Professor Hanu Tyagi of the University of Illinois Urbana-Champaign has co-written a paper that found when drugs are approved under the U.S. Food and Drug Administrations “Breakthrough Therapy Designation” (BTA) which speeds up approvals, lead to “a significantly higher number of serious adverse events after reaching the market.”
The co-author of the study is another Indian-origin scientist, Rachna Shah of the University of Minnesota.
The study was published by the Production and Operations Management journal.
Tyagi and Shah’s research also revealed that one specific monitoring mechanism can substantially offset this after-market risk, a January 12, 2026, news release from the University noted.
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“The Breakthrough Therapy Designation is something that’s not going away, because it has proven clinical benefits,” Tyagi is quoted saying in the press release. “It’s not without risk, but we can optimize it and make it safer, and that’s what we set out to do in this paper,” he added.
The expedited approval process was introduced in 2012, and has its critics and supporters from patients and the industry. The criticism was loudest during the COVID-19 vaccine approval process Tyagi notes.
“All of this highlights the speed-safety tightrope that the FDA must walk when approving these potential breakthrough treatments. Obviously, you want to make the most innovative drugs available to patients as quickly as possible while also upholding the medical oath of ‘Do no harm’,” he said.
Tyagi and Shah manually combed through FDA approvals for 300 drugs approved between 2012 and 2019.
“The quality of evidence that the FDA looks at to approve a drug was available to us, but it was buried deep within all this other information, so we had to do a lot of digging to tease out the information we needed,” Tyagi said.
The two researchers found that there was an average of 1,722 more serious adverse events per year when drugs were approved under the Breakthrough Therapy Designation than non-BTD drug.
They then went on to find a solution to this problem, in light of the fact that tbe BTD program was not going to be scrapped.
They found that when the “Risk Evaluation and Mitigation Strategies” tool was used, the number of adverse events was reduced to 875, almost half of the average.
“The findings suggest that safety measures such as REMS, which places the onus on firms and healthcare systems to manage risk, are far more effective than boxed warnings, which rely on prescribers and patients to change their behavior,” the researchers found.
“The term ‘breakthrough’ can create strong expectations of a benefit,” Tyagi said. “Warnings alone may not be enough when clinicians and patients think of a drug as transformative. Ultimately, structured safety programs, such as REMS, are much more effective,” he emphasized.
Tyagi and Shah recommend the FDA conduct REMs to ensure that all BTD approved drugs undergo that process to lower the risk of adverse events when they come to market.