NEW YORK – In a draft guidance issued this week, the US Food and Drug Administration said the benefit of conducting a tissue biopsy within a clinical trial may outweigh the risks when it is used, for example, to enroll patients based on a genomic biomarker or other criteria.
Still, the agency urged industry, trial investigators, institutions, and institutional review boards to minimize the risk from unnecessary biopsies and outlined in the draft guidance considerations for when to require tissue biopsies and when to make them optional within clinical trials of investigational medical products, including those supported by the US Department of Health and Human Services (HHS).
The document was assembled with input from HHS's Office for Human Research Protections, and the Oncology Center of Excellence (OCE), the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, and Office of Clinical Policy and Programs within the FDA.
"Tissue biopsies in clinical trials are often needed to determine eligibility or to understand the effect of the medical product being studied in the trial," said Richard Pazdur, director of the FDA's OCE and acting director of the Office of Oncologic Diseases at CDER, in a statement. "This new draft guidance builds on the agency's ongoing efforts to enhance clinical trials by providing recommendations to improve participant safety and further clinical research."
The guidance encourages clinical trial investigators to consider the purpose of the biopsy, the reason for its inclusion in the protocol, and the associated risks. A biopsy may be reasonable when the information can't be obtained from less invasive methods such as pathology specimens.
In trials of precision medicine products, for example, a biopsy may be needed to identify patients with HER2-positive cancer who are likely to benefit from a HER2-targeted therapy. Similarly, a tissue biopsy may be necessary to identify colon cancer patients who should not be enrolled in trials of certain EGFR antagonists that are more likely to cause toxicities in those with KRAS mutations.
The FDA also noted that biopsies may be reasonable to evaluate the primary or secondary endpoint of a clinical trial, to evaluate treatment response, and to establish a ground truth standard for performance testing of an investigational diagnostic test. In these cases, the agency writes, the protocol should clearly lay out the justification for the biopsy.
On the other hand, biopsies should be an optional enrollment criterion when needed for the evaluation of non-key secondary and exploratory endpoints or if investigators plan to store samples for unspecified future research. Patients must give informed consent for any biopsy and retain the right to withdraw that consent. Risks to the patient should be minimized as much as possible. The guidance includes additional provisions for the protection of children who participate in clinical trials, to ensure the biopsy directly benefits the patient or, if not, involves minimal risk.
Members of the public have 60 days to submit comments on the draft guidance.