The “New” Prostate Cancer InfoLink is by no means the first media outlet to have commented on the potential conflict between the idea of comparative effectiveness research (in large numbers of patients) and the the principles of personalized medicine. But we are pleased to see Dr. Francis Collins, the new director of the National Institutes of Health, weigh in in this topic.
According to Collins, “There is a potential collision here,” between the federal government’s very sensible desire to control health costs through comparative effectiveness research and the premise behind personalized medicine, in which medicines are carefully tailored to an individual’s genetic and biological makeup. Dendreon’s sipuleucel-T (Provenge), which The “New” Prostate Cancer InfoLink expects to see approved by the US Food and Drug Administration for treatment of hormone-refractory prostate cancer some time in the middle of next year, is a perfect case example of this collision.
Speaking on Monday at a forum coordinated by the American Association for the Advancement of Science, Collins stated that comparative effectiveness research, which has historically “lumped together” large numbers of people with a specific disorder to test the effectiveness of treatment A versus treatment B runs the risk of overlooking subsets of people for whom a drug might have a dramatic effect — either for good or for bad.
If we compare two treatments in studies that make the inherent assumption that everyone is roughly the same, “which we know they are not,” said Collins, then we are going to lose the chance to identify people who, for one reason or another, may respond particularly well — or particularly poorly — to treatment A or treatment B, for all sorts of possible reasons.
Some of the strongest advocates for comparative effectiveness research see these studies as a way to discover which of two treatments “works best” in large numbers of people. Collins has a different view.
“We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies,” Collins told the meeting, adding that these studies need to include genetic information that may allows researchers to identify genetic reasons why some people respond better than others to a particular form of treatment.
Dr. Margaret Hamburg, the equally new commissioner of the U.S. Food and Drug Administration, speaking at the same meeting, noted that clinical trials are commonly structured to determine whether a drug is safe and effective in a large group of patients, but these trials are not often structured to answer key questions about why some patients benefit while others do not. Hamburg also noted that studies that look at the genetic profile of patients and its role in how drugs work could strengthen a drug’s application, lending more scientific certainty about why a new drug works.
What is important here is that we are entering a phase in which efficacy and safety information in a large group of patient can not and should not be enough for the approval of important new drugs. We need to have at least some answers to the question why? In the recent past we have seen this sort of information evolve. We have some idea why trastuzumab (Herceptin) and lapatinib (Tykerb) are more effective in breast cancer patients with the HER2/neu gene. We have some idea why drugs like panitumumab (Vectibix) and cetuximab (Erbitux) are more effective in patients who have KRAS mutations. And we think we have a pretty clear idea why imatinib (Gleevec) works in in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).
Dendreon’s Provenge is highly likely to be the first truly personalized medicine to be approved by the FDA. We need to be able to understand why this new form of modified dendritic cell therapy works in some prostate cancer patients and not in others. It represents a paradigm for the future of the biologics industry and for cost-efficacy decision-making into the future. Who wants to have to pay for an expensive medicine that isn’t going to work in a specific patient — if we can just discover that before we give the patient the drug?!
Filed under: Drugs in development, Uncategorized Tagged: | comparative effectiveness, personalized medicine
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Perhaps this is the same kind of issue as faces screening?
It’s not enough to say that screening is or isn’t justified for the masses, but how to figure out which guys need to be screened. Or, since that seems unlikely to happen, given wide-population screening, how to figure out which guys that turn up positive need intervention.