Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings

George Mtove, Joshua Kimani, William Kisinza, Geofrey Makenga, Peter Mangesho, Stephan Duparc, Miriam Nakalembe, Kamija S Phiri, Russell Orrico, Ricardo Rojo, Pol Vandenbroucke, George Mtove, Joshua Kimani, William Kisinza, Geofrey Makenga, Peter Mangesho, Stephan Duparc, Miriam Nakalembe, Kamija S Phiri, Russell Orrico, Ricardo Rojo, Pol Vandenbroucke

Abstract

Background: Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials.

Main body: During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs.

Conclusion: Engagement with key stakeholders at international and national levels enabled the Sponsoring Entities to address challenges by aligning the study design with the requirements of health and regulatory agencies and to understand and address healthcare infrastructure needs prior to trial initiation. Local stakeholder engagement, including community members, study participants, and family enabled the investigators to address challenges by ensuring that study design and conduct were adapted to local considerations and ensuring accurate information about the study aims was shared with the public.

Trial registration: ClinicalTrials.gov, ID: NCT01103063 . Registered on 7 April 2010.

Keywords: Clinical trials; Community engagement; Local customs; Malaria; Resource-limited settings.

Conflict of interest statement

Authors’ information

Not applicable

Ethics approval and consent to participate

The main trial was approved by ethics committees and regulatory authorities from the respective countries. Written informed consent was obtained from each participant recruited for the main trial.

Consent for publication

Not applicable

Competing interests

George Mtove, Joshua Kimani, William Kisinza, Geofrey Makenga, Peter Mangesho, Miriam Nakalembe, and Kamija S. Phiri were investigators in the study to which this manuscript relates and received research funding from Pfizer related to the implementation and execution of the study objectives. Stephan Duparc is an employee of the Sponsoring Entity, Medicines for Malaria Venture. Russell Orrico, Ricardo Rojo, and Pol Vandenbroucke are employees of the Sponsoring Entity, Pfizer.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
International stakeholders. EMA, European Medicines Agency; MHRA, UK Medicines and Healthcare products Regulatory Agency; WHO, World Health Organization; LSHTM, London School of Hygeine and Tropical Medicine; MiP, Malaria in Pregnancy consortium
Fig. 2
Fig. 2
National stakeholders
Fig. 3
Fig. 3
Local stakeholders

