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


  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:

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

Malawi Medical Journal 34 (3); September 2022

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.

  1. Introduction
  2. How is a clinical trial considered pragmatic?
  3. The Timasamalirana Study
  4. A summary of key ethical regulatory issues and future considerations
  5. The Pragmatic-Explanatory Continuum Indicator
    Summary 2 (PRECIS-2)

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