterion will be applied) 
 Self-reported medical conditions (e.g. diabetes, hypertension, sexually 
transmitted infections, etc.). 
o Self-reported Ocular health / visual impairment 
 Requirement for, and current use of, glasses or contacts  
 Any condition that specifically affects vision (besides the 
need of glasses or contacts, (e.g. macular degeneration, etc.) 
 Any other medical condition that the participant has 
experienced or currently reports, and the date of diagnosis.  
Study participants’ self-report will serve as the source of 
these data and verification in medical records is not required. 
 Self-reported risk category:  
o Unprotected sex with men 
o Unprotected sex with women 
o Multiple sexual partners 
o Injection drug user 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 18 of 45 
o Born to an HIV positive mother 
o Sexual partner is HIV positive 
o Sexual partner is a bisexual male 
o Other 
 Self-reported pregnancy, if applicable. 
 
Oral Health 
 Responses to specific oral health questions - Specific presence or 
absence of oral health conditions 
o Cavities and/or fillings 
o Braces 
o Periodontal disease and/or bleeding gums 
o Oral fixtures; full or partial dentures 
o Specific last use of oral products, food and drink 
 Last food and/or beverage consumption 
 Tooth paste 
 Mouthwash or oral rinse 
 Smoking or smokeless tobacco 
4.6 Concomitant Medications 
For all study participants meeting inclusion / exclusion criteria, their self-reported    
current concomitant medications will be obtained and documented. Data 
documented throughout the study will include: 
 General concomitant medications, and herbal or dietary supplements. 
 Any medication to treat or prevent HIV (ARV and/or PrEP).   
4.7 Dispensing and Return of the OraQuick® HIV Self-Test Device 
 One OraQuick® Rapid HIV Self-Test will be provided to each participant who qualifies 
for self-testing.  At the conclusion of all testing, the used devices will be collected 
by the study staff and discarded in accordance with local requirements at the site.    
4.8 Participant Self Testing 
 
Study participants will be instructed to perform the self-testing using the 
OraQuick® Rapid HIV Self-Test.  The self-testing is to be completed under the direct 
observation of the study staff.  The study staff will verbally instruct the participant 
as follows: 
 
“This is the part of the study in which you will be asked to use the study product.  
With this product and the instructions provided, you can perform the test yourself.  
Although I will be in the room observing you, I will not be able to answer any 
questions or talk to you while you are using the product, but I will be looking to see 
how you use it.  When you are finished, I would like you to tell me what you think the 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 19 of 45 
test result is. I will also ask you questions about your experience and what you 
observed during the test.” 
 
The participant will then be permitted to perform the self-test. Their test result and 
any additional comments will be record in Appendix D - Participant’s OraQuick® HIV 
Self-Test Result Record Form. After the result interpretation portion, the Observer 
will ask the participant questions about the test procedure and complete Appendix 
F - Self-Test Questionnaire with the participant’s responses. 
4.9 Observations and Verification of Participant Self-Testing 
The self-testing site must minimally provide for the following: 
 Privacy from other study participants, or study staff other than the staff 
performing observations 
 Seating 
 Counter, desk, or other space to place the test kit 
 Adequate lighting, with the ability for the participant to control lighting 
 An obvious manner to measure time (wall clock, desk clock) 
 
Dependent upon the study sites’ physical layout, the research staff observing the 
study participant may or may not be visible to the participant.  In any case, the staff 
is not to interact with the participant during testing, unless intervention is required 
for a study participants’ wellbeing or privacy.  During the study participant self-
testing, the study staff will collect the following observational data for correct 
performance of the test.  These ratings will be collected as the Observational Ratings 
of Self-Test Performance. Data that will be collected are described in Appendix E - 
Observer’s data collection form.  
 
 
Observational Ratings of Study Participant-Self Test Performance include: 
 Did the study participant read the instructions for use? 
 Was the study participant able to find the test tube packet? 
 Did the study participant remove the test tube from the packet? 
 Did the study participant remove the cap from the test tube? 
 Did the study participant place the test tube in the holder? 
 Did the study participant have any difficulty with the test tube?   
 Was the study participant able to find the test stick packet? 
 Did the study participant remove the test stick from the packet? 
 Did the study participant touch the flat pad? 
 Did the study participant collect the sample correctly (1x upper and 
lower swab)?   
 Did the study participant place the test stick in the test tube correctly? 
 
