The Lived Experience Of Participants in an African RandomiseD trial (LEOPARD): protocol for an in-depth qualitative study within a multisite randomised controlled trial for HIV-associated cryptococcal meningitis

David S Lawrence, Katlego Tsholo, Agnes Ssali, Zivai Mupambireyi, Graeme Hoddinott, Deborah Nyirenda, David B Meya, Chiratidzo Ndhlovu, Thomas S Harrison, Joseph N Jarvis, Janet Seeley, David S Lawrence, Katlego Tsholo, Agnes Ssali, Zivai Mupambireyi, Graeme Hoddinott, Deborah Nyirenda, David B Meya, Chiratidzo Ndhlovu, Thomas S Harrison, Joseph N Jarvis, Janet Seeley

Abstract

Introduction: Individuals recruited into clinical trials for life-threatening illnesses are particularly vulnerable. This is especially true in low-income settings. The decision to enrol may be influenced by existing inequalities, poor healthcare infrastructure and fear of death. Where patients are confused or unconscious the responsibility for this decision falls to relatives. This qualitative study is nested in the ongoing AMBIsome Therapy Induction OptimisatioN (AMBITION) Trial. AMBITION is recruiting participants from five countries in sub-Saharan Africa and is trialling a novel treatment approach for HIV-associated cryptococcal meningitis, an infection known to affect brain function. We aim to learn from the experiences of participants, relatives and researchers involved in AMBITION.

Methods and analysis: We will collect data through in-depth interviews with trial participants and the next of kin of participants who were confused at enrolment and therefore provided surrogate consent. Data will be collected in Gaborone, Botswana; Kampala, Uganda and Harare, Zimbabwe. Interviews will follow a narrative approach including participatory drawing of participation timelines. This will be supplemented by direct observation of the research process at each of the three recruiting hospitals. Interviews will also take place with researchers from the African and European institutions that form the partnership through which the trial is administered. Interviews will be transcribed verbatim, translated (if necessary) and organised thematically for narrative analysis.

Ethics and dissemination: This study has been approved by the Health Research Development Committee, Gaborone (Reference: HPDME:13/18/1); Makerere School of Health Sciences Institutional Review Board, Kampala (Reference: 2019-061); University of Zimbabwe Joint Research Ethics Committee, Harare (Reference: 219/19), and the London School of Hygiene and Tropical Medicine (Reference: 17957). Study findings will be shared with research participants from the sites, key stakeholders at each research institution and ministries of health to help inform the development and implementation of future trials. The findings of this study will be published in journals and presented at academic meetings.

Trial registration: Registered at www.clinicaltrials.gov:NCT04296292.

Keywords: HIV & AIDS; clinical trials; qualitative research.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
AMBITION Trial schema. ART: antiretroviral therapy, EFA: Early Fungicidal Activity, SAEs: Serious Adverse Events, PK/PD: Pharmacokinetics/Pharmacodynamics
Figure 2
Figure 2
The Lived Experience Of Participants in an African RandomiseD trial (LEOPARD) Study Schema.

