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BY ANNE ROCHON FORD with Women and Health Protection
"Consumers should not have to second-guess the safety of what’s in their medicine cabinet."– U S Senator Charles Grassley, R-Iowa at the Congressional hearings on Vioxx, November 2004
After a quick survey of prescription drugs currently on the market, a visitor to planet Earth might well ask, "Don’t these people ever learn from past mistakes?" They would be referring to the disturbing number of drugs that are approved for use and later withdrawn, or continue to be sold with warnings attached to them, long after "enough" harm has been done to the hapless scores who have been swallowing them.
Consider this sorry list. And while all of these treatments or products were found to have serious side-effects, not all of them were actually removed from the market:
- Hormone Replacement Therapy, prescribed to millions of women world-wide for the relief of menopausal symptoms and a reduction in the risk of bone fractures and cardiovascular disease, found in 2002 to increase the risk of heart disease, strokes, invasive breast cancer and blood clots.
- Selective Serotonin Re-uptake Inhibitors (SSRIs), a class of anti-depressant drugs, where some of the most widely prescribed were later discovered to raise the risk of suicidal thinking and suicide attempts in teenagers.
- Baycol, a cholesterol-lowering drug (statin) manufactured by Bayer AG, withdrawn from the market in 2000 after some patients using it developed a severe and sometimes fatal muscle disorder.
- Depo-Provera, an injectable contraceptive drug given a black box warning label (a warning reserved for the most serious side-effects) by the United States Food and Drug Administration in November 2004 after studies showed serious loss of bone mineral density in young women, a concern raised by women’s health advocates in the early 1980s.
- Vioxx (rofecoxib), a popular pain-killer for arthritis, withdrawn from the market internationally in September 2004 after studies showed an increased risk of heart attacks and strokes in users.
For women in particular, this list is even longer. Drugs and devices such as thalidomide, DES, the Dalkon Shield I.U.D. and the Meme breast implant have all been found to cause serious (and on-going) problems long after they had been unleashed on an unsuspecting public.
Both these recent and past examples point to serious flaws in our drug approval process and to an even greater problem with the surveillance of drugs once they have been approved and are on the market.
The case of Vioxx is a stellar example of how warning signs of possible harm may be ignored, minimized or covered up, even when serious problems were revealed in the early stages of clinical trials. Despite the fact that studies from as early as 1999 showed the drug was dangerous (see side-bar, testimony by David Graham of the US Federal Drug Agency), sales of Vioxx were pushed by one of the heaviest direct-to-public marketing campaigns ever seen in the US, with a significant spill-over effect in Canada.
While Graham’s testimony refers to the approval of Vioxx in the United States, the situation here in Canada is equally problematic; the federal government also knew of problems long before a decision to withdraw the drug from the market was made. In fact, research conducted by the Institute for Clinical and Evaluative Studies in Ontario found as early as 2001 that there were serious problems with the drug (The Lancet, 364, Dec 4, 2004: 2021-2029).
The flaws in the current drug regulatory system in Canada were highlighted in a report of the all-party Parliamentary Standing Committee on Health in early 2004. In "Opening the Medicine Cabinet: First Report on Health Aspects of Prescription Drug Use," the Committee recommended sweeping changes in the drug approval system. Their report focused on problems with secrecy on the part of Health Canada and was critical of their practice of allowing drug companies to maintain complete control over the data from clinical trials. The Committee also expressed concerns about the impact of direct-to-consumer advertising of prescription drugs and the weaknesses in adverse drug reaction reporting—all factors that contributed to the delay in withdrawing Vioxx.
Do we have any reason to be hopeful that things are changing for the better and that we will see a reduction in the approval of drugs that do more harm than good? The picture is mixed.
Some observers cite the intense focus on rapid approval for new drugs, in evidence in the US since the mid-1990s, as a major contributor to the present problematic situation. This same shift, whereby the regulator is more likely to bow to the economic interests of the drug companies than to protect the safety of the consumer, has also been happening in Canada. This was evident in the Throne Speech of 2002 (and the subsequent 2003 Federal Budget) which called for speedier approval of drugs without a comparable emphasis on post-approval safety surveillance.
On the positive side is the Parliamentary Standing Committee on Health report that questioned this fast tracking of drugs. The report was an important wake-up call. The Vioxx scandal is another. Health Minister Dosanjh calling for mandatory reporting of adverse drug reactions by health professionals in December 2004 is another small step forward. But there are many important changes that are still needed before we have a system that puts the health protection of consumers above all other imperatives and ensures that the drugs women take have more benefits than harms.
To see the Canadian all-party Parliamentary Standing Committee on Health report, "Opening the Medicine Cabinet: First Report on Health Aspects of Prescription Drug Use" (2004), visit www.parl.gc.ca/InfocomDoc/Documents/37/3/parlbus/commbus/house/reports/healrp01-e.htm
For more from Women and Health Protection, visit: www.whp-apsf.ca
From David Graham’s testimony to the US Congressional hearings on Vioxx (Graham is the Associate Director for Science and Medicine in the US Food and Drug Administration, Office of Drug Safety):
Prior to approval of Vioxx, a study was performed by Merck named 090. This study found nearly a 7-fold increase in heart attack risk with low dose Vioxx. The labeling at approval said nothing about heart attack risks. In November 2000, another Merck clinical trial named VIGOR found a 5-fold increase in heart attack risk with high-dose Vioxx.
The company said the drug was safe and that the comparison drug naproxen, was protective. In 2002, a large epidemiologic study reported a 2-fold increase in heart attack risk with high-dose Vioxx and another study reported that naproxen did not affect heart attack risk. About 18 months after the VIGOR results were published, the FDA made a labeling change about heart attack risk with high-dose Vioxx, but did not place this in the "Warnings" section. Also, it did not ban the high-dose formulation and its use. I believe such a ban should have been implemented.
…The [drug approval] culture is dominated by a world-view that believes only randomized clinical trials provide useful and actionable information and that postmarketing safety is an afterthought. This culture also views the pharmaceutical industry it is supposed to regulate as its client, over-values the benefits of the drugs it approves and seriously under-values, disregards and disrespects drug safety.