Best selling drugs crashed and burned

RADAR Detector

Out with the new, in with the old.

A large majority of consumers would prefer to take a drug that’s been on the market for 10 years or more before trying a newer drug, according to a recent survey conducted by Medco Health Solutions.

You have to wonder; would that same survey have had a completely different outcome five years ago, or even one year ago? In the past few months we’ve seen some best selling drugs crash and burn amid safety concerns, while major drug companies and the FDA have taken hit after hit in the mainstream media.

And now, at exactly the time the FDA could use a complete image makeover, agency executives have made an astonishing decision that would be no less surprising than if FDA acting commissioner Lester Crawford called a press conference, drew a gun, and actually shot himself in the foot.

Hit and miss

What’s the primary job of the FDA? To insure food and drug safety, right? And how is that done? In the case of drugs, FDA executives rely on drug companies and doctors to report adverse reactions. This information is compiled in an FDA database. But gathering the information is only the first step. In some cases it takes several years to analyze the data in order to recognize and respond to a proven adverse reaction.

Under this system drug companies are basically being asked to police themselves. (That would be like asking Tony Soprano to, pretty please, not have anybody “whacked.”) But relying on reports of adverse reactions from doctors is also undependable. M.D.s are expected to report adverse reactions on a voluntary basis. But the process is time consuming and in some cases doctors may fear that investigations will draw malpractice
suits.

By some estimates more than 90 percent of all adverse reactions go unreported. And yet, according the Chicago Tribune, the FDA receives as many as 400,000 yearly reports of adverse reactions, and the worst of these reactions account for about 100,000 deaths each year.

RADAR network

Five years ago, Northwestern University researcher Charles L. Bennett, M.D., Ph.D., began building a better radar to detect adverse reactions to drugs. In fact, he called his project RADAR: Research for Adverse Drug Events and Reports.

Dr. Bennett’s process is fairly simple. Twenty-five doctors from five U.S. cities report their observations of potential adverse reactions, with special interest paid to the most serious reactions that could be fatal. When reports come in they’re then sent out to a larger group of researchers who begin to hunt for other reports. The FDA post-marketing database is one of the sources used for additional reporting.

To date, 16 different drugs and medical devices have been linked to adverse reactions that are potentially fatal. RADAR has identified severe adverse reactions in nearly 1,700 patients, and 10 percent of those patients died of complications associated with the reactions.

So has the FDA embraced Dr. Bennett’s RADAR? If you guessed “no” to that question, you’re on the right track. But even hardened cynics might be surprised at what happened next.

The big dog bites

One of the drugs that RADAR examined was Plavix, a popular clot-prevention drug. According to the Chicago Tribune, Dr. Bennett’s researchers reported that in rare cases Plavix may trigger a “catastrophic collapse of the blood system.” At Dr. Bennett’s urging the FDA added a warning to the drug packaging.

Dr. Bennett followed up the Plavix research with a study that compared how four years of adverse reactions to Plavix were tracked by the FDA, Bristol-Myers Squibb (BMS, the makers of Plavix) and the RADAR team. As reported in the February 2004 issue of the journal Stroke, Dr. Bennett scored RADAR’s effectiveness at 92 to 100 percent, while BMS scored between 8 to 58 percent and the FDA scored zero to 23 percent. Dr. Bennett gave the FDA a failing grade.

The FDA’s response? Apparently, someone at the agency was not very pleased. The Tribune reports that FDA officials reacted to the Stroke study by terminating Dr. Bennett’s access to the agency’s database.

The 16 to watch

Earlier this month the Journal of the American Medical Association published the RADAR conclusions of Dr. Bennett and his colleagues. The study included a list of these 16 drugs and medical devices that have produced adverse effects: Zolendronate, Amiodarone, Epoetin, Thalidomide, Gerncitabine, Ticiopidine, Gerntuzumab, Clopidogrel, Nevirapine, Flutamide, Sirolimus-eluting cardiac stent, rHu-MGDF (for thrombocytopenia), Bicalutamide, Enoxaparin, rHu-MGDF (for lymphomas), Paclitaxel-eluting cardiac stent.

If you’re currently using any of these drugs or devices, or if you know someone who is, it would be wise to talk to your doctor about the potential risks. But make sure he’s not relying on the FDA’s data.

Sources:
“Americans Prefer ‘Safer’ Older Drugs” Reuters Health, 5/6/05, reutershealth.com
“The Research on Adverse Drug Events and Reports (RADAR) Project” Journal of the American Medical Association, Vol. 293, No. 17, 5/4/05, jama.ama-assn.org
“RADAR Detects Sometimes-Deadly Drug Reactions” Elizabeth Weise, USA Today, 5/3/05, usatoday.com
“FDA Cut Off Critic’s Access to Drug Database” Ronald Kotulak, Chicago Tribune, 2/20/05, chicagotribune.com