Influential study slams FDA regulation of medical device industry

MINNEAPOLIS, MINNESOTA–2009 has been rough on medical device makers. From proposed multibillion dollar taxes to pay for health care reform to a recession that has weakened demand for pacemakers and stents, the industry has had a lot to gripe about.

But one issue that particularly bothers big and small device companies alike is a general perception that the Food and Drug Administration is embracing a more populist approach to regulation, making it harder for manufacturers like Medtronic Inc. to win approval for life-saving technologies.

Unnecessary tests! Endless questions! Expensive delays!  Egged on by a Democratic president and risk-averse Congress, the FDA, filled with young, idealistic brainiacs with no respect for precedent, is snuffing out innovation, the industry warns.

As it turns out, the precedent has been far from perfect. A major study published in the most recent issue of Journal of the American Medical Association or JAMA, criticized the FDA for using shoddy, incomplete research to approve high-risk heart devices.

“Premarket approval of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias,” according to the study, authored by three experts based at the University of California at San Francisco.

The study is important for two reasons: For the first time, researchers examined the strength of evidence behind premarket approvals (PMAs), the hardest type of FDA blessing to win. Secondly, the results were published by the AMA, the country’s top medical group, not some fire-breathing Congressman looking to score cheap political points at the expense of Corporate America.

The study makes a lot of eyebrow-raising claims about the scientific studies underlying PMAs. But they generally break down into three areas.

Lack of rigor In a perfect world, companies would perform multiple, randomized double-blind trials to limit bias and ensure scientific integrity. But after examining 123 studies and 79 PMAs from January 2000 to December 2007, the study found that only 27 percent and 14 percent of the studies were randomized OR blinded respectively, never mind both. In addition, 58 percent of the PMAs were backed by only one study.

More shockingly, in more than one-third of the PMAs, the authors weren’t able to determine if a single study was conducted in the United States. “Study populations should be representative of patient populations in which these devices will be used,” the study says. “The FDA guidelines stating that data from outside of the U.S.  be applicable to the U.S. population and U.S. medical pratices’ are increasingly important as more trials are conducted internationally.”

Incomplete or inconsistent information If you conduct a clinical trial, you have to state what you are trying to prove or measure.  But 14 percent of the studies didn’t contain any primary end points. Of 213 primary end points, 15 percent were “noninterpretable,” mostly because “no target goal of device performance was stated.”

The JAMA study also noted several discrepancies between the number of patients enrolled and those analyzed. Several studies also lacked basic demographic information, such as age, sex and race.

Questionable methods The JAMA report criticized studies for twisting information to more easily support their objectives. For instance, the study noted a high use of “surrogate end points.” Surrogates are less clinically meaningful outcomes that measure how a patient feels, functions, or survives.

“Surrogates may not be reliable predictors of actual patient benefit,” the JAMA study says. “Although surrogate outcomes are attractive because they decrease the time and costs required to do a study, they must be linked to a clinically meaningful end point to be valid.”

Predictably, FDA officials criticized the JAMA study of being overly harsh, noting the researchers were applying standards normally associated with drugs to medical devices. Ironically, the medical device industry has said the same thing of the FDA.

You can nitpick the JAMA study piece-by-piece, but the overall thrust is pretty damning. Remember folks, we’re talking about PMAs, the creme de la creme of federal device regulation. PMAs are no walk in the park, nor should they be. Studies without objectives? Studies with only one trial? Studies done completely outside of the U.S.? Really?

“The PMA is the most rigorous device-approval process and strict standards for cardiovascular devices are expected given their far-reaching effects, permanent nature and use in critically ill patients,” the JAMA study said. “The importance of the FDA seal cannot be overstated. Many manufacturers immediately encourage widespread use of their devices based on FDA approval.”

The FDA only exists if the public trusts the decisions it makes. Consider the recent U.S. Supreme Court decision that prevents patients from suing companies for product liability if the FDA approved the device. If the FDA doesn’t do its  job, where does that leave patients?

The study goes on to make one more important point. A critical piece of health care reform is comparative effectiveness research, (CER) which allows the government to only pay for things that actually work. Sounds fairly intuitive but experts say we’re paying top dollar for ineffective treatments. Companies like Medtronic say they support CER but worry about who will develop these standards.

But “at some point, you have to get started,” one med-tech executive said at the recent LifeScience Alley conference.

How about getting started with the FDA?