From the Journals

Expedited review programs not shortening drug development



Drug development times are not showing any signs of decreasing even though application review times at the Food and Drug Administration are improving, new research has shown.

A stamp saying "FDA approved." Olivier Le Moal/Getty Images

“Despite the accumulation of expedited programs that have reduced FDA review times, overall clinical development times have not become shorter, although it is not possible to know what role these programs may have played in preventing an increase in development times,” Jonathan Darrow of Harvard Medical School, Boston, and colleagues wrote in a study published Jan. 14 in JAMA.

Researchers noted that FDA approval times declined from more than 3 years in 1983 to less than 1 year in 2017, although total time from the authorization of clinical testing to approval has remained steady across that period at about 8 years.

“The resistance of total development times to efforts to shorten them could be the result of more submissions of applications for rare disease drugs, which can sometimes pose trial recruitment challenges; a shifting emphasis to more challenging therapeutic categories, such as central nervous system disorder treatments; longer time horizons needed to establish efficacy when early intervention is important (e.g., cancer); or other factors,” wrote Mr. Darrow and colleagues.

The authors also note that the value of the expanded review toolbox the FDA now employs is “unclear” as “the number of new drug approvals has not increased substantially over the past three decades.” This observation does not count biologics or generic approvals.

Research revealed that the mean annual number of new drug approvals (including biologics) was 34 from 1990 to 1999, 25 from 2000 to 2009, and 41 from 2010 to 2018. In addition, while the number of new drug approvals has remained at or below 60 per year, the portion of drugs using at least one expedited review program increased over time, with more than 80% of the 59 new drugs approved in 2018 being subject to at least one expedited review program.

“Although the FDA has on average applied its expedited programs to drugs offering larger health gains, it is difficult to assess whether these programs have incentivized greater therapeutic innovation or merely allowed more appropriate agency prioritization,” noted Mr. Darrow and colleagues.

And while it may be hard to truly understand the impact of the many expedited review programs that have been introduced at the FDA, there is still room for improvement in the process.

In an editorial published in JAMA, Joshua Sharfstein, MD, of Johns Hopkins University, Baltimore, suggested four reforms the FDA could examine.

“First, Congress and the FDA should rationalize the various programs for expedited review,” he wrote, noting that companies are using the Orphan Drug Act to prevent competition. “Fixing the system requires, at a minimum, promoting meaningful competition for non-orphan uses.”

Second, he wrote, the FDA needs to strengthen oversight of postmarket safety though more diligence in the operation of its Risk Evaluation and Management Strategies (REMS) program.

“Third, Congress should recalibrate the programs that provide companies with special marketing protections,” added Dr. Sharfstein, former FDA principal deputy commissioner. “One place to look is pediatric exclusivity, which has been estimated to cost the health care system more than $6 for every $1 spent by a company on a pediatric trial.”

And finally, “Congress should use patent and pricing incentives to accelerate the generation of definitive evidence under accelerated approval,” citing proposals to limit pricing or market exclusivity until companies complete studies that assess clinically relevant endpoints.

“These changes would reflect an evolution, not a revolution, of the FDA’s approach to new drug approval,” Dr. Sharfstein said. “These reforms could also bring greater order and thoughtfulness to the regulation of important new therapies, while enhancing safety and creating greater capability to afford truly transformative medical products.”

SOURCE: Jonathan Darrow et al. JAMA 2020 Jan 14. doi: 10.1001/jama.2019.20288.

Next Article: