Fatal flaws in the way new drugs are tested and marketed

Americans are likely to be exposed to unacceptable side effects of FDA-approved drugs such as Vioxx in the future because of fatal flaws in the way new drugs are tested and marketed, according to research to be presented at the annual meeting of the American Sociological Association (ASA).

"Drug disasters are literally built into the current system of drug testing and approvals in the United States," said Donald Light, the sociologist who authored the study and a professor of comparative health policy at the University of Medicine and Dentistry of New Jersey. "Recent changes in the system have only increased the proportion of new drugs with serious risks."

According to a 1999 report for the Institute of Medicine, adverse drug reactions (ADRs) are the fourth leading cause of death in the United States and more than two million serious reactions occur every year. ADRs can occur for a number of reasons, including improper prescribed dosage, drug abuse and drug interactions.

Light's analysis identifies the organizational foundations of patient risk from prescription drugs and suggests institutional reforms to help avoid or reduce future drug disasters.

According to Light, rather than using current approved drugs as benchmarks of efficacy, the existing testing system evaluates the effectiveness of new drugs based on their effects compared to placebos. Systematic reviews indicate that one in seven new drugs is superior to existing drugs, but two in every seven new drugs result in side effects serious enough for action by the U.S. Food and Drug Administration (FDA), including black box warnings, adverse reaction warnings, or even withdrawal of the drug.

Based on this system, Light asserts that new drugs are twice as likely to harm patients as to provide them with benefits superior to existing drugs.

Light's analysis suggests another flaw lies within the design of clinical trials. He contends that pharmaceutical companies frequently design their trails to minimize evidence of toxic side effects. To do so, they sample from a healthier population atypical of patients who will actually take the drug, excluding people who are older, poorer or who have multiple health problems. Trials are run long enough to pick up main effects but not to detect some long term side effects. Approvals are based on these data; so drugs with harmful effects sometimes get through.

"Based on our current system, the designation of 'safe and effective' on today's new drugs could be replaced with, 'apparently safe based on incomplete information, and more effective than a placebo,'" Light said.

With regard to government oversight, Light cites serious under-funding of the FDA, which creates a dependency on the pharmaceutical industry-the industry FDA regulates-to pay its staff. In return for drug company funding, Light says, the industry expects faster reviews, but faster reviews potentially fail to identify serious long-term side effects.

"Speed-up reviews for safety have more than tripled the number of 'black box warnings' of side effects or withdrawals after drugs are on the market," Light said. "Despite recent reforms to strengthen the FDA's role in protecting the public from harmful drugs, the harm-benefit ratio is worsening due to these reviews and relaxed rules that allow companies to promote drugs for unapproved uses."