Smackdown! Why We Need More Head-to-Head Drug Trials

As part of its plan for health reform, the Obama administration has lavished attention on a particular type of medical research: “comparative effectiveness” studies, which pit different treatments directly against each other to see which one works better. (They’re like medical cage matches: in this corner there’s Prozac; in the opposing corner there’s Zoloft.) The stimulus package included $1.1 billion for this type of research, which is often the best guideline doctors have for deciding how to treat their patients. You might assume that most pharmaceutical studies would be designed this way, which is why a new paper in the Journal of the American Medical Association is so damning. It turns out that fewer than two thirds of studies fall into the comparative-effectiveness category, and the reason, according to the paper’s authors, is chicanery on the part of drug companies.

The authors of the paper—Michael Hochman of the Keck School of Medicine of the University of Southern California, and Danny McCormick of Harvard Medical School/Cambridge Health Alliance—looked at 328 clinical trials that were recently published in prestigious journals. Two thirds of the studies were “devoted to the development of new therapies,” says Hochman, “not helping doctors use existing therapies more effectively.” Only two of the 328 studies bothered to examine which drugs were both effective and cheap—even though part of the reason the White House loves comparative effectiveness is its potential to cut back on health-care costs by making medicine more efficient. Instead, most of the studies compared new, expensive drugs to either no treatment or a placebo.

The reason is pretty obvious when you consider the economic incentives at stake. Pharmaceutical companies pay for the vast majority of large clinical trials—they’re the only ones who can afford to—and unsurprisingly, they tend to focus on developing new, moneymaking treatments instead of assessing old ones. If they put one of their promising drugs up against something that’s already out there, they may get a nasty surprise. The most famous example is probably the CATIE study, a huge federally funded project that compared four new antipsychotics used to treat schizophrenia—Risperdal, Seroquel, Geodon, and Zyprexa—with a 50-year-old generic drug called perphenazine. The generic, it turned out, was just as effective (and 10 times cheaper) than the first three costly new drugs. Zyprexa was a little better than the generic, but it caused extreme weight gain. No drug company would fund such a study, given the risk of making its product look bad. So the responsibility falls to the government and nonprofits, say the authors of the new paper:

We found that 87% of the comparative effectiveness studies we analyzed were funded entirely or in part by non-commercial sources, such as nonprofit foundations or government institutions. In addition, 91% of studies comparing medications with non-pharmacologic therapies (such as surgery or lifestyle changes) received non-commercial funding, as did 94% of studies comparing different medication strategies (such as different blood sugar targets in patients with diabetes) and 90% of studies comparing the safety profiles of medications. Non-commercial sources funded 100% of studies comparing the cost-effectiveness of different treatments.
The $1.1 billion in stimulus money could change that calculus, but it’s “probably nowhere near enough,” says Hochman. It’s also a one-time, nonrenewable grant, and there’s no guarantee that a new administration would embrace comparative-effectiveness research as Obama has—especially given the way the research has been misconstrued as a harbinger of health-care rationing.

What’s really needed is either a regular, annual source of funding for comparative-effectiveness studies—something built into the budget for the National Institutes of Health—or a change in the way the Food and Drug Administration works. “It will often approve these novel therapies after companies have simply shown they’re better than a placebo,” says Hochman. “Maybe they should be a little more strict in saying, ‘You know, you have to do better than that.’” In the last couple of years, a growing number of influential policy wonks—including the Nobel laureate Joseph Stiglitz—have gotten behind the even more radical idea that the government should just take pharma out of the picture and establish an independent agency to run all clinical trials. But of course any attempt to tighten regulations is “likely to go down like a lead balloon with pharma executives." Here’s an idea: maybe we should just test the drugs on them?