Ethics and regulatory complexities posed by a pragmatic clinical trial: a case study from Lilongwe,Malawi

Tiwonge Kumwenda Mtande1,2, Gonasagrie Nair2, Stuart Rennie2,3

  1. Centre for Bioethics in Eastern and Southern Africa (CEBESA), Kamuzu University of Health Sciences, Malawi.
  2. Centre for Medical Ethics and Law (CMEL), Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
  3. UNC Bioethics Center, Department of Social Medicine, University of North Carolina at Chapel Hill, USA.
    *Corresponding Author: Tiwonge Kumwenda Mtande; Email:


Pragmatic clinical trials generally rely on real world data and have the potential to generate real world evidence. This approach arose from concerns that many trial results did not adequately inform real world practice. However, maintaining the real world setting during the conduct of a trial and ensuring adequate protection for research participants can be challenging. Best practices in research oversight for pragmatic clinical trials are nascent and underdeveloped, especially in developing countries.
We use the PRECIS-2 tool to present a case study from Lilongwe in Malawi to describe ethical and regulatory challenges encountered during the conduct of a pragmatic trial and suggest possible solutions.
In this article, we highlight the following six issues: (1) one public facility hosting several pragmatic trials within the same period;(2) research participants refusing financial incentives; (3) inadequate infrastructure and high workload to conduct research; (4) silos among partner organisations involved in delivery of health care; (5) individuals influencing the implementation of revised national guidelines; (6) difficulties with access to electronic medical records.
Multiple stakeholder engagement is critical to the conduct of pragmatic trials, and even with careful stakeholder engagement, continuous monitoring by gatekeepers is essential. In the Malawian context, active engagement of the district research committees can complement the work of the research ethics committees (RECs).

Key words: real world data; pragmatic clinical trials; research oversight; research participants; guidelines; research ethics committee; PRECIS-2 tool; HIV; antiretroviral treatment.

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