What Did They Know and When Did They Know It?

Robert A. Schwartz, Attorney at Law

May 23, 2007

Bob Schwartz PhotoWyeth and other pharmaceutical companies tested, manufactured, marketed, distributed, promoted and sold Premarin, Prempro and MPA (the synthetic progestin used in Prempro), hormone-replacement drugs prescribed for post-menopausal women to treat some of the problems associated with menopause. For decades, Wyeth and other manufacturers vigorously promoted the hormone-replacement therapy as safe, effective and beneficial.

On July 9, 2002, however, the National Heart, Lung and Blood Institute halted the 16,600-patient Women’s Health Initiative clinical trial three years before it was scheduled to conclude. The trial was designed to evaluate the risks and benefits of Prempro hormone therapy in healthy, post-menopausal women. The institute shut down the trial after Women’s Health Initiative scientists determined that the risks of taking Prempro outweighed the benefits. Almost simultaneously, researchers at the National Cancer Institute reported that women who use long-term estrogen therapy (e.g., Premarin) are at a significantly increased risk of developing ovarian cancer.

Taken together, the two studies established that long-term use of hormone therapy increased the risk of cardiovascular disease, invasive breast cancer, pulmonary embolism, blood clots, strokes, heart attack and ovarian cancer. Wyeth and other manufacturers knew, or should have known, the severe risks their hormone therapy posed to women. The decades-long marketing and promotion of hormone therapy — either as combination estrogen and progestin therapy or estrogen alone — as safe and effective for post-menopausal women was false and misleading. Nonetheless, the drugs were marketed as safe and effective. Wyeth and other manufacturers knew, or should have known, the severe risks their hormone therapy posed to women.

Pharmaceutical litigation exists solely because the pharmaceutical companies do not fully disclose the risks of their drugs to anyone. They disclose what they want the world to know and start a game with the Food and Drug Administration. The FDA does not conduct scientific studies or test the drugs it is asked to approve. It simply reviews information from pharmaceutical manufacturers. It’s a classic example of the fox guarding the hen house.

To better understand not only this dilemma with the FDA approval process but also the incredible, tobacco-like attitude of the pharmaceutical industry, we have to look only at the recent news on hormone-replacement therapy. In December 2006, a well-respected physician at the M.D. Anderson Cancer Center reported that a decline in breast cancer incidence had been observed from 2002 to 2003 continued into 2004, supporting the hypothesis that the decline is tied to a decrease in use of hormone-replacement therapy among postmenopausal women, according to a study published Thursday in the New England Journal of Medicine. Dr. Peter Ravdin, a research professor in the Department of Biostatistics at M.D. Anderson Cancer Center, and colleagues presented data at the 29th annual San Antonio Breast Cancer Symposium in December 2006 showing that breast cancer incidence among U.S. women dropped by 7 percent from 2002 to 2003, possibly because of a decrease in HRT usage (Kaiser Daily Women’s Health Policy Report, 12/18/06). For the study, Ravdin and colleagues analyzed data from the National Cancer Institute’s Surveillance, Epidemiology and End Results study to determine the change in breast cancer incidence from 2001—the last full year before the government released findings of a large HRT study—to 2004 (USA Today, 4/19). The overall decline in breast cancer incidence from 2001 to 2004 was 8.6 percent, including a 6.7 percent drop from 2002 to 2003. In 2002, results were released from the Women’s Health Initiative study showing that HRT appeared to increase the risk of heart attacks, strokes, breast cancer and other health problems. As a result, millions of women ceased use of the drugs (Stein, Washington Post, 4/19). Prescriptions for HRT declined by at least 38 percent in 2003 and by an additional 20 percent in 2004. Researchers found that in 2003 and 2004, 30,000 fewer women developed breast cancer than would have been predicted by previous trends, and the incidence of breast cancer reached its lowest rate since 1987. Researchers found that the biggest decline in incidence—14.7 percent—was in estrogen-receptor–positive tumors, in which estrogen promotes growth. In estrogen-receptor–negative tumors, the decline was 1.7 percent (Maugh, Los Angeles Times, 4/19). Researchers estimate that 16,000 fewer cases of breast cancer are being diagnosed each year because of the decline in HRT use (Washington Post, 4/19).