Observers will also record the following:   
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 20 of 45 
 IFU language instruction the study participant used (French or English) 
 Time study participant starts the test (places the device in the test 
stand after collecting oral fluid). 
 Time of study participant reads the test. 
 Study participant’s apparent level of distress: 
o Calm 
o Appears anxious 
o Verbally communicates distress 
o Staff intervention required 
 
After the study participant has completed the self-testing they will be requested to 
provide their result to the staff.  The Observer will question the study participant, 
as follows: 
 
“According to the product instructions, can you please tell me what you think the 
result of your test is?” 
Any ambiguous verbal answer by the participant will have one attempt made to 
clarify it.  
 
The study participant’s response will be interpreted by a check box with five 
possible selections: 
 Do not have HIV / negative 
 May have HIV / preliminary positive 
 Test not working / invalid 
 Not sure / don’t know 
 Refused or ambiguous answer 
If the test could not be completed, this will also be documented. 
The Observer will also review the study participant’s interpretation of their test.   
4.10 Observer’s Interpretation of Study Participant’s Self-Test Result  
Following the completion of the study participant’s self-testing interpretation, the 
Observer will make their own interpretation of the study participant’s test result.  
This should be the site staff who observed the study participant’s self-test.  Data to 
be collected will be: 
 
 The Observer’s interpretation of the study participant’s self-test result.  
 
The Observer’s interpretation of the study participant’s self-test is intended to allow 
for review of the data regarding study participants’ potential failure to obtain a 
result versus incorrect interpretation of the result they do obtain.  
 
In the case of a truly invalid test by the study participant, the test will not be 
repeated.  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 21 of 45 
 
4.11 Interpretation of Results – Mock Devices 
At the end of the self-testing process, the Observer may ask subjects to participate 
in a ‘Mock Result Interpretation’ study that will involve interpreting a separate set 
of OraQuick® HIV Self-Test results prepared by the manufacturer. Participation is 
voluntary and up to 400 participants recruited from the 900 participants who 
consented for the device accuracy study will conduct this Mock Result 
Interpretation. If participant agrees to participate, they will be presented with five 
(5) OraQuick® HIV Self-Test mock result types and asked to interpret the results 
using the Self-Test instructions for use (IFU) as a guide. The five (5) mock devices 
will be the following:   
1. Strong Positive 
2. Weak Positive 
3. Negative 
4. Invalid (no control line present, test line present) 
5. Invalid (no control line or test line present) 
 
Mock devices will be presented in a randomized order to control bias.   
Although the self-test study participants will be interpreting the results of their own 
OraQuick® HIV Self-Test, the purpose of this sub-study is to document if intended 
users, (non-professional and inexperienced in HIV self-testing), can successfully 
interpret contrived/mock strong positive, weak positive, negative and invalid 
results. Results of this interpretation will be recorded by the Observer on Appendix 
G - Participant’s Mock OraQuick® HIV Self-Test Result Interpretation Record Form.  
4.12 Post-Assessment Questions/Label Comprehension 
Participants will answer a series of questions after they complete the OraQuick® HIV 
Self-Test assessment and Interpretation of Results – Mock Devices. Questions 
related to warnings and precautions and the key following information is included 
in the post-questionnaire:    
 What would you do next if your test results were negative? 
 What would you do next if your test results were positive?   
 What would you do if your test results were invalid?      
 Did you use the Instruction sheet to help you complete the test?  If No, 
please explain 
 Was the device easy to use?  If No, please explain 
 Are you confident you could perform this test on your own?  If No, 
please explain 
 Would you use this test again if it were available to you?  Would you 
recommend this test to others?   
 How long after ingesting food or drink should you wait to test? 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 22 of 45 
4.13 Confirmatory Procedures  
All self-test results will be confirmed using a HIV-1/HIV-2 Antigen/Antibody Combo 
Test (Comparator Method “CM”) performed on venous blood plasma at the central 
laboratory. A venous whole blood specimen will be collected from all study 
participants and sent to a central laboratory within 72 hours to establish the CM and 
any further confirmatory results for all participants. An appointment will be 
scheduled with the participants to return to the study site to collect their standard-
of-care testing result. The Laboratory Confirmatory testing decision tree is 
presented below.  
 
