By Clinical Informatics News Staff

March 19, 2018 Today FDA posted the first Clinical Study Report (CSR) as part of its Clinical Data Summary Pilot, an effort to increase drug approval transparency announced by FDA Commissioner Scott Gottlieb in January. The first CSR comes from Janssen Biotech for the approval of Erleada (apalutamide), the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer, as well the first to use the clinical trial result, or endpoint, of metastasis-free survival.

A CSR is meant to be a company-generated summary including a portion of the drug file, related to a clinical trial, that contains detailed summaries of the bottom line information on the methods and results of a clinical trial. It should include the study report body, the protocol and amendments, and the statistical analysis plan for each of the participating product’s pivotal studies. A CSR is a scientific document addressing efficacy and safety, FDA said in the January announcement. “We expect that making a CSR publicly available after a drug’s approval will provide stakeholders with more information on the clinical evidence supporting a drug application and more transparency into the FDA’s decision-making process,” the agency wrote in the press release.

Drug approval information, including details about clinical trials, is usually discussed in FDA review, but often there is no complete description of the important efficacy trials, including the trial protocols, descriptions of any modifications made during the trial itself, and an explanation of all of the results, writes Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research in a blog post today. CSRs are meant to bridge that gap, Woodcock writes, and FDA plans to release portions of the CSRs for the pivotal studies that supported FDA approval. “The reports will be redacted by FDA to exclude confidential commercial information, trade secrets, and personal privacy information. FDA will not release patient-level data,” she writes. “Our goal is to share more directly complete summaries of the clinical trial information we have evaluated to determine whether a drug is safe and effective.”

Participation in the pilot program is voluntary for sponsors. FDA said that it wanted to focus the pilot program on products that are “novel” and “of scientific interest”, but sponsors are not compelled to take part.

Janssen’s approval package posted online is for the February 14 approval of ERLEADA (apalutamide). It includes FDA’s approval letters and approved labeling as well as FDA’s application review files including chemistry reviews and risk assessment reviews.

Janssen’s CSR contribution is broken into three parts: the Clinical Study Report (an 891-page PDF); the study protocol (a 311-page PDF); and the statistical analysis plan (68 pages).

Woodcock writes: “We posted the CSR of the pivotal study with the regular action package. It’s a novel drug and we believe the CSR information, together with the FDA review, label, and other supporting documents, will facilitate a deeper understanding of how we reached our approval decision.”

FDA plans to post the CSRs from up to 9 approved new drug applications of participating sponsors throughout the pilot period. “We hope that reviewing the CSRs will help the scientific community better understand the information FDA used to evaluate an application and make an approval decision,” Woodcock writes. “At the end of the pilot we plan to seek comment from the public through a Federal Register notice to hear first-hand how the information was accessed and used. We hope to hear from a wide variety of stakeholders!”