Evidence Shortcuts Not Good for Breakthroughs: Professor
Yale School of Medicine cardiologist Harlan Krumholz says that the solution to speeding drug breakthroughs should not be taking shortcuts in evidence generation, but rather leveraging emerging methods and networks that can potentially generate robust clinical evidence faster, cheaper, and better. “In a digital age, we can push for better evidence without sacrificing much time,” Krumholz says in an NPR radio commentary.
He particularly questions use of surrogate outcomes that often can be obtained faster and are used in place of a patient outcome that would require more people to be studied over a longer period.
“The problem is that the effect of a drug on a single marker of risk like cholesterol, or even a group of markers, may not ultimately translate into whether that drug produces a benefit for a given patient,” Krumholz writes. “When you actually do the study that measures patient outcomes, the results can, and have, surprised us…. Most drugs cause numerous changes at the same time, and we can only know the overall effect by focusing on patient outcomes.”
He cites a study he was involved in that looked at 157 studies published in prestigious medical journals over two decades in which the surrogate outcomes indicated the drug or intervention was favorable. Only 25% of the studies ever had a major follow-up study using patient outcomes, he said, and of those, almost half reversed the initial conclusion.
He reports that former FDA commissioner Robert Califf said that “one must question the simplistic approach to reducing standards for evidence across the board advocated by some, particularly when FDA’s existing accelerated approval programs show that it is possible to create working pathways for streamlined drug development while maintaining standards that ensure ample empirical evidence.”
One solution that appears to be working, Krumholz says, is the Patient-Centered Research Foundation, that is leveraging relationships with patients and health systems, as well as the digital transformation in health data to innovate knowledge generation. “In the end,” he concludes, “shortcuts will generally not serve us best. They may be necessary at times, but the knowledge that the evidence is not strong should push us to redouble our efforts to create the means to rapidly generate the evidence we need and the public deserves.”