When his heart needed help a few years ago, Peter A. Chevalier shouldn't have had any trouble getting the most advanced pacemaker. He was then a research and development chief at Medtronic Inc., a leading medical-device maker. Although the company's newest pacemakers were on sale in Europe, the U.S. Food & Drug Administration hadn't approved them, forcing Chevalier to use an older, inferior model. Now, says Chevalier, the FDA is holding up approval for Medtronic's latest device, which offers a better method of adjusting heart rates based on the body's needs. "In an attempt to eliminate all risks, the FDA is delaying the entry of new technology," he fumes. "We have a situation bordering on a crisis."
Chevalier's is just one voice in a chorus of criticism being leveled at the FDA these days. Conservatives charge that the agency and its activist chief, David A. Kessler, have let thousands die by not approving lifesaving drugs and devices fast enough. GOP lawmakers vow to take a close look at the FDA, which regulates one-quarter of the U.S. economy. "There will be an effort to look at the agency and say: `You've failed the American public in many ways. Come in and justify yourself,"' warns Representative David M. McIntosh (R-Ind.), chairman of a new government reform and oversight subcommittee on economic growth and regulation.
FROZEN AIN'T "FRESH." Some on Capitol Hill are considering an overhaul of how the $970 million agency works. Among the most radical ideas: no longer requiring proof that drugs are effective as well as safe, and farming out product approvals to private organizations, as some European nations do. Some would let just about any drug or device be sold without agency review as long as it's labeled "not FDA-approved."
At the very least, say many industry executives, Congress should rethink the FDA's role as both an enforcement and product-approval agency. They believe Kessler's stepped-up enforcement may be taking resources away from product reviews. "Protecting the public health means approving new drugs as fast as possible--rather than devoting massive resources to go after the word `fresh' on [frozen] orange juice," says Kenneth P. Berkowitz, recently retired vice-president at Hoffmann-La Roche Inc.
The odds of radical change are slim, however. The FDA points out that ever since the thalidomide disaster more than 30 years ago, Congress has demanded that the agency ensure that drugs are both highly safe and effective.
The key question is whether or not to change how the agency balances risks and benefits. Should the FDA go further in allowing greater risks for drugs and devices that could be the only hope for patients with life-threatening illnesses? Should it give doctors more latitude in deciding whether treatments work?
Such trade-offs may have their price. Consumer advocates and even some drug companies are nervous about any effort to weaken the FDA's vetting procedures. "The very high standard of FDA review gives the medical community confidence in prescribing drugs," thus boosting sales, explains one biotech executive. GOP politicians realize that if they alter this balance or weaken FDA oversight, they risk being blamed for future disasters. No one wants a fiasco like the 1989 generic-drug flap, when drugmakers repeatedly deceived--and bribed--a weak, toothless agency.
While the debate over standards goes on, FDA defenders note it is already responding to long-standing criticism over the slow pace of product approval. Kessler declined to be interviewed. But FDA officials say the agency is on target to meet 1997 goals of slashing review times from 21/2 years to less than 1 year for all drugs thanks in part to 1992 legislation that lets it charge for applications. "By 1997, industry will realize that drugs are approved faster here than anywhere else in the world," says a top FDA official. Even some industry executives agree that the agency shouldn't be bashed for all delays and rejections. "If something is no more effective than a placebo and a company spends millions on trials to find that out, that's not the FDA's fault," says Ascher Shmulewitz, chief executive of device maker NeoVision Corp.
FASTER, FASTER. Still, critics aren't satisfied. Executives charge that the FDA remains obsessed with minimizing risk, thus keeping products off the market for years (table). And to speed up approvals, the agency is asking for more clinical data before the review clock starts ticking, they say. That actually lengthens the time between the start of development and submission to the FDA. A Tufts University study of FDA approvals from 1990 to 1992 shows that while review time for important drugs averaged only 20 months, compared with 31 months for all drugs, development time for these key products was three years longer. "The FDA process is too slow. Everyone knows it," says neurologist Leonard Berg, director of the Alzheimer's Disease Research Center at Washington University in St. Louis.
To some critics, nothing demonstrates FDA foot-dragging better than the chicken-pox vaccine Varivax. Since 1981, this vaccine has been tested safely on more than 10,000 people in the U.S. Since 1984, 2 million children in Europe and Asia have had versions of it. Yet Varivax is still lumbering though the FDA.
An FDA advisory committee first recommended approval in January, 1990, a year after Merck & Co. sought the O.K. Early last year, a second panel pronounced Varivax safe and effective. The Centers for Disease Control (CDC) and the American Academy of Pediatrics both urge universal use.
Yet the FDA is unapologetic about its tough stance. Data from 20 years' experience in Japan and elsewhere show that as many as 2% of inoculated children develop mild cases of chicken pox, a higher failure rate than other childhood inoculations. Regulators also worry that--years later--Varivax might qpawn adult cases of the disease or trigger related viral conditions, such as shingles.
