So how does a new pacemaker go from the drawing board on the inventor's desk at a manufacturer to being ready for implant into the human body? It has to be approved by the Food & Drug Administration (FDA). For Class III devices, the process is called pre-market approval or PMA.

A PMA is actually an application that a company makes to the FDA asking for its new pacemaker or ICD (or other high-risk device) to be commercially cleared for release. In other words, the company wants to be able to start selling its products to the American healthcare consumer.

Part of the PMA process involves collecting data on the device. The FDA is mainly interested in safety (which is self explanatory) and efficacy (which is a fancy term that means the device does what it says it does). Among the information that the FDA wants to see in a PMA are data from scientific studies proving the device is safe and efficacious.

In order to get that data, the manufacturer conducts studies or arranges for third parties to conduct studies on its behalf. The system works on checks-and-balances, that is, the manufacturers run the studies but the FDA has to approve them.

If the company can show the FDA sufficient data backing up its product, the product is cleared for market release. At that point, the paperwork of the PMA, including most of the study data, product manuals, and some correspondence, is made public.

The JAMA paper is the first time (to my knowledge–I may be wrong here) that anyone has gone back and dug through the studies used to support PMAs.

No one is charging that the process for approving pacemakers is flawed. The PMA methodology of submitting scientific study data to support a product's claims seems to be working. The notion that manufacturers conduct the studies and the FDA approves them has not been called into question, either. The problem raised in the Dhruva article in JAMA is this: the scientific data used to support these PMAs is not as scientifically rigorous as it ought to be.

Are they right? The JAMA article makes a pretty compelling case, but we do not know exactly why manufacturers ran the studies the way they did and why the FDA accepted them. There may be more to the story than we are seeing.

Furthermore, there are a lot of pressures right now on the entire healthcare industry. Americans want better medical care at lower prices and faster turnaround times from the FDA. In demanding so much, it appears we have come up short in some areas. The problem may not be that studies were imperfect but that we need to make hard choices: do we want more stringent, scientifically sound cardiac device approvals and, if so, are we willing to take the time and pay the cost?

When a new pacemaker is evaluated by the FDA, the manufacturer is asked to submit what is loosely called "data," but that makes it seem like it's no big deal. Data come from a variety of sources, including all kinds of clinical and bench testing. Manufacturers are expected to conduct and fund these tests which the FDA monitors. The results of all of these studies (the "data") are then reviewed by the FDA and play a major role in whether or not the device is approved so that it can be sold in the U.S.

The FDA approval process (technically called "clearance" since the FDA really does not "approve" or put a stamp of approval on anything; it clears for market release) is important. The U.S. Supreme Court has found that if the FDA approves a pacemaker or other medical device for sale, manufacturers are somewhat protected in the event that patients sue the manufacturer over the device.

Two studies were recently released (just this week) that indicate the FDA is likely going to be increasing scrutiny on medical devices like pacemakers and stents. One study was conducted by the FDA itself in conjunction with Beth Israel Deaconess Medical Center in Boston. That study found that in the clinical trials submitted to the FDA for use in product approvals from the time 2000 to 2007, about 40% of the studies used for cardiac devices lacked "high-quality data" about the treatment or safety goals of the study.

Nobody so far has made any connection that lack of high-quality data has led to substandard devices being approved. However, the first study by the FDA itself showed that data it accepted was not sufficient.

A second study was conducted by researched at the University of California San Francisco was just published in the prestigious Journal of the American Medical Assoociation. Dr. Rita Redberg was one of the investigators and she was quoted in the New York Times as saying that many cardiac device trial lacked sufficient "scientific rigor." This study was more critical of the FDA but has come under fire itself.

One of the problems with the California study, according to the New York Times article, was that authors tried to make standards in drug testing applicable to testing pacemakers and other devices and clinical trials for devices have be conducted differently for many reasons.

While experts continue to wrangle out the issues, this definitely means that the approval process for pacemakers and defibrillators will be scrutinized even more intensively in 2010 and beyond. Chances are very good that some of the procedures in place right now will be changed. In fact, the FDA already started to review its device approval procedures back in 2007 and that will continue in the wake of these two studies.

Fallout from these studies will go beyond pacemakers to include other "medical devices," like implantable hips and knees, spinal implants, and implantable pumps.

What does all this mean? For patients, it means that future pacemakers may be subject to more scientifically sound study. That's good news. For manufacturers, it may mean more expensive studies or some lost time as the confusion gets sorted out. The best possible outcome of this finding is that the medical community will join forces with the FDA to achieve practical, workable, but scientifically sound ways to evaluate new pacemakers and other medical devices.