FDA Finalizes Three Guidances to Broaden Cancer Clinical Trial Eligibility
核心洞察
The FDA Oncology Center of Excellence (搜索) finalized three guidance documents addressing performance status, washout periods, and laboratory values to expand cancer (搜索) clinical trial participation.
Fewer than 5% of cancer (搜索) patients currently receiving treatment are enrolled in clinical trials, despite over 70% expressing willingness to participate.
The guidances recommend broadening eligibility criteria to include patients with lower performance status, tailoring washout periods with scientific rationale, and avoiding overly restrictive laboratory-value exclusions.
The US Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) has finalized a trio of guidance documents aimed at broadening eligibility criteria for oncology clinical trials, addressing what the agency describes as a critical barrier to patient participation. The documents, posted on July 27, target three specific areas where rigid criteria have historically limited enrollment: performance status, washout periods and concomitant medications, and laboratory values.
Fewer than 5% of cancer (搜索) patients currently undergoing treatment are enrolled in clinical trials, even though more than 70% express a willingness to participate, according to OCE. "Unnecessarily restrictive eligibility criteria may slow subject accrual, limit patients' access to clinical trials, and lead to trial results that do not fully represent treatment effects in the patient population that will ultimately use the drug," the three guidances state in their preambles.
The finalization advances one of the goals of the US Department of Health and Human Services' Operation TrialBlazer Initiative, a coordinated federal effort designed to accelerate drug development and reclaim America's edge in clinical research. The documents also build on FDA efforts dating back to 2019 to reform eligibility criteria that are not based on sound science, and stem from workshops conducted with ASCO (搜索) and Friends of Cancer Research (搜索).
Performance Status: Rethinking the Yardstick
The final guidance on "Cancer (搜索) Clinical Trial Eligibility Criteria: Performance Status" addresses one of the most common eligibility criteria in oncology trials—performance status (PS), which the FDA calls a "yardstick" to measure how well a patient can perform ordinary tasks and carry out activities of daily living. Many trials are limited to high-functioning subjects with good PS and exclude lower-functioning subjects based on scales such as the Eastern Cooperative Oncology Group (ECOG) and Karnofsky (KPS).
The guidance recommends broadening eligibility criteria to include patients with a wider range of performance status. The FDA notes that some patients may have a low performance status because cancer (搜索) has made them sick, but this status could improve once the patient is enrolled in the trial. Changes from the draft to the final guidance include updates on additional considerations for sponsors regarding the impact of including patients with lower performance status on trial retention and sample size.
The final guidance specifies that its recommendations are specific to adult patients in oncology trials, noting that pediatric patients may be assessed on different scales such as Lansky and may be subject to unique considerations.
Washout Periods: Moving Toward Scientific Rationale
The final guidance on "Cancer (搜索) Clinical Trial Eligibility Criteria: Washout Periods and Concomitant Medications" encourages sponsors to assess the need for time-based washout periods between stopping a cancer drug and starting an experimental drug. The guidance states that washout periods and concomitant medication exclusions "often vary across trials for similar therapeutic classes and diseases and should be appropriate for the trial under consideration."
The FDA emphasizes that eligibility criteria should be tailored to the population being studied and the goals of the clinical investigation. The guidance reflects a general approach to broadening eligibility rather than providing prescriptive criteria. Sponsors are urged to justify exclusion criteria with disease- and drug-specific scientific rationale rather than vague statements such as "Exclude patients taking concomitant medications."
The final guidance adds clarifying text defining a washout period as a "treatment-free period intended to allow a prior therapy and/or its effects on the body to be eliminated or reduced to acceptable levels preventing additional toxicity and/or interfering with the pharmacokinetics/pharmacodynamics (PK/PD) of the investigational drug when a new therapy is started."
Laboratory Values: Accounting for Population Diversity
The final guidance on "Cancer (搜索) Clinical Trial Eligibility Criteria: Laboratory Values" outlines general principles for selecting laboratory-based eligibility criteria, such as minimum blood counts. The guidance emphasizes that overly strict laboratory-based exclusion criteria can negatively impact patient enrollment and the diversity of populations in clinical trials.
The document highlights that laboratory value abnormalities may represent manifestations of the underlying malignancy or comorbidities that do not otherwise preclude safe participation. It also notes that laboratory values may vary among healthy individuals across different age groups and racial and ethnic populations. As an example, the guidance points to the Duffy null phenotype, which has a high prevalence in African Americans and is associated with lower absolute neutrophil counts but not with greater risk of infection. "Laboratory-value criteria that do not take these differences into account can hamper efforts to enroll a representative population," the guidance states.
The three guidance documents apply to investigational drugs or biological products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).