Clinical trial safety population size: analysis of drug approvals for rare and common indications by FDA Center for Drug Evaluation and Research

Abstract

Background: Limited prevalence diseases present challenges for drug development and for the amount of safety information available to prescribers and patients when a drug is approved for marketing.

Objective: To inform the issue of safety populations for rare disease drug clinical development programs, we analyzed the relationship between pre-marketing trial safety population size and estimated US disease prevalence as compared to common disease drugs.

Methods: We based the analysis on therapeutic new molecular entity drug and original biological product marketing applications approved by FDA’s Center for Drug Evaluation and Research between 1 January 2010 and 19 June 2013.

Results: While drugs for rare diseases have small trial safety population sizes relative to common disease drugs, a larger proportion of patients are studied relative to the number of US patients with the approved indication. We did not find an excess of safety labeling changes or other post-marketing safety actions for the rare disease drugs over the observation period of our study.

Conclusions: The overall assessment of benefit-risk within the context of disease characteristics, patient population and drug effects determines whether a safety database is adequate to support marketing approval. We encourage frequent communication between rare disease drug developers and FDA to facilitate efficient clinical programs that meet marketing approval standards, and maximal utilization of all appropriate strategies to accrue post-market safety data and enhance safety of use.

Keywords::

• clinical trial
• drug approval
• patient safety
• prevalence
• rare diseases

Acknowledgments

We are grateful to Robert Ball, Mwango Kashoki and Sandra Kweder for critical reading and comment. All are employed by the FDA and have not received compensation for this work.