The drug’s label, however, suggested the exact opposite ideal, advocating for the lowest effective dose for the shortest period of time. Essner noted in his speech that his words were the paraphrased hopes a former director of the National Institutes of Health had once expressed for the future of HRT — and besides, Wyeth lawyer Hubbard adds, this meeting was a sales rally, a pep talk of sorts for the troops, not a literal directive. Physicians would get their prescribing information not through Wyeth representatives, but through labels — labels that have always been FDA-approved.
But according to court testimony, the troops were indeed selling the idea of “Prempro for life” to doctors — and not just for hot flashes. Heart disease, Alzheimer’s … it was all fair game for salespeople doing their job, even though neither of those uses was affirmed by the FDA. And in the case of heart disease, the claim of protection was later proven wrong.
THE BURR IN Prempro’s saddle has always been the breast cancer risk. It started the same day the drug was approved, with the FDA noting: “The true effect of HRT on breast cancer incidence and mortality must be considered the most important safety issue.” The agency required that breast cancer studies continue.
Wyeth lawyers and researchers insist that previous testing on the estrogen-plus-progestin combination (E+P) that makes up Prempro was extensive, but as late as 1995, the company’s own sales training booklet noted that there were no large-scale, long-term studies to support the safety and efficacy of the combined hormone regimen (though the next sentence muses, “The perception of Ob-Gyns is that the continuous combined regimen of estrogen and progestin is a well-studied, safe regimen”).
“The FDA okayed it,” Millrood says, “because they felt there was a need for the drug. And they trusted that the company would abide by scout’s honor — that they’d seriously approach the breast cancer issue, that they would tell people to use it, for now, only for the short term.”
The plaintiffs’ counsel are adamant that Wyeth could have, should have, done more — more testing, more warnings — especially in light of “red flags, which were everywhere,” Millrood says. Red flag: A 1989 article, “The Risk of Breast Cancer after Estrogen and Estrogen-Progestin Replacement,” published in the New England Journal of Medicine and reporting slightly increased risk of breast cancer with estrogen, possibly increased with the added progestin. Wyeth advised its sales force: “Under no circumstances should you initiate discussions concerning this study. If asked about the study, be factual. You should continue to present the benefits.”
Through the years, the company also considered how it might manage the media. Confidential memos highlighted by the plaintiffs discussed how to “downplay the value of” a 1996 study that found breast cancer among lean women using E+P, advocating a “dismissive strategy” that would suggest the media was “inappropriately creating a public health scare.” “Dismiss and distract,” read the handwritten scrawl. “We must be prepared to deal with press so headlines do not read ‘WARNING,’” said another. There would be op-eds placed in media, and an education campaign, spearheaded by the National Council on Aging, to raise “awareness and concern about various age-related diseases to neutralize fear of breast cancer.” Wyeth contends that these cited directives were drafted by outside consultants, and that the company didn’t follow the advice, for the most part.
But the question, muffled as it may have been, didn’t go away. In 1990, the International Agency for Research on Cancer (IARC) was considering classifying estrogen as a carcinogen of the breast. Wyeth — which at this point listed the possible link on its own label — formed a task force of doctors to help inform the IARC, so that it wouldn’t define a definitive relationship between the two.
The company line is clear: Wyeth maintains it always made sure the labeling on the drug was accurate, reflecting everything that evolving science knew about the drug.
The label — sure. But there are so many other ways of getting the message out.