Evaluation Study of RDTs Detecting Antibodies Against HCV

Study Overview
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Brief Summary
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The study aims to evaluate 13 different HCV RDTs (10 on-market, 3 under development) for their diagnostic performance and operational characteristics in archived EDTA plasma samples, originating from patients from different geographical regions (Nigeria, Georgia, Cambodia, Belgium) and with or without HIV co-infection.

Detailed Description
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Background and rationale: Screening of past exposure to Hepatitis C Virus (HCV) infection is done by detection of HCV specific antibodies. In Low and Middle Income Countries (LMICs), where equipped laboratories and trained staff are limited, Rapid Diagnostic Tests (RDTs) are widely used for HCV screening. Although many RDTs are available on the market, only some of them received CE-IVD marking and only two have been validated by WHO Pre-Qualification (PQ). More quality-assured tests are needed to establish effective screening programmes in LMICs. Furthermore, an important research gap is the lack of studies on the impact of HIV positivity on RDT performance, as it is estimated that 2-15% of people living with HIV are co-infected with HCV. The evaluation of RDT performance on clinical samples collected in different geographic regions as well as from HIV co-infected individuals, would allow to identify tests with a performance meeting or having the potential to meet WHO quality standards. Concept: This is a multicenter laboratory evaluation study using archived, frozen plasma samples. Sensitivity and specificity of RDTs will be measured against a composite reference standard that consists of two WHO prequalified Enzyme Immunoassays (EIAs) (Murex Anti-HCV EIA version 4.0, Fujirebio Innotest HCV Ab IV) and a Line Immunoassay (LIA) (MP Diagnostics HCV blot 3.0). Samples are assigned as anti-HCV negative or anti-HCV positive based on the results of all three assays. RDT results will be read by three independent readers to evaluate inter-reader variability (differences in visual interpretation, i.e. presence or absence of test and control line). For each RDT, two independently produced lots will be tested for each sample to assess lot-to-lot variability (differences in RDT result for the same sample). Furthermore, rate of invalid runs will be assessed and a technical appraisal is completed for each RDT. Primary objective: 1.1 Evaluation of sensitivity and specificity of anti-HCV RDTs in archived plasma samples, collected from HCV-infected and HCV-uninfected individuals not co-infected with HIV, measured against the composite reference standard composed of two Enzyme Immunoassays (EIAs) and a Line Immunoassay (LIA). 1.2 Evaluation of sensitivity and specificity of anti-HCV RDTs in archived plasma samples, collected from HCV-infected and HCV-uninfected individuals who are all co-infected with HIV, measured against the composite reference standard composed of two EIAs and a LIA. Secondary objectives: 2.1 Evaluation of sensitivity and specificity of anti-HCV RDTs in archived plasma samples, collected from HCV-infected and HCV-uninfected individuals, both co-infected and not with HIV, measured against the composite reference standard composed of two EIAs and a LIA. 2.2 Evaluation of operational characteristics of anti-HCV RDTs: inter-reader variability; lot-to-lot variability; rate of invalid runs 2.3 Technical appraisal of each RDT product per manufacturer

Official Title
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Evaluation Study of Rapid Diagnostic Tests (RDTs) Detecting Antibodies Against Hepatitis C Virus

Conditions
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Hepatitis C

Intervention / Treatment
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* Diagnostic Test: 13 Rapid Diagnostic Tests and reference tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria of archived samples: Non-hemolytic plasma samples with EDTA used as anticoagulant Sample were frozen at -20°C or lower on the day of processing and stored at -20°C or lower until they are used in this study Samples pre-characterized for, HCV, HIV serology status using assays routinely used at the sites and approved for diagnostic use by a local health authority. If available, samples should also be characterized for HBV status. Samples taken from subjects aged ≥18 years Availability of informed consent to use the sample in future research Exclusion Criteria: - Samples not stored correctly

