Sam Uretsky

Customers are Right Until Proven Wrong

It seemed like a good idea at the time. In 1992, Congress passed the Prescription Drug User Fee Act (PDUFA). It’s obvious that they didn’t give it much thought. It takes about 10 seconds to come up with “Medication Evaluation Speed-up System” or “Corporations Really Enjoy Expanded Patronage.” PDUFA pretty much tells the story — any law with a name that doesn’t obfuscate its purpose must have something wrong with it.

Simply, the pharmaceutical manufacturers were complaining that it took too long for a new drug application to be approved by the Food & Drug Administration. The answer was to impose fees, $100,000 in 1992 rising to $233,000 in 1997, for expedited review. There were other fees as well, both an annual participation fee and fees for drugs already marketed. Significantly, the industry had to be convinced the plan would work, and staff members from the offices of Rep. Henry Waxman and Sens. Edward Kennedy and Orrin Hatch had to sell the plan. The bill was approved unanimously.

Somebody saw what was coming. Dr. Joseph Fins, an instructor at Cornell University Medical School, wrote a letter to the New York Times warning of conflicts of interest, and proposing alternative financing plans. Dr. Fins was right. When PDUFA was reauthorized in 1997, it was subject to performance goals set by industry, to make sure they were getting what they were paying for. The agency was required to review 90% of priority new drug applications within 180 days and non-priority new drug applications with 10 months.

By 2001 the time it took for a drug to go from submission to approval dropped by almost 50%, from roughly two years to about one. Significantly, the rate of approvals jumped from 60% to 80%. Eight drugs approved between 1993 and 2001 had to be withdrawn from the market because of toxicity, and were associated with an estimated 1,200 deaths. Reports of adverse drug reactions increased by 89%.

Perhaps most significantly, according to congressional testimony, the FDA started calling the drug companies “customers” and thought of itself as a supplier of services. Whenever it looked as if resources weren’t adequate to meet the standards set by the industry, staff could be pulled from other activities, such as monitoring adverse reactions, to work on approvals. Not on “evaluations” — “approvals.” The pharmaceutical companies, which originally had to be talked into the plan by representatives from two dedicated Democrats who must have had the best intentions, had co-opted the agency developed to limit abuses by drug companies.

On May 21, 2007, the New England Journal of Medicine published a report on its web site entitled “Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes,” which showed that rosiglitazone, a widely-used drug for treatment of type II diabetes, the sort of diabetes that is increasingly common in the United States, was associated with a higher rate of heart attack and heart disease than placebo. The drug, sold under the brand name Avandia, had been on the market since 1995, and the data analyzed to get this result was the original data that had been provided by the manufacturer to the FDA. Normally, this information would not have been available to any but the study sponsor and the FDA, but GlaxoSmithKline had agreed to make some information available as part of a settlement with the State of New York. The raw data for these studies wasn’t available for analysis, although it was available to both the sponsor and the FDA.

The majority of drug studies conducted are never published, and even these are subject to various forms of publication bias. Researchers rarely rush to publish studies that don’t have a significant outcome, and study sponsors have no inclination to have unfavorable results published. Since there’s very little money available for conducting studies comparing old, off-patent drugs with the newer ones, the medical journals are routinely filled with studies showing that the latest drugs are superior to the older ones. It offers a feeling of steady progress that simply isn’t there. It also means that even the most diligent clinician, one who studies the professional journals carefully, is misinformed — and that misinformation carries over to the way patients are treated.

The trouble is, sometimes cooperation doesn’t work. Some adversarial relationships are essential — the press is the enemy of the government, and regulatory agencies are the enemy of the industries they regulate. Respect is permissible, but friendship isn’t.

The problem started when drug companies were allowed to pay a “user fee” instead of a tax. The FDA stopped being a watchdog and became a restaurant waiter, dependent on tips to make a living. More and more drugs are approved, because that’s what the FDA does for a living — and then have to be withdrawn when the hazards become to big to hide.

Hey — it seemed like a good idea at the time.

Sam Uretsky is a writer and pharmacist living on Long Island, N.Y.

From The Progressive Populist, July 1-15, 2007

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