ASCO and Friends of Cancer Research (Friends) jointly issued new recommendations to further efforts to broaden eligibility criteria in cancer clinical trials with the goal of making clinical trials more accessible to patients.1 The joint recommendations are detailed in a series of articles published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
The series provides a comprehensive examination of eligibility criteria for cancer clinical trials with recommendations to address five specific areas: treatment washout periods,2 concomitant medications,2 prior therapies,3 laboratory reference ranges and test intervals,4 and patient performance status.5
“Clinical trial access must be recognized as a health equity issue. Overly restrictive eligibility criteria without scientific justification have led to an underrepresentation of older adults, racial/ethnic and sexual/gender minorities, and patients with well-managed comorbidities,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO. “We’re proud to continue our collaboration with Friends of Cancer Research to make eligibility criteria less restrictive so that clinical trial populations can be more inclusive and representative of cancer patient populations and improve results for all patients.”
Trial eligibility criteria are designed to protect participant safety and define an appropriate study population. However, overly restrictive eligibility criteria can limit the participation of patients in a clinical trial who share critical characteristics with those likely to be treated based on the study’s results. These restrictions make it difficult for clinicians to fully understand how a more diverse patient population typically seen in clinical practice will respond to a therapy post-approval. Overly restrictive eligibility criteria can also reduce patient access to potentially life-prolonging novel treatments and slow down the generation of research results. Using recommendations made by ASCO and Friends in 2017,6 a new analysis of data from CancerLinQ Discovery® (CancerLinQ’s deidentified real-world data product for researchers) found that expanding just three common eligibility criteria—renal function measures, presence of brain metastases, and history of prior malignancy—increases the percentage of patients with lung cancer potentially eligible for clinical trials almost twofold.7
To address this issue, ASCO and Friends worked with stakeholders throughout the cancer research community to develop evidence-based, consensus recommendations that are focused on expanding eligibility criteria to make trial populations more reflective of the general cancer population, reduce clinical trial complexity, and exclude patients from trials only where it is warranted due to safety concerns. Implementation of the recommendations, ASCO and Friends assert, can expedite patient recruitment, accelerate learning, decrease the trial “failure rate” due to slow enrollment, increase opportunities for patient participation and benefit, and make trial results more generalizable to the population that would use the treatment in routine clinical care.
“As new cancer therapies are being developed, we must think broadly about how eligibility criteria are determined,” said Jeff Allen, PhD, President and Chief Executive Officer of Friends. “We need to find an optimal balance between improving patient access to clinical trials and the methods used for robust evaluation of safety and efficacy of new therapies. Modernizing eligibility criteria for enrollment will bring more trials to more patients and ultimately help inform the optimal use of new medicines more quickly.”
The published recommendations were developed by stakeholders from ASCO, Friends, academic and community research sites, the U.S. Food and Drug Administration, National Cancer Institute (NCI), patient advocates and advocacy groups, NCI National Clinical Trials Network Groups, and the pharmabiotech industry.
New Recommendations to Expand Eligibility Criteria and Simplify Trial Operations
In 2016, ASCO, Friends, and the FDA formed a collaboration to address overly restrictive cancer clinical trial eligibility criteria. Project leadership selected five criteria that commonly lead to the exclusion of specific patient populations from clinical trials (brain metastases, minimum age for enrollment, HIV status, organ dysfunction, and prior or concurrent malignancies) and tasked multistakeholder working groups with recommending less restrictive eligibility criteria addressing these five factors. An ASCO–Friends Joint Research Statement and supporting working group papers were published in the Journal of Clinical Oncology in 2017.6
As a result of efforts by ASCO and Friends to disseminate and encourage the implementation of those recommendations, in September 2018, the NCI revised protocol template language
based on the recommendations, stating that the updated criteria should be implemented where possible in active protocols and included in future Experimental Therapeutics Clinical Trials Network and National Clinical Trials Network trial protocols. Additionally, in July 2020, the FDA released four final guidance documents recommending broadening eligibility criteria related to brain metastases, HIV and hepatitis B/C infections, organ dysfunction and prior/concurrent malignancies, and minimum age requirements.
ASCO and Friends will continue to work closely with the FDA, NCI, trial sponsors, institutional review boards, contract research organizations, and patient groups to disseminate the latest recommendations, share analyses, and help to successfully implement changes in protocols to broaden eligibility criteria appropriately.