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Regulatory Focus – Experts Seek Tweaks to FDA Draft Guidance on Clinical Trial Diversity

Regulatory Focus – Experts Seek Tweaks to FDA Draft Guidance on Clinical Trial Diversity

Recent US Food and Drug Administration (FDA) draft guidance on enhancing clinical trial populations’ diversity should discuss the role of real-world data/evidence (RWD/RWE), comments to FDA say.

The public comment period on FDA’s draft guidance closed with 90 submissions, including from PhRMA, Roche/Genentech, the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT Center), the National Center for Health Research (NCHR), the American Society of Clinical Oncology (ASCO) and the National Association for Rare Disorders (NORD), among others.

Most commenters generally support the issuance of the draft guidance as a step in the right direction to enhance diversity in clinical trials. Yet several ask for references to or discussion about the role of RWD/RWE, touting the use of sources like registries to help fill in gaps of information. Friends of Cancer Research (FOCR) and Roche/Genentech say that FDA should cite its work to advance the use of RWE to better reflect real-world patient populations.

FDA has been exploring additional ways to further support industry use of RWE as part of clinical studies under the agency’s RWE framework, released last December. The commenters argue for the RWD/RWE efforts to be more supportive of enhancing diversity in trial populations.

The MRCT Center recommends addressing the use of RWD/RWE “to help collect clinical data in diverse patient populations, particularly for later phase studies and potentially to decrease the number of subjects needed for clinical studies.” PhRMA “encourages FDA to consider how RWE/ RWD may be used to help provide information on effects of the drug in broader patient population.” The research and policy center and PhRMA say that RWE/RWD have the potential to complement and support clinical trial results while increasing the diversity of patients studied.

There is also consensus across commenters for the guidance to note how to make the best use of patient input for informing clinical trial designs and to describe strategies to improve enrollment for unrepresented patients in clinical trials based on demographics versus non-demographics.

“FDA should consider referencing these activities and note the role of patient input in informing clinical trial designs, identifying the needs of specific patient populations, and recognizing opportunities to reduce patient burden,” says FOCR. PhRMA and the MRCT Center echo this recommendation. The MRCT Center believes “the role of participant/patient/public engagement throughout the clinical trial planning and conduct process could be expanded in the document, and reference to the FDA guidance on Patient-Focused Drug Development would be helpful.”

The draft guidance lacks a clear distinction between demographics versus non-demographics, according to PhRMA, the MRCT Center and Bridge Clinical Research. “It would be important to include examples of exclusion criteria based on demographic criteria, and examples of broadening eligibility and recruitment strategies in these populations,” the MRCT Center writes.

BIO, NCHR and ASCO also note the need for incentivizing the adoption of the drafted requirements, once finalized, to achieve the aim of the guidance. “The degree of impact for proposed changes will depend upon clarity in the final guidance and FDA’s willingness to enforce and/or incentivize adoption of these requirements on sponsors and research programs,” BIO notes.

NORD and ASCO laud the draft guidance and show support for a range of proposals, from engaging with patient groups early on in the drug development process to re-enrolling patients from early-phase trials into later-phase trials. Yet ASCO requests more guidance, including on the transition from dose escalation to the cohort expansion phase.

Several commenters also request the inclusion of additional strategies to increase participation for underrepresented populations by increasing the number of specific subgroups, including transgender individuals, African Americans, Latinos, Asians, women and elderly patients.…