The Case for Loosening Trial Eligibility Reins

At Pharma 2023 this past spring, Dirk Reitsma, MD, senior vice president, therapeutic area head of oncology, medical, and scientific strategy for PPD, part of Thermo Fisher Scientific, presented “Inclusivity in Oncology Clinical Trials.” With the many barriers to achieving diversity of populations in all clinical trials, oncology studies have additional challenges, according to Reitsma. Those include overly restrictive eligibility criteria and complicated protocol design.

Restrictive eligibility criteria has been a concern for many oncology researchers, who believe these trials should reflect a broader real-world population. Six years ago, the American Society of Clinical Oncology and Friends of Cancer Research recommended that trials broaden eligibility to include brain metastases, HIV status, organ dysfunction, and prior or current malignancies. In 2021, the groups added the following criteria: washout periods, concomitant medications, performance status (PS), laboratory tests, and prior therapies.

Broadening these criteria could improve inclusivity. For example, Reitsma presented data that showed by allowing for brain metastases, other malignancies, and lowered renal function, broadened eligibility in a non-small cell lung cancer trial was improved by 46% overall, 4% for women, and 6% for people over 75. In a specific pancreatic cancer, traditional criteria made 42.4% of Blacks ineligible vs. 33.2% of whites; while ineligibility based on HIV and hepatitis B and C impacted Blacks by 50% over whites.

PS also was singled out in Applied Clinical Trials, with authors noting: “There are problems with clinical trials using the PS threshold because it does not reflect real-world patients. First, it is restrictive without always having a strong clinical rationale and reports show that PS threshold used in clinical trials may exclude patients who are capable of tolerating treatment and benefiting from it.”

In fact, the authors found in their data that a PS of ECOG 2 (typical measure used in eligibility evaluation) removes about 50% of viable options, while a score of ECOG 3 pretty much eliminates any trials for patients.

There are other considerations for oncology trials participation: drop-outs based on side effects; the erroneous belief that participants will always receive a placebo; and the current shortage of chemotherapy drugs, impacting trial designs with standard-of-care and comparator arms.

We recently spoke to SCRS, and its Oncology Site Solutions Summit next April will explore best practices and insights into these challenges.

Lisa Henderson is the editor-in-chief of Applied Clinical Trials