Human Subjects/Research Participants

Under US federal regulations, when a clinical researcher obtains data about an individual as part of an intervention or interaction and/or collects identifiable private information, the individual is considered a human subject. In recent years, the term research participant has gained favor, but it is not recognized in federal regulations.

Human subjects are covered by the Federal Policy for the Protection of Human Subjects, or Common Rule (45 CFR 46 subpart A), as well as FDA regulations, which are implemented by institutional review board (IRB) oversight. (See the chapter on Consent, Disclosure and Non-disclosure for more on the Federal Policy and mechanisms to protect human subjects.)

In individually randomized clinical trials, where an individual provides consent to be given different interventions, identifying the research participant is fairly straightforward. Many of the regulations and oversight for governing clinical research were designed with this type of research in mind.

With pragmatic clinical trials, defining research subjects can be more complicated because the intervention in a pragmatic trial may target clinicians and/or patients, and outcomes may be measured on both. For example, in the EMBED NIH Collaboratory Trial, clinicians treating adults with opioid use disorder in the emergency department were given training and computerized clinical decision support to improve the rate of buprenorphine therapy initiated in the emergency department (Melnick et al 2019). Thus, the intervention was at the clinician level and clinicians were considered the subjects of the research.

Although the research team developed criteria to identify patients with opioid use disorder, and analyses were conducted on data from these patients, the patients were not considered human subjects, as described in their protocol paper: “Patients are not considered human subjects by Health & Human Services (HHS) regulation 45 CFR 46.102(f) since: (1) no identifiable private information will be collected, (2) the intervention does not target the patient and (3) deidentified [electronic health record] data will be collected retrospectively without interaction with the patient” (Melnick et al 2019).

Others Who Are Affected by the Research

In addition to research participants, there are others who may be affected by the conduct of research. For example, research activities may affect the routines of treating clinicians, bedside nurses, and patients’ family members who come to visit.

The Common Rule and FDA regulations are limited to the protection of human subjects/participants as defined above, but individual institutions have a range of policies and procedures for the conduct of both healthcare and research that may apply to those who, although not human subjects, may be affected by the research. For example, there may be an institutional requirement to notify all practitioners who may work with patients who are included in a specific research study. Or in some situations, notification of patient visitors and/or family members may be required. For example, in the TiME NIH Collaboratory Trial, which evaluated the duration of dialysis sessions (Dember et al 2019), the dialysis unit staff were provided information about the trial both before and during the trial. In addition, dialysis unit staff as well as patients were notified when the trial ended, and provided a summary of the trial findings. Even when there are no such policies, consideration of others affected by the conduct of the research is good practice.

In addition, patients, caregivers, and patient advocacy groups may be affected by the findings of the trial. Effective communication with these groups at study initiation can help with both implementation of the trial and broader implementation of trial interventions if they are shown to be effective (Smalley et al 2015). Effective communication can build trust in the clinical trials process and may help with recruitment in future trials.