Scientific discovery relies on a formal system, established through federal regulations, designed to protect people who volunteer to participate in studies. This system clearly defines Human Subject Research (HSR) and mandates ethical oversight. Understanding these definitions and regulations is important for anyone involved in or considering participation. HSR governance ensures investigations meet high ethical standards, balancing the pursuit of knowledge with participant safety and welfare.
Defining Human Subject Research
The official definition of Human Subject Research (HSR) is a two-part standard rooted in the Federal Policy for the Protection of Human Subjects, known as the Common Rule (45 CFR 46). The first part defines “Research” as a systematic investigation, including development, testing, and evaluation, designed to contribute to generalizable knowledge. This excludes activities not intended to be shared broadly, such as a clinician evaluating a unique treatment for a single patient.
The second part defines a “Human Subject” as a living individual about whom an investigator obtains data through intervention, interaction, or identifiable private information. Intervention involves physically manipulating the subject or their environment, such as administering a drug or applying a psychological stimulus. Interaction means communication or contact, like conducting surveys or interviews.
Identifiable private information includes details a person reasonably expects will not be made public, such as medical records or biological specimens, where the identity can be ascertained by the researcher. If a study meets both criteria—intent to generalize findings and collection of such data from a living person—it formally meets the criteria for HSR. Researchers must use this framework to determine if their project requires review before data collection begins.
Categories of Research Activity
HSR takes many forms, typically categorized by the degree of intervention applied to participants. Interventional studies, often called clinical trials, are the most recognized type. These studies involve prospectively assigning participants to different groups to test a specific intervention, such as a new drug, a medical device, or a behavioral therapy.
In contrast, observational studies do not involve assigning an intervention; researchers simply observe and record outcomes. Examples include cohort studies, where researchers follow individuals over many years to track the long-term effects of a lifestyle choice like smoking. These studies are important for understanding disease progression and risk factors in real-world settings.
The third category involves research on data and biological specimens, often without direct interaction. This includes the secondary use of existing identifiable materials, such as analyzing coded tissue samples or reviewing electronic health records. If the researcher has access to the link connecting the data or specimen back to the individual, the project is classified as HSR and requires oversight to protect privacy.
Ethical Oversight and the IRB
The need for formal oversight stems from a history of unethical practices, such as the Tuskegee Study, which demonstrated the potential for harm when vulnerable populations are exploited. In response, the Belmont Report established three foundational ethical principles that govern all HSR: Respect for Persons, Beneficence, and Justice. Respect for Persons requires securing informed consent and protecting those with diminished autonomy.
Beneficence mandates that researchers maximize potential benefits while minimizing risks of harm to participants. Justice requires that the burdens and benefits of research are distributed fairly across the population. The Institutional Review Board (IRB) is the mechanism responsible for enforcing these principles at an organizational level.
The IRB is a federally mandated committee, typically composed of scientists, non-scientists, and community members, that reviews, approves, and monitors HSR. Before a study can begin, the IRB must ensure that the risks to subjects are reasonable in relation to the anticipated benefits. They also ensure the process for obtaining informed consent is adequate, protecting the rights and welfare of research subjects throughout the study.
Activities Not Requiring Human Subject Review
Not every activity involving people or data falls under the regulatory definition of HSR, meaning not all require IRB review. A common example is Quality Improvement (QI) or Quality Assurance (QA) projects, designed solely to assess and improve the performance of an internal program or service. Since the intent of QI projects is to create internal change, not to develop knowledge generalizable to a wider field, they are excluded.
Similarly, public health surveillance activities, such as outbreak investigations conducted by a government authority, are generally not considered HSR. These activities are mandated by law to protect public health and are not systematic investigations designed to create generalizable knowledge. Scholarly and journalistic activities, like oral history or biography, are also excluded when they focus on documenting the experiences of specific individuals rather than drawing broad conclusions.
Research using truly de-identified data or data from publicly available sources, such as the U.S. Census, also falls outside the HSR definition. This is because the information cannot be linked to a living individual. These exclusions provide necessary boundaries, allowing institutions to conduct routine operational and educational functions without triggering the formal regulatory requirements.