Commentary: Increased Transparency Needed at the FDA

A group of top investigators have created a Blueprint for Transparency at the FDA to help further the development of safe and efficacious new products.

Information regarding the regulatory process of medical products tends to stay within the FDA because of regulations and policies that, for many years, broadly defined what was considered confidential.

In 2010, the agency created a Transparency Task Force to determine whether the regulations and policies should be modernized.

“Since 2010, the ground has tilted further in favor of transparency at the FDA,” the authors wrote. “Patient advocates, academic researchers, and legislators have expressed frustration about policies that prevent understanding of the pipeline for new drugs. In place of the FDA, third parties are aggregating disclosures by medical product companies to investors and selling them as information services.”

With the recent change in the presidential administration, the investigators believed it was the opportune time to reexamine the FDA’s policies and practices to support public transparency. The group developed a Blueprint for Transparency at FDA.

“FDA is more than agency that makes regulatory decisions,” said Joshua Sharfstein, MD, former FDA principal deputy commissioner, who organized the project. “It is also a repository for scientific analysis and data that, if more widely available, would improve understanding of existing therapies, the pharmaceutical pipeline and opportunities for innovative product development.”

The authors noted that some of the potential benefits of increased transparency in the regulatory process include:

· Higher quality and greater quantity to inform medical education and guide clinical practice.

· Faster innovation, as researchers, industry, and investors can more easily and thoroughly understand successes and failures.

· An improvement in FDA processes, with greater ability to study how companies and the FDA interact.

· Increased public understanding and confidence in the activities of the agency.

The blueprint has 5 focus areas that, in total, contain 18 recommendations. Per the blueprint, the 5 focus areas the FDA should improve on are as follows:

1. Disclose more information about key milestones in the application process.

a. FDA should disclose basic information about investigational notices, the filing of marketing applications and the existence of clinical holds.

b. Disclosures of investigational notices and marketing applications should include the class of medication and mechanism of action, if known.

c. Numbers for all trials conducted or relied upon as pivotal for marketing approval should be included in disclosures of investigational notices and new applications for ClinicalTrials.gov.

d. When entering a Special Protocol Assessment, the FDA should release the text relevant to safety and efficacy after the study is completed.

e. After a clinical hold related to safety or efficacy has been issued or release, the FDA should release a summary of the reasons within 10 days.

f. The FDA should disclose whether a marketing application has been designated for an expedited development or review program and, if so, provide a scientific basis for that designation.

g. Disclose written requests for pediatric studies at the time requests are made, as well as other documents indicating agreement on changes to the initial request.

2. Disclose more of the agency’s own analysis and decision-making.

a. When products are not approved, the agency should disclose communications to companies.

b. The agency’s clinical and statistical review of products not approved, or for which the marketing applications are abandoned or withdrawn should be made public, and should issue guidance on the definition of abandonment.

c. Pooled data sets should be masked and de-identified as appropriate, and the analyses of these data sets should be made available to the medical and research community through clinical data repositories.

3. Disclose more about the application and review process for generic drugs and biosimilars.

a. Disclose basic information about the filling of generic drug applications.

b. Disclose the portions of Complete Response Letters to generic drug manufacturers that relate to bioequivalence.

c. Disclose the filing of abbreviated biologics licensing applications, including the name of the sponsor, the reference biologic product, and whether the application is for biosimilarity or interchangeability.

d. Portions of a Complete Response Letter should be disclosed with respect to an abbreviated biologics licensing application that relate to the biosimilarity to, or interchangeability with, the reference biologic product.

4. Correct misleading information in the market.

a. The agency should correct misleading information where there is the potential for substantial confusion about the safety or efficacy of a medical product for both approved and unapproved uses.

5. Disclose data from scientific studies to enhance understanding of medical products.

a. Disclose Clinical Study reports submitted to the FDA in support of a marketing application. To the extent possible, the FDA should harmonize standards on CSR release with the European Medicines Agency.

b. Release final reports that fulfill Postmarketing Requirements and Postmarketing Commitments, at the time the FDA considers the sponsor’s obligation to conduct a study to be fulfilled.

c. In instances of clinical trial data—–including patient-level data––that is not available to independent investigators through industry-sponsored websites, then the FDA should make data available through clinical data repositories, with policies on deidentification to protect patient privacy.

“Following the path set out by this Blueprint for Transparency will take energy and persistence, but it is well worth the effort,” the authors wrote. “Greater transparency at FDA will lead to safer and more effective medical products, with lasting benefits for clinical care, scientific progress, and public health.