Analysis: FDA's efforts to speed drug approval may have led to less rigorous clinical outcome requirements

An analysis published in JAMA suggests that efforts by the FDA to speed the development and approval of drugs may have led to a reduction in the amount of evidence available when the agency reviews an application and an increase in the use of more surrogate measures in clinical trials. However, the authors noted that regulatory programmes, including orphan drug, fast track and priority review designations, have "not clearly led to an increase in new drug approvals or to reduced total development times."

Lead author Jonathan Darrow said that the changes, which have seen the proportion of new drug approvals supported by at least two pivotal trials fall from 80.6% between 1995 and 1997 to 52.8% in 2015 to 2017, may lead to less confidence in the approval process and "an erosion of the 'FDA-approved' brand." Darrow remarked "patients and physicians need to focus on the evidence and not the fact of FDA approval. How big are the benefits, and how certain are we of the benefits?"

The analysis looked at the number and types of prescription drugs approved by the FDA from 1983 to 2018 and how the approval process and regulations changed during this period. Findings showed that the average annual number of new drug approvals, including biologics, was 34 from 1990 to 1999, decreasing to 25 from 2000 to 2009, and increasing to 41 from 2010 to 2018. The time that the FDA spent reviewing each new drug dropped during the same period, from 2.8 years in the late 1980s to about 7.6 months in 2018, Darrow added.

Meanwhile, the proportion of products approved with the Orphan Drug Act designation increased from 18% between 1984 and 1995 to 41% in 2008 to 2018. The analysis also found that the use of the accelerated approval, fast track and priority review programmes has increased over time, with 81% of new drugs benefiting from at least one of these in 2018.

Darrow noted that despite the introduction of the incentive programmes "there has been no strong upward trend in the number of drug approvals, which on average has remained about 30 new drugs approved per year since the 1980s." Darrow added that "we found there was a relatively stable period between when clinical trials began and when drugs were approved. We did not see a steep decline in the clinical development period."

However, the analysis also showed that over the same period, the median annual number of generic drugs approved rose from 284 between 1985 and 2012 to 588 from 2013 to 2018, leading to greater competition. The researchers concluded that "while retaining policies that encourage efficient review, Congress and other government officials should also consider the implications of less rigorous clinical outcome requirements and whether the current complex array of regulatory programmes should be simplified."

In response to the analysis, the FDA said "we are concerned that the researchers do not adequately consider the marked changes in the types of drugs and the patient populations targeted by development programmes that FDA now reviews, compared to those from just 10 or 20 years ago, nor the type, quality, and extent of data FDA routinely receives now compared to decades ago." The agency added that it believes that a failure to take those "marked changes" into account "can result in inaccurate conclusions."

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