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Pink Sheet — US FDA, NCI Collaboration Deepens To Include Clinical Trial Innovation ‘Think Tank’

Pink Sheet — US FDA, NCI Collaboration Deepens To Include Clinical Trial Innovation ‘Think Tank’

The US Food and Drug Administration and National Cancer Institute are collaborating to incubate clinical trial system improvements in an expansion of the partnership between the agencies.

Monica Bertagnolli, who had been NCI director before recently being confirmed as National Institutes of Health director, said the “think tank” grew out of an idea discussed last year and now includes NCI, the FDA, and group chairs from the NCI’s National Clinical Trials Network.

“That team is working together and they’re doing really hard work because innovation is really difficult,” she said 14 November during the Friends of Cancer Research Annual Meeting. “It’s exciting to see the ideas that have come.”

Bertagnolli would not give details about what innovations the group was considering, but suggested they would be “truly transformative.”

“Why haven’t you seen them sprouting already? It’s because these are transformative ideas that take some significant spade work even to get going,” she said. “I’m thrilled to see what this group has started to do and we hope to continue to see more.”

The clinical trial innovation group represents further growth of the collaboration between the FDA and NCI. Both are working on the Pragmatica Lung trial, which is a simplified study of ramucirumab and pembrolizumab versus standard of care in stage IV or recurring non-small cell lung cancer.  (Also see “Project Pragmatica: US FDA’s OCE Initiative Aims To Encourage Simple Clinical Trials” – Pink Sheet, 21 Nov, 2022.)

Both already have called on industry to expand clinical trial eligibility to encourage more diverse participation.  (Also see “Oncology Clinical Trial Eligibility Expansion A Focus For US FDA; Sponsors Overcoming Initial Hesitation” – Pink Sheet, 15 Apr, 2021.)

The two agencies, along with the Foundation for the NIH, also want to start a public-private partnership to create a repeatable development process for developing drugs for ultra-rare cancers. Ideally, the partnership would address cancers with high unmet need and no commercial viability because the patient populations are too small.  (Also see “Ultra-Rare Tumors: Public-Private Partnership Eyed To Boost Drug Development” – Pink Sheet, 6 Sep, 2023.)

Richard Pazdur, director of the FDA’s Oncology Center of Excellence, also has suggested that NCI work with pharma companies to enroll US patients in oncology clinical trials.  (Also see “US FDA’s Pazdur Suggests NCI Should Help Sponsors Enroll Clinical Trials For Innovative Drugs” – Pink Sheet, 18 Nov, 2022.)

Postmarket Research System Needs To Change, Califf Says

FDA Commissioner Robert Califf, who appeared with Bertagnolli during the conference session, said the postmarket clinical trial setting requires the most changes.

Califf said some changes may be necessary in early phase rare disease and oncology trials, but added “I think that system works well and I don’t think we want to mess with it too much.”

“We’re not talking about early drug development or even up to the first indication for most situations,” Califf said. “That has to be a very detailed system to collect everything because you don’t know what you’re going to find when you put a new molecule or a new device in a human being. We’re talking about later on. We need to do things differently to make them better.”

Califf has pushed clinical trial reform since returning to the FDA in 2022, arguing they are too cumbersome. He has advocated for increased use of electronic health records and shortened consent forms.  (Also see “Califf Laments Shift To Ex-US Clinical Trials – As Well As Pace Of Reforms At Home” – Pink Sheet, 12 Jan, 2023.)

Califf also has said more data transparency will help improve the clinical trial system.  (Also see “Califf Outlines Clinical Trial Reform Message, Which Could Travel With Him To Commissioner’s Office” – Pink Sheet, 22 Nov, 2021.)

Report Outlines Potential Postmarket Research Changes

On the same day as the conference, the Reagan-Udall Foundation released a report with several recommendations for enhancing postmarket evidence generation. Ideally, those studies could fill gaps in clinical practice guidelines, but may require a different approach than the pre-market research enterprise.

“The current system used to generate evidence in support of initial marketing applications is complex, expensive, time-consuming and may not be necessary to deliver the information needed to close evidence gaps in clinical practice or to optimize the use of products already shown to be safe and effective,” the report states.

The first of the 30 recommendations in the report is for streamlining the system to support efficient and effective postmarket evidence generation, such as by allowing simpler protocols and endpoints, broader eligibility criteria, and less adverse event reporting.

“Creating and implementing standard, structured clinical data elements and automating electronic data capture is necessary to ensure success,” the report states.

The expert panel that wrote the report also suggested creating new or using existing “regulatory programs that promote use and expedited review of postmarket pragmatic evidence generation studies to support expanded indications, label changes or to meet other regulatory requirements.”

The report authors said FDA leadership should release pragmatic evidence generation principles and appropriate study design, analysis and data quality standards. They also recommended the agency consider creating internal review policies for assessing pragmatic evidence generation studies separate from those for pre-clinical research.

Califf already has teased potential postmarket studies for Alzheimer’s treatments, as well as obesity drugs.  (Also see “Califf Plans US FDA, NIH Collaboration On Postmarket Evidence Generation” – Pink Sheet, 25 May, 2023.)