The NewStandard ceased publishing on April 27, 2007.

New Drug Danger Revelations Point to Need for Reform, Critics Say

by Lila Bernstein

With yet more already-marketed medicines raising the ire of consumer advocates and regulators alike, momentum is building for reform of the government’s drug approval and monitoring procedures.

Dec. 19, 2004 – A consumer advocacy group called for a ban on two popular arthritis medications Friday after revelations that they may pose serious health risks. Also on Friday, the US Food and Drug Administration warned physicians and patients that one of the drugs, Pfizer Incorporated’s Celebrex, may cause increased risk of cardiovascular events. Though the FDA said it had not yet determined that it was necessary to take the drug off the market, the agency issued a recommendation that doctors and patients consider alternatives or cut dosage to the "lowest effective" amount.

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Concerns over the safety of Celebrex had emerged into the mainstream in late September when a similar drug, was voluntarily pulled from the shelves by its manufacturer. Pharmaceuticals giant Merck pulled the plug on its best-selling Vioxx in response to confirmation of earlier evidence that the drug increased heart risks. Celebrex and Vioxx, along with another Pfizer drug, Bextra, belong to the same class of drugs. Bextra too raised safety concerns recently when a study found an increased risk for cardiac events in users who have undergone heart surgery.

Some scientists say it has not come as a surprise that the COX-2 inhibitors, which work by blocking the COX-2 enzyme, may affect the heart. The enzyme is linked to pain and inflammation, but is also thought to have qualities that protect the heart. As early as four years ago some researchers had theorized that preventing the enzyme from working could affect its ability to benefit the heart.

The FDA said Friday that it was issuing its Celebrex warning because it had been informed by Pfizer and the National Cancer Institute (NCI) that a clinical trial testing the use of Celebrex to prevent colon polyps had to be stopped when researchers discovered an increased heart risk for those taking the drug in high doses. But the FDA said that "previous large studies of Celebrex, including clinical trials and epidemiology studies, have not suggested [cardiovascular] risk found in the NCI polyp study.

For its part, Pfizer said it did not plan to recall Celebrex, but was taking steps to "fully understand the results and rapidly communicate new information to regulators, physicians and patients around the world."

In a press statement, Pfizer’s chairman and chief executive, Hank McKinnell said the "clinical trial results are new" and that the findings in the polyp study are "unexpected and not consistent" with other studies.

But Public Citizen, a nonprofit consumer advocacy organization, called McKinnell’s statement misleading. The group pointed to previous findings by an FDA physician who observed that Celebrex may reduce blood flow to the heart. That physician, Dr. Douglas C. Throckmorton, deputy director of the Division of Cardio-Renal Drug Products at the FDA, also found that people taking Celebrex experienced a higher incidence of atrial fibrillation, a type of heart rhythm disturbance, compared to those taking other pain medications. In the 2001 report, Throckmorton was careful to note that the number of people in his review was small and that a larger study was necessary to draw conclusions.

Public Citizen also pointed to a study published in 2000 by the Proceedings of the National Academy of Sciences, which found that rabbits treated with celecoxib, the active drug in Celebrex, and another COX-2 inhibitor were less able to withstand heart attacks. It was that study that gave scientists clues into the COX-2 enzyme’s cardioprotective qualities.

"Even before today’s announcement by Pfizer about the heart attack risks associated with Celebrex, Public Citizen’s Health Research Group was preparing a petition to the [FDA] to ban both Celebrex and the other Pfizer COX-2 drug, Bextra," said Dr. Sidney Wolfe, of Public Citizen, in a press statement. "In February 2001, we testified at an FDA advisory committee hearing that the cardiac risks of Celebrex and Vioxx demanded a black box warning for both drugs." A black box warning is the FDA’s most serious type of warning label.

Wolfe added, "Two months later, in the April 2001 issue of our newsletter Worst Pills, Best Pills News, we urged patients not to use either drug because there are safer alternatives."

The recent disclosures about Celebrex and Bextra, just the latest in a string of pharmaceutical controversies, have led to severe criticism of the FDA’s drug approval process from consumer advocacy groups, scientific community, lawmakers and the general public.

The Journal of the American Medical Association (JAMA) recently published a scathing editorial pointing out the various conflicts of interest arising from the FDA’s monetary dependence on the pharmaceutical companies it is charged with regulating. Since the 1992 passage of the Prescription Drug User Fee Act, the FDA has collected hundreds of millions of dollars in user fees from drug companies. Since then, according to the General Accounting Office, the approval time of most drugs has more than doubled.

The pharmaceutical industry also spends huge sums of money pressing its case to its own regulatory agency. Confidential documents obtained by the New York Times in June 2003 revealed that the drug industry group Pharmaceutical Research and Manufacturers of America (PhRMA) planned to spend $4.9 million lobbying the FDA during the next fiscal year.

JAMA editors, Phil B. Fontanarosa, Drummond Rennie, and Catherine D. DeAngelis, also criticized the current process used to monitor the safety of drugs once they have been approved by the FDA and are in wide, long-term use. Pointing to the largely "voluntary" and "passive" system in which the drug companies are relied upon to evaluate the safety of their own products and report to the FDA, JAMA said the process was rife with incomplete data and conflicts of interest.

"[Because] of conflicts of interest or perhaps other reasons, some companies may neglect to fully acknowledge reports that indicate harm and [may] fail to initiate proper studies to determine risk," wrote the editors.

Since the Vioxx scandal, pressure has been growing for the government to create an independent drug safety board or agency that would be tasked with post-marketing surveillance of pharmaceuticals. The FDA’s critics say the agency cannot be trusted to sufficiently evaluate drugs after it has approved them for use.

Wrote the JAMA editors, "It is unreasonable to expect that the same agency that was responsible for approval of drug licensing and labeling would also be committed to actively seek evidence to prove itself wrong."

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The NewStandard ceased publishing on April 27, 2007.

Lila Bernstein is a contributing journalist.

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