SECRETS KILL

What were McNeil's attorneys trying to hide? Documents and testimony suggest that the company knew for years about the possibility of serious allergic reactions to Zomax but suppressed the information to preserve the drug's sales. In the Bible, Leviticus admonishes that one must not "put a stumbling block before the blind." You rarely hear it from the clergy, but a drug company that deceives physicians by knowingly failing to inform them fully and promptly of the hazards of a prescription drug is doing just that. The blind are of course the doctors' patients, nearly all of whom are ignorant of the complex pros and cons of the drug. So they must - blindly - trust their physicians, and perhaps pay with their health, safety, even their lives. That may have happened in the case of Zomax.

According to McNeil internal documents, during premarket testing of Zomax in the seventies, the company received reports that several users had suffered severe but nonlethal allergic reactions. These reactions should have been recognized as anaphylactic almost immediately, because Zomax is almost identical to Tolectin, a McNeil prescription arthritis drug that accounts for an extraordinary share of anaphylactic reactions among drugs in its class. But McNeil's testers neither identified the reactions correctly nor reported them in FDA-required labeling. According to a report by Patrick Seay, the company's regulatory affairs chief, one McNeil official complained around that time that the company was "reporting too many adverse reactions on our drugs." But the company had a more palatable explanation when later questioned by the Post. The premarketing evidence, they said, had been inconclusive.

The FDA apparently agreed. Despite investigators' concerns about the possible cancer risk, the drug received federal approval in October 1980, a decision based largely on the belief among key agency personnel that the painkiller was as effective as morphine. Did the FDA cite a study to justify that crucial belief? No, FDA officials later admitted - no such study existed. Nevertheless, the drug immediately went on sale, and the carcinogen question was brushed aside. Within four months, Zomax had captured 11 percent of the prescription painkiller market.

Determining cancer risks may take awhile, but allergic reactions are easier to see. Shortly after marketing began, McNeil received reports of several more reactions. So in July 1981 - nine months after it started promoting the drug - McNeil revised the prescribing instructions to disclose that "anaphylactoid reactions have been reported." But the disclosure was tucked away in the "precautions" section, not in the more conspicuous "warnings" section - a decision that one of McNeil's own executives later decried as a triumph of sales over safety. Seay, the regulatory affairs chief, noted in a 1984 overview of marketing strategy that the marketing division had gained "a greater role in the content and changes of the package insert" at the expense of the medical side. "We resisted too much and waited too long," he wrote. And he was right. But package labeling wasn't the half of it.

Association (JAMA) of a case of anaphylactic shock in a Zomax user, a directive to play down the report went out to McNeil's sales force. "This information is being sent to you so you will be fully prepared to respond to a physician or pharmacist who initiates discussion on the article," the memo said. "You should not bring up the subject."

The memo may as well have been a cue to the FDA, which looked into the matter after the JAMA report but did nothing. Inside McNeil itself, however, the subject wouldn't die. Later that year, a McNeil researcher reviewing the 178 known reactions to Zomax discovered a pattern: Many of the reactions occurred in people who took the drug intermittently. Intermittent users were Zomax's largest market, about 75 percent; any adverse reactions among this group of casual users would unquestionably slow sales. So under the guise of informing the public, McNeil did a little damage control. In the spring of 1982, it drafted a "Dear Physician" letter to 200,000 doctors specifying that reactions might occur in intermittent users. By the time the letter was mailed, however, it consisted of a single, and singularly vague, sentence: "Hypersensitivity upon reexposure or extended use cannot be ruled out." The word "intermittent" had been excised.

But McNeil appeared to be apprehensive even about that mild statement. Just seven days after the mailing, the company launched a new, high-pressure sales campaign. "We're calling it |Operation 111,'" sales vice president Thomas H. Odiorne said in an April 16 mailgram. "Now, if that sounds like war, well, in our world of selling that's what it is." Explaining the name "Operation 111," the mailgram said that McNeil hoped to reap $111 million in annual sales of sister drugs Zomax and Tolectin. For the next 10 weeks, the mailgram instructed, the sales force was to concentrate exclusively on the two products.

Not everyone at McNeil was happy with that war cry. The tension between profits and public safety came to a head in two days of meetings in February 1983 at McNeil headquarters in Spring House, Pennsylvania. Three of the firm's top physicians, including Dr. James A. Dale, an associate medical director, told the company president that they were so concerned about the safety of Zomax that they themselves would not prescribe it. But McNeil executives, accountable to James Burke, refused to recall the drug, deciding instead to strengthen the warning in the labeling. In the company's view, this was the prudent course, given what was known at the time. But while the new warning was being prepared, McNeil learned of fatal anaphylactic shock in three Zomax users.

Another jolt followed quickly: Several nonfatal anaphylactic reactions in Syracuse, New York, were reported by a local television station that featured a Syracuse physician's account of his own life-threatening reaction to Zomax. This was the first bad publicity for Zomax to appear in the lay press, and it was such publicity that McNeil most feared. The next day, March 4, McNeil announced it was recalling the drug from the U.S. market. The decision was made by Burke himself.