The document provides a detailed analysis of various study designs to clarify the National Institutes of Health (NIH) definition of a clinical trial, using 25 specific case studies as illustrative examples. Each case is evaluated according to three primary NIH criteria: involvement of human subjects, prospective assignment of subjects to an intervention, and identification of health-related biomedical or behavioral outcomes. The cases systematically differentiate between studies that qualify as clinical trials and those that do not.
Studies that qualify as clinical trials consistently involve human subjects who are prospectively assigned to an intervention—with the intention of evaluating health-related biomedical or behavioral outcomes; these include drug comparisons, behavioral interventions, dose-response investigations, and diagnostic tool comparisons. Conversely, studies that do not meet the clinical trial criteria typically lack prospective assignment, health-related outcomes, or direct involvement of human subjects (such as those using only de-identified samples, evaluating comprehension of materials unrelated to health, or focusing solely on device feasibility without affecting patient care). Throughout, the document underscores the importance of precise, prospective design, and medically relevant outcomes in classifying research as a clinical trial, thereby serving as a useful guide for researchers and institutional review boards in study classification and regulatory compliance.
