An umbrella review of ethical challenges in clinical trials conducted in low and middle income countries

Abstract

Clinical trials are considered as a robust study design to establish which therapeutic interventions including vaccine discovery and developments, and diagnostic tests are most applicable to the public. However, there are many ethical implications of conducting clinical trials in low- and middle-income countries (LMICs). Henceforth, we adapted the methodology of an umbrella review to delineate the evidence regarding the ethical considerations on clinical trials in LMICs. This review applied the PRISMA guideline for search strategy and article screening and used AMSTAR-2 for quality appraisal. This study was registered in PROSPERO (CRD42022325204), and the search was performed on 10 February 2026. Our collection retrieved 3,189 records from eight databases. A final number of 19 systematic reviews met all inclusion criteria and were included in this review. Our result recurrently identified several specific population groups as central to ethical discussions in clinical trials conducted in LMICs. Thematic analysis of literature identified six overarching domains of ethical concerns: informed consent and participant autonomy; vulnerable populations and inclusion; community and stakeholder engagement; risks and exploitation; justice and post-trial obligations; & governance and publication ethics. The communities in LMICs, not being fully aware of their rights, and considering they may lack knowledge of the history of frequent exploitation and structural marginalization, are more vulnerable to ethical infractions than wealthy nations. To attain health justice, ethical standards now in place must be upheld and implemented.