FDA's drug safety challenge: Making improvements without adverse events

These are trying times for the Food and Drug Administration. It's long been considered the world's gold standard in ensuring the safety and efficacy of prescription drugs. But in recent months, the agency has suffered some black eyes.

The first occurred when problems emerged regarding clinical trial data indicating that there could be an increased risk of suicidal behavior among children and teens who initiate therapy with antidepressant medicines. The result was significant soul-searching both within the FDA and beyond regarding how such data are collected.

But this was only the beginning. Recently, when findings of cardiovascular risks linked to COX-2 inhibitors surfaced, FDA processes to ensure the safety of prescription drugs before and after they reach the marketplace once again were in the spotlight -- this time the focus of even more intense public and congressional scrutiny.

The upshot now is a newfound level of oversight and activity. For instance, the FDA has made an effort to shore up its own systems. The agency announced Feb. 15 the creation of a new Drug Safety Oversight Board comprised of FDA members as well as medical experts from other Dept. of Health and Human Services' agencies and government divisions. Last month it also published guidance documents to help the pharmaceutical industry improve how it assesses and manages drug risk. Also in the works is a Drug Watch Web page, which will include the newest information for physicians and patients about safety risks for previously and newly approved drugs.

Meanwhile, lawmakers have their own ideas about drug safety. At a March 3 hearing, Senate Health, Education, Labor and Pensions Committee Chair Mike Enzi (R, Wyo.) foreshadowed the likelihood of congressional action to address "the current shortcoming in our drug approval system."

One thing is certain. As these developments continue both inside and outside the FDA, it is critical that those making policy decisions be mindful of the enormous impact such changes can bring. In that spirit, the American Medical Association offered at the same hearing a series of recommendations to improve drug safety and risk communication without undermining physicians' ability to practice medicine.

Lawmakers and agency officials should use these suggestions as guideposts.

It's a given, of course, that the primary way in which the FDA affects physician practice is by approving a prescription drug or biologic. It is also important to note that since the Prescription Drug User Fee Act became law in 1992, new drugs are reaching the patients who need them more quickly. The AMA advocates that any steps taken to enhance drug safety be accomplished without reversing this trend.

But as more drugs do become available, the AMA also recognizes the need to implement more active postmarketing surveillance mechanisms, rather than relying on the MedWatch program, which is a passive approach dependent on voluntary reports of suspected adverse drug events.

Of particular concern to physicians, however, is the format of package inserts of prescription drugs. It is one of the key elements worthy of fine-tuning.

These documents, designed to inform physicians about a drug's risks and benefits, have become long and complex reading rather than a useful resource, containing so much technical data that it is difficult to weed out critical information such as dosage, contra-indications, major risks and potential drug interactions.

In 2000, the FDA issued a proposed rule to make the package insert more user-friendly. The AMA supports this effort and urges the rule's finalization, which some say is imminent.

The Association's other concerns include the preservation of physicians' ability to prescribe drugs off-label and the need for continued collaboration between the FDA, the pharmaceutical industry and physicians to develop better risk communication tools. Any such tools should be crafted to avoid unintended consequences such as decreased patient access to valuable medical treatments.

For the vast majority of prescription drugs, the package insert combined with effective postmarketing surveillance should constitute an effective risk-management plan. Additional controls such as patient agreements, enrollment programs or special prescribing rules should be used only as a last resort to keep products with unique benefits on the market.

Obviously, decisions about FDA processes for drug approval, postmarketing surveillance, product labeling, off-label use and risk management inevitably interact with the work practicing physicians do every day. As efforts to enhance safety move forward, it is important that they are developed with prudence and with the goal of doing no harm, neither to individual patients nor to the art and science of medicine.