Odell Buggs walked into the federal courthouse in downtown Rochester, N.Y., on a cold and snowy Tuesday in December last year, not knowing what to expect. She walked out with a promise from one of the world's biggest pharmaceutical manufacturers to pay her $1.3 million.
Six years earlier, Buggs, then a 28-year-old counselor for needy children, had suffered a stroke that her doctors attributed to an ingredient in her over-the-counter decongestant, Tavist-D. She sued the manufacturer, Novartis AG, saying its cold pills had left her with brain damage.
The Swiss-based company's defense was that the ingredient, phenylpropanolamine, or PPA, was in dozens of cold remedies and appetite suppressants, and had been taken in billions of doses with no ill effects.
But by the time Buggs arrived in court, Novartis knew, though the public didn't, that Yale University researchers had tentatively concluded that PPA was linked to a slight risk of a certain type of stroke in young women. The company offered to settle, and Buggs accepted. The settlement called for Buggs to keep the terms confidential.
Buggs had hoped for a trial and news coverage. Instead, she remained silent until last month, when the Food and Drug Administration announced plans to ban phenylpropanolamine, saying the Yale study had led them to estimate that PPA had caused 200 to 500 strokes each year and that the risk, though slim, outweighed the drug's benefits.
Drug companies said the Yale scientists were wrong and that the drug was safe. Buggs was elated. "Now," she said, "people will see."
The case offers a glimpse into how companies marketing PPA worked aggressively to assuage concerns about the safety of a drug that for six decades was a staple in medicine cabinets. It also sheds light on a larger issue: Pharmaceutical companies, which spend more than $20 billion a year researching and developing medicines, devote far less attention to examining how their drugs are used.
In the case of PPA, safety questions simmered for two decades in scientific circles, in the courts and in Washington. In each arena, an examination of court records and other public documents shows, pharmaceutical companies or their representatives tried to tamp down the public debate.
In the scientific circles, a university pharmacologist acted as a reviewer for medical journals considering whether to publish reports on PPA research while he was on the payroll of the leading maker of diet pills, Thompson Medical Co. His anonymous critiques helped relegate some articles that questioned PPA's safety to little-known medical journals.
In the courts, PPA makers faced more than two dozen lawsuits and usually demanded confidentiality agreements when they settled. In two cases, patients died. In another, the court record was sealed. In Washington, Sandoz Pharmaceuticals Corp., a predecessor to Novartis and the original manufacturer of Tavist-D, pressed regulators to keep cold medicines out of their PPA safety review.
Thompson Medical no longer exists. It sold its diet pill line to Chattem Pharmaceuticals, whose officials declined comment. Novartis officials, citing pending litigation, also would not discuss the issue.
Dr. R. William Soller, senior vice president of the Consumer Healthcare Products Association, the trade group that represents manufacturers of over-the-counter medicines, said the industry had long shared voluminous research with the FDA, "all of which basically supported PPA's safety."
The agency was not convinced. In 1992, it demanded a more thorough investigation, the Yale study. The industry helped design it and paid for it, a cost of more than $5 million.
Such research is rare, said Dr. Louis Lasagna, an expert on drug development at Tufts University who helped oversee the Yale study at the request of Soller's group. He said pharmaceutical manufacturers do not devote enough research to looking at "what makes your drug more effective or more tolerable" and added, "There's very little money spent on it. The emphasis is on getting the drug to market."
The Yale study bought PPA six additional years of shelf life. Had it not been under way in 1994, said Dr. Charles Ganley, director of the FDA's division of over-the-counter drugs, "the agency probably would have proceeded to take PPA off the market back then."
Meanwhile, PPA generated hundreds of millions of dollars in sales for the companies that marketed it. Republican Sen. Ron Wyden of Oregon, who as a congressman in 1990 held hearings on the diet industry, said in a recent interview that he was troubled by the delay.
"This is a textbook case," Wyden said, "for how a powerful industry that is willing to pull out the stops can be successful in preventing an objective evaluation of an important drug ingredient."