Broadening Eligibility Criteria to Make Clinical Trials More Representative

Eligibility criteria are necessary in clinical trials to define the patient population under study, isolate the potential effect of an investigational drug, and ensure that the trial is conducted safely. However, excessive or overly rigid eligibility criteria may impair the rate of trial accrual, restrict patient access to investigational drugs, and limit the ability to generalize the results to the broader population of patients who will ultimately use the drug.

In 2016, ASCO and Friends of Cancer Research (Friends) began a joint project to develop and advance specific strategies to change the exclusionary nature of eligibility criteria. ASCO-Friends working groups composed of patient advocates, drug/biotech manufacturers, investigators, and regulators developed consensus recommendations for eligibility criteria on the following topics: 1) Brain Metastases, 2) HIV/AIDS, 3) Organ Dysfunction and Prior and Concurrent Malignancies, and 4) Minimum Age for Enrollment.

On October 2, 2017, an ASCO-Friends joint research statement and four supporting manuscripts on the topic were published in the Journal of Clinical Oncology.

ASCO and Friends are now working to advance broad implementation of the recommendations. Updates made by the National Cancer Institute's (NCI) Cancer Therapy Evaluation Program (CTEP) to its Generic Protocol Template in September 2018 and February 2022 follow the ASCO-Friends recommendations closely. Studies in the NCI's Experimental Therapeutics Clinical Trials Network (ETCTN) and National Clinical Trials Network (NCTN) are encouraged to implement the changes. In July 2020, the U.S. Food and Drug Administration (FDA) published four final Guidance for Industry documents related to cancer clinical trial eligibility criteria (see below). ASCO and Friends collaborated to provide draft language for those documents and submitted a joint statement of support during the public comment period.

On February 9, 2021, a second ASCO-Friends joint research statement and four additional supporting manuscripts were published in Clinical Cancer Research. An analysis of the potential impact of the 2017 ASCO-Friends recommendations was also published as part of this bundle.

ASCO is interested in staying abreast of steps that sponsors are taking to implement the recommendations. If your organization or network plans to update its trial protocols according to the ASCO-Friends recommendations or has already made similar updates, please consider emailing the ASCO CENTRA (Center for Research & Analytics) team to share your experience.

 

Journal of Clinical Oncology Special Series on Eligibility Criteria (published October 2, 2017):

Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement

Modernizing Clinical Trial Eligibility Criteria – Recommendations of the ASCO-Friends of Cancer Research HIV Working Group

Modernizing Clinical Trial Eligibility Criteria – Recommendations of the ASCO-Friends of Cancer Research Brain Metastases Working Group

Modernizing Clinical Trial Eligibility Criteria – Recommendations of the ASCO-Friends of Cancer Research Organ Dysfunction, Prior or Concurrent Malignancy, and Comorbidities Working Group

Modernizing Clinical Trial Eligibility – Recommendations of the ASCO-Friends of Cancer Research Minimum Age Working Group

Re-Evaluating Clinical Trial Eligibility Criteria – Analysis of Investigational New Drug Applications in 2015

 

NCI CTEP Generic Protocol Updates (updated December 17, 2021)

NCI Recommended Protocol Text and Guidance based on Joint Recommendations of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends)

 

FDA Final Guidances for Industry Related to Broadened Eligibility Criteria (published July 10, 2020)

Cancer Clinical Trial Eligibility Criteria: Patients with HIV, Hepatitis B Virus, or Hepatitis C Virus Infections

Cancer Clinical Trial Eligibility Criteria: Brain Metastases

Cancer Clinical Trial Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies

Cancer Clinical Trial Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients

 

Clinical Cancer Research Publications on Eligibility Criteria (published February 9, 2021):

Continuing to Broaden Eligibility Criteria to Make Clinical Trials More Representative and Inclusive: ASCO-Friends of Cancer Research Joint Research Statement

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Washout Period and Concomitant Medication Work Group 

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

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

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Laboratory Reference Ranges and Testing Intervals Work Group

Impact of Broadening Trial Eligibility Criteria for Patients with Advanced Non-Small Cell Lung Cancer: Real-World Analysis of Select ASCO-Friends Recommendations

 

Additional Resources from ASCO

Read the ASCO in Action Policy Issue Brief (2017)

Download a PowerPoint slide deck that outlines the first round of ASCO-Friends recommendations (2017)

Download the ASCO-Friends Recommended Protocol Text and Guidance for Inclusion/Exclusion (2018)

Read the ASCO in Action post (2021)

Download a PowerPoint slide deck that outlines the second round of ASCO-Friends recommendations (2021)

Watch a recording of the April 9, 2021 ASCO-Friends virtual event: Modernizing Eligibility Criteria in Clinical Trials: How We Can Improve Patient Access and Representation (2021)

Read the Cancer.Net blog post: "How Are Eligibility Criteria for Clinical Trials Changing to Help People With Cancer?" (2021)

Read ASCO Connection Q&A blog posts: "How Will Expanded Eligibility Criteria Impact Clinical Trial Study Design?" (Part 1 and Part II) and "How Will Expanded Eligibility Criteria Improve Access to Clinical Trials for Patients With Cancer?" (2021)