References

    1. Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res 2010;85:1–18. 10.1016/j.antiviral.2009.10.002
    1. Epstein S. Democracy, expertise and AIDS treatment activism. : Kleinman DL, . Science, technology and democracy. New York, USA: SUNY Press, 2000.
    1. UNAIDS . Miles to go - closing gaps, breaking barriers, righting injustices. Global AIDS Update 2018. Geneva: UNAIDS, 2018.
    1. Lawrence DS, Youssouf N, Molloy SF, et al. . AMBIsome therapy induction optimisation (ambition): high dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: study protocol for a phase 3 randomised controlled non-inferiority trial. Trials 2018;19:649. 10.1186/s13063-018-3026-4
    1. Rajasingham R, Smith RM, Park BJ, et al. . Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017;17:873–81. 10.1016/S1473-3099(17)30243-8
    1. Molloy SF, Kanyama C, Heyderman RS, et al. . Antifungal combinations for treatment of cryptococcal meningitis in Africa. N Engl J Med 2018;378:1004–17. 10.1056/NEJMoa1710922
    1. Tenforde MW, Gertz AM, Lawrence DS, et al. . Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis. J Int AIDS Soc 2020;23:e25416. 10.1002/jia2.25416
    1. Beardsley J, Wolbers M, Kibengo FM, et al. . Adjunctive dexamethasone in HIV-associated cryptococcal meningitis. N Engl J Med 2016;374:542–54. 10.1056/NEJMoa1509024
    1. Molyneux CS, Peshu N, Marsh K. Understanding of informed consent in a low-income setting: three case studies from the Kenyan coast. Soc Sci Med 2004;59:2547–59. 10.1016/j.socscimed.2004.03.037
    1. Leach A, Hilton S, Greenwood BM, et al. . An evaluation of the informed consent procedure used during a trial of a Haemophilus influenzae type B conjugate vaccine undertaken in the Gambia, West Africa. Soc Sci Med 1999;48:139–48. 10.1016/S0277-9536(98)00317-7
    1. Houghton G, Kingdon C, Dower M, et al. . What women think about consent to research at the time of an obstetric emergency: a qualitative study of the views of a cohort of World maternal antifibrinolytic trial participants. BJOG 2018;125:1744–53. 10.1111/1471-0528.15333
    1. Corneli AL, McKenna K, Perry B, et al. . The science of being a study participant: FEM-PrEP participants' explanations for overreporting adherence to the study pills and for the whereabouts of unused pills. J Acquir Immune Defic Syndr 2015;68:578–84. 10.1097/QAI.0000000000000525
    1. Gikonyo C, Bejon P, Marsh V, et al. . Taking social relationships seriously: lessons learned from the informed consent practices of a vaccine trial on the Kenyan coast. Soc Sci Med 2008;67:708–20. 10.1016/j.socscimed.2008.02.003
    1. Ssali A, Poland F, Seeley J. Volunteer experiences and perceptions of the informed consent process: lessons from two HIV clinical trials in Uganda. BMC Med Ethics 2015;16:86. 10.1186/s12910-015-0073-1
    1. Katz AWK, Mensch BS, Woeber K, et al. . Understanding women's motivations to participate in MTN-003/VOICE, a phase 2B HIV prevention trial with low adherence. BMC Womens Health 2019;19:18. 10.1186/s12905-019-0713-6
    1. Geissler PW, Kelly A, Imoukhuede B, et al. . 'He is now like a brother, I can even give him some blood'--relational ethics and material exchanges in a malaria vaccine 'trial community' in The Gambia. Soc Sci Med 2008;67:696–707. 10.1016/j.socscimed.2008.02.004
    1. Fisher JA. Expanding the frame of "voluntariness" in informed consent: structural coercion and the power of social and economic context. Kennedy Inst Ethics J 2013;23:355–79. 10.1353/ken.2013.0018
    1. Gamble C, Nadel S, Snape D, et al. . What parents of children who have received emergency care think about deferring consent in randomised trials of emergency treatments: postal survey. PLoS One 2012;7:e35982. 10.1371/journal.pone.0035982
    1. Kenyon S, Dixon-Woods M, Jackson CJ, et al. . Participating in a trial in a critical situation: a qualitative study in pregnancy. Qual Saf Health Care 2006;15:98–101. 10.1136/qshc.2005.015636
    1. Corrigan O. Empty ethics: the problem with informed consent. Sociol Health Illn 2003;25:768–92. 10.1046/j.1467-9566.2003.00369.x
    1. Behrendt C, Gölz T, Roesler C, et al. . What do our patients understand about their trial participation? assessing patients' understanding of their informed consent consultation about randomised clinical trials. J Med Ethics 2011;37:74–80. 10.1136/jme.2010.035485
