Abstract
PURPOSE: Restrictive eligibility criteria induce differences between clinical trial and "real-world" treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials. EXPERIMENTAL DESIGN: A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as selection criteria for clinical trials. The working group made recommendations to minimize restrictions based on prior therapies within the boundaries of scientific validity, patient centeredness, distributive justice, and beneficence. RECOMMENDATIONS: (i) Patients are eligible for clinical trials regardless of the number or type of prior therapies and without requiring a specific therapy prior to enrollment unless a scientific or clinically based rationale is provided as justification. (ii) Prior therapy (either limits on number and type of prior therapies or requirements for specific therapies before enrollment) could be used to determine eligibility in the following cases: a) the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy; b) the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory; and c) in randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received. (iii) Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies. CONCLUSIONS: Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation.See related commentary by Giantonio, p. 2369.