Ethical Principles in Phase IV Studies

Phase IV post-marketing studies on a pharmaceutical product have been increasing in number and presumably in importance recently. This growing number of phase IV studies has led to a greater need to examine the applicable ethics at this stage. Building on our previous work on ethics in phase IV studies, we propose that the following ethical principles are indispensable to implementing ethics in phase IV: (A) When discussing the possibility of waiving informed consent (IC), it is -necessary to consider such discussions within the sphere of human rights. (B) The fact that there are a variety of phase IV studies is ethically significant. (C) Study type differences warrant different ethical treatment with respect to issues of IC eligibility for waiver, the manner of obtaining IC, and the content of the IC form. (D) The ethical evaluation of phase IV should assume a therapeutic orientation. (E) The weighing of risks and benefits is a shared responsibility between research ethics committees and sponsors/investigators. (F) In balancing risks and benefits, assuming a therapeutic orientation and applying expected utility theory, the following constraints are in order: the benefit utility table must include the direct benefits; the weight of direct benefits cannot be negligible in comparison with other benefits; and the risk table must include both risks due to study participation and to experimental intervention.