FDA Issues New Guidance to Expand Clinical Trial Eligibility

FDA Issues New Guidance to Expand Clinical Trial Eligibility

In April, The U.S. Food and Drug Administration (FDA) released three draft guidance documents focused on increasing participation and diversity in oncology clinical trials. The proposed guidance focuses on three areas ––– washout periods and concomitant medicines, patient’s performance status, and laboratory values.

These proposals are part of the FDA’s recent push to expand the criteria for participating in oncology clinical trials after it was determined some sponsors weren’t using sound science to develop eligibility guidelines.

At the beginning of each document, the FDA notes: “Eligibility criteria are sometimes more restrictive than necessary, and expanding eligibility criteria to be more inclusive is one trial design consideration that may improve the diversity of clinical trial populations.”

Let’s take a closer look at each draft guidance document.

1) Washout periods and concomitant medicines

Washout periods refer to the weeks or months between recent cancer treatments and current therapies. The FDA’s draft guidance notes that although many oncology trials include washout periods, sponsors should tweak them to meet their specific trial protocols. For instance, if a washout period is necessary, the sponsor must provide data that illustrates going forward without one would present excess risks.

The section on concomitant medications discusses how many sponsors exclude elderly patients from oncology trials because they’re more likely to take one or more prescription drugs. The draft guidance says these patients should “only be excluded from trial participation when relevant known or predicted drug-drug interactions and potential overlapping toxicities will impact the safety of trial participants.” In other words, the fact that a potential trial participant takes concomitant medicines shouldn’t necessarily prevent them from trial enrollment.

2) Laboratory values

The document on laboratory values explains how overly restrictive laboratory-based exclusion criteria can negatively affect patient recruitment and diversity. 

To counter this common barrier, the FDA encourages sponsors to tailor eligibility criteria to the drug under investigation, including its pharmacokinetics and pharmacodynamics (PK/PD), mechanisms of action, and anticipated toxicities.

For example, if an investigational drug or therapeutic isn’t likely to cause hepatic toxicity, the guidance states “hepatic entry criteria should be sufficiently broad to avoid unnecessary exclusions of patients.” 

3) Patient’s performance status

Performance status (PS) assesses how well a patient can perform routine tasks and activities of daily living (ADL), and is a cornerstone of eligibility in most oncology trials. However, the FDA’s draft guidance notes that many trials only accept high-functioning participants and exclude lower-functioning ones. 

The guidance document notes that “restrictive eligibility criteria may result in a group of trial participants who do not reflect the clinical and demographic diversity of patients with the indicated disease.” This means that the efficacy and safety outcomes experienced by high PS patients may not accurately depict the same outcomes for patients with low PS. The FDA argues that by expanding eligibility to include both high PS and low PS patients, it’s possible to get a more accurate overview of a drug or therapy’s benefits. 

Currently, measurements of PS are based on one of two scales: Karnofsky (KPS) and Eastern Cooperative Oncology Group (ECOG). The FDA says alternative clinical tools, like the comprehensive geriatric assessment, are better at “evaluating older adults’ overall health status and better than KPS at predicting chemotherapy toxicity.” 

The guidance suggests using other types of data as well, including patient-reported outcome assessment data. The authors say this information “can provide both baseline and longitudinal data that can complement clinician-assessed PS.” Likewise, wearable technologies, like smartwatches and actigraphy devices, can provide additional information “to compare with clinician and patient reports.” 

To see the draft guidance documents in full, click here

Members of the public have until June 25th to submit comments. You can do that online or, you can send written comments to:

Dockets Management

Food and Drug Administration

5630 Fishers Lane, Rm 1061

Rockville, MD 20852

Written comments should be identified with the docket number: FDA-2024-D-1376

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