How to Enroll Participants in Research Ethically

Abstract

REGULATIONS STIPULATE THAT, TO PROVIDE VALID CONsent for research, potential participants must be competent, understand the essential elements of consent, and make a voluntary decision. According to European Union guidelines, valid consent requires that the decision to enroll is “taken freely” by a “person capable of giving consent.” In contrast, regulations provide almost no guidance on what steps investigators should take to determine whether participants provide valid consent before enrolling them. When this issue is addressed at all, investigators typically are directed to adopt a uniform approach of “ensuring” that the conditions for valid consent have been satisfied. According to the Declaration of Helsinki, investigators should enroll participants only after “ensuring that they have understood”; guidance on US regulations similarly maintains that investigators “should ensure” that participants understand. Investigators cannot determine with certainty whether potential participants are competent, understand, and make voluntary decisions. For example, a voluntary decision requires that the participant has not been inappropriately influenced by others. To assess this possibility, investigators can ask whether anyone is pressuring potential participants. While such discussions provide evidence, even the most thorough assessment cannot establish definitively whether individuals are being inappropriately pressured. Thus, if the mandate “to ensure” that the conditions for valid consent have been satisfied requires definitive evidence, regulations set a standard that is impossible to meet. If this mandate is instead understood as being silent on the question of how much evidence investigators need, existing regulations fail to address the practical challenge of when it is ethical to enroll participants in research. This Commentary attempts to address this challenge by introducing the concept of validating consent. Validating consent refers to the steps investigators should take to assess whether potential participants provide valid consent. Investigators should not be required to determine with certainty that participants’ consent is valid. Instead, investigators should be permitted to enroll potential participants when they have sufficient evidence that the participants have provided valid consent. Evidence Standards in Criminal and Civil Trials The literature on informed consent focuses on the conditions that must be satisfied for consent to be valid, without acknowledging that it is not possible, in practice, to be certain whether these conditions obtain. As a result, the literature provides essentially no guidance on when individuals may engage in joint activities that require valid consent. Standards in criminal and civil trials provide a source for beginning to develop such guidance. Human participants research is designed to generate knowledge that can be used to improve the health and wellbeing of the public. To promote this end, society establishes studies in which investigators expose participants to risks and burdens. Criminal and civil courts similarly have been established by society to promote safety and wellbeing. While criminal and civil trials differ from research in many ways, standards have been developed for the level of evidence required to conclude that individuals are guilty or liable and may be exposed to legal burdens. Analysis of these standards offers insight into the steps investigators should take before concluding that participants have provided valid consent and may be exposed to the risks and burdens of research. First, the goal of criminal and civil trials is to impose sanctions on individuals only if they are guilty or liable. Yet judges and juries are not required to be certain of guilt or liability; they are required only to have sufficient evidence. Similarly, the consent process is designed to enroll participants only when they provide valid consent. Yet investigators should be permitted to enroll participants when they have sufficient evidence that the participants have provided valid consent. Second, societies could stipulate that a finding of guilt or liability may be rendered only after each case is investigated for 5 years. While this requirement would increase the chances that legal burdens are imposed only on the guilty and liable, it would be impractical. What steps investigators are required to take to assess whether participants provide valid consent should similarly be sensitive to what is feasible.