Understanding FDA’s Blueprint for Transparency

Scott Gottlieb’s tenure as Food and Drug Administration commissioner has, to date, been defined by two terms not generally associated with the agency — predictability and imagination.

Earlier this year, in one of his first public addresses, Gottlieb discussed the agency’s ongoing “Blueprint for Transparency” initiative.

Recently, the FDA officially launched its pilot project to publicly release portions of clinical trial-related summaries from pivotal trials, with initial data coming from Janssen’s recently approved Erleada (apalutamide), which is for patients with prostate cancer that has not spread.

About 1,000 pages of Janssen’s partially redacted clinical study reports for Erleada were published, including information on the trials’ protocols and statistical analysis plans. A Janssen spokesperson told “Focus” that the company’s interest in such a transparency initiative and in furthering other research efforts coincided with its submission for Erleada. The spokesperson also said Janssen did not redact the study report or the protocol and also did not review the FDA assessment report prior to its posting.

Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, wrote in a blog post that by releasing the clinical study reports, the agency hopes to enhance the accuracy of information used in scientific publications; increase stakeholders’ understanding of the basis for FDA’s approval decisions; and inform physicians and other health care providers about the detailed results that regulatory decisions were based on.

The release of the study reports, which can run hundreds of pages, will allow researchers and others (per Gottlieb) “to do more analysis around our decision-making,” especially on the safety and efficacy of new drugs. Some of the information is already released by the agency but in a format that is difficult for lay audiences to use. So, in some respects, “transparency” will also mean “more user-friendly.”

The FDA is also exploring whether there is a “subset” of “complete response letters” that can be released. Such letters to drug companies detail why their drugs were not approved, looking at possibly releasing information involving safety issues.

Critics of the pharmaceutical industry have long complained that the companies don’t always give the public accurate and comprehensive explanations of why their products were rejected. It’s also been a thorn in the side of agency reviewers who are regularly blamed by companies when they receive CRLs. The release of (properly redacted) CRLs will ensure that the reasoning behind them (and the appropriate assignation of blame) will be more balanced.

Gottlieb singles out complete response letters as a “place where we should ask hard questions because there’s some very important information in those communications.” Releasing this information could advance public health, for example by publicizing a safety threat, or by helping other companies avoid known pitfalls and thereby getting drugs onto the market more quickly.

“There might be other products on the market or other products in development that are affected by the agency’s judgment,” Gottlieb said. “If there are ways to redact those letters from commercial competition information, to make that sort of bottom-line important information available, I think that we should look at that.”

As we progress through the many factors involved in data transparency, here are some issues we need to consider:

— The FDA is at the nexus of vast amounts of patient-level clinical data: What role will transparency play in making such information available? How might the agency accomplish such a task? How would it be funded? And where does such an initiative fall on the agency’s long list of urgent priorities?

— Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play? Should there be formalized transparency consortia? Should it be global?

— Can transparency become a competitive advantage as well as a public health imperative?

According to Sir Alasdair Breckenridge, former chairman of the Medicines and Healthcare products Regulatory Agency, and chair of the United Kingdom’s former Emerging Science and Bioethics Advisory Committee, transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – the more you give it, the more it wants.”

Breckenridge suggests four key questions:

(1) Should the public have access to data based on which regulatory decisions are taken?

(2) What are the advantages and disadvantages of increased transparency?

(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?

(4) Will increased transparency lead to increased trust in regulators and the industry?

On that last point, Breckenridge points out that increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.

Transparency cannot be “for thee but not for me.”

And he offers five keystones for moving forward:

(1) Agreement on timing of release of information;

(2) Agreement on nature of information to be released;

(3) Standards of protection of personalized data;

(4) Standards for meta-analyses;

(5) Rules of engagement for observational studies.

Gottlieb’s intimate knowledge of the health industry psyche, viewed by some as his greatest flaw — is actually his most unique and important asset. He recognizes that predictability is power in pursuit of the public health and, in imagining an FDA that can (indeed must!) color outside the lines, pays heed to Bertrand Russell’s maxim that, “Science may set limits to knowledge, but should not set limits to imagination.”

Peter J. Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.

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