"Regulating Medical Devices: Two Views of the Balance of Risk and Benefits," M.E. Online Exclusive, July 2008

July 2008

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Regulating Medical Devices: Two Views of the Balance of Risk and Benefits

by Harry Hutchinson, Executive Editor

The healthy human body is an efficient, robust system. Of course, it is not always healthy. Sometimes parts break or wear out, or the immune system doesn’t block out an occasional infection.

In those cases, if they’re severe enough, we need human-made products to help correct the problem. But no matter what we put into the body—drug, artificial joint, heart rhythm regulator, dental crown—it is not going to be as good as the original. And we can also expect unintended consequences.

Even laymen know that taking a drug can produce side effects. But when it comes to an implant, whether it’s an artificial knee or a defibrillator, the patient’s expectations often run very high, and that can lead to disappointment. According to a veteran of the medical technology business, it may be time for the medical field to mount an education campaign to give the public a more realistic idea of what they can expect of modern medical marvels.

That was one of the points made by Paul Citron during his presentation at the Frontiers in Biomedical Devices Conference, sponsored by ASME Emerging Technologies. Citron, a retired executive of Medtronic Inc., a manufacturer of medical technologies based in Minneapolis, spoke with Mechanical Engineering by phone a few days after the conference, which was held in June in Irvine, Calif. “The public has a set of expectations for their medical devices that set them up for disappointment,” he said. “The best design is the body. Man-made devices can’t be as effective or as elegant.”

The public needs to be better informed of the benefits and risks of devices and needs help in setting its expectations, and also in understanding “therapy trade-offs,” he said. One of his suggestions is that, perhaps in addition to the list of books that includes Wine for Dummies, there should be Medical Devices for Dummies.

According to Citron, “Biomedical engineers must become involved in public education and setting public policy.”

Citron called his presentation “The Medical Device Innovation Engine: Internal and External Forces That Affect Its Performance.” He sees many forces that influence the development of medical devices, and some of them, including the way medical products are approved by the government, may have grown unrealistically burdensome and perhaps should be reviewed.

Citron’s presentation included a slide based on a 2003 poll of members by the Advanced Medical Technology Association. The group asked members to list the top ten impediments to innovation in the development of medical devices. The U.S. Food and Drug Administration’s regulatory requirements came in at the top of the list. Second was the cost of clinical research, and third was Medicare coverage and reimbursement requirements.

The regulatory process is indispensable. It is designed to develop a clear understanding of the benefits a product can offer patients and the risks it incurs. It can identify useless products and those that do more harm than good, and keep them out of the market.

A society tries to reach a reasonable balance between how much time and expense it is willing to incur to avoid the risk of harm, and how much risk it is willing to accept in order to bring the benefits of new therapies to patients in need.

In the United States, it is the mandate of the Food and Drug Administration to make risk-benefit decisions about the products it regulates. Donna Lochner, deputy director of the FDA’s Division of Cardiovascular Devices, also delivered an address to the Biomedical Devices Conference.

In her presentation, “The FDA and Medical Device Regulation: Challenges and Opportunities,” Lochner outlined the agency’s job and described programs it has initiated.

Although Citron’s and Lochner’s presentations were independently developed and were delivered separately, they had many points in common. There was no debate between Lochner and Citron, but they presented two views of what both speakers regard as an essential safeguard for public health.

Citron believes it is time for the United States to revisit its balance of risk and benefits. The U.S. system may be putting so much emphasis on the effort to avoid harm, that it is unnecessarily increasing the cost and the time it takes to bring benefits to patients. As he sees it, “Some patients may be willing to take a greater calculated risk rather than waiting for another clinical study that might take too long. That is, too long for them.”

For medical devices in particular, there may be ways to reduce the time and cost of bringing a product to market. As Citron sees it, there are cases where the effort to avoid harm in some cases, especially when therapies can save lives, puts patients at the risk of dying before therapies are approved.

In a telephone interview, Lochner told us that the FDA makes allowances for the desperately ill through a mechanism called a “compassionate use exemption.” A product not yet given final approval, but for which there are no known safety concerns apparent to a clinician, is usually approved for use on a case-by-case basis. Depending on circumstances, approvals are generally granted within 30 calendar days, Lochner said, and sometimes they are granted immediately.