 
Laboratory Testing Procedure for HIV EDTA Blood and Plasma 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receive EDTA Blood from Sites 
Centrifuge and Collect plasma from blood 
Conduct Comparator Method (4th 
gen Ag/Ab test on Plasma 
If Reactive conduct Geenius 
confirmatory test 
If Non-Reactive, no further testing, 
record result as HIV Negative 
If Reactive, record as 
HIV Positive 
If Non-Reactive, 
conduct NAT 
If NAT Reactive, record 
as HIV Positive 
If NAT Non-Reactive, 
record as HIV Negative 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 23 of 45 
For venous blood collection, the study site personnel will follow standard 
phlebotomy procedures. A maximum of 7 mL of whole blood will be collected by 
the study site personnel using a lavender top (EDTA) blood collection tube for HIV 
confirmatory testing done at the laboratory from study participants.  
All clinical laboratory testing will be performed using a 4th generation HIV-1/HIV-
2 Antigen/Antibody Combo Test. 
4.14 Additional Procedures and for Study Participants with Preliminary Positive Self-
Test Results 
Any study participant who has a preliminary positive OraQuick® HIV Self-Test result, 
as determined by the trained Observer’s interpretation of the study participant’s 
self-test will be counseled by the appropriate study staff regarding the meaning of 
their result consistent with current guidelines and local standard operating 
procedures (SOPs) for HIV counseling knowing that this test is investigational and 
that their laboratory results will be the official reportable results. 
4.15 Additional Procedures for Study Participants with Negative Results 
Any study participant who has a negative OraQuick® HIV Self-Test result, as 
determined by the trained Observer’s interpretation of the study participant’s self-
test will be counseled by the appropriate study staff regarding the meaning of their 
result consistent with current guidelines knowing that this test is investigational and 
that their laboratory results will be the official reportable results.   
4.16 Compensation for Study Participants 
Participants will be compensated for their time and effort in this study. The 
compensation amount will be up to $75 in total. On the 1st visit to the clinic and 
upon completion of the main study procedures (Appendix H), the participant will 
receive $50 and if they return in two weeks for their laboratory test result, they will 
receive the remaining $25. 
5. QUALITY CONTROL AND ASSURANCE 
Quality Control on the study will be done following the Standard Operating 
Procedures developed for the study and those generic to the organization. The 
Research Manager assumes overall responsibility for ensuring all procedures are 
adhered to and quality controlled.  
5.1   
Training 
Prior to the study, the Principal Investigator will ensure that all study staff are 
trained on the protocol and all study procedures.     
5.2   
Trained Researcher/ Observer Responsibilities 
 The site will provide a minimum of two (2) trained Observers responsible for 
 enrolling eligible participants, collecting samples, and running, interpreting, and 
 documenting the results of the OraQuick® HIV Self-Tests. Prior to the beginning 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 24 of 45 
 of the study, all trained observers will receive appropriate training that covers 
study procedures, as well as, instructions for performing the test. 
5.3 
Study Monitoring 
The study will be monitored by the Research Manager or designate to ensure 
compliance with local laws and regulations and to ensure data quality.  This person 
has the obligation to follow the study closely and in doing so, will routinely visit 
the site(s) at periodic intervals, to assess study status and review study procedures 
and applicable documents. Site visits can be in person or virtual, depending on any 
pandemic-related restrictions in place during the study period. They will also 
maintain necessary telephone and email contact. The monitor will maintain 
current personal knowledge of the study through observation, review of study 
records and source documentation, and discussion of the conduct of the study 
with the Principal Investigator and study staff.  
 
6. DATA ANALYSIS 
 
Data Management Processes 
All participant data will be collected using tablets on the survey software tool 
Qualtrics. All tablets are password-protected. Qualtrics software stores 
participant data on local, secure servers in Toronto. Only the St. Michael’s Hospital 
Research staff will be able to access the data from the Qualtrics servers. This data 
will be password-protected. Data will then be downloaded and saved to secure 
encrypted servers at St. Michael’s Hospital for further analysis. Data monitoring 
will be performed daily by the St. Michael’s Hospital Research staff. All data will 
be stored on secure servers at St. Michael’s Hospital until the data analysis stage 
of the project. All study data will be tabulated using appropriate software and 
methods. Data will be archived by the study Sponsor and maintained for 7 years 
after the end of the study.  
 
