In the Age of Personalized Medicine and Right to Try, Have Big Clinical Trials Become Obsolete?
​​​[Posted on: Thursday, May 31, 2018]

An opinion piece in the Wall Street Journal this week raises an interesting question: is the era of large Phase 3 clinical trials coming to an end. It is a reasonable argument that when treatments can be customized to patients via personalized therapies, and the benefit of a new drug can be supported by real world patient experience from compassionate use, why do we still need large Phase 3 trials to get FDA approval. And that is true that most new therapies with significant benefit do not require large Phase 3 trials any more. There are many mechanisms whereby the market approval can be expedited. The sample size for a clinical trial is based on the expected difference between control and active groups. In personalized therapy, the difference between control and active is much larger due to targeting the treatment to only those patients with high likelihood of benefit, hence the trial size is generally smaller. If the improvement in the treated group is significantly high, the new drug may be designated as a Breakthrough therapy and get approved based on as few as one small clinical trial. As clinical trials get smarter with adaptive designs and innovative strategies, it is expected that we will need few large traditional Phase 3 clinical trials for market approval. Most likely, such large trials will be limited to cases where either the drug is a me-too drug in a crowded field, the different between active and control is small, or the drug is expected to be used by such a large group of patients that personalization is not feasible. It is true that a decade later, large Phase 3 trials may be lot fewer than they currently are.