Analysis reveals the truth about FDA's expedited approval processes and patient access

University of Illinois Chicago researchers studied 135 products that received U.S. Food and Drug Administration approval through orphan drug and expedited approval program designations. They found that it took nearly three years for these drugs and biologics to be incorporated into the clinical guidelines doctors use to help determine treatment for their patients.

The findings suggest that despite efforts to speed up the availability of these products, which are commonly expedited because of their potential to treat rare, serious or life-threatening conditions, the most direct guidance on patient access to the treatments is still delayed.

This analysis provides evidence that expedited approval processes are only the first step to bring needed treatment options to patients who have rare diseases or have exhausted other options. FDA approval is not the end of the story when it comes to patient access. We need to do a much better job of planning ahead so that clinicians are aware of and have confidence in administering newly available treatments much earlier."

Ryan Rodriguez, study corresponding author, clinical associate professor of pharmacy practice, UIC College of Pharmacy

The findings are reported in the medical journal BMJ Open.

For their analysis, Rodriguez and his colleagues identified products with one or more expedited designations -; priority review, accelerated approval, breakthrough therapy and/or fast track -; approved from January 1992 to February 2020 using publicly available data from FDA databases. They excluded cancer-related products from their analysis. Using PubMed and guideline databases, the researchers looked for published guidance documents influencing U.S. practice that included each product.

Among the 135 non-oncological orphan products identified, the researchers found that 97% were designated priority review, 50% fast-track, 16% breakthrough therapy, and 14% accelerated approval. More than half (60%) received two or more designations.

While about 74% of products were included in a guidance document, the median time to inclusion was 2.87 years. Similarly, of the products not found in a guidance document, more than half (54%) had received "recent" approval, in 2018 or later.

The researchers found that products were more likely to be included in a guidance document if they had received two or more designations. Products were also more likely to be included in guidelines if they received fast-track designation compared to priority review designation.

The authors say these findings are particularly important considering that the annual number of orphan drug designations assigned by the FDA has increased over the last two decades. According to one study from 2018, the number has increased from roughly 60 in 2002 to 427 in 2017. The predicted mean annual growth rate for orphan products (11%) is more than double the predicted rate for non-orphan products (5%).

"It's very likely that use of these designations will continue and even increase over the coming years, so it's critical that we build parallel processes to reduce the access delays we may see today for this growing category of products," Rodriguez said.

The authors suggest that the three-year delay may be attributed, in part, to the resource investment required for rigorous guideline development -; a process they say can be streamlined. They also suggest that the delay from approval to guidance may be related to the limited scientific evidence available at the time of product approval but are quick to point out that this is surmountable.

"Recommendations for use of orphan drugs should be supported by robust evidence; such evidence may not be immediately available, and professional societies may deem full guidance production or revision unjustified. Nonetheless, statements regarding the limited evidence and recommendations for restricted, yet appropriate, use can still be useful to policymakers in justifying coverage decisions," according to Rodriguez and his colleagues.

In conclusion, the authors write, "More timely development of guidance documents after approval of these products could encourage more rapid and appropriate uptake into practice and could be initiated when FDA approval is anticipated."

Rodriguez said, "This data shows us there is a problem and that consequences fall on the patient -; I hope researchers, regulators, industry and medical societies alike read our study and see that there is a great opportunity to get more treatment options to patients simply by considering actions that encourage appropriate inclusion of orphan and expedited program products in relevant guidelines."