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HCV-only infected<br>Archived frozen plasma samples from individuals that were characterised to be HCV-antibody positive or HCV-antibody negative (HCV-only infected). These samples are characterised for their HIV status (negative). | Diagnostic Test: 13 Rapid Diagnostic Tests and reference tests<br>* Rapid diagnostic tests: HCV antibody test (under development); bioLytical Laboratories DPP® HCV (under development); Chembio Diagnostic Systems HCV-Ab Rapid Test; Beijing Wantai Biological Pharmacy Enterprise Rapid Anti-HCV Test; InTec First Response HCV Card Test; Premire Medical Corporation Signal HCV Ver 3.0; Arkray healthcare TRI DOT HCV; J. Mitra & Co Triplex HIV, HCV, HBsAg; Biosynex SA Standard Q HCV Ab; SD Biosensor HCV Hepatitis Virus Antibody Test; Artron Laboratories SD Bioline HCV; Abbott Diagnostics OraQuick HCV; OraSure Care Start HCV Rapid Test (under development); Access Bio Reference tests: Enzyme Immunoassays (EIAs): Murex Anti-HCV EIA version 4.0; Fujirebio Innotest HCV Ab IV Line Immunoassay (LIA): MP Diagnostics HCV blot 3.0<br>|
| HCV/HIV co-infected<br>Archived frozen plasma samples from HCV-positive or HCV-negative individuals who are HIV infected (HCV/HIV co-infected). | Diagnostic Test: 13 Rapid Diagnostic Tests and reference tests<br>* Rapid diagnostic tests: HCV antibody test (under development); bioLytical Laboratories DPP® HCV (under development); Chembio Diagnostic Systems HCV-Ab Rapid Test; Beijing Wantai Biological Pharmacy Enterprise Rapid Anti-HCV Test; InTec First Response HCV Card Test; Premire Medical Corporation Signal HCV Ver 3.0; Arkray healthcare TRI DOT HCV; J. Mitra & Co Triplex HIV, HCV, HBsAg; Biosynex SA Standard Q HCV Ab; SD Biosensor HCV Hepatitis Virus Antibody Test; Artron Laboratories SD Bioline HCV; Abbott Diagnostics OraQuick HCV; OraSure Care Start HCV Rapid Test (under development); Access Bio Reference tests: Enzyme Immunoassays (EIAs): Murex Anti-HCV EIA version 4.0; Fujirebio Innotest HCV Ab IV Line Immunoassay (LIA): MP Diagnostics HCV blot 3.0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimates of sensitivity and specificity, with 95% confidence intervals, of RDTs for the detection of anti-HCV antibodies in individuals not co-infected with HIV. | Point estimates of sensitivity and specificity, with 95% confidence Intervals based on Wilson's score method, will be computed for all samples HCV+ve/HIV-ve and HCV-ve/HIV-ve; the calculation was performed for all RDT manufacturers and individually for each lot. The estimates were calculated on the overall sample population. | 6 months | 
| Point estimates of sensitivity and specificity, with 95% confidence intervals, of RDTs for the detection of anti-HCV antibodies in HIV co-infected individuals. | Point estimates of sensitivity and specificity, with 95% confidence Intervals based on Wilson's score method, were computed for all samples HCV+ve/HIV+ve and HCV-ve/HIV+ve; the calculation was performed for all RDT manufacturers and individually for each lot. The estimates were calculated on the overall sample population. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimates of sensitivity and specificity, with 95% confidence intervals, of RDTs for the detection of anti-HCV antibodies in the overall sample population. | Point estimates of sensitivity and specificity, with 95% confidence intervals based on Wilson's score method, were computed for all samples: HCV+ve/HIV-ve, HCV-ve/HIV-ve, HCV+ve/ HIV+ve and HCV-ve/HIV+ve; the was performed for all RDT manufacturers and individually for each lot. The estimates were calculated on the overall sample population. | 6 months | 
| Operational characteristics | Inter-reader variability: Fleiss Kappa Coefficient (κ) of inter-reader variability per RDT; manufacturer lot Lot-to-lot variability: coefficient of lot-to-lot variability (percentage agreement) per RDT manufacturer Rate of invalid runs: Percent of invalid runs per manufacturer lot | 6 months | 
| Technical appraisal rating on kit instructions, packaging, labelling and test conduct, on a Likert scale | Averages of likert-scale scores will be calculated and serve to understand the user-friendliness of the RDT; there is no expected outcome, the scale rating is used to collect consistent feedback from users; scale scores are as follows: 1=poor, 2=needs improvement, 3=satisfactory, 4=good, 5=excellent | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnosis, HIV coinfection, Rapid diagnostic test