Human Subjects/Research Participants

Under US federal regulations, when a clinical researcher obtains data about an individual as part of an intervention or interaction 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.

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

Identifying a research subject can be straightforward, such as in conventional explanatory clinical trials, where individuals are randomly assigned to a study arm or identifiable data are collected. However, it can be more challenging when the study intervention targets clinicians, or both clinicians and patients, a common feature of pragmatic clinical trials.

For example, in EMBED, an NIH Collaboratory Trial, clinicians treating adults with opioid use disorder in the emergency department received training and computerized clinical decision support to improve the rate of buprenorphine therapy initiation (Melnick et al 2019; Melnick et al 2022). Thus, the intervention was delivered at the clinician level and clinicians were the subjects of the research.

Although the EMBED research team developed criteria to identify patients with opioid use disorder and conducted the analyses using deidentified data from these patients, the patients were not considered human subjects. As the research team explained, “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).

Although patients in the EMBED trial were not considered research subjects, in some trials both clinicians and patients may be considered subjects. The identification of subjects is not always straightforward, and researchers should work with their IRB to make the final determination.

Others Who Are Affected by the Research

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

While the Common Rule and FDA regulations are limited to the protection of human subjects, individual institutions have a range of policies and procedures for both the delivery of healthcare and the conduct of research that may apply to persons who, although not human subjects, may be affected by the research. For example, an institution may require notification of all practitioners who might work with patients who are included in a research study. In some situations, notification of family members and visitors may be required. For example, in TiME, an NIH Collaboratory Trial that evaluated the duration of dialysis sessions (Dember et al 2019), all dialysis unit staff were provided information about the trial both before and during the trial. In addition, dialysis unit staff and patients were notified when the trial ended and were 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 the implementation of the trial and the sustainment and dissemination of interventions that are shown to be effective (Smalley et al 2015). Effective communication can build trust in the clinical research process and help with recruitment in future trials.