Data Reporting  
Data analysis and reporting will be performed by the Research Manager and study 
consultants. A research report will describe the study area, the study population, 
the execution of the research, and present the study results. The report will 
present both qualitative and quantitative discussions of the outcomes of the 
study. 
 
Primary Analysis 
The primary analyses will be sensitivity and specificity of study participants’ self-
interpreted self-test results with the OraQuick HIV Self-Test versus the HIV status 
as determined by the 4th generation EIA and confirmatory testing if necessary.  The 
95% confidence interval will also be determined by the Wilson Score Method.  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 25 of 45 
 Sensitivity = [TP / (TP + FN)] x 100, where 
o TP (true positive) is positive OraQuick® HIV Self-Test in 
agreement with HIV positive status  and 
o FN (false negative) is negative OraQuick® HIV Self-Test 
discordant with HIV positive status.  
 Specificity = [TN / (TN + FP)] x100, where 
o TN (true negative) is negative OraQuick® HIV Self-Test in 
agreement with HIV negative status , and 
o FP (false positive) is positive OraQuick® HIV Self-Test discordant 
with HIV negative status.   
 
Invalid and unknown/unsure results and participants with inclusion/exclusion 
violations will be excluded from the sensitivity and specificity analysis.  All 
excluded participant results will be documented with the reason why.     
 
 
Secondary Analysis 
Secondary efficacy analysis may be performed for the following sub-groups listed 
below.  If conducted, it will include descriptive statistics of the sensitivity and 
specificity analyses among various subgroups for each specificity and sensitivity 
for the following factors: 
 Age. 
 Language capabilities (self-reported). 
 Educational level. 
 Literacy level  
 Risk Factors 
 Risk Populations 
Additional secondary efficacy analyses will include the descriptive statistics of the 
following: 
 Observational Ratings of Study Participant Self-Test Performance 
 Trained User’s (Observer) Interpretation of Study Participants Self-Test 
Result 
 Participant Mock Study Results  
 
Demographics 
The following will be summarized with descriptive statistics:   
 Demographic Data  
 Background Data  
 Medical History  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 26 of 45 
 
Error and Failure Rates 
Specific critical and non-critical steps are identified from the OraQuick® HIV Self-
Test Instructions for Use. 
Critical errors occur when participants perform operational errors during the assay 
which could potentially invalidate the results, such as specimen collection errors 
or terminating the process before completion. 
Non-critical errors occur when participants perform errors that may deviate from 
the Instructions for Use but do not invalidate results. The successful completion 
of tasks will be evaluated as a percentage of the overall process, with all critical 
errors identified.  
Errors are defined in the table below:   
Task 
Category (critical / 
non-critical) 
Reads the instructions for use 
Critical 
Able to find the test tube packet 
Non-Critical 
Remove the test tube from the packet 
Critical 
Remove the cap from the test tube 
Critical 
Placed the test tub in the test stand (holder) 
Critical 
Able to find the test stick packet 
Non-Critical 
Remove the test stick from the packet 
Critical 
Touching the flat pad 
Critical 
Correctly collected the oral fluid sample 
Critical 
Placing the device in the test tube (developer vial) 
Critical 
Read the results within the 20-40 minute window 
Critical 
 
