Pacemakers treat rhythm disorders and rhythm disorders are statistically more likely to occur in older people. I have read that the average age of a pacemaker patient in the U.S. is 73. True, kids get pacemakers, even babies, but most people who need pacemakers are older individuals.

There are cases on record where a pacemaker has been implanted for the first time in a centenarian, and replacements in people over 100 are not unheard of.

But when a person is 80 or 90 years old, does a pacemaker really help? In this particular study of 157 people in the 80-90 age bracket who received a pacemaker to help manage their heart condition, a full 75% found that the pacemaker improved their symptoms.

That's pretty amazing, considering that about half of these patients (45%) were in nursing homes to begin with. While the article did not contain specifics about this, the nursing home patients probably had other conditions and symptoms.

If three-quarters of these elderly patients benefited from pacing, it is likely that younger, fitter, stronger patients would have similar if not better results.

The article is entitled Survival and functional independence after implantation of a permanent pacemaker in octogenarians and nonagenarians: a population based study and it appeared in 1996 in the Annals of Internal Medicine.

Physicians in Heidelberg, Germany, have been studying severe clinical depression and believe that it is related to the habenula, a tiny nerve network within the brain. It appears that when the habenula becomes overactive, the person gets depressed; likewise, when the habenula calms down, the depression lifts.

Credit for this theory goes to Dr. Alexander Sartorius who works at the Brookhaven National Laboratories in New York. The next challenge was how to take that insight and translate it into a medical therapy.

A pacemaker-like device was developed. The pulse generator was implanted in the chest, like a regular cardiac pacemaker, and leads plugged into the pulse generator. But these leads did not go to the heart. Instead, the leads went upward into the brain so that the electrodes could stimulate brain tissue.

Dr. Karl Kiening of Heidelberg University Hospital performed the delicate surgery in the first-ever implant in January 2010 to treat depression. Such "brain pacemakers" already exist to treat Parkinson's Disease and other disorders.

The electrodes send out low-voltage pulses to stimulate certain areas of the brain, much as a heart pacemaker sends out low-voltage pulses to stimulate cardiac tissue.

The patient who underwent the first implant for depression had good results. In fact, when her pacemaker was turned off because she had to undergo a different, unrelated medical procedure, her depression returned but was banished as soon as her brain pacemaker was reactivated.

The medical name for this technique is "deep brain stimulation." While results are good and the technology for this kind of device exists, the biggest obstacle is that the surgery requires pinpoint accuracy to get the electrodes in the proper position.. Furthermore, the habenula are located in the center of the brain, making surgical access particular challenging.

While it may seem counterintuitive, stimulating the habenula appears to have a calming effect on these little nerves.

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?

But you don't have to. We can give you the Cliff's Notes version.

The first thing you need to understand is how a new pacemaker or defibrillator gets approved by the FDA so that it can be sold commercially. That's so involved it appears in another article here called "The PMA Approval Process." For now, let's just say that there is a rather lengthy involved procedure before the FDA will clear a new cardiac device for market release.

Part of that approval process involves studies which are typically conducted by the device manufacturer. The FDA uses the data or results from those studies when it makes a decision on whether the device is safe and effective.

The Dhruva article went back and pulled these old studies. The authors looked at studies in support of new cardiovascular devices (pacemakers, ICDs, stents) that were conducted from 2000 to 2007 and it "studied the studies."

Scientific articles are very precise, so let's get precise. The Dhruva team looked at studies involving a total of 78 different cardiac devices. That amounted to a total of 123 different studies. What they wanted to do was find out if these studies were scientifically sound. Were they well designed? Were they clear? Did they really measure what they set out to measure?

Most scientific studies used for medical evidence rely on certain well-known scientific principles to help make the studies sound. One of them is called "randomization." A randomized study basically puts people into the study or into different groups in the study "at random." It has been observed that when a study is not randomized, the investigators or people doing the study can sometimes consciously or subconsciously steer certain patients into or out of the study or into or out of specific groups. When that happens, it is called "selection bias."

For example, if you are testing a high-blood pressure medicine and you only test it on very young, fit people, you'll probably get better results than if you test it on old people with a bunch of health problems. Randomization attempts to filter out selection bias.

Most of the time, randomization is done with computer support. Patients are evaluated to see if they meet study criteria (they must meet certain criteria) and then to see if they have exclusion criteria (things that would automatically rule them out) and then they should be entered into the study or into study groups at random.

Another type of scientific system used in studies is the "control." A control group is a group of patients who basically undergoes everything in the study, except they do not get the treatment–they get either no treatment or whatever the current state-of-the-art treatment is. For instance, if you're testing a new blood pressure medication on patients who have high blood pressure, the "treatment group" would get the new medication and the "control group" would get the old medication or whatever is currently considered the state-of-the-art.

The idea is that the control group shows how people would do if they were treated the way we treat patients today. It gives you a benchmark against which you can measure the treatment group.

