How best to interpret the minimal risk threshold in the EU Regulation on Clinical Trials?

Biomedical research involving minors or other persons incapable of giving consent raise many complex ethical issues, particularly when the research offers no prospect of direct therapeutic benefit to the participants. To protect such individuals from exploitation and undue risks that compromise their dignity, integrity, rights, and well-being, most ethical and regulatory standards prohibit the enrollment of incompetent subjects in studies that have no therapeutic potential, unless participation involves only minimal risk and burden. This well-established standard has also been adopted by Regulation (EU) No 536/2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/EC, which recently entered into force. However, the provisions of the Regulation defining the minimal risk threshold are so ambiguous and confusing that they can easily be interpreted in ways that are unethical and inconsistent with the overall goals of the legislation. This paper critically analyzes the minimal risk requirement of the Clinical Trials Regulation and offers an ethically and legally sound interpretation of the threshold in “non-therapeutic” clinical trials involving selected categories of vulnerable subjects.