Harvard researchers have found a disturbing pattern with drugs that have been pulled off the market. They found that medicines approved right on deadline by the Food and Drug Administration are more likely to cause safety problems later than those cleared with more time to spare. Congress has set deadlines for the FDA to speed the arrival of new medications. However, lots of folks believe that the drug manufacturers take advantage of the criteria used in connection with the deadlines. The Harvard analysis of decades of drug approvals, published in the New England Journal of Medicine last month, provides the first scientific evidence supporting some of the complaints relating to the system. As expected, the FDA challenges the findings. But, Dr. Steven Nissen, the Cleveland Clinic’s influential cardiology chief, sees things differently. Dr. Nissen observed:

The article is a wake-up call. It puts the FDA in a very difficult situation when they’re trying to make complex decisions under these very, very tight deadlines. We’ve got to reevaluate now whether that’s good public policy.

The Congressional deadlines imposed on the FDA in 1992 allowed drug makers to pay millions of dollars in fees directly to the cash-strapped agency so it could hire more reviewers and clear a backlog of pending drug applications. In return, the FDA had to make a decision — either approve or reject — on 90% of all drug candidates within 12 months of their application. If it failed to meet the deadlines the agency would lose money. The deadline was only six months for drugs that were classified as “lifesaving,” which were given high priority. In 1997, Congress tightened the deadline for most drugs to ten months. As a result of the concern about risky drugs, Harvard professor Daniel Carpenter took a closer look at the impact:

• First, he found approval is 3.4 times as likely in the two months leading up to the user-fee deadline as at any other time.
• Drugs approved in that just-before-deadline period had a four- to five-fold higher rate of later being withdrawn or requiring serious safety warnings, compared with drugs approved faster or those that miss the deadline.

There are a number of drugs that were late date approvals that had to be pulled from the market. The following are among on-the-brink approvals that later caused problems:

• The painkiller Vioxx was pulled off the market in 2004 for increasing the risk of heart attacks and strokes;
• Bextra was gone in 2005;
• The diabetes drug Rezulin was withdrawn in 2000 for liver problems;
• Cholesterol-lowering Baycol was pulled in 2001 for causing muscle damage; and
• More recently, the diabetes blockbuster Avandia was linked to heart risks last year, getting a strict new warning label.

Dr. Carpenter acknowledged that lots of folks must work under deadlines, observing that for the FDA, “these deadlines are kind of stand-ins for pressure” to approve. Dr. Jerry Avorn of Brigham and Women’s Hospital in Boston, who co-authored the study, observed:

FDA staffers by their own admission feel very much under the gun as these deadlines loom. If they’re forced to make decisions prematurely, they may not make the right decisions. That needs to be debated openly.

Unfortunately, because of the tight budget climate in Congress, industry user fees are unlikely to be replaced with taxpayer dollars. In fact, Congress reaffirmed the user-fee provisions last year. According to reports, it’s unclear if lawmakers would even revisit the deadline issue this year. The review process for new drug applications definitely needs to be fixed. If the industry user fee law is causing problems, it should be changed. There appears to be lots that is wrong at the FDA. It’s pretty scary when you consider that the agency is charged with protecting the public from unsafe drugs.

Source: USA Today and Associated Press

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