Robert Califf’s vision for making FDA's institutional knowledge more accessible to the public could include tapping its most senior and experienced staff to help chronicle an agency oral history.

He noted that respected leaders like Center for Drug Evaluation and Research Director Janet Woodcock and Deputy Center Director for Clinical Science Robert Temple have made and influenced a number of decisions during their extensive FDA careers.

Califf, who is in the midst of his sixth month as deputy commissioner for medical products and tobacco, said in an Aug. 3 interview with “The Pink Sheet” that “we’ve got to get what’s in their brains out for more general knowledge and understanding.”

But since they continue to work full-time, neither of them likely would have time to publish a memoir or write their thinking on every major decision they made over the years. So Califf proposed having someone act as a kind of human Dictaphone.

Robert Califf

Source: Duke Photography

“I think young people could do that,” Califf said. “I think there’s tremendous value in oral histories and presentations and interviews that people can access on the web. ... These people are a national treasure and we need to get their knowledge out of their brains and into more widespread understanding.”

The deputy commissioner for medical products and tobacco oversees CDER as well as the centers for devices and radiological health, tobacco products, biologics evaluation and research and the Office of Special Medical Programs.

Califf is expected to help overall decision-making as well as encourage work between the various centers. Former Commissioner Margaret Hamburg created the position as part of a 2011 reorganization Also see "FDA's Spielberg To Focus On Cross-Center Collaboration, Hamburg Says" - Pink Sheet, 1 August, 2011..

Knowledge management is one of several issues that Califf hopes to tackle during his tenure.

While is it widely known that FDA has a massive repository of data and expertise within its walls, much of it remains unavailable to the public. Califf said organizing and publicizing that information will help people “know how to avoid mistakes to focus on the things that work.”

He said the goal is not to ensure things stay the same, but to try to find “important insights into how to adapt to the new world.”

“I think I’ve had over 100 briefings since I’ve come to the FDA and the wealth of knowledge in, for example, our legal team … they have seen so much and I wish that everything that was in my briefings could be organized and put out there for people to see and understand,” Califf said. “It’s been an amazing education for me.”

Califf arrived at the agency in February amid much speculation as a potential successor to Hamburg ([A#00150202008]).

Hamburg left the agency several weeks later and Stephen Ostroff became the acting commissioner ([A#00150209018]).

Temple Teaches, Incorporates Learning Into Guidance

In some ways, a lot of FDA institutional knowledge already is communicated externally through guidance and to reviewers during their internal training.

Temple said in an Aug. 6 interview that much of what he learns through his FDA work eventually gets incorporated into guidance for industry. He said issues such as non-inferiority trials and enrichment studies originated from lectures that he researched and gave.

“Once you know something you’re sort of obliged to put it in somewhere,” Temple said.

New drug reviewers at FDA take an eight- to 10-session course taught by Temple that includes a number of things that agency officials discovered, including how the agency learned to conduct dose response studies and account for all patients in trials and not drop them.

Temple wasn’t opposed to further laying out agency precedence, but he was not sure how it can be done outside of how it already occurs. He also said there are a number of ex-FDA staff that could contribute to the effort.

Much insight already is incorporated into FDA practice, he said, but it may be advantageous to explain why things are done certain ways.

“To the extent that they don’t know where it came from, it wouldn’t be a bad idea to explain where it came from,” Temple said. “If you don’t do that, the practices erode.”

Video, Web Histories Further FDA Transparency Efforts

If anything more winds up being published, it could serve as a valuable resource for drug sponsors and fill a need FDA already has acknowledged.

Califf said it will be important to release the oral histories in multiple formats.

“Three- to five-minute short clips are very popular now and useful so people can actually look and listen when they have a spare minute,” he said.

The effort also likely would represent another advance for FDA transparency.

Woodcock has said the agency has to do a better job outlining why it makes certain decisions for the benefit of those who are trying to learn from them Also see "Regulatory Flexibility Staring Contest: Will Industry Or FDA Blink First?" - Pink Sheet, 24 October, 2011..

Temple also has said in the case of biomarker and surrogate endpoint approvals, the agency must publish what it believes the “reasonably likely to predict clinical benefit” standard means Also see "Biomarkers In Orphan Studies Still Need Past Experience, FDA Says" - Pink Sheet, 27 May, 2013..

Product sponsors and other stakeholders now use guidances and regulations as well as information from product approval or compliance documents to gain insight into FDA thinking.

But in many cases, even with that material, questions remain. One example is the breakthrough therapies program, where sponsors continue to ask FDA to better articulate its requirements for gaining the designation.

Agency officials have repeatedly said they know a breakthrough when they see it ([A#00141201005]).

The agency already has started better articulating its decision-making process for new drug approvals.

As part of PDUFA V, the agency integrated its formal benefit-risk framework into the drug approval process. Reviewers are asked to write their reasoning and thinking behind various decisions, which is included in the formal record Also see "FDA’s Structured Benefit-Risk Assessment Framework To Come Online In FY 2014" - Pink Sheet, 11 March, 2013..

A more extensive library of FDA precedent and policy also could potentially relieve it of criticism.

Amid concerns about rigid FDA adherence to policy when it comes to approving rare disease treatments, attorney Frank Sasinowski and colleagues found that the agency, as it had long stated, demonstrated increased flexibility with the evidence required for orphan drug approvals Also see "Orphan Products Mostly Approved With Regulatory Flexibility, NORD "Catalog" Finds" - Pink Sheet, 17 October, 2011..

Sasinowski also found the agency used considerable flexibility when determining the evidentiary requirements for an accelerated approval Also see "FDA Flexible With Accelerated Approval Evidence, Analysis Finds" - Pink Sheet, 2 September, 2013..

Decision Science, Biomarkers Also On Agenda

Califf also wants to improve what he calls the science of decision-making.

He said knowledge about the process of making decisions is growing.

“In many ways because there’s so many precedents at the FDA, there’s sort of an intuitive knowledge of how to do it that’s passed down,” Califf said. “But I think it would be really great to advance the sort of explicit deep understanding of decision-making.”

Califf also is interested in refining FDA understanding of biomarkers and surrogate endpoints as well as patient-reported outcomes.

He said many diseases soon will be reclassified based on physiologic data because now so many things can be measured in a patient while giving a treatment.

The issue will be important as more targeted therapies are developed. President Obama called for more funding to support precision medicine in his State of the Union speech Also see "‘Precision Medicine’ Gets R&D Funding Push In President’s Speech" - Pink Sheet, 21 January, 2015..

Biomarker and precision medicine also gained a lot of attention in the House 21^st Century Cures Act.

The Cures bill included provisions intended to improve the agency’s biomarker qualification system and other changes intended to get innovative treatments to patients faster ([A#14150710004]).

Califf said every division within FDA is working on biomarker and related issues. He wrote in a July 16 blog post that in many cases progress toward cures for diseases is hampered by a lack of understanding of its biology.

“The paucity of reliable biomarkers in some diseases highlights the critical need for more research if we are to make much needed progress,” Califf wrote.

Califf's blog post coincided with FDA’s release of a report on targeted drug development. That report took a defensive tone, stating that focusing on regulation will not help researchers better understand diseases and develop cures Also see "Blame The Science, Not Regulation, For Targeted Therapy Shortfalls – FDA" - Pink Sheet, 27 July, 2015..

If Califf's oral history project is successful, such reports may no longer be necessary – everyone will already understand and appreciate what FDA does.

Oral History Of Drug Development: FDA’s Califf Wants Woodcock, Temple To Share Their Stories

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