Opinion ID: 1381810
Heading Depth: 3
Heading Rank: 3

Heading: Wyeth's Interactions with the FDA Regarding Hormone Replacement Therapy

Text: Wyeth sought FDA approval of Prempak, a combination product containing Premarin and a progestin tablet, in the 1980s. Wyeth did not support its application with its own study, but instead relied on the then-available studies to substantiate the efficacy and safety of Prempak. The FDA denied the application, concluding that the studies were inadequate and that Wyeth was unable to assure the long term safety of the combination treatment for human use. By the early 1990s, Wyeth was well aware of the FDA's position that the data on estrogen use in combination with progestin was insufficient. In an internal memo dated August 22, 1990, Justin Victoria explained that the FDA had denied Wyeth's applications for combination packaging, informing Wyeth that it could not approve a combination without an adequate, well-controlled clinical trial that evaluated the overall benefits and risks of the combination. The memo stated that the FDA remain[ed] unconvinced of the overall safety and effectiveness of combined estrogen/progestin therapy. Wyeth and Upjohn also attended the 1990 and 1991 meetings that the FDA held to address, among other issues, the concern that hormone replacement therapy was associated with an increased risk of breast cancer. Both meetings concluded that the current available evidence was insufficient and inconclusive, as some studies showed an increased risk and others did not. Scroggin's regulatory expert and a former Chief Medical Officer with the FDA, Dr. Suzanne Parisian testified at trial that the FDA would have expected Wyeth to take these meetings seriously and that Wyeth should have viewed the 1990 meeting as a red flag. Wyeth, however, considered the meeting a success, celebrating it as a non-event. In 1991, Wyeth sought FDA approval of its Premarin marketing plan and the plan's centerpiece, a magazine. In a February 21, 1991, letter to Wyeth, the FDA's Acting Director of the Division of Drug Advertising and Labeling stated that the FDA view[ed] this campaign in its entirety to be a form of extremely insidious hidden persuasion and a marketing ploy masquerading as concern for the health of postmenopausal women. The letter described the magazine as a house organ, faulting it as misleading for failing to clearly state Wyeth's sponsorship and for stating that the magazine was provided by a pharmacy. Moreover, the letter criticized the magazine's articles as misleading. The letter remarked that the campaign  intentionally misleads the reader into thinking that her physician is somehow responsible for providing it to her. Wyeth subsequently altered the campaign. In 1994, the FDA approved Prempro, a combination packaging of estrogen and progestin, on the condition that Wyeth perform a post-marketing study on the risk of breast cancer. Dr. Parisian testified that the FDA cannot force a pharmaceutical company to perform safety tests and suggested that approval was granted as a means of compelling the study. Such a study would take eight or nine years to complete. Following the FDA's approval of Prempro, Wyeth requested that its support of the following two studies satisfy its obligation to study the breast cancer risk: the WHI study and the Women's International Study of Long-Duration Oestrogen After Menopause. The WHI study was underway and was evaluating whether combination use of estrogen and progestin provided long-touted cardiovascular benefits. Although the FDA had previously expressed skepticism that the WHI study could evaluate the breast cancer risk, it approved Wyeth's proposal.