 
Sample Size 
Sample size for this study was based on the Health Canada Guidance Document:  
Guidance for Manufacturers of Human Immunodeficiency Virus (HIV) Rapid 
Diagnostic Tests (RDTs) for use at the Point of Care or for Self-Testing.14 The sample 
size requirements for a near-patient study with untrained self-testers is a 
minimum of 900 laypersons with unknown HIV status, including 400 persons at 
risk for HIV infection (e.g. IDU, MSM, etc.). To assess the ability of untrained self-
testers to correctly interpret a variety of pre-made mock (contrived) devices test 
results, a minimum of 400 persons are required. A minimum of 200 self-testers are 
required to assess for label comprehension.14  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 27 of 45 
It should be noted that the OraQuick ADVANCE® HIV-1/2 Rapid Antigen Test is not 
intended for use by individuals that are known to be HIV positive.        
7. OBLIGATIONS OF THE INVESTIGATOR 
7.1   
Retention of Records  
Data collected throughout the duration of the study will be stored for 7 years on 
secure servers at St. Michael’s Hospital. After this time period, all data will be 
destroyed by the SMH Study Team. This storage strategy is compliant with St. 
Michael’s Hospital Data Security to store/encrypt all data. Electronic data will be 
securely and confidentially stored and will not contain any identifying information. 
Other sites that obtained data though data transfer will also destroy any data after 
7 years of study completion.  
If an investigator moves, withdraws from an investigation, or retires, the 
responsibility for maintaining the records may be transferred to another person, 
who is willing to accept the responsibility. 
7.2  
Device Accountability  
The principal investigator or his/her designees will maintain accurate records of 
all investigational assays/devices used in each study performed under this 
protocol.  Damaged, dropped, or otherwise destroyed devices will be noted and 
documented on the device accountability form. 
7.3  
Protocol Amendments  
Amendments to the protocol must be submitted in writing to the REB for approval 
before participants are enrolled into an amended protocol, except where it is 
necessary to eliminate an immediate hazard to participants or where the changes 
involve only logistical or administrative aspects of the clinical study. This should 
be fully documented. Protocol amendments must be prepared by the Principal 
Investigator responsible for the study and reviewed and approved according to 
local authorities and REB/EC. With the exception of administrative changes, any 
modifications or additions to this study protocol require a justified, written 
protocol amendment that must be approved by the Principal Investigator, local 
authorities, and REB/EC. Amendments potentially affecting the safety of study 
participants, the scope of the investigation or the scientific quality of the study, 
require approval. A copy of the written approval must be maintained by the 
Principal Investigator. 
Examples of amendments requiring such approval are: 
 A significant change in the study design 
 An addition or deletion of a test procedure for safety monitoring 
These requirements for approval should in no way prevent any immediate action 
from being taken by the investigator or the sponsor in the interests of preserving 
the safety of all study participants included in the trial. If an immediate change to 
the protocol is deemed necessary by the investigator and is implemented by 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 28 of 45 
him/her for safety reasons, the study Principal Investigator should be notified and 
the REB/EC should be informed within ten (10) working days. 
 
7.4  
Protocol Violations and Deviations 
The Principal Investigator or designate must document and explain in the 
participant’s source documentation any deviation from the approved protocol. 
The principal investigator or designee may implement a deviation from, or a 
change of, the protocol to eliminate an immediate hazard to trial participants 
without prior REB approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol 
amendments should be submitted to the REB for review and approval and to the 
regulatory authorities, if required. 
 
A deviation from the protocol is an unintended or unanticipated departure from 
the procedures or processes approved by the REB and agreed to by the principal 
investigator or designee. Deviations usually have an impact on individual 
participants or a small group of participants and do not involve inclusion, exclusion 
or primary endpoint criteria.  
 
A protocol violation occurs when there is non-adherence to the protocol that 
results in a significant, additional risk to the participant, when the participant or 
principal investigator or designee has failed to adhere to significant protocol 
requirements (inclusion and exclusion criteria) and the participant was enrolled 
without prior approval, or when there is non-adherence to regulations or some 
ICH GCP guidelines.  
 
Protocol violations and deviations will be documented by the Research Manager 
or designate throughout the course of monitoring visits. Principal investigators or 
designees will then be notified in writing of violations and deviations. The REB 
should be notified of all protocol violations and deviations in a timely manner. 
 
7.5 
Adverse Events and Adverse Device Events Reporting  
7.6 
7.5.1 
Adverse Events 
Adverse events shall be reported as per section 59 and section 62 of the 
Medical Device Regulations. Any Serious Adverse Event or Adverse Device 
Event which may occur in a Participant from this population will be 
reported to the Principal Investigator.   
 
Assessment of adverse events (AE) will be carried out during all parts of the 
study.  An AE is defined as any untoward medical occurrence in a 
Participant using the device under this protocol, which does not necessarily 
have a causal relationship with this use.  An AE, therefore, can be any 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 29 of 45 
unfavorable and unintended sign, symptom, or medical condition 
temporarily associated with the use of the study product, even if the event 
is not considered to be related to the study product. 
 
