Taking drug safety seriously [Archives:2005/861/Health]

July 21 2005

By Curt D. Furberg

Health hazards – nuclear reactors, guns, and contaminated foods – surround all of us, so governments take an active role in limiting these hazards through regulations, which, in many cases, are very successful. But the situation is far different concerning the safety of prescription drugs. Indeed, as far as protecting the public is concerned, drug safety is the regulator's neglected stepchild.

The magnitude of the problem is huge. In the United States alone, it is estimated that every year up to 100,000 patients die due to serious adverse drug reactions (ADR's). If true, drug-induced death would qualify as the fourth or fifth leading cause of death (depending on which mortality estimates are used). Moreover, the direct annual hospital costs attributable to ADR's run into the billions of dollars, and this does not include all the suffering that ADR's cause that does not lead to hospitalization (or death).

The difficulties in determining cause and effect must be acknowledged. Whether a patient's death or hospitalization is due to a particular drug, the underlying illness, or a combination of the two can be hard to determine. But this makes drug safety all the more important.

Inherent to drug safety is the fact that all drugs, in addition to their benefits, cause harm in certain patients. Drug approval and use requires a careful weighing of desirable and undesirable effects. These judgments vary, depending on whether they are made by a drug company, which stands to benefit from sales, or a patient at risk of suffering a serious adverse effect.

Incomplete knowledge complicates this assessment. The rush to get new drugs to market often leads to inadequate safety documentation. More than half of all approved drugs produce a serious adverse reaction that is not known at the time of regulatory approval.

For example, when the new class of painkillers called Cox-2 inhibitors was introduced, regulators, physicians, and patients were unaware that these drugs could cause heart attacks and strokes. Tens of thousands of innocent patients – perhaps more – suffered such ADR's before the first two drugs of this class were withdrawn.

Proper and complete documentation of harmful drug effects is difficult. Spontaneous reporting rates to regulatory agencies are low – approximately 1% – and ongoing monitoring is passive in many countries.

There is also a general reluctance to report unfavorable drug effects. Physicians may feel guilty and fear litigation, drug companies worry about the threat to corporate profits and regulatory agencies must face the question: “Why was the drug approved in the first place?”

It is especially difficult to attribute an adverse reaction to a drug if the medical event is common in the user's age group or in the condition being treated. Because the risk of heart attacks is high in older people, many of whom have arthritic pain requiring treatment with painkillers, it took six years to link Cox-2 inhibitors to a two- to three-fold increase in the risk of heart attacks.

A recent Harris Survey in the US concluded that 60% of adults are either not confident at all or not very confident that drug makers will publicly and in a timely manner disclose data on their products' adverse effects. Their skepticism is hardly groundless: internal documents obtained in recent lawsuits reveal that drug companies often fail to submit critical safety information to regulatory agencies, as required by law, and fail to communicate such information to physicians and patients.

One problem is that the consequences for neglecting drug safety are non-existing or minimal. The time has come to get serious:

– Citizens and government must make drug safety a priority and commit adequate resources to fixing the problems;

– Penalties for drug companies' failure to report and communicate safety information must be increased dramatically if they are to serve as effective deterrents;

– Regulatory agencies need enforcement authority so that stricter rules can be implemented;

– The drug-safety problem must be seen as a systemic failure. It is unfair to blame clinicians for serious ADR's, particularly in the absence of complete safety information. Fixing the problem requires full cooperation from clinicians, but this requires ending their fear of litigation. This approach works well in the airline industry: pilots reporting near misses are not penalized;

– Patients need to be better informed about the risks of prescription drugs and more involved in detection and reporting. Package inserts in fine print are useless;

– Monitoring of ADR's must be more pro-active. This requires more funding, which should come from the main beneficiary of drug sales – the pharmaceutical industry – just as oversight of aviation safety is funded by the airlines.

Above all, the success of any comprehensive effort to improve drug safety hinges upon establishing an independent office of drug safety to advocate, coordinate, and provide direction to the regulatory agenda. Such an office exists in the United Kingdom. Other governments should follow this model in order to fulfill their neglected role as guardian of public health.

Curt D. Furberg, a member of the US FDA Advisory Committee on Drug Safety and Risk Management, worked for 11 years at the US National Heart, Lung, and Blood Institute and now teaches at Wake Forest University School of Medicine.