Failure to fully document risks of osteoporosis drug is ‘reckless’
Chicago Tribune, Sunday, April 19, 1998
Eli Lilly recently began running full-page color ads for Evista, a synthetic hormone with both estrogenic and antiestrogenic effects, in major national and regional newspapers Tile ads claim that Evista offers “a new way to prevent osteoporosis,” but at the same time admit that “its effect on fractures is not yet known.” The ads also claim that women taking Evista had no increased risks of breast and uterine cancers, in contrast to conventional hormone replacement therapy, and that it reduces LDL or bad cholesterol blood levels. This should be welcome news to women worldwide particularly as osteoporosis has now reached epidemic proportions, affecting 15 million to 20 million American women each year; osteoporosis causes more than a million fractures, including 250.000 hip fractures, and kills some 50,000 elderly women, from complications as a result of their fractures.
While warning of some possible side effects, such as blood clots or hot flashes, Lilly fails to warn of the more serious risks of ovarian cancer. A company sponsored article in the Dec. 4, 1997 issue of The New England Journal of Medicine also ignores this risk. Lilly’s pre-market clearance study, however, clearly shows that Evista induces ovarian cancer in both mice and rats. Furthermore, carcinogenic effects were noted at dosages well below the recommended therapeutic level. However, the study concluded: “The clinical relevance of these tumor findings is not known.” Lilly reached this conclusion despite the strong scientific consensus that the induction of cancer in well designed tests in two rodent species creates the strong presumption of human risk. Nevertheless, Lilly fails to disclose this critical information in its ads and in its “warning” to patients.
Responding to such criticisms by one of us (Samuel Epstein) during a broadcast of the “Jim Lehrer Newshour” earlier this year [Jan. 12], a Lilly spokesman claimed that the carcinogenic effects of Evista in the ovaries of sexually mature rodents are irrelevant to such risks in postmenopausal women, as their ovaries are inactive, and, therefore, no warning is necessary. Apart from the fact that the rodent studies were specifically designed to evaluate Evista’s safely. Ovarian cancer is a scientifically documented complication of long term estrogen replacement therapy in post-menopausal women. Also disturbing is the claim that Evista poses no risks of breast and uterine cancers, based on clinical trials over only some 40 months, a period totally inadequate to possibly measure any such risks.
Ovarian cancer strikes about 24,000 women in the United States every year, accounting for 4 percent of all female cancers. About 15,000 women die annually from ovarian cancer, making it the most lethal of all female reproductive cancers. Lilly’s suppression of its own evidence of ovarian cancer risks from Evista is reckless and threatening to women’s health and life. Equally reckless is the Food and Drug Administration’s December 1997 marketing clearance, especially in the absence of any requirement for warning. Such conduct clearly merits urgent congressional investigation, Evista should be withdrawn from the world market immediately. As importantly, a “cancer alert” should be sent to the more than 12,000 women who have participated in U.S. and international clinical trials, in the absence of fully informed consent. The doctrine of informed consent is ethically and legally protective only when all facts relevant to benefits and risks are affirmatively disclosed. This is clearly not the case with women who have been involved in the Evista trials. These women should be offered semi-annual lifelong surveillance for the early detection of ovarian cancer at Eli Lilly’s expense.
Samuel S. Epstein, M.D.
Chairman, Cancer Prevention Coalition
c/o University of Illinois at Chicago
School of Public Health, M/C 922
2121 W. Taylor Street
Chicago, IL 60612