substudy

A substudy is a secondary study conducted within the framework of a larger main study. It is designed to address additional questions that are not the primary focus of the main study, often by examining a subpopulation, collecting new data, or analyzing secondary endpoints. Substudies can reuse data already gathered in the main study or require separate data collection, sampling a subset of participants or extending follow-up for specific outcomes.

In design terms, a substudy may have its own protocol, objectives, sample size, endpoints, and statistical analysis plan. It should be pre-specified in the study protocol or approved as an amendment, and require appropriate ethical and regulatory oversight, including informed consent and data privacy considerations. In pharmaceutical and clinical research, substudies are common for pharmacokinetic measurements, biomarker analyses, imaging assessments, safety signals, or quality-of-life evaluations.

Analytically, substudies must address multiplicity and interpretive context. Findings are generally considered supplementary to the main study and should be reported with attention to limitations, such as selection bias if the substudy sample differs from the overall population.

Substudies help explore mechanisms, identify subgroups, or generate hypotheses while leveraging existing cohorts. They are distinct from pilot or feasibility studies and from external replication efforts. When results are confirmatory, they require prespecified endpoints and adequate statistical power within the substudy population to support conclusions. Examples include a pharmacokinetic substudy within a phase 3 trial or a biomarker substudy analyzing blood samples.