When patients enter a controlled study, they are assigned to either be in the treatment group or the control group. (Okay, some studies are more complex and have multiple groups, but let's use a simple example here.) The patient should be assigned to the group at random. However, it has been observed that sometimes bias enters the study when doctors and patients know what group they're in. For instance, if a patient knows he is in the treatment group, he may respond better or imagine he's doing better than he really is because he knows he's getting the "improved new medicine." Likewise, doctors doing the study may rate patients better or worse depending on what they think of the treatment. This is another form of bias.

One way to cut that bias out–and make the study more rigorous and scientifically sound–is to "blind" the study. In some studies, the patients are blinded but the doctors aren't. This means the patient does not know if he is in the treatment or control group–he has no clue. But the doctors and other healthcare professionals do. That is a single-blind study.

Sometimes a study can be designed so that neither patients nor those who care for them (doctors, nurses, and so on) know who is in which group. That's a double-blind study. Double-blind studies are considered the most scientifically sound because it reduces bias to the maximum extent possible.

Last but not least, scientific studies have "endpoints." An endpoint is a goal at which you measure the result. For instance, if you test that high blood pressure pill, the endpoint of your study might be blood pressure readings that are at or below 120/80. An endpoint should be something measurable and objective. The idea is that if the patient achieves the endpoint, it's counted; if the patient does not achieve the endpoint, it's counted. At the end of the study, you have an objective result.

In other words, the endpoints of a study cannot be things like "the patient felt better" or "the patient looked better" or "the treatment worked." It has to be measurable and specific.

Now that you know all of this, we're ready to see what the Dhruva team found out and published in JAMA.

1. Most of the studies used to support these cardiovascular devices were not randomized. (In fact, only 27% were randomized, less than one third).

2. Only 14% of these studies were blinded (we're talking any kind of blinding, that is single-blind).

3. About 52% of the studies used a control, but some of these controls were not as rigorous as they could have been.

4. Most of the endpoints (88%) used what is called a "surrogate measure." That means they had an endpoint and it was something that could be measured, but what they were measuring was something that stood in for something else. For instance, in some ICD studies, the study endpoint was that the lead could be implanted successfully. That was a surrogate for proper lead function since successful implant is associated with lead success. Surrogate measures are actually quite common in scientific studies and they are practical, but they have to be used carefully since not all surrogates work well.

5. About three-quarters of the studies (78%) had some numerical discrepancies, that is, the number of patients enrolled in the study did not work out to match the amount of data collected. It often happens that some people enroll in a study and fail to complete it for any number of reasons (their choice, a move, other health problems). However, studies should account for all patients, even if not everyone completes the study.

That is what the JAMA paper found and it is pretty alarming. But let's point out what the JAMA authors did not say.

The paper did not say that the FDA approved any cardiovascular devices that were dangerous. The paper made no links between shortfalls in studies and devices of questionable quality being approved. While the paper does not rule that out, you can't jump to conclusions. The paper mainly calls the FDA and the medical community to action to help improve how cardiovascular devices are approved.

Second, the paper makes a comparison between drug studies and device studies. Drugs are approved in a similar fashion, through testing, but drug tests are typically randomized, controlled, double-blinded study. To be fair, though, device testing is a different animal. You can test a drug by giving one group of people an active pill and the control group a sugar pill. But how do you test a pacemaker? Do you implant pacemakers in one group but not in another? (And wouldn't the people who did not get the pacemaker realize they were the control group?) And how would you blind physicians treating these patients … if a physician had to program a pacemaker, he would know who had a pacemaker!

While I am being overly simplistic, it is a fact that device studies pose a bit more of a challenge than drug studies in terms of meeting randomization, controls, and blinding goals. Drug studies may be the "gold standard," but device studies cannot necessarily match the drug study methodologies.

It is natural to read an article like this and think: whose fault is this? The article does not really say and I cannot say, either, but I can state that manufacturers (who conduct the studies) and the FDA (who allow and accept the studies) must both share some of the blame.

However, the FDA side of the story is not that simple. Right now, the FDA and all organizations involved in health care are facing unprecedented scrutiny and cost containment issues at the same time that the public wants higher standards but faster turnaround times. Not all of these things are simultaneously possible.

Meanwhile, medical device companies are not immune to these same things. They are being scrutinized in the wake of healthcare reform. The economic downturn has impacted them as well. They also feel the public's demands for more advanced technology and better devices, but how can they deliver those things with more regulation and less money?

There is no doubt more to this story. The FDA itself conducted a study which uncovered that it could do a better job in device approvals. No doubt manufacturers are going to feel public pressure.

Meanwhile, as a person with a medical device, there is no reason to believe that your pacemaker or ICD is not safe and effective. Most medical devices are built on the "platform" of older, established technology with just some new innovations and upgrades added. Devices are monitored for problems, and there is no evidence I have ever seen that our current device monitoring system and recalls does not work in terms of identifying and dealing with potentially dangerous devices. Devices approved by the FDA have been studied and evaluated, even if these investigators found shortcomings in the studies.