Adverse events will be collected from the time the informed consent 
signed until the completion of all study procedures during an individual 
study visit. Information about all AEs, whether volunteered by the 
Participant, discovered by investigator questioning, or detected through 
physical examination, or other means, will be collected and recorded on 
the Adverse Event CRF (Appendix J) and followed as appropriate.  
As much as possible, each AE will also be described by: 
1. 
Its duration (start and end dates) 
2. 
The severity grade (mild, moderate, severe) 
3. 
Its relationship to the study product (definite, probably, possibly, 
unrelated) 
4. 
The action(s) taken and 
5. 
Any relevant outcome. 
7.7  
Severity of Adverse Events 
The investigator is to classify the severity of an AE according to the 
following definitions: 
 Mild: The Participant is aware of signs or symptoms, which are 
easily tolerated. 
 Moderate: The signs and symptoms are sufficient to restrict, but 
not prevent, usual activity. 
 Severe: The Participant is unable to perform usual activity. 
The maximum intensity of an AE (mild, moderate, or severe) will be 
assessed at each visit taking into account the possible range of intensity of 
the symptom(s). 
7.8 
 Relationship of Adverse Events to the Device 
The investigator is to classify the relationship of an AE to the investigational 
product according to the definitions outlined below. 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 30 of 45 
Association 
Definition 
None 
(unrelated) 
(1) The existence of a clear alternative explanation or (2) 
non-plausibility. 
Possible  
A clinical event with a reasonable time sequence to product 
use, but which could also be explained by concurrent 
disease or other agents.  
Probable  
A clinical event with a reasonable time sequence to product 
use, unlikely to be attributed to concurrent disease or other 
agents, and which follows a clinically reasonable response 
on withdrawal. 
Definite 
The properties of the study device and the course of the AE 
after treatment indicated involvement of the study product 
in the occurrence/worsening of the AE and no indication of 
other causes existed. 
7.9  
Serious Adverse Events (SAE) 
The ICH Guideline E2A, entitled “Clinical Safety Data Management:  
Definitions and Standards for Expedited Reporting” defines a serious 
adverse event (SAE)/experience or reaction as being any untoward medical 
occurrence which: 
 Is fatal or life-threatening 
 Requires or prolongs hospitalization 
 Results in persistent or significant disability/incapacity  
 Is medically significant, may jeopardize the participant, and may 
require medical or surgical intervention to prevent one of the 
outcomes listed above or 
 Is a congenital anomaly/birth defect. 
Events not considered to be serious adverse events are hospitalizations 
for the:  
 Routine treatment or monitoring of the studied indication, not 
associated with any deterioration in condition 
 Treatment, which was elective or pre-planned, for a pre-existing 
condition that did not worsen and/or 
 Treatment on an emergency, on a participant-by-participant basis 
for an event not fulfilling any of the definitions of serious given 
above and not resulting in hospital admission.  
To ensure participant safety each SAE must also be reported to the sponsor 
or its designee and to the responsible REB within 72 hours of learning of 
the occurrence. 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 31 of 45 
7.10 
 Adverse Device Effects (ADE) 
 An Adverse Device Effect (ADE) is any AE that occurs to the participant 
 as a result of using the device (i.e., is Possible, Probable or Definite in 
 relationship).   
 Unanticipated Adverse Device Effects (UADEs) 
 An Unanticipated Adverse Device Effect is any adverse events that the 
 principal investigator determines to be attributable to an investigational 
 specimen collection device that is serious or not previously identified in 
 nature, severity of degree of incidence in the current protocol or 
investigator  
brochure.   
 For all ADEs (AEs related to the use of the device) that are unexpected, 
 unanticipated AND serious, the investigator should notify the responsible  
 REB/EC and the manufacturer within 72 hours or learning of the 
 occurrence. 
7.11 
Confidentiality of Participant Specimens and Information 
Participant confidentiality will be carefully maintained. All documents, 
 reports, and other records will be identified in a manner designed to 
 maintain participant confidentiality. Participants will only be identified in 
the study by their PID number. Testing records and laboratory specimens 
will be coded to protect the participants' confidentiality.  All records will be 
 kept in a secure storage area with limited access. Clinical information will 
not be released without the written permission of the participant, except 
as necessary for monitoring and auditing by the regulatory authorities or 
the Research Manager. The Principal Investigator and all employees 
involved with this study may not disclose or use for any purpose other than 
 performance of the study, any data, record, or other unpublished 
 confidential information disclosed to those individuals for the purpose of 
the study. All computers will be password-protected and records can only 
be accessed by permitted study staff. Compliance with Federal and 
Provincial Data Protection regulations, including the Personal Information 
 Protection and Electronic Documents Act (PIPEDA 2000) will be ensured 
