The unique status of first-in-human studies: strengthening the social value requirement

•Most interventions tested in FIH studies will not lead to any societal benefit.•Research participants should be safeguarded from enrolling in futile FIH studies.•We provide guidance on how to assess the social value of medical interventions.•FIH studies should receive unique status in international guidelines.

For clinical research to be ethical, risks need to be balanced by anticipated benefits. This is challenging for first-in-human (FIH) studies as participants are not expected to benefit directly, and risks are potentially high. We argue that this differentiates FIH studies from other clinical trials to the extent that they should be given unique status in international research ethics guidelines. As there is a general positive attitude regarding the benefits of science, it is important to establish a more systematic method to assess anticipated social value to safeguard participants not only from enrolling in risky, but also in futile trials. Here, we provide some of necessary steps needed to assess the anticipated social value of the intervention.