Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Prior Therapies Work Group

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.

Figure 1.. Conceptual framework to guide the use of prior therapy as selection criteria in clinical trials.

We encourage the use of this conceptual framework early in the process of clinical trial design, in order to minimize the barrier to entry. We encourage shared decision-making between the patient and the healthcare provider in selecting treatment options including treatment within a clinical trial. In general, clinical trials should be designed with the aim of achieving greater inclusivity with minimal restrictions placed on trial entry. Decisions regarding whether exposure to existing therapy should be required prior to administering an investigational therapy should consider the risks (i.e., known or unknown safety profile) and the efficacy of the therapy, and the availability of alternative treatments. In a clinical setting wherein the standard of care treatment provides a high likelihood of cure such as may be the case for some in an adjuvant setting or for some advanced lymphomas or pediatric cancers, it may be appropriate to restrict access to experimental therapy until after disease progression, relapse or intolerance of such existing treatments. However, in the non-curative setting a requirement for receipt of such ‘standard’ options is not recommended unless there is sound scientific or clinical rationale to support the restriction.

Figure 2.. Frequency of the use of prior therapies as inclusion and/or exclusion criteria in clinical trials as part of the ClinicalTrials.gov exercise categorized by phase, drug class and tumor type.

ClinicalTrials.gov was accessed on July 23, 2019. Trials with any component of Phase I trials (e.g. Phase I/II) were categorized as Phase I trials. The working group defined inclusion and exclusion criteria based on prior therapies as those criteria that did not have a specified washout period. Any criteria based on prior therapies that included a washout period was categorized as “washout period criteria” and not evaluated in this assessment.