FDA to Begin Publishing Clinical Study Reports & Possibly Select CRLs
A new FDA pilot program will publish information from sponsor-produced clinical study reports (CSR) — starting with documents volunteered by companies following a drug’s approval — as part of broader agency efforts to boost transparency in clinical trials and streamline the review process.
Making CSRs publically available will provide more clarity on the FDA’s decisionmaking process, as well as offer detail into the clinical evidence submitted in successful NDAs, according to FDA Commissioner Scott Gottlieb, who described clinical transparency as a tide that can lift all boats.
Specifically, the CSR pilot program will publish the study report body, trial protocol and amendments, as well as statistical analysis plans. Patient privacy, trade secrets and confidential commercial information will continue to be redacted.
“This will be the first time that the FDA is proactively disclosing clinical summary reports from sponsors to the public,” he said.
“It can enable stakeholders to better address common challenges in the product development process, identify areas requiring additional postmarket research and generate the data necessary to meet the FDA’s gold standard for assuring safety and efficacy,” Gottlieb said Tuesday at a transparency symposium hosted by the Johns Hopkins Bloomberg School of Public Health.
In addition, the FDA hopes to use this initiative to make its clinical review processes more efficient, in the pursuit of team-based drug reviews in CDER.
By allowing the publication of a CSR, and linking that clinical data to the several, disparate memos produced by FDA staff in the course of a review, the agency will be able to consolidate the documents into a single memo, Gottlieb said — one that would outline the consensus or disagreements shared among reviewers.
Additionally, delivering a consolidated review opinion would lend itself to a more team-based approach, he said, describing pushes in CDER to move toward the more collaborative process employed in medical devices. And in the future, this transparency will be essential to establish new, trustworthy review pathways for technologies such as real-world data, wearables and advanced trial designs.
CDER plans to start with nine, hopefully novel NDAs, covering a variety of disease areas, and will begin reaching out to sponsors this month to gauge interest. In addition to a dedicated FDA webpage, the published CSRs will appear in the Drugs@FDA portal, alongside a drug’s approval information after it is granted.
The agency is also exploring its legal authority to publish complete response letters (CRLs) it believes have significant public health value.
Unfortunately, processing, redacting and publishing all individual CRLs — a goal long-sought by FDA transparency advocates and investors — would present too much of a challenge to the agency’s workload and would be “administratively burdensome,” Gottlieb said.
However, the relevant letters could contain important safety findings that could inform clinical practice and research, possibly by warning companies away from potentially futile or duplicative studies, or harmful drug-drug interactions.
Certain types of letters could include those that request additional clinical trials, or for products belonging to a class of already marketed drugs, Gottlieb speculated.
But Gottlieb doesn’t want this initiative to turn into a simple clearinghouse for investor information, or for inside looks into a company’s performance. “We have policies in place to make referrals to the SEC,” should any discrepancies exist, Gottlieb said. “This has to have some bottom-line value to patients.”
As to whether the FDA’s approach will become mandatory, Gottlieb said that will be worked out through the pilot. By comparison, the European Medicines Agency began its effort to publish clinical study reports and protocols from all new drug submissions, regardless of approval status, in October 2016 (CWWeekly, Oct. 24, 2016).
In addition, the FDA plans to increase the transparency and trackability of studies registered on ClinicalTrials.gov by adding each study’s unique, eight-digit NCT number to all agency communications about specific drugs and clinical trials, including product labeling and advisory committee meeting materials.
“Members of the patient, academic and scientific communities can then use this number to follow and track clinical research from a drug’s development throughout the regulatory process,” Gottlieb said.
Thomas Wicks, chief strategy officer for TrialScope, described including the NCT number as an interesting initiative that will bring clarity to the agency’s decisionmaking, but cautioned the number alone may not provide the full picture.
“Applications submitted to the FDA may also include clinical trials that were not required to be posted on ClinicalTrials.gov,” Wicks said. “An alternative might be to include the trial sponsors’ unique study ID for all studies submitted in an application, and then provide the NCT number where available.”
The NCT number may also allow for more accurate third-party assessments of disclosure compliance, he said.
The symposium, in which Gottlieb announced the program, was originally intended to focus on the publication of a new blueprint for transparency at the FDA, published as a special supplement to the Journal of Law, Medicine & Ethics. The supplement covers five key focus areas and offers several recommendations — some of which ended up being pre-empted by the agency’s announcement of the CSR and NCT initiatives.
Namely, the FDA should disclose more information about key milestones in the application process, such as clinical holds, Special Protocol Assessments and requests for pediatric studies, as well as offer more insight into its analysis, decisionmaking and generic review processes.
In addition, the blueprint for transparency authors urged the FDA to take a more active role in correcting misleading information in the marketplace, and to disclose data that would help the public better understand certain medical products.
The blueprint and accompanying articles are available here: http://aslme.org/media/downloadable/files/links/j/l/jlme-45-4-supp-full-download_1.pdf.