THE ETHICAL FOUNDATIONS OF CLINICAL RESEARCH: SHIFTING THE PARADIGM OF PARTICIPATION.THE CASE OF PHASE 0 CANCER TRIALS.

In this dissertation I consider the ethical foundations of clinical research and propose a shift towards a new framework. Since the beginning, the ethical foundations of clinical research have been focused on the protection of human subjects, with a strong emphasis of the importance of the informed consent process and on issues of vulnerability, coercion, and exploitation. This is understandable, as the ethical guidelines regulating clinical research worldwide (Nuremberg Code, Helsinki Declaration, Belmont Report) were born in the aftermath of the WWII. But the historical context has changed, and the emphasis on the protection of subjects may be anachronistic today and have deleterious repercussions on the clinical research enterprise, by placing the regulatory bar too high. My case-study is the first Phase 0 clinical trial performed at NCI-NIH, the ABT-888 study. Phase 0 trials are clinical studies, which have no intention to treat and are performed before the traditional Phase 1 studies, with the aim of proving in humans a molecular mechanism of action which has been demonstrated in the animal models. In this work I first analyze the traditional topics in the ethics of clinical research, such as informed consent, the possibility of therapeutic misconception or misestimation, the vulnerability of terminally ill subjects. I then consider the arguments in favor and against the so-called “duty to participate in clinical research”, providing an extensive overview of the ethical debate. Considered the pros and cons, I conclude that there are sufficiently solid ethical arguments to support a shift in our attitude towards participation in research from the traditionally conceived super-erogatory view to a, even if imperfect, moral duty. I then switch to the policy level, and propose some practical implementations of the ethical arguments in favor of the duty in research based on the libertarian paternalistic view developed by Sunstein and Thaler. To conclude, the ethical foundations of clinical research need to be reshaped: we all have an interest in the advancement of medical research, and participation in research should be seen both as a duty and a right. Trust should become one the fundamental value of these new foundations, which also have practical implications, for the rewriting of Helsinki Declaration.