    1. World Medical Association Declaration of Helsinki . Ethical principles for medical research involving human subjects. Jama 2013;310:2191–4.
    1. Roberts I, Prieto-Merino D, Shakur H, et al. . Effect of consent rituals on mortality in emergency care research. Lancet 2011;377:1071–2. 10.1016/S0140-6736(11)60317-6
    1. Newman JT, Smart A, Reese TR, et al. . Surrogate and patient discrepancy regarding consent for critical care research. Crit Care Med 2012;40:2590–4. 10.1097/CCM.0b013e318258ff19
    1. Coppolino M, Ackerson L. Do surrogate decision makers provide accurate consent for intensive care research? Chest 2001;119:603–12. 10.1378/chest.119.2.603
    1. Kingori P. Experiencing everyday ethics in context: frontline data collectors perspectives and practices of bioethics. Soc Sci Med 2013;98:361–70. 10.1016/j.socscimed.2013.10.013
    1. Afolabi MO, Okebe JU, McGrath N, et al. . Informed consent comprehension in African research settings. Trop Med Int Health 2014;19:625–42. 10.1111/tmi.12288
    1. Tam NT, Huy NT, Thoa LTB, et al. . Participants' understanding of informed consent in clinical trials over three decades: systematic review and meta-analysis. Bull World Health Organ 2015;93:186–98. 10.2471/BLT.14.141390
    1. Fairhead J, Leach M, Small M. Where techno-science meets poverty: medical research and the economy of blood in the Gambia, West Africa. Soc Sci Med 2006;63:1109–20. 10.1016/j.socscimed.2006.02.018
    1. Geissler PW. ‘ Kachinja are Coming!’: Encounters Around Medical Research Work in a Kenyan Village. Africa 2005;75:173–202. 10.3366/afr.2005.75.2.173
    1. Geissler PW, Pool R. Editorial: Popular concerns about medical research projects in sub-Saharan Africa--a critical voice in debates about medical research ethics. Trop Med Int Health 2006;11:975–82. 10.1111/j.1365-3156.2006.01682.x
    1. Thakur KT, Mateyo K, Hachaambwa L, et al. . Lumbar puncture refusal in sub-Saharan Africa: a call for further understanding and intervention. Neurology 2015;84:1988–90. 10.1212/WNL.0000000000001561
    1. Pflugeisen BM, Rebar S, Reedy A, et al. . Assessment of clinical trial participant patient satisfaction: a call to action. Trials 2016;17:483. 10.1186/s13063-016-1616-6
    1. McGrory E, Irvin A, Heise L. Research Rashomon: lessons from the Cameroon pre-exposure prophylaxis trial site. Washington DC: Global Campaign for Microbicides at PATH, 2009.
    1. Mack N, Omullo P, Odhiambo J. Implementing good participatory practice guidelines in the FEM-PrEP preexposure prophylaxis trial for HIV prevention among African women: a focus on local stakeholder involvement. Open Access J Clin Trials 2013;5:127–35. 10.2147/OAJCT.S45717
    1. Geissler PW. 'Transport to where?': reflections on the problem of value and time à propos an Awkward practice in medical research. J Cult Econ 2011;4:45–64. 10.1080/17530350.2011.535335
    1. Farmer P. Can transnational research be ethical in the developing world? Lancet 2002;360:1266. 10.1016/S0140-6736(02)11357-2
    1. Molyneux S, Geissler PW. Ethics and the ethnography of medical research in Africa. Soc Sci Med 2008;67:685–95. 10.1016/j.socscimed.2008.02.023
    1. Kingori P, Gerrets R. Morals, morale and motivations in data fabrication: medical research fieldworkers views and practices in two sub-Saharan African contexts. Soc Sci Med 2016;166:150–9. 10.1016/j.socscimed.2016.08.019
    1. Monroe A, Nakigozi G, Ddaaki W, et al. . Qualitative insights into implementation, processes, and outcomes of a randomized trial on peer support and HIV care engagement in Rakai, Uganda. BMC Infect Dis 2017;17:54. 10.1186/s12879-016-2156-0
    1. Vischer N, Pfeiffer C, Limacher M, et al. . "You can save time if…"-A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa. PLoS One 2017;12:e0173796. 10.1371/journal.pone.0173796
    1. Franzen SRP, Chandler C, Enquselassie F, et al. . Understanding the Investigators: a qualitative study investigating the barriers and enablers to the implementation of local investigator-initiated clinical trials in Ethiopia. BMJ Open 2013;3:e003616. 10.1136/bmjopen-2013-003616

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