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# Breakthrough Therapy Evidence Misconceptions
- URL: https://www.fdaweb.com/breakthrough-therapy-evidence-misconceptions/
- Published: 2018-07-17T12:00:00.000Z
- Updated: 2026-09-15T00:19:42.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5141892

Doctors and patients appear to have misconceptions about the strength of evidence to support FDA breakthrough therapy designation, according to a study by Yale School of Medicine researchers. “The analysis revealed that therapies granted this designation often reach the point of regulatory approval with trial data that lacks randomization and controls, and often consists of small numbers of enrolled patients,” an online *MD Magazine* [post](https://www.mdmag.com/medical-news/misconceptions-exist-about-clinical-evidence-for-breakthrough-therapies-examination-suggests?ref=fdaweb.com) says. 

Lead researcher **Joseph Ross** said that when approvals are based on shorter and smaller clinical trials, there is greater uncertainty at the time of approval. He describes it as uncertainty over whether the effect observed in the single small trial will be observed in a larger population or replicated in another trial; uncertainty over whether the effect observed over the short term will persist over the longer term, or whether new risks, or even benefits, might be observed over the long term; and uncertainty over whether the effect observed on the outcomes used in the shorter trials — usually surrogate markers of disease, like a laboratory test — will be confirmed by eventual demonstration of safety and benefit based on clinical outcomes like improved mortality or improved symptoms.

“To me, if we are going to be 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 of time,” Ross told the magazine, “resolving some of this uncertainty and making sure that the drugs are associated with the benefit/safety profile that we expect based on the initial clinical studies, allowing clinicians and patients to make fully informed decisions about whether to use these novel treatments.”