Written by Denise Quek
In today’s era of globalization, there are substantial debates on the ethics of conducting transnational clinical trials. Clinical trials, with the purpose to confirm the effectiveness and to scrutinize the side effects of a new drug with statistical certainty, are essential in the discovery of new treatments for diseases. Taking place all around the world, however, there is a worrying trend of advanced countries relocating clinical trials to impoverished countries. Such a trend is only possible due to the increased convenience of decreased time consumption, cost and governmental scrutiny driven by globalization (Pierik, 2015). Despite the creation of a perfect market whereby the supply of trial participants matches the demand of multinational pharmaceuticals, the question of how such trials might harm individuals through the exploitation and violation of their human rights is raised. More specifically, the conditions in which a placebo-trial design may be accepted. While emphasizing the importance of ensuring a regulatory scheme sufficient for protecting the interest of test subjects in relocated trials, this essay attempts to explain how such interests can be protected, through evaluating the predominant ethical standards used when conducting transnational clinical trials.
Clinical trials within the Netherlands can only be conducted after the submission of a Clinical Trial Application dossier has acquired a favorable opinion and a statement of no-objection from both the Ethics Committee and the Central Commission on Research in Humans respectively (Roffel, n.d.). Similar to the approval process of clinical trials by the Food and Drug Administration in the United States, the dossier is evaluated based upon the scientific and ethical criteria of the clinical trial (Roffel, n.d.). If the scientific requirements are what assures reliable results, then the ethical requirements are what assures the protection of participants. Scientific requirements, therefore, include things like ensuring that the medication is safe and effective before authorization of use, whereas ethical requirements, on the other hand, include things like ensuring that the test is designed in a way in which possible risks are minimized to its fullest (Roffel, n.d.). For relocated trials, only domestic scientific requirements apply equally. This is because, regardless of trial location, results have to always be reliable. Ethical requirements on the other hand differ. Requirements enforced domestically are not necessarily enforced on relocated trials since a relocated trial is no longer within domestic jurisdiction, thus, giving grounds for the host country to determine their own ethical requirements (Roffel, n.d.).
This, in theory, is difficult to practice in real life. Regulation is often criticized as too paternalistic by imposing domestically endorsed ethical standards on such relocated trials, or too lenient for imposing no ethical standards. These issues stem from different levels of access to health care and different legal regimes concerning medical bioethics. The employment of an ethical guideline that is endorsed on a wider spectrum through international alliances or treaties is therefore needed. Even though such regulatory schemes exist, examples being the Declaration of Helsinki (DoH) and the Statement of Good Clinical Practice (GCP), however, they are insufficient with loopholes within each. The problem with the DoH is that it is too generic in the sense that it is merely a general statement of ethical principles that cover all forms of medical research involving human subjects. For relocating trials, a more specific framework is required. Because of its transnational character, it involves many different countries with differences in medical provisions and legal regimes. With the GCP on the other hand, it is a problem in the sense that it gives researchers too much authority in deciding a participant’s risk in a trial by allowing placebo-controlled trials if seen as appropriate for the population. Placebo-controlled trials are trials in which the effectiveness of an experimental drug is compared against an inactive substance. This is in contrast to active-controlled trials whereby the effectiveness of an experimental drug is compared against an established treatment that has already been proven to be effective (Pierik, 2015). In fact, companies would always hunt for places that allow a placebo-controlled trial not only because the former allows for an easier and more robust interpretation of results, but also because it is cheaper to use a placebo. Hence, despite it being unsafe for participants, placebo-trials are generally more preferred. Yet, the GCP makes it easy for companies to conduct such trials. If companies wanted to use placebo-controlled trials, all they need to do is to relocate into another country where a better, alternative treatment is not available. Researchers are given full authority to decide the criteria for appropriateness. It is for these reasons, that the Universal Declaration of Bioethics and Human Rights (UDBHR) should be implemented (Pierik, 2015).
The Netherlands can adopt the UDBHR as a base for its ethical standards, without having to forego their current scientific standards. With the UDBHR as a base, the contextual standard of care is built upon two requirements – requirement to responsiveness to local needs and humanitarian importance requirement (Pierik 2015). By adopting the UDBHR, it specifically addresses the issue of exploitation, since it is explicitly stated that members of the control group would have the right to receive the most effective treatment amongst those available. It provides the contextual standard of care that must be provided to control groups. Furthermore, in comparison to the DoH, it is more lenient in the sense that it is more flexible, allowing for context-specific circumstances. For example, it would allow for a placebo-control trial design if the whole population, to which the prospective medicine is targeted for, does not have access to a better alternative. This, in contrast to the case of the DoH, would not have been allowed. It opens up the access of placebo-controlled trials to the poor population that would either have no access to treatment, resulting in more people with access to treatments.
As illustrated above, current regulatory regimes are insufficient in protecting the fundamental interests of test subjects and it is the best option for the adoption of the UDBHR as a base for ethical guidelines.
Pierik, R. (2015). Human Rights and Regulation of Transnational Clinical Trials. Political Studies, 63, pp. 870-886
Roffel, A.D. (N.d.). Favourable Regulatory Procedures in The Netherlands Phase I-IIa. Retrieved from: https://prahs.com/resources/whitepapers/WP-Regulatory-Procedures-NL.pdf