As with any type of clinical research, it is important to protect the rights, interests and welfare of human subjects. This is based on the ethical principle of respect for persons (or autonomy). This principle generally requires that a competent person has a right to decide what is or is not done to them. In research, the primary mechanism for achieving this is through the informed consent process.
Who Might Need to Be Protected/Considered?
The issue of identifying a research subject is fairly straightforward in conventional research where a patient is assigned randomly to one intervention or another, and the overarching regulations governing research were designed with this type of clinical research in mind.
The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is a set of rules for the protection of human subjects (45 CFR 46 subpart A). The Common Rule defines a human subject as “a living individual about whom an investigator (whether professional or student) conducting research obtains
(1) Data through intervention or interaction with the individual, or
(2) Identifiable private information §46.102.”
With pragmatic clinical trials (PCTs), identifying those who need to be considered—and the appropriate methods for respecting their autonomy—becomes more complicated. The authors of the article “Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials” define three categories of research participants in pragmatic clinical trials: direct participants, indirect participants, and collateral participants (Smalley et al. 2015). Recognizing the different individuals and manner in which they are affected by pragmatic research can help to ensure their rights and welfare are protected. For example, because PCTs are conducted in real-world settings, they may affect individuals by way of routine exposure to an environment (e.g., a hospital). When PCTs are cluster randomized (the unit of randomization is the facility, provider, community, etc.), individuals may be indirectly exposed to an intervention. In other words, they may not be the direct target of the intervention (direct participant), but they may be exposed to it nonetheless (indirect participant). Finally, although this group is not considered in US federal research regulations, collateral participants exist; these are patients, caregivers, and patient advocacy groups who may be affected by the occurrence or findings of the trial. Consideration of this population and effective communication with them is of critical importance (Smalley et al. 2015).
What Are the Risks to Participants?
The idea behind informed consent is that people need to be afforded the opportunity to weigh the relative risks, possible benefits, and potential burdens of a research before deciding to participate. The risks involved in some research are largely informational—the risk of harm is not physical at all—but comes from inappropriate disclosure of private information. For other research, the risks involved may be deemed “minimal” by an IRB, especially if the treatments being compared are each considered standard of care and the research interventions do not pose substantial risks or burdens.
With PCTs, there may be several approaches to respecting the autonomy, rights, and welfare of an individual. In this chapter, we review three broad approaches: informed consent, disclosure and authorization, and non-disclosure. We also examine data on people’s preferences regarding consent, disclosure and authorization, and non-disclosure. In appendices, we discuss the relevant regulations and regulatory oversight bodies.
- Introduction Consent, Disclosure, and Non-disclosure
- Informed Consent
- Alternative Approaches to Disclosure and Authorization
- Non-disclosure of Research Activities
- Data on Different Approaches to Disclosure
- Appendix: US Regulatory Agencies
- Appendix: Regulatory Frameworks
- Appendix: Institutional Regulatory Oversight
- Appendix: Emerging Regulatory Issues
Ethical and Regulatory Issues in Pragmatic Clinical Trials:
This page provides background and links to a series of 12 articles on the ethics and regulatory challenges in pragmatic clinical trials. Each article in the special issue of Clinical Trials describes an issue in detail (e.g., privacy, informed consent) and, where possible, attempts to provide guidance for future pragmatic clinical trials.
This document provides a collection of tools and resources aimed at helping a broad audience of stakeholders understand the ethical and regulatory requirements related to collecting, using, sharing, and disclosing PCOR data.
The Federal Policy for the Protection of Human Subjects
Article defines three categories of research participants in pragmatic clinical trials: direct participants, indirect participants, and collateral participants