Clinical trials in developing countries: Implications for ethical conduct and research integrity

Introduction: Clinical trials are increasingly outsourced to developing countries. Cost-effectiveness, manpower availability, and a large population make developing countries amenable to trials. Issues related to ethical integrity of such trials are well documented. Little has been done to ensure that particpants are protected from undue harm or are not coerced in any way to ensure participation.

Methods: This study systematically reviewed articles using several databases, PubMed, Medline and EBSCO with mesh terms: clinical trial ethics and developing countries. The objective of this study is to overview ethical discussions on international clinical trials and assess measures taken to protect participants.

Results: We found 365 articles of which 65 were review papers. The four main issues addressed are: integrity of trial results, patient consent, researchers' obligations towards patients and research on infectious diseases. Clinical trials are not routinely registered nor subject to rigorous IRBs in developing countries. It is important to define healthy volunteers since trials may involve upto 20,000 subjects, yet there is little consensus on the definition.Pharmaceutical firms face recruitment problems with tighter exclusion criteria, alongwith resultant losses in revenue and time. Weaker inclusion criteria may lead to inadequate statistical power, possibly invalidating the clinical outcome. Patient consent: Patient recruitment and consent materials may not be understandable, may not list all risks and may be coercive and misleading, particularly when translated into various languages. Sometimes patients may be unaware of their participant status. Large populations in developing countries live on less than one USD a day, thereby creating a purely financial incentive at the risk of particpants' health when paid for particpation. Researchers' obligations to trial participants: Currently the Alien Tort Statute can redress trial participant claims in an international court. Disputes and arbitrations are largely between the manufacturer and individual. The WHO & UN have discussed international laws on clinical trials in greater detail; however, there are few safeguards in place since such laws may not supercede individual country mandates. Post trial obligationas of Pharma are not adequately discussed. Research on developing world diseases: Pharma often researches chronic diseases that afflict western nationas as opposed to focusing on infectious diseases that developing countries face, possibly due to the lack of foreseeable profits.

Conclusion: Ethical conduct of international clinical trials will remain questionable. More compelling initiatives by WHO, UN and other international organizations are necessary to adequately protect human subjects given this trend toward outsourcing clinical trials.