 throughout the study conduct. 
7.12 
Investigator Documentation  
Prior to beginning the study, the Investigators will be asked to comply with 
ICH E6 (R1) 8.2 by providing the following essential documents, including 
but not limited to: 
 An original investigator-signed investigator agreement page of the 
protocol 
 An REB-approved Consent Form, samples of any site 
advertisements for recruitment for this study, and any other 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 32 of 45 
written information regarding this study that is to be provided to 
the participants  
 REB approval for the study site jurisdiction if required above a 
central REB approval 
 Curriculum vitae for the principal investigator and each 
investigator. They will be signed and dated by each investigator at 
study start-up, indicating that they are accurate and current.  
 Principal investigators or designee and institutions involved in the 
study will permit study-related monitoring, audits, review, and 
regulatory inspections by providing direct access to all study 
records. 
7.13 
Study Termination  
Although REACH 3.0 has every intention of completing the study, it 
reserves the right to discontinue the study at any time for clinical or 
administrative reasons. The end of the study is defined as the date on 
which the last participant completes their last visit to the study site.   
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 33 of 45 
8. References 
1.  
Kurth AE, Cleland CM, Chhun N, Sidle JE, Were E, Naanyu V, et al. Accuracy and 
Acceptability of Oral Fluid HIV Self-Testing in a General Adult Population in Kenya. AIDS 
Behav [Internet]. 2016 Apr 1 [cited 2021 Mar 12];20(4):870–9. Available from: 
https://pubmed.ncbi.nlm.nih.gov/26438487/ 
2.  
Choko AT, MacPherson P, Webb EL, Willey BA, Feasy H, Sambakunsi R, et al. Uptake, 
Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing 
for HIV in Blantyre, Malawi: A Community-Based Prospective Study. Bangsberg DR, 
editor. PLOS Med [Internet]. 2015 Sep 8 [cited 2021 Mar 12];12(9):e1001873. Available 
from: https://dx.plos.org/10.1371/journal.pmed.1001873 
3.  
Pant Pai N, Sharma J, Shivkumar S, Pillay S, Vadnais C, Joseph L, et al. Supervised and 
Unsupervised Self-Testing for HIV in High- and Low-Risk Populations: A Systematic 
Review. Weiser SD, editor. PLoS Med [Internet]. 2013 Apr 2 [cited 2021 Mar 
12];10(4):e1001414. Available from: https://dx.plos.org/10.1371/journal.pmed.1001414 
4.  
Miller CM, Ketlhapile M, Rybasack-Smith H, Rosen S. Why are antiretroviral treatment 
patients lost to follow-up? A qualitative study from South Africa. Trop Med Int Heal 
[Internet]. 2010 Jun [cited 2021 Mar 12];15(SUPPL. 1):48–54. Available from: 
https://pubmed.ncbi.nlm.nih.gov/20586960/ 
5.  
Johnson C, Baggaley R, Forsythe S, Van Rooyen H, Ford N, Napierala Mavedzenge S, et al. 
Realizing the potential for HIV self-testing [Internet]. Vol. 18, AIDS and Behavior. Springer 
New York LLC; 2014 [cited 2021 Mar 12]. Available from: 
https://pubmed.ncbi.nlm.nih.gov/24986599/ 
6.  
Kalibala S, Tun W, Cherutich P, Nganga A, Oweya E, Oluoch P. Factors associated with 
acceptability of HIV self-testing among health care workers in Kenya. AIDS Behav 
[Internet]. 2014 Jun 29 [cited 2021 Mar 12];18(SUPPL. 4):405–14. Available from: 
https://link.springer.com/article/10.1007/s10461-014-0830-z 
7.  
US Food and Drug Administration. FDA - OraQuick ADVANCE Rapid HIV-1/2 Antibody Test 
[Internet]. US FDA. 2020 [cited 2021 Apr 1]. Available from: 
https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/oraquick-
advance-rapid-hiv-12-antibody-test 
8.  
US Food and Drug Administration. FDA - OraQuick In-Home HIV Test [Internet]. US FDA. 
2020 [cited 2021 Apr 1]. Available from: https://www.fda.gov/vaccines-blood-
biologics/approved-blood-products/oraquick-home-hiv-test 
9.  
World Health Organization. WHO Prequalification of In Vitro Diagnostics Public Report: 
OraQuick HIV Self-Test (WHO ref. num: PQDx 0159-055-01; OraSure Technologies, Inc.) 
[Internet]. Geneva; 2019 Nov [cited 2021 Apr 1]. Available from: 
https://apps.who.int/iris/bitstream/handle/10665/251857/9789241511742- 
10.  
Gauss E. Unitaid and HIV/AIDS [Internet]. 2017 Jul [cited 2021 Apr 1]. Available from: 
www.unitaid.org 
11.  
Unitaid. Marketplace and technology landscape: HIV rapid diagnostic tests for self-
testing, 3rd Edition. Geneva; 2017.  
12.  
World Health Organization. Technical Specifications Series for submission to WHO 
Prequalification - Diagnostic Assessment Human: TSS-1: Immunodeficiency Virus (HIV) 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 34 of 45 
rapid diagnostic tests for professional use and/or self-testing [Internet]. Geneva; 2016 
[cited 2021 Apr 1]. Available from: 
https://apps.who.int/iris/bitstream/handle/10665/251857/9789241511742-
eng.pdf;sequence=1 
13.  
International Council for Harmonisation of Technical Requirements. ICH Efficacy 
Guidelines [Internet]. ICH. [cited 2021 Apr 1]. Available from: 
https://www.ich.org/page/efficacy-guidelines 
14.  
Health Canada: Therapeutic Products Directorate -  Health Products and Food Branch. 
Guidance Document: Guidance for Manufacturers of Human Immunodeficiency Virus 
(HIV) Rapid Diagnostic Tests (RDTs) for use at the Point of Care or for Self-Testing 
[Internet]. Ottawa; 2017 Nov [cited 2021 Mar 15]. Available from: 
https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-
devices/application-information/guidance-documents/human-immunodeficiency-virus-
rapid-diagnostic-tests-home-use.html#table1 
 
