Review

. 2024 Apr;9(4):383-392.

doi: 10.1016/S2468-1253(23)00315-1. Epub 2024 Feb 15.

Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection

Marion Delphin¹, Khadija Said Mohammed², Louise O Downs³, Sheila F Lumley⁴, Elizabeth Waddilove¹, Dorcas Okanda⁵, Nadia Aliyan⁶, Marije Van Schalkwyk⁷, Motswedi Anderson⁸, Ponsiano Ocama⁹, Tongai Maponga¹⁰, Judith Torimiro¹¹, Collins Iwuji¹², Thumbi Ndung'u¹³, Philippa C Matthews¹⁴, Jantjie Taljaard⁷

Affiliations

¹ The Francis Crick Institute, London, UK.
² The Francis Crick Institute, London, UK; Division of Biosciences, Faculty of Life Sciences, University College London, London, UK.
³ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, John Radcliffe Hospital, Oxford, UK; Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
⁴ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, John Radcliffe Hospital, Oxford, UK.
⁵ Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
⁶ Kilifi County Hospital, Kilifi, Kenya.
⁷ Division of Infectious Diseases, Department of Medicine, Stellenbosch University-Tygerberg Academic Hospital, Cape Town, South Africa.
⁸ The Francis Crick Institute, London, UK; Botswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, Botswana; Africa Health Research Institute, Durban, South Africa.
⁹ College of Health Sciences, Makerere University, Kampala, Uganda.
¹⁰ Division of Medical Virology, Stellenbosch University-National Health Laboratory Service Tygerberg Business Unit, Cape Town, South Africa.
¹¹ Molecular Biology Laboratory, Chantal Biya International Reference Centre for AIDS Research, Yaounde, Cameroon.
¹² Africa Health Research Institute, Durban, South Africa; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
¹³ Division of Infection and Immunity, University College London, London, UK; Africa Health Research Institute, Durban, South Africa.
¹⁴ The Francis Crick Institute, London, UK; Division of Infection and Immunity, University College London, London, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases, University College London Hospital, London, London, UK. Electronic address: philippa.matthews@crick.ac.uk.

PMID: 38367632
PMCID: PMC7616036
DOI: 10.1016/S2468-1253(23)00315-1

Review

Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection

Marion Delphin et al. Lancet Gastroenterol Hepatol. 2024 Apr.

. 2024 Apr;9(4):383-392.

doi: 10.1016/S2468-1253(23)00315-1. Epub 2024 Feb 15.

Authors

Affiliations

¹ The Francis Crick Institute, London, UK.
² The Francis Crick Institute, London, UK; Division of Biosciences, Faculty of Life Sciences, University College London, London, UK.
³ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, John Radcliffe Hospital, Oxford, UK; Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
⁴ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, John Radcliffe Hospital, Oxford, UK.
⁵ Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
⁶ Kilifi County Hospital, Kilifi, Kenya.
⁷ Division of Infectious Diseases, Department of Medicine, Stellenbosch University-Tygerberg Academic Hospital, Cape Town, South Africa.
⁸ The Francis Crick Institute, London, UK; Botswana Harvard AIDS Institute Partnership, Princess Marina Hospital, Gaborone, Botswana; Africa Health Research Institute, Durban, South Africa.
⁹ College of Health Sciences, Makerere University, Kampala, Uganda.
¹⁰ Division of Medical Virology, Stellenbosch University-National Health Laboratory Service Tygerberg Business Unit, Cape Town, South Africa.
¹¹ Molecular Biology Laboratory, Chantal Biya International Reference Centre for AIDS Research, Yaounde, Cameroon.
¹² Africa Health Research Institute, Durban, South Africa; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
¹³ Division of Infection and Immunity, University College London, London, UK; Africa Health Research Institute, Durban, South Africa.
¹⁴ The Francis Crick Institute, London, UK; Division of Infection and Immunity, University College London, London, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases, University College London Hospital, London, London, UK. Electronic address: philippa.matthews@crick.ac.uk.

PMID: 38367632
PMCID: PMC7616036
DOI: 10.1016/S2468-1253(23)00315-1

Abstract

The WHO African region bears a disproportionate burden of morbidity and mortality related to chronic hepatitis B virus (HBV) infection and accounts for an estimated 70% of new HBV infections worldwide. We investigated the extent to which HBV clinical trials represented populations in this region by searching the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for interventional clinical trials published in English between database inception and May 29, 2023, using the search term "Hepatitis B". We identified 1804 unique clinical trials, of which 18 (1·0%) recorded involvement of the WHO African region. There is no evidence that the number of HBV clinical trials in this region has improved over time. The diversity of new interventions and industry sponsorship in the WHO African region were low, with trials of HBV comparing poorly with those of other endemic infectious diseases (eg, malaria, HIV, and SARS-CoV-2). HBV research and clinical trial investigations have neglected the WHO African region, leading to profound health inequities. HBV clinical trials are urgently needed to evaluate the efficacy of newly discovered therapeutics and to ensure that interventions can be equitably distributed and deployed as they become available.