Varivax offers a classic example of the FDA's juggling act. How should regulators assess risks, and who should make the final decisions? "The FDA believes it knows best how to strike this balance," says Alan M. Slobodin of the conservative Washington Legal Foundation. "But maybe it's better for patients to decide in consultation with their doctors."
That's the view of supporters of the Alzheimer's drug tacrine, sold under the brand name Cognex. There's no other drug to treat this debilitating disease, which affects 4 million Americans. But for seven years, the agency refused to clear tacrine, prompting protests from victims, doctors, and families desperate for anything that will help. Officials reply that it took years to show even a minuscule benefit and that the drug has serious side effects. "There is a clash between the right of the individual [to get any drug] and the duty of government to prevent harm," Kessler said in a 1992 speech defending the delay on tacrine. He added it would be "foolish" to put "useless drugs" on drugstore shelves just to push products out faster.
DISMAYED. But criticisms from drugmakers pale before complaints from the medical-device industry, which lacks the pharmaceutical companies' long history of FDA scrutiny. Virtually unregulated until 1976, such devices were examined only for engineering performance, not clinical results, through most of the 1980s. Inevitably, defective heart valves and other devices reached the market. And when questions arose about the safety of others, such as breast implants, Kessler learned to his dismay that the agency's Center for Devices & Radiological Health had no data on them and couldn't answer questions from Congress about the products' safety.
Under pressure from both Kessler and lawmakers, the device-review process ground to a halt. What's more, the agency and Congress had raised the bar for new approvals. Under the Safe Medical Devices Act of 1990, most devices need to show only that they are "substantially equivalent" to products already on the market. But the law also allows the agency to ask for some safety and efficacy information if the device contains new technology. The industry charges that the FDA is using this provision to require far too much evidence. "It's not the role of the FDA to determine relative efficacy," says Medtronic's Chevalier. Instead, he says, decisions about which products work better "ought to be made by the medical community."
The FDA's more exacting standards have been a blow to an industry made up mostly of small companies. "Studies have had to be larger and longer than in the past," complains J. Casey Mc-Glynn, a Silicon Valley lawyer who specializes in technology issues. That has driven up the cost of developing truly novel devices from $25 million to $75 million since 1990, says Medtronic CEO William W. George, citing industry figures. The rising expense has driven many companies to Europe, where approvals are faster and cheaper.
The industry is also working hard to make the U.S. climate more hospitable, rallying powerful allies such as House Speaker Newt Gingrich (R-Ga.) to their cause. Gingrich, who has called Kessler "a bully and a thug," has also blasted the agency for refusing to allow tests of a pump, available in Europe, designed to make cardiopulmonary resuscitation more effective. He insists that Americans are dying unnecessarily because it's not available here. But researcher Michael Callaham of the University of California at San Francisco says that there's no firm evidence so far that the pump in question works better than standard CPR. And the FDA is reluctant to permit tests--because the patients, who are unconscious, cannot give their consent.
The coming months promise pitched battles on all these issues. Even within the FDA, there's an argument going on over whether the reviews for thousands of simple, noncontroversial devices such as tongue depressors might better be farmed out to private organizations.
Any significant change to the FDA's standards, mission, or responsibilities, however, would require new legislation. And so far, the agency's Republican critics haven't begun to discuss what changes--if any--they really want to make. Indeed, Congress' most recent actions, the 1990 Medical Device Act and a 1994 dietary supplement bill, moved in the direction of stricter regulation. What's more, some AIDS activists say the agency has been approving some drugs too quickly, without enough clinical testing to figure out the best way to use them, or even if they work. Outside the Beltway, says Kenneth I. Kaitin, deputy director of Tufts University's Center for the Study of Drug Development, "there's now less attention on increasing drug availability and more attention on protecting the public."
Once again, the FDA may get caught in the middle. And just as Congress did in 1990, lawmakers will have to grapple with a very hard question: How will patients be served best?
The FDA Under Siege
Conservative critics charge that FDA red tape is killing industries-and people-by keeping valuable products off the market. Here are some of the cases they cite-and the FDA's response:
CRITICS CHARGE ... THE FDA RESPONDS...
The FDA could have prevented - The pump may not work any bet-
thousands of heart-attack deaths ter than ordinary CPR. And there's
by approving tests of the "cardio- no way to get the victim's consent.
pump," used for CPR.
Alzheimer's victims suffered when The drug has severe side effects.
the FDA took seven years to approve Years of testing showed limited
By not approving the Sensor Pad The pad may actually make detection
to help detect breast lumps, the FDA more difficult, and the company
placed thousands of women at risk. hasn't done the necessary trials.
Chicken pox vaccine, under devel- The vaccine might have long-term
opment for 21 years, is still not detrimental effects. Besides,
approved by FDA. chicken pox is not a deadly disease.
Advanced pacemakers are avail- Benefits of the new device are still
able in Europe, but not in the U.S. not established.