This is distinct, she said, from the humanitarian device exemption, which is intended to expedite approval of devices that address so-called “orphan diseases,” which are illnesses or conditions that affect fewer than 4,000 individuals in the United States. A device that Citron and Lochner both referred to as an example of this kind of exemption is the pediatric mechanical circulatory support device, which is used for children with a rare, severe cardiac condition.

Many conventional medical devices, Lochner said, are routinely approved with little or no delay. Most Class I devices, which are considered low risk, including elastic bandages, examination gloves, and hand-held surgical instruments, do not require pre-market approval or clearance. The rules for them require that the manufacturer be registered with the FDA and notify the agency of the product that it intends to sell. The company must meet certain listing, labeling, and manufacturing requirements.

Class II devices, which include powered wheelchairs, infusion pumps, and monitoring equipment, are generally cleared within 90 days. About 10 to 15 percent of them require clinical data and take longer, Lochner said.

The FDA requirements for approval of Class III devices—high-risk, life-sustaining products, including stents, defribrillators, brain stimulators, and hip replacements—can take years to meet. Costs run into many millions of dollars generally because of the need for clinical studies. An entire industry has been created of companies that specialize in organizing and conducting clinical trials for manufacturers. There are teaching hospitals where the trials have become a source of revenue.

It is this area where Citron suggests that some of the rules be simplified, because a change could save significant amounts of money and time, without substantially increasing risk. One of his suggestions to reduce cost concerns clinical trials. The trial of an implanted device could refer to historical data on patients with similar conditions whose fate is already known, instead of creating a costly placebo group. This historical data could be compared to the progress of a group that has received the device being tested.

Current practice in clinical trials of an active device—a first-in-class brain stimulator, for example—is to implant a device in every volunteer patient meeting entry requirements for the trial. Only half the devices, however, are turned on. After a certain period in the trial, the patients may be asked to return and the deactivated devices will be turned on. At the same time, the devices that are activated will be turned off.

Relying on historical data rather than a placebo group would reduce the number of people and procedures involved.

Citron compared European and U.S. times for approval. An example is a device developed by Medtronics under the name Activa. It is a neurostimulator used to treat symptoms of Parkinson’s disease. The device received its European approval in April 1998. U.S. approval came 44 months later, in March 2002.

In addition to the length of time and the cost of research to meet FDA requirements, once a product is approved, a device must pass a second approval by the Centers for Medicare and Medicaid Services to approve the treatment for reimbursement under those programs.

The time for an additional approval not only delays treatment further for many patients, it also prolongs the time that companies must wait to start making back their investments. It is a difficult challenge, particularly for small high-tech firms, Citron said.

From the FDA’s perspective, there is a large job to do. Lochner’s division is one of five in the Office of Device Evaluation, which is one of eight offices in the Center for Devices and Radiological Health. The FDA operates six centers.

The FDA’s budget, like all budgets, limits the number of people available to carry out the agency’s mission. What’s more, Lochner said, the rapid pace of emerging technologies makes it hard to maintain expertise in all new areas.

The Center for Devices and Radiological Health operates the Medical Device Fellowship Program, under which it invites health professionals to participate in the regulatory process for medical devices.

According to the program’s Web site, http://www.fda.gov/cdrh/mdfp/, “CDRH established the Medical Device Fellowship Program to increase the range and depth of collaborations between CDRH and the outside scientific community. The MDFP offers short and long-term fellowship opportunities for individuals interested in learning about the regulatory process and sharing their knowledge and experience with medical devices from the relatively simple to the highly complex.”

Lochner said the program helps meet the need for specialists in emerging technologies. She said that in 2007 the program involved 40 fellows, including 21 physicians and other medical professionals, and 13 biomedical engineers. Others were computer experts, statisticians, and a law and policy expert.

A separate program, called the Critical Path Initiative, aims to mount national projects to modernize the scientific process through which medical products are brought to market.

The Initiative grew out of a report issued in March 2004 under the title “Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products.” The report explored why there had been a decrease in the number of innovative medical products submitted for approval at a time of advances in biomedical sciences.

It was followed in March 2006 by the FDA’s Critical Path Opportunities List. The list was developed with extensive public contributions, and describes the areas presenting opportunities to improve the product development sciences and the regulatory process.

Topics include improving evaluation tools and streamlining clinical trials. The report and the list are available online at http://www.fda.gov/oc/initiatives/criticalpath/.