References

    1. Okello G, Jones C, Bonareri M, Ndegwa SN, McHaro C, Kengo J, et al. Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya. Trials. 2013;14:142. doi: 10.1186/1745-6215-14-142.
    1. Shapiro HT, Meslin EM. Ethical issues in the design and conduct of clinical trials in developing countries. N Engl J Med. 2001;345:139–142. doi: 10.1056/NEJM200107123450212.
    1. Pare Toe L, Ravinetto RM, Dierickx S, Gryseels C, Tinto H, Rouamba N, et al. Could the decision of trial participation precede the informed consent process? Evidence from Burkina Faso. PLoS One. 2013;8:e80800. doi: 10.1371/journal.pone.0080800.
    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;23:355–379. doi: 10.1353/ken.2013.0018.
    1. Kingori P. Experiencing everyday ethics in context: frontline data collectors perspectives and practices of bioethics. Soc Sci Med. 2013;98:361–370. doi: 10.1016/j.socscimed.2013.10.013.
    1. Kingori P. The “empty choice”: a sociological examination of choosing medical research participation in resource-limited Sub-Saharan Africa. Curr Sociol. 2015;63:763–778. doi: 10.1177/0011392115590093.
    1. Chuan VT, Schaefer GO. Research in resource-poor countries. The Hastings Center Bioethics Briefings. . Accessed 15 Mar 2017.
    1. Osamor PE, Grady C. Women’s autonomy in health care decision-making in developing countries: a synthesis of the literature. Int J Womens Health. 2016;8:191–202. doi: 10.2147/IJWH.S105483.
    1. Kimani J, Phiri K, Kamiza S, Duparc S, Ayoub A, Rojo R, et al. Efficacy and safety of azithromycin-chloroquine versus sulfadoxine-pyrimethamine for intermittent preventive treatment of Plasmodium falciparum malaria infection in pregnant women in Africa: an open-label, randomized trial. PLoS One. 2016;11:e0157045. doi: 10.1371/journal.pone.0157045.
    1. World Health Organization. World Malaria Report 2013. . Accessed 15 Mar 2017.
    1. World Health Organization . Updated WHO policy recommendation. 2012.
    1. Sagara I, Oduro AR, Mulenga M, Dieng Y, Ogutu B, Tiono AB, et al. Efficacy and safety of a combination of azithromycin and chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in two multi-country randomised clinical trials in African adults. Malar J. 2014;13:458. doi: 10.1186/1475-2875-13-458.
    1. Chandra R, Ansah P, Sagara I, Sie A, Tiono AB, Djimde AA, et al. Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study. Malar J. 2015;14:108. doi: 10.1186/s12936-015-0620-8.
    1. Participants in the 2001 Conference on Ethical Aspects of Research in Developing Countries. Moral standards for research in developing countries: from “reasonable availability” to “fair benefits.” Hast Cent Rep. 2004;34:17–27.
    1. Benatar SR, Daar AS, Singer PA. Global health challenges: the need for an expanded discourse on bioethics. PLoS Med. 2005;2:e143. doi: 10.1371/journal.pmed.0020143.
    1. Denburg A, Rodriguez-Galindo C, Joffe S. Clinical trials infrastructure as a quality improvement intervention in low- and middle-income countries. Am J Bioeth. 2016;16:3–11. doi: 10.1080/15265161.2016.1170230.
    1. Perrey C, Wassenaar D, Gilchrist S, Ivanoff B. Ethical issues in medical research in the developing world: a report on a meeting organised by Fondation Merieux. Dev World Bioeth. 2009;9:88–96. doi: 10.1111/j.1471-8847.2008.00229.x.
    1. Lairumbi GM, Parker M, Fitzpatrick R, English MC. Forms of benefit sharing in global health research undertaken in resource poor settings: a qualitative study of stakeholders’ views in Kenya. Philos Ethics Humanit Med. 2012;7:7. doi: 10.1186/1747-5341-7-7.
    1. Wendler D, Shah S. Involving communities in deciding what benefits they receive in multinational research. J Med Philos. 2015;40:584–600. doi: 10.1093/jmp/jhv017.
    1. Douglas-Jones R. A single broken thread: integrity, trust and accountability in Asian ethics review committees. Durham Anthropol J. 2012;18:13–27.
    1. Hedgecoe AM. Trust and regulatory organisations: the role of local knowledge and facework in research ethics review. Soc Stud Sci. 2012;42:662–683. doi: 10.1177/0306312712446364.
    1. Hynes T. The issue of “trust” or “mistrust” in research with refugees: choices, caveats and considerations for researchers. Geneva: New Issues in Refugee Research, UNHCR; 2003. pp. 1–25.
    1. Pratt B, Lwin KM, Zion D, Nosten F, Loff B, Cheah PY. Exploitation and community engagement: can Community Advisory Boards successfully assume a role minimising exploitation in international research? Dev World Bioeth. 2015;15:18–26. doi: 10.1111/dewb.12031.
    1. Manda-Taylor L. Establishing community advisory boards for clinical trial research in Malawi: engendering ethical conduct in research. Malawi Med J. 2013;25:96–100.
    1. Lefeber Y, Voorhoever H. Practices and beliefs of traditional birth attendants: lessons for obstetrics in the north? Tropical Med Int Health. 1997;2:1175–1179. doi: 10.1046/j.1365-3156.1997.d01-219.x.
    1. Grietens KP, Ribera JM, Erhart A, Hoibak S, Ravinetto RM, Gryseels C, et al. Doctors and vampires in sub-Saharan Africa: ethical challenges in clinical trial research. Am J Trop Med Hyg. 2014;91:213–215. doi: 10.4269/ajtmh.13-0630.
    1. Kingori P, Muchimba M, Sikateyo B, Amadi B, Kelly P. “Rumours” and clinical trials: a retrospective examination of a paediatric malnutrition study in Zambia, southern Africa. BMC Public Health. 2010;10:556. doi: 10.1186/1471-2458-10-556.
    1. Pfizer . Building infrastructure: Good Clinical Practice and Ethical Review Clinical Case Study Series. 2009. pp. 1–6.
    1. Hurst SA. Vulnerability in research and health care; describing the elephant in the room? Bioethics. 2008;22:191–202. doi: 10.1111/j.1467-8519.2008.00631.x.
    1. Chiumento A, Khan MN, Rahman A, Frith L. Managing ethical challenges to mental health research in post-conflict settings. Dev World Bioeth. 2016;16:15–28. doi: 10.1111/dewb.12076.
    1. Fitzgerald DW, Marotte C, Verdier RI, Johnson WD, Jr, Pape JW. Comprehension during informed consent in a less-developed country. Lancet. 2002;360:1301–1302. doi: 10.1016/S0140-6736(02)11338-9.
    1. Tekola F, Bull SJ, Farsides B, Newport MJ, Adeyemo A, Rotimi CN, et al. Tailoring consent to context: designing an appropriate consent process for a biomedical study in a low income setting. PLoS Negl Trop Dis. 2009;e482:3.

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