Do Clinical Trials Work?
Illustration: Ruth Gwily

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In a long form article in the New York Times, Clifton Leaf (the author of “The Truth in Small Doses: Why We’re Losing the War on Cancer – and How to Win It”) asks a large and provocative question “Do Clinical Trials Work?”.
In this article Mr. Leaf dissects the challenges and limitations of traditional clinical trials to identify subsets of patients termed “responders” who break the curve and do well when others do not. This article highlights a hallmark double-blind- randomized-controlled study in glioblastoma multiforme (GBM) conducted by Dr. Mark Gilbert of MD Anderson Cancer Center. In the study 600 patients with GBM were randomly assigned to treatment with Avastin, a targeted therapy, or placebo. The results were surprising disappointing in that there was no difference in survival between the two groups.
By the book, this trial was nearly flawless in its design and conduct and as such reveals the Achilles heel of such trials, and suggest further directions. One such direction is further understanding why some patients respond when others do not. It highlights the need for “biomarkers” or predictive signs clinicians can detect to know who will respond to which drug. This principal of precision medicine not only to find these patients the treatment that will help them survive but also saves the non-responders from unnecessary toxic and costly therapy.
Some 3 years later researchers are still working harder to identify biomarkers for cancer responders. Some breakthrough discoveries have been made such as V600 mutations in melanoma which respond to BRAF inhibitors such as vemurafenib but many drugs and patients remain without such decisive markers.
Lastly, Mr. Leaf highlights the next generation of clinical trials like I-SPY (and now I-SPY-2) which aim to not only detect new biomarkers as well as those that aim to use them to target treatments.