Experts' Capsule Summaries may be Hard Pills to Swallow

Pharmaceutical experts make decisions that affect the health of millions of Americans. Billions of dollars in drug sales depend on their word.

But, how independent are those experts?

According to an article in USA Today ("FDA advisers tied to industry," by Dennis Cauchon, Sept. 25, 2000), more than half the experts hired to advise the government on the safety and effectiveness of medicine have financial relationships with the very companies that will be impacted by their decisions.

Many of these experts have a direct financial interest in the drug or topic they are asked to evaluate.

Conflicts range from helping a pharmaceutical company develop a medicine to serving on an advisory committee for the Food and Drug Administration that judges the drug. Conflicts also can mean lucrative speaking engagements, consultation fees, research grants, "star" faculty status, patent royalties or stock ownership in the pharmaceutical corporation with options that increase if the drug is approved by the FDA.

Although federal law generally prohibits the FDA from using experts with financial conflicts of interest (45 C.F.F. §941.1, et. seq.), the FDA reportedly waived that restriction more than 800 times in a recent two-year period, according to the USA Today report.

And now these conflicts appear to be having public repercussions. As many as 10 drugs have been pulled from shelves in the last three years alone, an unprecedented number of reversals in so short a time. Some 22 million Americans were prescribed those drugs.

Certainly the pharmaceutical companies had lots to gain, having generated more than $5 billion in sales from these drugs before they were withdrawn. Some of these drugs were pulled after reports of severe side effects or deaths.

One was a diet pill. Another was for heartburn. Still another was a painkiller. Yet another was an antibiotic for which other, safer antibiotics were already available on the market.

For instance, Lotronex, a drug for treating irritable bowel syndrome, was pulled off the market late last year when it was linked to five deaths, the removal of a patient’s colon and other bowel surgeries.

Redux, a diet pill, was pulled after just about a year on the market after it was found to cause heart valve damage in some patients. It was suspected to have been linked to 123 deaths. This drug was marketed as a diet pill that was widely used in formulations of fen-fen-phen, and its manufacturer haw twice agreed to set aside $4.75 billion to settle lawsuits related to the drugs’ potential to cause heart-valve damage.

The painkiller Duract was approved by the FDA, despite the possibility of the drug’s causing liver toxicity. The drug was withdrawn in 1998 after 11 months on the market after being cited as a suspect in 68 deaths, including 17 that involved liver failure.

Removal of drugs from the market has caused the medical community to examine the cause for the FDA’s concentration on speed rather than caution in the approval process.

One factor points to the connection of physicians and medical researchers to the pharmaceutical industry.

Another is a phenomenon that began about a decade ago. For most of its history, the FDA operated on the physicians’ creed, "First, do no harm." It approved new prescription medicines at a slow pace.

But in the early 1990s the demand for drugs to fight the AIDS virus escalated. Congress told the FDA to work closely with pharmaceutical firms in an effort to market new medicines more quickly. Regulations were issued giving the FDA discretion to "accelerate approval of certain new drugs" for serious or life-threatening conditions.

In 1992 the Prescription Drug User Free Act (H.R. 6181, 102d Cong., 106 Stat. 4491) was passed, which established goals that call for the FDA to review drugs within six months or a year.

The real question was whether Congress wanted not more reviews but more approvals. One cannot help but look at the $44 million the pharmaceutical industry has contributed to the major political parties and presidential and congressional candidates in the last 10 years to see the possible dynamics behind the change in the law.

The FDA’s overzealousness is evident in that since 1993, hundreds of new drugs have been approved. In 1988 only 4 percent of the new drugs introduced into the world market were approved by the FDA. But in 1998, the FDA’s approvals rose sharply to 66 percent.

Some have questioned the impact of moonlighting consultants or researchers – working ostensibly on the public’s behalf – who are advising the FDA on which medicines should be approved for sale, what the warning labels should say and how studies of drugs should be designed.

In forging direct and sometimes inappropriate links to the very industry they are evaluating, the independence of such a vital regulatory agency is being questioned. Perhaps even an independent arm of the FDA may be appropriate to handle drug recalls rather than the same officials who approve the drug for public use.

Granted, the review process for a new drug application is no simple task. Voluminous medical data must be mastered within just several months’ time.

Certainly the approval of every drug involves a weighing process of the benefits versus the risks. Those risks may be higher given a greater severity of the illness.

But, doctors’ connections to the drug industry lead one to question whether they are merely providing a company the evidence it wants to hear. Would those researchers’ results be different if no financial ties or incentives existed?

There is a need to promote medical advancements, and who better to do so than physicians working in conjunction with drug companies. But, tighter controls ensuring the researchers’ independence are necessary to protect the public’s health.