Lay user evaluation of the Panbio™ HCV Self Test: A prospective, multi-centre observed untrained user study.
Study Summary
This is a prospective, multi-centre study designed to evaluate the usability of the Panbio™ HCV Self Test, when performed by untrained lay users in an observed study setting. The Panbio™ HCV Self Test detects antibodies to Hepatitis C Virus (HCV). The study validation will be conducted in accordance with the World Health Organisation’s technical guidance on Hepatitis C rapid diagnostic tests for professional use and/or self-testing (TSS-16).
Background and Rationale
Hepatitis C is a liver disease caused by the hepatitis C virus. The virus can cause both acute and chronic disease, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. Globally, Hepatitis C virus infects around 71 million people per year, resulting in 700,000 deaths. The WHO estimates that only 21% of individuals chronically infected with HCV are diagnosed, and the WHO HCV targets include increasing the diagnoses to 90% by 2030. WHO guidelines, published in 2021, strongly recommend offering self-testing for HCV as an additional approach to HCV testing services.
Investigational Device Description
The Panbio™ HCV Self Test, is a lateral flow test, designed for the qualitative detection of antibodies specific to HCV in finger-stick whole blood. The test is designed to be used by lay users and uses a sample volume of 10 µL. The professional use version test (Bioline HCV Test) is commercially available and has previously been clinically validated by the manufacturer, demonstrating a sensitivity of 99.3-100% and a specificity of 98.1-100%.
Lay User Participants and Observers
Lay User Participant: Refers to a self‐tester who collects a finger-stick sample and tests it with the Panbio™ HCV Self Test.
Observer: A study staff member (trained healthcare worker) who observes the lay-user performing the self-test. The observer and other study staff members can be either a laboratory technician or a non-laboratory healthcare professional (nurse, MD) or a non-certified, but trained healthcare worker (as per WHO definition).
Objectives
The primary objectives of this study are:
- To assess the concordance between the Panbio™ HCV Self Test, as performed by lay users based on self-collected finger-stick samples, and the Panbio™ HCV Self Test performed by a trained health care worker, who also will collect the finger-stick sample required for the test.
- To establish clinical performance (concordance with the reference test) for the Panbio™ HCV Self Test, as performed by lay users using finger-stick whole blood samples, when compared to reference testing using venous plasma samples. All samples will be tested by the Abbott Architect or Alinity anti-HCV test; samples with a positive test result will be further tested using recombinant immunoblot assay (RIBA). The second anti-HCV test must confirm the initial positive anti-HCV result for the anti-HCV reference result to be classified as positive. Samples which have a positive Architect or Alinity anti-HCV test result but a negative or indeterminate follow-up HCV antibody test result will be classified as having an indeterminate reference result. Each sample will also be tested using an HCV RNA assay, for the purposes of patient management and sub-analyses.
- To evaluate usability of the test. Separately, under protocol SDRD-I-029-P, usability will be evaluated in a questionnaire, to ensure that the participant understands the meaning of a negative test and that a positive test requires professional verification.
The secondary objectives of this study are:
- To assess the usability of the Panbio™ HCV Self Test, as performed by lay users based on a questionnaire evaluation by the lay user participant and by the study staff observer. In the observer questionnaire, particular attention will be paid to compliance regarding factors considered critical for the test, such as reading the IFU/ QRG and applying the correct test volume.
- To assess the concordance between the self-test results interpreted by the lay user and by the observer.
Usability testing, consisting of the interpretation of mock devices and labelling comprehension will be evaluated under a separate protocol (SDRD-I-029-P).
Inclusion and Exclusion Criteria
Participants aged 14 or over who agree to all aspects of the study and are able and willing to provide informed consent, will be prospectively enrolled.
The study will aim to enrol some participants without any previous experience of rapid diagnostic testing. However, other participants will likely have been tested professionally/self-testing for e.g. malaria, hepatitis C, or HIV.
Participants will be enrolled from low and high prevalence settings. Where possible, participants will also be enrolled from both HCV low-risk and high-risk groups from the low and high prevalence settings.
Statistically sufficient numbers of participants from various categories regarding educational level, economic status, gender and age will be enrolled.
Participants with prior self-testing experience outside a clinical trial will be considered representative of the general population and will not be excluded. However, efforts will be made to enrol participants without prior self-testing experience.
Participants meeting any of the following criteria will be excluded from the study:
- Participant has already participated in this study on a previous occasion.
- Participant is aware of their HCV status
- Participant is deemed unfit for the study by the Investigator.
- Participant has a condition deemed unfit by the Investigator to safely perform or receive the test.
- Participant is a practising health-care professional or laboratory scientist / technician or has prior medical or laboratory training or experience
- Participant is currently enrolled in a study to evaluate an investigational drug or vaccine.
- Participant has a visual impairment that cannot be restored using glasses or contact lenses or is unable to read the Instructions for Use (Literate cohort).
- Participant is unwilling or unable to provide informed consent.
- Participant has participated in the study “Lay user evaluation of the Panbio™ HCV Self Test: A prospective, multi-centre usability study to evaluate lay user labelling comprehension and test result interpretation”.