Ravdin said the study results do not mean that all women should discontinue use of HRT because the “risk of developing breast cancer from use of these hormones is relatively small, and for some women with menopausal symptoms, the benefits of hormone therapy are well worth the risk” (Peres, Chicago Tribune, 4/19). Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center said that “we can’t prove” the decline in breast cancer incidence is because of a decline in HRT use, “but it is such a substantial reduction that you would need something big to have occurred to explain it. If it is not hormone replacement therapy, we still need to explain it” (Los Angeles Times, 4/19). Marcia Stefanick of Stanford University said that “these data add to the message that we really should be discouraging women from initiating menopausal hormones. We need to stop underplaying those risks. They are very real” (Washington Post, 4/19).

Pretty convincing scientific information, right? Not if you are in a constant state of denial. Dr. Joseph Camardo of Wyeth noted that there was not a sharp decline in 2004, though hormone use fell an additional 20 percent that year. He also argued that the rapid decline in incidence so soon after the drop in hormone use was biologically implausible. Camardo noted that the labeling for hormone replacements already carries a warning about the potential risk of ovarian cancer.

Wyeth spokeswoman Candace Steele wrote in an e-mail message that ”breast cancer is a complex disease and the causes are not known.” At this point, she said, ”it is simply inappropriate to make any speculative statements” based on the analysis. And, she added, ”clearly, more studies are warranted.”

Wyeth’s own website has its response by Camardo to the news:

“Reports such as this cause confusion,” says Joseph Camardo, M.D., Senior Vice President of Global Medical Affairs for Wyeth Pharmaceuticals. “The hypothesis put forth in this report does not change what we know about hormone therapy, which is based on data from numerous, more rigorous studies including the Women’s Health Initiative. These randomized trials provide a higher level of evidence on the risk/benefit profile of hormone therapy.” “Hormone therapy remains a good health care choice for the appropriate woman seeking the relief of moderate to severe menopausal symptoms, including hot flashes, night sweats and vaginal atrophy, and the prevention of postmenopausal osteoporosis,” adds Dr. Camardo.

Wyeth continues to support the appropriate use of hormone therapy and recommends that it be used at the lowest dose for the appropriate duration consistent with treatment goals and risks for the individual woman. Women experiencing menopausal symptoms are encouraged to speak with a health care professional to determine whether it might be the right treatment option for them. Wyeth urges women to continue to have routine mammography exams as recommended by the American Cancer Society and as advised in product information provided to patients using hormone therapy.

Always sure of itself, its self-righteousness and its altruistic conduct, Wyeth appended this disclaimer to the bottom of its response:

The statements in this press release that are not historical facts are forward-looking statements based on current expectations of future events and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include the inherent uncertainty of the timing and success of, and expense associated with, research, development, regulatory approval and commercialization of our products, including with respect to our pipeline products; government cost-containment initiatives; restrictions on third-party payments for our products; substantial competition in our industry, including from branded and generic products; data generated on our products; the importance of strong performance from our principal products and our anticipated new product introductions; the highly regulated nature of our business; product liability, intellectual property and other litigation risks and environmental liabilities; uncertainty regarding our intellectual property rights and those of others; difficulties associated with, and regulatory compliance with respect to, manufacturing of our products; risks associated with our strategic relationships; economic conditions including interest and currency exchange rate fluctuations; changes in generally accepted accounting principles; trade buying patterns; the impact of legislation and regulatory compliance; risks and uncertainties associated with global operations and sales; and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption “Item 1A, RISK FACTORS.” The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

So, what did they know and when did they know it? That is the question to be answered and that is why Wyeth and the other manufacturers of hormone-replacement therapy products are in litigation. Without this litigation, the victims and their loved ones would never know the truth.