Understanding FDA's Blueprint for Transparency

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Earlier this year, in one of his first public addresses, FDA Commissioner Scott Gottlieb discussed the agency's on-going “Blueprint for Transparency” initiative.

This week 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.

Up to eight more recently approved new drug applications (NDAs), whose sponsors volunteer to participate, are expected to be a part of the pilot program.

Janet Woodcock, director of 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 healthcare providers about the detailed results that regulatory decisions were based on.

The FDA has long said it is sharply limited in what information it can release because it often is dealing with drug companies' proprietary material. That may be changing. In January, the agency started a pilot program to release clinical study reports for recently approved drugs. These summaries, which are generated by drug-company sponsors of the treatments, spell out the methods and results of clinical trials. The data don't include patient-identifiable information.

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. One key question to ponder then is, “more user-friendly” for whom?

The FDA is also going to make it easier to track clinical-research information by adding a study's identifier number from ClinicalTrials.gov to all FDA materials for a specific product. ClinicalTrials.gov is the database of studies maintained by the National Institutes of Health. This has been long discussed and is long over-due.

On another transparency issue, Gottlieb said the agency is exploring whether there is a “subset” of “complete response letters” (CRLs) that can be released. Such letters to drug companies detail why their drugs were not approved. He said the FDA is 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 understands that regulatory transparency cannot be a “for thee but not for me” proposition. Per the Commissioner, “We should be making sure that we try to provide as much information back into the market of ideas as possible. There are places across this agency where we bottle up too much information.”

He 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 get 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.”

It's worth noting that Gottlieb has faced some criticism over not releasing all CRLs. He's noted that doing so would be too burdensome for the FDA right now, since administrators would have to spend time redacting exclusive information. But considering how to release a subset of CRLs is a step in the right direction, even if it's not yet representative of complete transparency. 

As the debate around clinical trial transparency is certainly nothing new, with some arguing that the ClinicalTrials.gov registration requirement in the Food and Drug Administration Amendments Act (FDAAA) isn't being properly implemented and that more transparency (and oversight) is needed to satisfy full public disclosure and address the issue. As we progress through the many factors involved in data transparency, here are some issues we need to consider:

Should the FDA make patient-level clinical data available? If so, how would the undertaking be pursued and funded?

Should the government regulate transparency independently, or should it loop in private parties? And what role should patients play?

Should there be a formalized transparency consortia? If so, should it be global?

Finally -- Can transparency be leveraged as a competitive advantage, as well as a public health imperative?

According to Sir Alasdair Breckenridge, former Chairman of the MHRA and Chair of United Kingdom's Department of Health 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.”

Sir A. 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?

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

On that last point, Dr. 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 several keystones for moving forward, such as the timing and nature of information to be released, standards of protection of personalized data, and rules of engagement for observational studies.

Dr. Gottlieb has a unique mindset. He understands the inner workings of the health industry. But he also imagines a new health industry, one where the FDA can and does break tradition for the better.



Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest.


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