FDA in Brief: FDA advances new guidelines for analysis of clinical trials evaluating safety of drug and biologic products

November 6, 2018

Media Inquiries

“By combining safety data from across different randomized controlled trials and using proper statistical methods to evaluate this pooled information, we can sometimes provide a more precise measure of the safety of a product. This is especially true when it comes to events that may be uncommon or not specifically addressed by the primary outcome measures of any single trial. Because these meta analyses can influence regulatory decisions, rigorous principles should be applied to these studies,” said FDA Commissioner Scott Gottlieb, M.D. “The draft guidance issued today will assist sponsors of drug and biological products in designing safety meta-analyses of randomized controlled trials using best practices and will describe the elements we intend to consider in our evaluation of meta-analyses for regulatory purposes. Our goal is to encourage more pooled studies to evaluate important safety events. Meta-analyses can be conducted in the pre-and post-market setting, and the recommendations in this draft guidance, when finalized, will apply to both. Sponsors apply the principles described in this draft guidance when planning and conducting a meta-analysis of randomized controlled trials to better assess the safety of a drug product.”

Today, the U.S. Food and Drug Administration is making available a draft guidance, Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products. When finalized, it will provide guidance to applicants submitting investigational new drug applications, new drug applications, biologics license applications, or supplemental applications on the appropriate use of prospective meta-analyses to assess a product risk. The term meta-analysis, as used in the draft guidance, refers to the combining of evidence from relevant studies using appropriate statistical methods to allow inference to be made to the population of interest. A key benefit of this approach is the aggregation of data to provide a higher statistical power and more robust point estimate than may be possible from the measure available from an individual study. In performing a meta-analysis, an investigator must make choices that can affect the results. These decisions include how an investigator searches for studies to include in the meta-analysis, selecting studies to be included based on prospective and objective criteria, dealing with incomplete data, analyzing the results and accounting for publication bias. This draft guidance focuses on meta-analyses that are developed for the purpose of evaluating safety data from randomized controlled trials.

Evaluating the safety of a regulated drug product is a fundamental responsibility of the FDA. Meta-analyses conducted to evaluate safety questions present a unique opportunity to detect and quantify the risk of a safety event and may help provide a more precise estimate of risk of uncommon serious adverse events by combining information from multiple trials. The draft guidance, when finalized, will also describe the factors that the FDA intends to consider when evaluating the strength of evidence provided by a meta-analysis.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.