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 35 of 45 
9. Appendices 
1) Appendix A: OraQuick HIV Self-Test Instructions for Use (IFU) 
2) Appendix B: Informed Consent Template 
3) Appendix C: Enrolment Questionnaire 
4) Appendix D: Participant’s OraQuick® HIV Self-Test Result Record Form  
5) Appendix E: Observer’s Data Collection Form 
6) Appendix F: Self-Test Questionnaire with the Participant’s Responses 
7) Appendix G: Participant’s Mock OraQuick® HIV Self-Test Result Interpretation 
Record Form 
8) Appendix H: Visit 1 Completion Form 
9) Appendix I: Participant’s Confirmatory Test Results Record Form (Visit 2 
Completion) 
10) Appendix J: Adverse Event Reporting Form 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 36 of 45 
Appendix A: OraQuick HIV Self-Test Instructions for Use (IFU) 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 37 of 45 
Appendix B: Informed Consent Template 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 38 of 45 
Appendix C: Enrolment Questionnaire 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 39 of 45 
Appendix D: Participant’s OraQuick® HIV Self-Test Result Record Form  
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 40 of 45 
Appendix E: Observer’s Data Collection Form 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 41 of 45 
Appendix F: Self-Test Questionnaire with the participant’s responses  

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 42 of 45 
Appendix G: Participant’s Mock OraQuick® HIV Self-Test Result Interpretation Record Form  
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 43 of 45 
Appendix H: Visit 1 Completion Form 
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 44 of 45 
Appendix I: Participant’s Confirmatory Test Results Record Form (Visit 2 Completion) 
 
 
 

OraQuick® HIV Self-Test Study - Protocol 
 
 
 
 
Version 1: 13-Jul-2021 
CONFIDENTIAL   
 
 
 
 
 
 
 
 
Page 45 of 45 
Appendix J: Adverse Event Reporting Form