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Bill Frist and Susan Dentzer: The right prescription for biomedical innovation

The Hill

Thursday, September 1, 2016

If you were a patient suffering from a disease, and you read about a treatment option for your illness, you would probably be eager to learn more. Imagine that the drug, device or other intervention had been on the market for several years, and studies showed that it was especially effective in some patients – but in others, it was useless, or even harmful. You’d want to know which group you were in, to make a fully informed decision about whether to use the drug or device, or not.

Welcome to the world of real-world evidence in health care – information derived from the practical or actual experience of patients. This world can look very different from the idealized settings of randomized, controlled clinical trials (RCTs) that help regulators determine whether a drug or device can be allowed onto the market.

RCTs are considered the “gold standard” of scientific evidence. By assigning patients randomly either to a “study arm” in which they get the new intervention, or a “control arm” in which they get a placebo or the standard treatment, researchers can isolate those results produced by the new drug. But these trials are typically filled with relatively small groups of carefully preselected patients, and usually are not reflective of the far broader population of people who may eventually use the new drug, or device, or the practices of the far larger circle of physicians who will prescribe it.

It can be startling how different the results appear when tens of thousands, or even millions, of patients start using drugs in the real world. RCTs often do not include patients of varied demographics, patients with multiple illnesses, or those taking a combination of medications. Over the past two decades, the Food and Drug Administration (FDA) has ordered several dozen drugs removed from the market when harmful or deadly side effects surfaced in these broader populations. Oftentimes, these reactions weren’t evident, or were barely hinted at, in the earlier clinical trials.

Fortunately, real-world evidence can emerge on the positive side as well. Tysabri, a drug for multiple sclerosis, was taken off the market in 2005 due to serious adverse events in some patients — but was then re-introduced when real-world studies showed that the benefits to most patients outweighed the risks. In today’s world of “precision medicine,” when treatments will be increasingly customized to specific patient characteristics and preferences, capturing similar findings from real-world use will be more important than ever.