Uninformed refusals: objections to enrolment in clinical trials conducted under an Exception from Informed Consent for emergency research

Abstract

Clinical trials in emergency situations present unique challenges, because they involve enrolling individuals who lack capacity to consent in the context of acute illness or injury. The US Department of Health and Human Services and Food and Drug Administration regulations allowing an Exception from Informed Consent (EFIC) in these circumstances contain requirements for community consultation, public disclosure and restrictions on study risks and benefits. In this paper, we analyse an issue raised in the regulations that has received little attention or analysis but is ethically complex. This challenge is when to solicit and honour objections to EFIC trial enrolment, including from non-legally appointed representatives. We address novel questions involving whose objections should be honoured, what level of understanding is necessary for objections to be considered valid and how hard investigators should work to offer an opportunity to object. We present a set of criteria that provide conceptual and practical guidance. We argue that objections should be honoured if they undermine one of the key assumptions that allows for the permissibility of EFIC trials: that individuals would likely not object to enrolment based on their values or preferences. We then clarify the practical implications of this approach through examination of three cases of refusal in an EFIC study.

Do National and International Ethics Documents Accord With the Consent Substitute Model for Emergency Research?

“…Furthermore, their model continues to be cited regularly in the emergency research literature. 27,28 The International Compilation of Human Research Standards (2020) was used as a starting point to identify states that have specific guidance on emergency medical research, but are not in the European Economic Area (plus the United Kingdom) or among the 12 ratifying states of the Council of Europe's Additional Protocol. 29 To ensure accuracy of interpretation, our analysis was limited to states providing documentation in English.…”

A response to Al et al. Trials 2023;24:233

“…I for one hope that research ethics will not devolve to the “ethics” of the marketplace. Moreover, while it might be argued that these methods might be used simply to enhance the likelihood of potential subjects paying attention and hearing or reading a research pitch (or consent form), people are completely free to give “uninformed refusals.” [ 8 ].…”