Protecting Research Participants While Reducing Regulatory Burdens

The Department of Health and Human Services (HHS) has proposed sweeping revisions to the federal regulations for the protection of human research participants. The goal is to “enhance protection while simultaneously eliminating unreasonable burdens.”¹ Although the goal is admirable, some changes intended to remove unnecessary regulatory burdens may allow serious risks (ie, the probability of harm is significant, not merely possible or conceivable), particularly to highly vulnerable participants (ie, participants' ability to give free and informed consent is seriously compromised).

In this Commentary, 3 major issues in the Advance Notice of Proposed Rule-Making (ANPRM)—ensuring risk-based protections, institutional review board (IRB) reviews of multisite studies, and informed consent—are discussed. New policies to reduce regulatory burdens should be coupled with procedures to protect participants if research poses serious risks, involve highly stigmatizing conditions, or include significantly vulnerable participants.

The ANPRM proposes that all survey and interview studies involving adults will be “excused” from IRB review and approval, even if participants are identifiable and regardless of topic.¹ Such minimal risk studies would require only “registration” with an institutional office using a “brief form,” and research may commence immediately after registration of the study.¹

The ANPRM establishes the presumption that social science research in adults is minimal risk and thus excused from IRB review. However, several exceptions should not be excused. A single characteristic may not determine whether a survey or interview study requires IRB review and additional protections for participants. The ANPRM's proposed criterion of “emotionally charged” is both underinclusive and overinclusive. Several characteristics may move one social science study out of the excused category, whereas another cluster of characteristics may move another study in. A survey on access to care may require IRB review because it asks about immigration status and use of someone else's health insurance. The research assistant, a resident of the target community who will know some participants, will read the survey to low-literacy participants. Breaches of confidentiality would put participants at serious legal and economic risk. A focus group study with survivors of recent natural disasters may require IRB review because the highly sensitive topic may trigger severe emotional reactions that need to be addressed.

Registration should include a process to identify social science research that should undergo IRB review and approval. Operationally, investigators could be asked to describe the research questions and participants and complete a questionnaire to determine whether (a) the risks are serious because breaches of confidentiality may lead to legal penalties, physical harm, social rejection, or loss of housing or employment; (b) the topics of research are highly personal, sensitive, or stigmatizing, including human immunodeficiency virus (HIV) infection, sexually transmitted infections, reproductive health, illegal activities, domestic violence, sexual abuse, or suicidality; and (c) the participants are significantly vulnerable because of poor literacy or health literacy, cognitive or communication defects, low socioeconomic status, membership in a discrete group that has undergone stigma or discrimination, or recent traumatic experience with personal loss or natural or man-made disasters,² or because they are subject to authority of others.³

The answers to these screening questions might trigger various graduated actions, including requests for additional information; review by IRB staff, designated IRB members, or full committee; or delaying the start of the study until review is completed. This process should be designed not to be unduly burdensome for the large majority of social science projects that are minimal risk.

Using regulations to sort behavioral science research projects into “excused” and “requiring IRB review” raises several concerns. Problems with detailed new regulations may become apparent only after implementation.⁴ Highly prescriptive regulations may be poorly accepted by those regulated, offering IRBs and investigators little incentive to suggest improvements. Once adopted, regulations are difficult to modify and may not accommodate changing circumstances,⁴ including new research techniques such as Internet-based questionnaires and immediate surveys of disaster survivors.^{2 ,5} As an alternative to detailed regulation, agency guidance, if regularly updated, can be more flexible and nuanced. Guidance also can encourage quality improvement in the registration and screening process for social science research, based on experiences of research institutions.

The ANPRM proposed that all domestic multisite studies be reviewed by a single IRB of record and asked whether local IRB review should be required for sites in resource-poor countries.¹ For multinational studies, sites may vary sharply in culture, values, and assessments of benefits and risks of research. A US-based IRB might not appreciate how local conditions significantly increase the risk of a study or complicate the informed consent process, even for social science studies. Host country IRBs, however, may identify such problems. Thus, the default policy for multisite international studies should not be reliance on a single IRB. Similar challenges in balancing protection with regulatory efficiency might also occur in some multisite studies conducted entirely in the United States, if sites have markedly different views of the risks and benefits of the study. Although the presumption for domestic multisite studies may be a single IRB of record, exceptions should be recognized. In models of central IRB review, one IRB provides a detailed review to site IRBs, who may defer to this review, modify local recruitment, consent, and data collection procedures to provide extra protections (but not the study design or instruments) or choose not to participate in the study. Ideally, during protocol development, local concerns and suggestions have been elicited and addressed.

The ANPRM proposes to shorten and simplify consent forms and encourage use of standard consent templates as an alternative to IRB scrutiny of study-specific consent forms.¹ It suggests that oral consent may be appropriate for social science research with adults. These proposals are important steps forward.⁶ However, in-depth attention to the consent process is appropriate for certain studies, particularly those involving serious risks. For instance, in HIV prevention trials, participants may experience serious harm if they fail to understand that the study intervention is not standard care and may be ineffective or even harmful and that they need to continue risk reduction measures. Misconceptions about clinical research are common among participants in many types of trials.⁷

To strengthen the consent process, the registration procedures and IRBs need to identify studies that should be exceptions to any presumption in favor of “template” consent forms. Researchers can develop innovative ways to educate participants about the disease being studied, clinical research generally, and the specific research project.⁸ They can also assess participants' comprehension of key aspects of the study,⁸ shifting ethical focus away from consent forms.

Challenges to consent are compounded if some participants are vulnerable in the context of the specific study because of compromised ability to make informed, voluntary choices or significantly higher risk for adverse events than other participants.³ Such vulnerability should trigger proportionate IRB oversight. For example, the registration process for excused protocols should include a checklist to assess whether significantly vulnerable participants are targeted and might experience serious risks. If so, investigators should describe what measures will ensure that consent is appropriate and risks minimized. Measures to protect vulnerable participants should not exclude them from studies of health needs and conditions in underserved communities and should not discourage such studies. To minimize barriers and delays, IRBs and the HHS should post and regularly update guidance and best practices for protecting vulnerable participants. Community advisory boards can identify risks that are salient at a site, strengthen the informed consent process, and suggest how to build community support for the study and recruit participants.^{9 - 10}

In conclusion, overseeing research involving human study participants requires a complex balance of countervailing goals. In areas described, the proposed new regulations are a desirable step toward reducing unnecessary regulatory burdens. However, adequate safeguards must be in place to ensure that well-intentioned changes do not inadvertently leave research participants at inappropriately serious risk.