Exploratory studies support clinical proof-of-concept in specific populations with the condition or disease for which the drug is targeted. If data are favorable, then conduct further clinical evaluations to confirm early detection. The purpose of these evaluations may be to improve effective doses and treatment regimens (including concomitant medications) for follow-up studies, to improve the definition of target populations, to provide a more robust safety profile for the drug, and may include assessment of potential study endpoints for further study. Initial efficacy exploratory studies can use a variety of study designs, including concurrent controls, self-controls, and determination of dose-response relationships. Other studies may include modeling early or interim outcome data to predict clinical outcomes to inform the design of subsequent larger confirmatory studies.

Confirmatory studies aim to confirm the original evidence accumulated at an early stage that the drug is safe and effective for the intended indication and population. The purpose of these studies is to provide sufficient evidence for marketing authorization and to provide complete information for completing the Guide for Use and Formal Drug Information. Their goal is to evaluate the drug in a larger population at risk for the condition or disease. These subjects more accurately represent the patient population who will receive medication once approved, and may include subpopulations of patients with frequent or potentially associated diseases (eg, cardiovascular disease, diabetes, liver and renal impairment), and to confirm the feature that the patients with these baseline conditions can have the safe and effective use of medication.

Confirmatory studies can further explore the dose-response relationship, or study a wider population, different stages of disease, or concomitant medications. For drugs that are expected to be administered long-term, a trial of prolonged exposure to the drug should be performed (ICH E1 Clinical Safety of Long-Term Use). Regardless of the duration of administration, the duration of action of the drug often guides the need to understand long-term effects and thus guide the study follow-up time.

Confirmatory studies usually use a randomized parallel design. Complex adaptive or innovative designs may be used to achieve efficiencies or test hypotheses as data accumulates during the research process.