Aspirin-Reye’s Chronology : Threat of Suits Delayed Warning Process
Here is an abbreviated chronology of the Reye’s syndrome-aspirin controversy:
- Jan. 14, 1982: Three hours before the American Academy of Pediatrics’ monthly newsletter was to go to press, three representatives of Schering-Plough Inc. showed up in the office of Dr. M. Harry Jennison, then the Academy’s executive director.
Schering-Plough, maker of orange-flavored St. Joseph’s Aspirin for Children, was concerned about one newsletter item that alerted pediatricians to the suspected risk of Reye’s posed by giving aspirin to children with chicken pox or the flu.
Jennison remembers the meeting vividly:
“They wanted to make it very clear that if (newsletter) went out, we would face a very serious lawsuit,” he said.
Jennison pulled the Reye’s item, but he sent a special advisory in the next month’s newsletter. The academy’s Committee on Infectious Diseases in June recommended that warning labels be required on all aspirin bottles.
- March 12, 1982: Schering-Plough sent its own letter to thousands of pediatricians, advising that “there is no valid scientific data” directly linking aspirin and Reye’s. “Therefore,” the company said, “you should feel confident in continuing to recommend aspirin for the reduction of fever in children.”
- June 4, 1982: U.S. Health and Human Services Secretary Richard S. Schweiker said that available evidence justified requiring warnings on all bottles of aspirin products. The Aspirin Foundation of America began an intense lobbying effort to convince him otherwise.
By order of President Reagan, all new regulations had to be evaluated for cost-effectiveness by the White House Office of Management and Budget. So Dr. Joseph White, president of the aspirin group, arranged to meet with James J. Tozzi, then an OMB official.
Tozzi said he checked the aspirin lobby’s complaint with an outside scientific expert and then told the Food and Drug Administration: “You have not made your case.”
“Procedurally, it was the best decision I ever made,” Tozzi said recently. He now directs a Washington-based consulting firm that specializes in companies seeking regulatory relief.
- Nov. 18, 1982: Schweiker retracted his proposal, calling the idea of warning labels premature.
- Oct. 7, 1983: Government and Aspirin Foundation officials met to discuss 470,000 educational pamphlets the FDA was about to distribute to 4,200 supermarkets nationwide. After the meeting, the pamphlets, which cost $18,000 to produce, were stashed in a warehouse. They have since been destroyed.
Within a month, the FDA had produced a new pamphlet, but with significant changes.
Of the statistical link between Reye’s and aspirin, the original pamphlet said: “Many medical experts . . . agree this apparent relationship cannot be ignored.” The revised version read: “The validity of these studies has been questioned by some experts.”
The original cautioned that “in most cases, it is unwise to give aspirin to a child with viral illness, and it is also unnecessary.” To the question of whether parents should avoid giving aspirin to children with flu symptoms, the revised answer began: “Not necessarily.”
- Fall, 1983: The Committee for the Care of Children, an industry-paid group of pediatricians, sent an attorney’s letter to broadcasters nationwide, asking them not to run the FDA’s public service announcements on Reye’s. Any station that did air the spots would be required to give the doctors’ group equal rebuttal time under the “Fairness Doctrine of Federal Law,” the letter said.
The announcements were not widely used.
- Nov. 5, 1984: Public service announcements produced by the committee were lambasted as “seriously misleading” by several government health agencies. The “medical bulletin on Reye’s syndrome” did not mention aspirin, but advised: “We do know that no medication has been proven to cause Reye’s.”
A supermarket pamphlet produced by the group did mention aspirin, under the caption: “Myths about R.S.”
“Recent studies suggest an association between aspirin and Reye’s, especially in children with influenza or chicken pox,” the pamphlet said. “We believe, and most authorities now agree, that these studies cannot be interpreted in this way. All medical experts agreed that aspirin does not cause R.S.”
- Jan. 9, 1985: HHS Secretary Margaret Heckler, citing preliminary data from a Public Health Service study, asked all aspirin manufacturers to begin using warning labels voluntarily.
Several independent aspirin makers, including Schering-Plough, acted promptly and decisively to place warning stickers on packages, and changed labels to feature the association between Reye’s and aspirin.
The eight large aspirin suppliers of the Aspirin Foundation did not re-label all their products until the end of August. Their new labels only suggested that parents to consult a doctor before giving the product to children.
White said the companies decided not to mention Reye’s syndrome on the label because “there was some disagreement about what the impact was of putting something on a label that wasn’t true.”
- Aug. 27, 1985: The New England Journal of Medicine, about to publish the findings of the preliminary government study, received a letter from Schering-Plough. The letter suggested that the company needed to review the data before publication so that the “prestige of the Journal” would not be involved in “questionable science.”
Marcia Angell, deputy editor of the journal, said the article “was published on its merits and reviewed in the usual way. Its publication was not because of anything the aspirin industry did or in spite of anything they did.”
- Sept. 4, 1985: White, in a letter to Heckler, accused the government researchers of misrepresenting the most recent findings in order to back up earlier work. He asked that the report not be used to draw any conclusions.
- Dec. 17, 1985: The FDA, citing the diversity of labels and the lack of specific mention of Reye’s syndrome on some of them, asked for and received legislation requiring warning labels, effective May 30, 1986.
- Fall, 1986: A committee of the National Academy of Sciences’ Institute of Medicine, overseeing the government’s investigation of Reye’s, decided that enough data had been gathered to warrant publication.
The study was to collect records of at least 100, perhaps 200 Reye’s syndrome cases for comparison. After a review of 27 cases, the evidence was overwhelming, said Dr. Floyd Denny, chairman of the Reye’s syndrome task force. Moreover, new cases were becoming rare as aspirin use declined.
“We would have loved to have 200 cases,” said Denny, a professor at the University of North Carolina at Chapel Hill, “but that would have been just impossible.”
- Nov. 12, 1986: White wrote the institute panel and asked that it continue the government study as long as necessary to find and review 200 cases.
Dr. Eugene Hurwitz, the chief researcher on the project at the Centers for Disease Control, estimated it would have taken at least six years to find even 100 statistically appropriate cases, “if you could do it at all.”
“What’s too long? And who cares how long it takes if the public is going to be protected?” White replied.
- March 2, 1987: White met with government officials to review the latest study, scheduled for publication in the Journal of the American Medical Assn. At the meeting were Don Newman, HHS undersecretary, Dr. Robert E. Windom, assistant secretary of health, Hurwitz and other researchers flown in from Atlanta and representatives of the Institute of Medicine and the FDA.
A spokesman for Windom described the meeting as routine, but one participant commented: “People at that level don’t routinely review studies.”
White left the meeting with a promise he would receive a copy of the article before it was published. The editors at the AMA Journal moved publication of the report up a month--because it was so important, they say.
