To increase the pace of rare disease drug approvals, the FDA should embrace nontraditional data, deploy new forms of analysis and be more open about its decisions, according to a new report from the National Academies of Sciences, Engineering, and Medicine.
Many rare conditions have small pools of patients, making it difficult to run the gold standard in drug development: a randomized, placebo-controlled study. Over time, the FDA has warmed up to data from other sources, such as natural history studies that record changes in a patient’s disease.
But the regulator needs to do more, according to the National Academies, which published the report on Thursday. That kind of thinking is part of a wider movement to spur more rare disease drugs and overhaul regulatory constructs, aspects of which have drawn pushback from FDA traditionalists.
The National Academies states that greater reliance on biological signals and analysis methods like Bayesian statistics — a set of mathematical rules for using new data to continuously update clinical trials — can bolster drug reviews.
“Several novel approaches for analyzing relevant data on drug safety and efficacy can make it possible to generate useful information for regulatory decision-making based on limited data,” the authors wrote. “Further acceptance of these methods on the part of regulatory agencies and sponsors would better enable the use of alternative and confirmatory data as well as data collected through traditional randomized clinical trials for rare diseases and conditions.”
Other types of information that can power studies include patient registries and electronic health records. To get the most out of the information, the FDA should publicly share more about why certain studies failed or succeeded, according to the report. Such examples could serve as a playbook for patients and drugmakers embarking on regulatory review.
“An understanding of the opportunities as well as the gaps and inadequacies in alternative and confirmatory data would help guide data collection strategies on the part of patients, caregivers, sponsors, and researchers, and ensure that the data gathered are both relevant and robust enough to support regulatory needs,” the federal organization wrote in the report.
There are potential legal challenges in such disclosures, but the National Academies states that the FDA could mirror its European regulatory counterpart — the EMA — in what’s shared. It’s but one way the two regulators could collaborate and harmonize their regulatory approaches.
The FDA gathers input from people living with rare diseases, but the report found that the agency could do more to collect natural history data, including by expanding a grant program run by the FDA’s Office of Orphan Products Development. Further, the agency should work with the EMA on services that help drug sponsors, investigators and patient groups find the best regulatory pathway for a new drug.
The report, sponsored by the Department of Health and Human Services, was undertaken after a request from Congress to review how rare drugs are evaluated. It was written by biostatisticians, professors, rare disease advocates, industry representatives and others.