Of the 46 drugs approved under breakthrough designation, 25 were for oncology. The FDA often allows for a lot of flexibility with trial sign in oncology due to the high unmet need.
The author mentions a lack of trials being double-blinded, having a placebo or active comparator and clinical outcome vs. surrogate marker.
All of this is quite common outside of the breakthrough drug designation. Nothing new here. Double-blinding a trial isn't as big a deal when what you are measuring is not impact by observer bias (tumor size). In addition, if you're measuring a surrogate marker (that is an accepted proxy for clinical outcomes), you don't need a comparator arm.
I don't think any of these findings should be all that surprising or concerning.
Why is this the case? Wouldn’t there be concerns that a study population might be different from the general population and thus require an internal control?
FDA acknowledges that FVIII levels can serve as a proxy for clinical outcome (reduced bleeding episodes) in hemophilia A.
Our understanding of what is "normal" in FVIII blood levels is such that a single arm, surrogate biomarker study is sufficient for approval.
That was the focus of the JAMA article.
Have you ever tried to measure something like this and analyze the data? There are so many ways to skew the results...
That's not even to mention basic stuff like handling the treated rats more carefully so they are less stressed, etc.