Since initial experiments don’t always reveal a drug’s dangers, the Food and Drug Administration maintains a system of “postmarketing surveillance.” Doctors and drug companies pass along patients’ complaints, regardless of merit, and the agency watches for patterns. The FDA’s epidemiologists have long worried about the number of Halcion users reporting psychiatric disturbances such as anxiety, memory loss, hostility, even psychosis. In 1989, after two agency studies showed that Halcion was spawning more than its share of such reports, the FDA convened an advisory panel to examine the trend and hear what Upjohn knew about it. Speaking for the company, Dr. Roy Drucker, a vice president, cautioned that spontaneous reports provide only a signal of possible trouble. He added that “there is no information available to the Upjohn Company, outside this meeting, that would tend to substantiate that signal.” The committee accepted Drucker’s assertion and voted not to impose special restrictions on the drug. Upjohn has since used the same argument to deflect countless questions about Halcion’s safety. But according to a former company scientist, there’s more to the story.
From the time Halcion hit the U.S. market in 1983 until shortly before he left Upjohn in 1990, Dr. William Barry directed the company’s own postmarketing-surveillance program. In portions of a taped deposition shown during the Wacaser trial this month, he made dear that by 1989 he had detected the same trends as the FDA scientists and had spent years voicing concern. Barry testified that as early as 1983, he had written a memo describing an unexpected number of amnesia complaints from Halcion users; in 1984, he determined from an in-house study that people on high doses were reporting more amnesia, confusion and hallucinations than people on low doses. (One wouldn’t expect to see such a pattern if the problems were unrelated to the drug.) Barry also testified that he later urged the company to consider stronger warnings about such reactions as paranoia, psychosis and homicidal behavior.
Upjohn argues that because Barry’s work was based on the same kind of reports as the FDA’s analysis, it doesn’t shed any additional light. Anecdotal reports can never pinpoint the frequency of a reaction, says spokeswoman Kaye Bennett.
No one, including Barry, would claim otherwise. What’s remarkable is Upjohn’s willingness to dismiss years of analysis and concern. Barry’s account suggests that dismissing safety concerns about Halcion has become a virtual company policy. He testified that during his tenure, the firm created a standing task force called the Halcion Worldwide Committee to defend the drug from criticism. Barry won’t elaborate on the committee, or anything else, but testimony from other court cases gives a sense of the group’s priorities. In a 1987 company presentation that has been discussed in court proceedings, the scientist in charge of the committee recounted monitoring the fate of a study linking prolonged Halcion use to severe daytime anxiety. The Upjohn scientist, Dr. Robert Purpura, was able to report that two journals had rejected the study and that a third would likely follow. Court papers show that an Upjohn official credited the company with blocking publication.
The study, by Prof. Ian Oswald and Dr. Kirstine Adam of Edinburgh, Scotland, was eventually published in the German medical journal Pharmacopsychiatry. Bennett now dismisses the notion that Upjohn tried to derail the study, noting that the other journals rejected it “on its own merits.” She declines, however, to discuss the Halcion Worldwide Committee. “We have consistently resisted efforts by plaintiffs’ attorneys-and their expert witnesses-to try cases in the media,” she says. “We don’t believe that the media is the right place to resolve litigation, [or] to debate the scientific merits of a pharmaceutical product.”
In Maryland this week, the FDA’s advisory committee on psychopharmacological drugs is taking a closer look at those merits. Upjohn maintains that if the panel looks beyond the spontaneous reports and examines controlled trials, Halcion will be vindicated. “We expect that … Halcion … will be given a fair review,” says Bennett. The drug’s critics are equally confident that in examining the whole clinical record, the committee members will see why countries like France, Spain and England are imposing restrictions or bans. What’s clear is that Upjohn, having sidestepped legitimate safety questions for nearly a decade, will finally have to address them in earnest.
