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COTA Collaboration: Helping FDA Figure Out What's Possible and What's Not in Embrace of Real-World Evidence

COTA Collaboration: Helping FDA Figure Out What's Possible and What's Not in Embrace of Real-World Evidence

A Conversation With Chief Medical Officer Andrew Norden, MD, MPH, MBA

When it comes to generating evidence that leads to a drug approval, the randomized controlled trial (RCT) is the gold standard. The first published trial appeared in the literature more than 70 years ago,1 and over the past 30 years, the scientific community has developed the principles of evidence-based medicine,2 in which RCT results inform clinical practice guidelines.



Norden: There’s a lot of discussion about this issue.… What should the end points in a real-world evidence-based analysis be? The truth is, the field is new enough that I don’t think there’s a definitive answer to this question. COTA and a number of other entities that work on real-world data and evidence generation from that data have been engaged collaboratively in a project put together by Friends of Cancer Research.


We published a white paper online last year9 in which we begin to address this question: Which end points that are derived from real-world data are predictive of end points that are derived from clinical trials? I think that are used for end point determination are not well standardized, and there is some controversy about the extent to which these end points are predictive of overall survival or other clinical trial-based end points.


One thing that was heartening to see with the Friends of Cancer Research, is that 6 or 7 partners generated real-world evidence end points in different ways, but we actually came to the same answers. And we found there was a very high correlation between progression-free survival assessed using real-world data and overall survival, which is, of course, a critically important end point in cancer research. So, there’s encouraging preliminary evidence that suggests that real world–based end points like progression-free survival, time to treatment progression, time to treatment discontinuation… are correlated with clinical trials–based end points and with overall survival.


But I think we need more time to become confident about the situations where real-world end points may serve as adequate surrogates and where we must rely on clinical trials to get bias-free results.



1. Streptomycin treatment of pulmonary tuberculosis. Br Med J. 1948;2(4582):769-782.
2. Strauss SE, Sackett DL. Using research findings in clinical practice. BMJ. 1998;317(7154):339-342. doi: 10.1136/bmj.317.7154.339.


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