A New Approach to Simplifying and Harmonizing Cancer Clinical Trials—Standardizing Eligibility Criteria

Abstract

ancer clinical trial accrual remains a persistent challenge. Difficulties recruiting and retaining representative participants result in prolonged study duration, premature trial closure, heightened costs of clinical research, and delayed advances in the field. Many oncology trials close prematurely, and those that do finish are generally extremely costly. Multiple factors contribute to these problems, including complexity of trial protocols, lack of access to trial sites, and stringent eligibility criteria. 1 Clinical trial sponsors rely on eligibility criteria to control the characteristics of study participants to generate interpretable and reproducible results. Over the past several decades, however, the number and specificity of eligibility criteria have increased substantially, further slowing accrual and limiting generalizability of study findings to real-world populations. 2 In response to these trends, several multistakeholder efforts have sought to modernize eligibility criteria to ensure that more patients can access therapies in development. [3][4][5][6][7][8][9] These activities focused primarily on reforming approaches to developing clinical trial eligibility criteria. LUNGevity Foundation (hereafter, LUNGevity), a nonprofit patient advocacy or-ganization committed to increasing quality of life and survivorship of people with lung cancer, formed a scientific and clinical research roundtable initiative to streamline lung cancer clinical trials. To date, this group has issued 2 sets of recommendations regarding eligibility criteria. 10,11 To address the need for consistency in how clinical trial eligibility criteria are defined and listed in protocols, LUNGevity collaborated with the US Food and Drug Administration (FDA) and the National Cancer Institute (NCI) to address 3 challenges arising from confusing and inconsistent eligibility criteria in clinical trials for advanced-stage non-small cell lung cancer (NSCLC): (1) patients, caregivers, and clinicians often face difficulties navigating trial protocols to determine eligibility because publicly available trial search engines do not standardize the listing of inclusion and exclusion criteria; (2) increasingly numerous and stringent eligibility criteria exclude a growing proportion of patients; and (3) heterogeneous study populations render cross-trial comparisons difficult.Herein, we present the result of this effort: a prioritized list of recommended terms for inclusion and exclusion criteria in first-IMPORTANCE Clinical trial sponsors rely on eligibility criteria to control the characteristics of patients in their studies, promote the safety of participants, and optimize the interpretation of results. However, in recent years, complex and often overly restrictive inclusion and exclusion criteria have created substantial barriers to patient access to novel therapies, hindered trial recruitment and completion, and limited generalizability of trial results. A LUNGevity Foundation working group developed a framework for lung cancer clinical trial elig...

Quantitative evaluation of the impact of relaxing eligibility criteria on the risk–benefit profile of drugs for lung cancer based on real‐world data

“…Additionally, for patients with advanced tumors, participating in confirmatory trials could be regarded as an alternative of treatment regimen; therefore, irrational setting of eligibility criteria could also cause equity issue. 13 Therefore, the US Food and Drug Administration (FDA) and the National Cancer Institute (NCI) have clearly pointed out that the current restrictions on eligibility criteria lack scientific basis and should be simplified and relaxed to ensure population diversity in clinical trials. 13 A series of guidelines and consensus have been issued to provide recommendations regarding appropriate eligibility criteria for clinical trials of cancer drugs or biological products since 2020.…”

“…13 Therefore, the US Food and Drug Administration (FDA) and the National Cancer Institute (NCI) have clearly pointed out that the current restrictions on eligibility criteria lack scientific basis and should be simplified and relaxed to ensure population diversity in clinical trials. 13 A series of guidelines and consensus have been issued to provide recommendations regarding appropriate eligibility criteria for clinical trials of cancer drugs or biological products since 2020. 14 Pharmaceutical enterprises are encouraged to be proactive in increasing the enrollment of underrepresented populations when evidence supports such inclusivity.…”

“…Overly stringent eligibility criteria undeniably present a significant scientific and practical barrier, notably impeding the progress of drug R&D and inflating associated costs. Additionally, for patients with advanced tumors, participating in confirmatory trials could be regarded as an alternative of treatment regimen; therefore, irrational setting of eligibility criteria could also cause equity issue 13 …”

“…Additionally, for patients with advanced tumors, participating in confirmatory trials could be regarded as an alternative of treatment regimen; therefore, irrational setting of eligibility criteria could also cause equity issue. 13 …”

Travel Time and Distance and Participation in Precision Oncology Trials at the National Cancer Center Hospital

“…The burdens of time and costs associated with travel to the trial sites also account for the low likelihood of cancer clinical trial participation . Cancer clinical trials for novel therapies are predominantly offered at a limited number of high-volume facilities and academic centers located in major urban areas . Patients living in rural areas require referral to high-volume facilities and academic centers for cancer clinical trial participation, which entails travel time, travel expenses, and other costs not covered by insurance (hotel, meals, toll tax, and parking) .…”