In other words, your pacemaker or ICD has been tested by the manufacturer, studied, and approved by the FDA, even if some of the methods used were not the most rigorous ones from a scientific standpoint. It may indeed be time to tighten up the approval testing methodologies and to try to find better ways to run device tests that align more closely with the pharmaceutical model.

For many pacemaker people, these things are easily avoided. But many people need regular MRI scans to monitor ongoing conditions, such as cancer. Besides that, people really cannot predict if they might suddenly be put in a situation where an MRI scan is prudent if not crucial. But if you have a pacemaker, that's a no-no.

An MRI is a special imaging technique that helps doctors get a visual picture of soft tissues, including organs and possibly tumors. Many MRIs are like giant tubes; the patient is placed on a gurney and then pushed inside the MRI. The MRI machine takes a sequence of images which are then assembled together by the device's software to create the scans. During the sequence of images, the MRI may make a noisy pounding noise. An MRI can take many minutes to produce. In recent years, the claustrophobia-inducing tube-type MRI machine has been replaced by so-called "open MRI" machines and even standing MRIs (that's where you stand up throughout the scan).

The problem with MRIs and pacemakers is inherent in the "M" in MRI. MRIs use powerful magnets to create their images. Magnets can mess with the pacemaker's internal workings. In fact, one way to "reset" a pacemaker and cause it to "safety pace" (pace without sensing) is to put a magnet directly over it. Furthermore, the pacemaker is made out of metal and the magnetic force of the MRI machine can pull on the pacemaker as attracts it.

But an even bigger issue is that the MRI machine can start to heat up the pacemaker and the lead. If the pacemaker and lead(s) get too hot, they burn delicate cardiac tissue. An MRI can be potentially life threatening to a pacemaker person!

Right now, most pacemaker people who need some kind of scan of soft tissue can opt for a CT-scan (or "CAT" scan) which is generally considered safe for pacemaker patients. However, there are times when an MRI is better for what the doctor needs to see. In 2007, a total of 26 million MRIs were conducted in the U.S.; it's a familiar and reliable and frequent type of medical imaging.

Medtronic, the world's largest pacemaker manufacturer, has a new pacemaker on the way to approval. It's called EnRhythm MRI SureScan. The pacemaker was explicitly designed to be MRI-safe. It is rumored–but we cannot confirm it–that other manufacturers are working on similar producs.

Right now, EnRhythm MRI SureScan is not commercially available. It is currently under consideration by the FDA.

So how did a woman from the little town of Wimberley, Texas, get the first one ever to be implanted? The 45-year-old woman found out she needed a pacemaker after suffering some fainting spells. The problem was that she had Cushing's disease, which was caused by a couple of tumors on or around her pituitary gland. The woman needed to get an MRI every six months to monitor the condition which is associated with fatigue, weakened bones, and muscle weakness.

Her conundrum was that the pacemaker she needed would make it impossible to monitor her Cushing's disease. She visited a hospital in Austin and talked to a cardiologist there who knew about the MRI-safe pacemaker in development. The cardiologist got in contact with the Medtronic's representative who worked with officials at the company and the FDA to get special permission to use the new pacemaker before it is officially approved. This kind of special dispensation is known in the business as "compassionate use."

Compassionate use of a device allows the FDA to waive restrictions and will let the woman get a pacemaker that is not yet commercially on the market. To get a compassionate use waiver, one has to work with both the manufacturer and the FDA (not to mention the doctor) and complete a great deal of paperwork.

Fortunately for the woman from Wimberley, Texas, it was completed relatively quickly and she was able to get her MRI-safe pacemaker and also make some news as the first woman to get the MRI-safe pacemaker.

Although it is always a little bit tricky to "predict" when products will be approved by the FDA, it is anticipated that the MRI-safe pacemaker will be cleared for market release in the spring of 2010.

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.

It would run entirely on energy harvested from within the body. That's right, no battery.

Since the battery takes up the lion's share of real estate in any implantable cardiac device, getting rid of a battery could make the devices radically smaller. But manufacturers might decide to keep the pacemakers roughly the same size and just fill up that space now taken up by the battery with greater memory and more circuits so that pacemakers could get smarter than ever.

Many manufacturers would like to offer more monitoring functions, diagnostic reports, memory for stored ECGs, and sensors but just lack the space in today's streamlined pacemakers. By getting rid of the battery, devices might just gain more advanced functionality.

Pacemakers run on electrical energy and the SIMM system would be the same, except this voltage would come from the differential between the heart's upper chambers and lower chambers. The biggest hurdle to developers so far is the fact that cardiac energy is typically low-frequency, and it is easier to get energy from high-frequency sources.

So far, prototypes have been able to get about one-third of the energy they need from the body's natural heart function. Studies to date confirm that this SIMM device does not stress the heart or drain energy from it. However, the device is still in development and more studies are needed.