Study Design
This study will enrol at least 900 literate adult lay user participants (Self-Testers). At least 200 participants will be enrolled in each of two high-prevalence (> 2%) geographically diverse populations, and at least 500 Self-Testers will be enrolled as part of a low-prevalence (< 2%) population. In addition, 65 literate adolescents, aged 14-17, of whom at least 5 will be HCV antibody reference-positive, will be enrolled. Furthermore, 220 illiterate participants aged 14 years old or older, of whom at least 17 will be HCV antibody reference-positive, will be enrolled. The study will be conducted in Pakistan and in South Africa.
Eligible participants presenting at a participating clinical site for routine medical care, or by invitation to the study, will be approached for enrolment. The enrolment may also occur in Outreach study settings. The purpose of the study and its potential risks and benefits will be explained to potential study participants. Each participant will be enrolled in the study only after giving written informed consent or consent with a thumb impression in the presence of an impartial witness who also signs the consent form. For participants 14-17 years old, parental / caregiver consent will be collected; this can be either a signature or a thumb impression in the presence of an impartial witness who also signs the consent form. After confirming that a participant is eligible for study participation and obtaining informed consent, a study-specific participant identification number (ID) will be assigned to the participant. Participant demographics and a brief medical history will be collected. A study specific venous blood collection will be obtained from all participants.
The participant will be provided with a Panbio™ Self Test, including the Instructions for Use. The Instructions for Use will include a Quick Reference Guide (QRG) and a QR code with a link to an instructional video, which the participants may choose to access. No additional training will be provided to the participant. Each participant will collect one finger-stick whole blood sample and will perform and interpret the Panbio™ HCV Self Test. All procedures for testing and result interpretation, including sample collection and extraction will be conducted by the participant following the Instructions for Use provided in the kit.
A trained observer (study staff member) will observe the whole process and record their observations. The observer will monitor and evaluate how the participant is conducting and interpreting the test, with special attention paid to steps identified as critical, such as reading the IFU and collecting and applying the correct sample volume. The observer will record their observations related to the test procedures in an observer questionnaire. During the observation, the observer will not assist with the testing or result interpretation.
Each HCV Self-Test will be interpreted first by the study participant and followed immediately by the observer, who is blinded to the participant’s reference test results, and who will also photograph the test at the time of interpretation. The observer will interpret the results within the correct time window.
Each participant will be asked to fill out a user evaluation questionnaire to record the usability of the self-testing.
A study staff member will then collect a finger-stick sample from the participant and will also perform a test using the Panbio™ HCV Self Test.
For the professional Panbio™ HCV test, the observer who interpreted the participant’s self-test result can collect the finger-stick sample and perform the test procedure, but the study staff member interpreting the ‘professional run test result’ will be blinded to the participant’s medical history self-test result. Hence, two study staff members are required for assessing the Panbio™ HCV Self Test. The test result will be photographed at the time of result interpretation.
The venous study sample will be used to obtain reference result(s) for evaluating the self-test performance.
The reference test result(s) of the venous whole blood specimen will be used to link participants to clinical management.
If a participant agrees to HIV testing, a study staff member will also conduct an HIV rapid test based on a finger-stick sample for each participant, for purposes of stratifying participants based on HIV status in the analyses.
All study data will be recorded on case report forms (CRFs) and transferred into an electronic data capture (EDC) database.
All other aspects of the participant’s care will remain the same with no deviation from prescribed practice.
The Panbio™ HCV Self Test validation will be conducted in accordance with the World Health Organisation’s TSS-16 guidance on Hepatitis C rapid diagnostic tests for professional use and/or self-testing (2021 update), ISO 20916:2019 (In vitro diagnostic medical devices — Clinical performance studies using specimens from human participants — Good study practice), the study protocol, Good Clinical Practice and the respective local medical device laws.
Duration of Participant’s Study Participation and Total Study Duration
Each participant’s involvement in the study will last approximately 1-2 hours. Results of the investigational Panbio™ HCV Self Test are for research use only and will not be used for clinical decision making. The study enrolment is anticipated to occur during 3-4 months.
Statistical analysis
The Panbio™ HCV Self Test sensitivity, specificity and accuracy (overall concordance) will be reported, in comparison with the laboratory reference result(s) and in comparison with the professionally conducted Panbio™ HCV Self Test result.
From the total number of participants enrolled, the study will enrol at least 70 participants with a reference-positive HCV antibody result, and at least 175 participants with a reference-negative HCV antibody result. Among the literate adolescent participants, at least 5 will be HCV antibody reference-positive. 220 illiterate participants aged 14 years or older will be enrolled, among whom at least 17 will be HCV antibody reference-positive.
With 70 HCV-positive participants and 95.7 % point estimate sensitivity with 87% lower bound of the 95% confidence interval, 80 % power will be obtained. At least 95% point estimate sensitivity is required.
With 175 HCV-negative participants and 98.3 % point estimate specificity with 95% lower bound of the 95% confidence interval, 80% power will be obtained. At least 98.1% point estimate specificity is required.