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Conflict of interest statement

Declaration of interests MD, EW, and PCM receive funding from The Francis Crick Institute. PCM is funded by a Wellcome fellowship (ref 110110/Z/15/Z) and the University College London National Institute for Health and Care Research Biomedical Research Centre and receives funding from GlaxoSmithKline to support a doctoral student in her team. LOD and SFL receive doctoral funding from the Wellcome Trust. CI has received research grant funding from Gilead Sciences. All other authors declare no competing interests. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps, text, and institutional affiliations.

Figures

**Figure 1. Protocol and decision tree associated with investigation of HBV Clinical Trials (CT).**
The International CT Registry Platform (ICTRP) from the World Health Organization (WHO), and ‘ClinicalTrials.gov’ registries were searched. Search criteria were ‘Hepatitis B’. Data from each registry were merged, and CT were excluded to remove (1) duplicates, (2) studies with missing location data or (3) those that did not meet criteria for HBV-related interventional CT, (i.e: studies categorized as ‘observational’ or patients were not infected with HBV or were not part of the evaluation of an antiviral drug against HBV). The material is presented according to the standardized PRISMA reporting criteria.

**Figure 2. Contrasting geographical distribution of HBV seroprevalence and HBV clinical trials (CT).**
**(A)** Map representing geographical distribution of HBsAg seroprevalence in 2019, figure adapted from (1). **(B)** Map representing numbers of CT associated with HBV in each country from 1983 to March 2023.

**Figure 3. Hepatitis B Clinical Trials (CT) by location, over time, and according to agent(s) under review, between 1983 and 2023.**
**(A)** CT phases according to WHO geographical region. Total numbers are presented for each bar. ‘Not Applicable’ refers to CT where the information was not disclosed in the databases. **(B)** Cumulative number of CT per year by region. **(C)** Pie chart to show agents represented in 18 CT in the WHO Africa region. NA - nucleos/tide analogue; TLR - Toll-Like Receptor; STOP-NUC - STOP NUCleotides; ASO - Anti-Sense Oligonucleotides; GSK - GlaxoSmithKline Pharmaceutical Ltd.

Figure 4. Comparison of Clinical Trial (CT) distribution in the WHO Africa region (between 1970 and 2023) for four pathogens HBV (panels A-C), malaria (panels D-F), HIV (panfels G-I) and SARS-CoV-2 (panels J-L).
First column shows maps of WHO Africa region (countries shown in colour) representing number of CT per country (panels A, D, G, J); second column shows number of CT identified per WHO region (panels B, E, H, K); third column shows main sponsors of HBV CT by WHO region (panels C, F, I, L). In bar plots, total numbers are displayed for each bar.

**Figure 5. Challenges and suggested recommendations associated with establishing Clinical Trials (CT) for HBV infection in the WHO Africa region.**
AC3T: African Consortium for Cancer Clinical trials (29); AMA: African Medicine Agency (30); CSO: Civil Society Organisation; IDeAL: Initiative to Develop African research Leaders (31); MEPI: Medical Education Partnership Initiative (32); PACT: Pan African CT registry (33); PLWHB: People Living With Hepatitis B, PTA: Post-Trial Access.

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Comment in

Equity in clinical trials for hepatitis B.
Mitchell T, Nayagam JS, Mbelle MN, Kabagambe K, Agarwal K. Mitchell T, et al. Lancet Gastroenterol Hepatol. 2024 Jun;9(6):501-502. doi: 10.1016/S2468-1253(24)00083-9. Lancet Gastroenterol Hepatol. 2024. PMID: 38734004 No abstract available.

References

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1. Hepatitis B vaccines: WHO position paper – July 2017. [Internet]. [08.30.2023] Available from : https://www.who.int/publications-detail-redirect/WER9227.
1. Sonderup MW, Spearman CW. Global Disparities in Hepatitis B Elimination—A Focus on Africa. Viruses. 2022 Jan 3;14(1):82. - PMC - PubMed
1. Rumgay H, Arnold M, Ferlay J, Lesi O, Cabasag CJ, Vignat J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022 Dec;77(6):1598–606. - PMC - PubMed
1. Overview | Hepatitis B (chronic): diagnosis and management | Guidance | NICE. NICE; 2013. [Internet] [08.30.2023]. Available from: https://www.nice.org.uk/guidance/cg165.

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Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection

Affiliations

Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous