In 2012, the U.S. Food and Drug Administration (FDA) created Breakthrough Therapy designation. The Washington Post reports on a new study conducted by Yale School of Medicine researchers and published in the Journal of the American Medical Association that looks at the designation and the drugs that received it.
In 2012, the U.S. Food and Drug Administration (FDA) created Breakthrough Therapy designation. It was designed to expedite the development and review of drugs for serious conditions where preliminary clinical data suggested it might show substantial improvement over the drugs available. When a drug receives Breakthrough Therapy designation, it is eligible for Fast Track designation, which cuts several months out of the review process, “intensive guidance on an efficient drug development program, beginning as early as Phase I,” and an organizational commitment from senior managers in the agency.
The Washington Post reports on a new study conducted by Yale School of Medicine researchers and published in the Journal of the American Medical Association that looks at the designation and the drugs that received it.
The Post writes, “Giving these drugs ‘breakthrough’ status comes with a side benefit: an evocative name. The word ‘breakthrough’ suggests scientific triumphs and miracle cures to many people, including physicians. Companies and medical reports often tout the ‘breakthrough’ designation for experimental drugs that have not yet been proved effective.”
One of the key findings of the study was that as the drugs were accelerated through development, testing tended to be less rigorous. For example, The Post writes, “researchers conducting clinical trials take steps, such as randomly assigning patients to groups that receive the drug or a placebo, but no randomized trial was used for 40 percent of the approved drugs, the Yale School of Medicine study found. To avoid unconscious bias, patients and researchers are ‘blinded’ so they do not know who is getting the drug and who is not. Nearly half of the trials, in this case, did not include a placebo, according to the study. In half, patients or their physicians were aware of who was getting the drug and who was not.”
Many of the trials were shorter and smaller, which creates some uncertainty over the results. Joseph Ross, associate professor of medicine at Yale, told The Washington Post, “If we are going to making this trade-off to allow novel drugs to come to market on the basis of evidence that is generally accompanied by greater uncertainty, we must be committed as a clinical and scientific community to ensuring that high-quality, rigorous post-market trials are conducted within a reasonable period.”
Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, told The Post that the study’s authors didn’t take into account the strength of the evidence and has too much of an academic mindset in evaluating trial design. “This is probably the trajectory of drug development, as the science advances so much,” she said. “What has been traditional drug development is changing, and I know that’s causing discomfort, but we’re very confident the drugs out there are making tremendous benefit for patients.”
Woodcock generally has an excellent reputation, but came into tremendous controversy in 2016 over the approval of Sarepta Therapeutics’ Duchene muscular dystrophy (DMD) drug Exondys 51. There were at least three major opponents to approval within the FDA. Ronald Farkas, clinical team leader, left the agency just prior to approval. The agency’s acting chief scientist, Luciana Borio, and Ellis Unger, director of the office of drug evaluation, strongly opposed approval, arguing that Sarepta did not provide substantial evidence of the drug’s effectiveness.
But Woodcock pushed it through, overruling her staff. The final decision then went to Robert Califf, then FDA Commissioner. Evidence suggests Califf had similar reservations as Borio and Unger, but sided with Woodcock. There is some suggestion that Woodcock also took into consideration Sarepta’s financial position should the drug have been rejected.
Which also seems to underline that the FDA, under pressure from consumers to get drugs to market faster, might be developing methods that not all scientists think is good science. And it’s worth pointing out that the public, in general, simultaneously demands faster drug approvals while also wanting them to be completely safe and reliable, but have low prices. It’s tough to have it both ways.
