The Cancer Burden

Can Platform Trials Speed Cancer Drug Development?

Cooperation among drugmakers is needed to make these group-effort trials work

Ed Silverman

Earlier this year, the FDA required drugmakers to add information on product labeling about the possible increased risk of heart attacks and strokes associated with low testosterone treatments. The move came after sustained controversy over cardiovascular safety and allegations of inappropriate marketing of the widely prescribed drugs.

Testosterone treatments have, at times, been promoted to help reverse aging, but safety concerns prompted heated debate amid dueling medical studies that yielded conflicting results. However, the agency is of the opinion that the medications have not been shown to help men with low testosterone levels reverse the aging process.

But to sort out the uncertainty, the FDA later asked drugmakers to jointly conduct a controlled clinical trial in a bid to speed needed research because there have not been any “randomized, controlled trials …appropriately designed to evaluate cardiovascular outcomes with testosterone use,” FDA staffers wrote in an essay in the Aug. 20, 2015, issue of the New England Journal of Medicine.

By encouraging the various drugmakers to “work together on a single trial,” the agency is pushing an approach that is of increasing interest — the platform trial. Rather than having, say, four drugmakers run four separate trials, with each testing their products against a placebo, one common trial involving randomized patients can presumably simplify the process for comparative testing.

As a group of researchers recently noted in the JAMA, platform trials are, essentially, an extension of adaptive trials. “An adaptive trial allows pre-specified changes in key trial characteristics … in response to information accumulating during the trial. However, most adaptive trials focus on evaluating a single treatment in a single population,” they wrote.

Why is this seen as advantageous? They explained that “platform trials have the potential to accelerate efforts to identify effective treatments, especially combination treatments and treatments tailored to particular subgroups of patients, for challenging diseases.” In short, the process holds the promise of getting the best treatment to patients faster than the current system relying on conventional trials.

There is another reason. Such trials “can reduce the cost of conducting trials by reducing the number of patients as well as length of the study,” says Jagpreet Chhatwal, a senior scientist at the Institute for Technology Assessment at Massachusetts General Hospital and an assistant professor at Harvard Medical School. “And I think these trials are likely to be used more frequently in the future.”

Of course, there are issues with more widespread adoption. A key factor is competition among drugmakers, which are understandably reluctant to cede too much control, according to Jason Connor, a co-author of the JAMA essay who is an assistant professor at the University of Central Florida College of Medicine and a director at Berry Consultants, which specializes in adaptive clinical trial design.

“We have to get drug companies to collaborate with one another,” he says. “In these situations, they give up control over the trial and what investigators do, and the criteria for exclusion and inclusion for patients. Companies may want to micromanage things [in order to] make their drugs look good. But in these cases, a third party controls the trial and then these companies simply hop on with their drug.” Any number of entities might serve as those third parties, including government agencies and public–private partnerships of various kinds. In some cases, patient advocacy groups might be involved.

The concept is starting to catch on. One prominent example is the I-SPY 2 trial, which is being run by a public-private partnership that includes the National Institutes of Health and the FDA to test new treatments for women with high risk, fast-growing breast cancers. Up to a dozen medicines from different companies are being tested. The trial is expected to cost $27 million over five years.

There is a caveat, though. “Reducing development costs does not reduce drug prices,” warns Roger Longman, who heads Real Endpoints, a research company that tracks payment issues. So even if platform trials are more widely adopted, payers should not assume that they will see lower prices that would help them with their budgets.

Ed Silverman founded the Pharmalot blog and has covered the pharmaceutical industry for 20 years.