Controversial Drug Makes a Comeback

(pieces of an article in NY Times)

In 1983, the morning sickness drug Bendectin was removed from the market amid a barrage of lawsuits claiming that it caused birth defects. Now, in what medical and legal experts say, is a shame that  it may be brought back.

A small privately held Canadian company, Duchesnay Inc., is working with the Food and Drug Administration to gain permission to market a generic version of Bendectin, which it calls Diclectin. Duchesnay is already selling the drug, its only product, in Canada, labeling and marketing it specifically for pregnant women.

The company says -- and medical experts agree -- that dozens of studies, many prompted by the litigation, have failed to find that Bendectin poses any dangers to pregnant women or their fetuses. And the drug agency said that since Bendectin was withdrawn by its maker, independently of the agency, and was not withdrawn for reasons of safety or efficacy, it might not be difficult to bring it back.

Andrea C. Masciale, a lawyer for the agency, explained that all Duchesnay had to do was show the F.D.A. that its generic Bendectin was chemically the same as the original drug. No clinical studies or research are required, which simplifies the process of its reintroduction. ''We think they can achieve a product that is the same as Bendectin and therefore come in with a generic version of Bendectin,'' Ms. Masciale said.

The development has stunned medical and legal experts, who say that the possible Lazarus-like re-emergence of Bendectin is so bold and unprecedented that they are at a loss for comparisons.

For many drug companies, birth defect experts, obstetricians and law professors, the Bendectin story is unforgettable. Bendectin is the only drug withdrawn from the market solely because of litigation, said Jeffrey Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America. Even the United States Supreme Court eventually weighed in on the matter.

''Bendectin was the archetypical case of junk science scuttling a perfectly safe product,'' said Dr. Michael Greene, the director of maternal-fetal medicine at Massachusetts General Hospital in Boston.

But Prof. David Bernstein, a law professor at George Mason University in Virginia, said it was only a twisted sort of poetic justice to bring back Bendectin. ''There's no justice to the company who spent over $100 million in litigation, not to mention having their chief executives tied up in litigation for years and years,'' Professor Bernstein said.

By 1980, 10 percent to 20 percent of pregnant women in the United States were taking Bendectin. But soon afterward, as the lawsuits mounted, Bendectin became tainted like thalidomide, the sedative that caused horrific birth defects when women took it early in pregnancy.

Women who took Bendectin and had babies with birth defects, especially limb defects like missing fingers or missing bones from an arm or a leg, found it hard to believe scientists who said that such things simply happen by chance and that the millions of women who took Bendectin had no more children with birth defects than those who did not take the drug. One out of every 2,000 American babies born each year has a limb defect and about 2.5 percent of babies have birth defects. Yet even if Bendectin was safe, as its defenders argued, few women or their doctors wanted to use it.

Memories have faded over the decades. Now, doctors say, many of their pregnant patients have never heard of the drug. That means that if Bendectin does return, it may come in as a fresh product to a generation that has no prejudice against it, medical experts said.

Eric Gervais, Duchesnay's executive vice president, is optimistic that he will get the drug agency's approval to market his generic version of Bendectin. Mr. Gervais said he was confident that the drug would sell as well in the United States as it had in Canada. There, he said, each year the company sells 70,000 bottles of Diclectin, each containing 100 pills. ''North America is indeed in need of this product,''

Dr. Anthony Scialli, a professor of obstetrics and gynecology at Georgetown University School of Medicine, agreed. ''There's a huge amount of safety data on Bendectin,'' Dr. Scialli said. ''It was the best studied medication in pregnancy of all time -- not just for nausea and vomiting, but the best studied, period.''

And once it was withdrawn from the market, surrounded by accusations that it caused birth defects, he said, doctors became afraid to give pregnant women any medications to relieve nausea and vomiting. That, Dr. Scialli said, led to an unfortunate situation.

When Bendectin's maker, Merrell Dow, removed the drug from the market, it said it was doing so because the cost of defending itself against an avalanche of lawsuits was simply too great. It was not jury verdicts or punitive damages that took their toll but simply the expense of dealing with thousands of lawsuits, said one of the company's lawyers, Frank Woodside of Cincinnati. In fact, Mr. Woodside said, the company prevailed in court. ''We have never ultimately lost a case,'' he said.

Soon, even insurance for Bendectin became an issue, Mr. Woodside said. ''Before they finally pulled it off the market, the insurance was going to cost them more per year than the amount they sold -- not the profit but the amount they sold,'' he recalled.

The litigation eventually made legal history. Lawyers representing women who said the drug had damaged their children brought experts into court who, critics said, were not qualified to comment and were propounding what critics called junk science. In 1993, the Supreme Court ruled on the matter, concluding that judges are to act as gatekeepers and ensure that ''any and all scientific testimony or evidence admitted is not only relevant, but reliable.''

The result, some legal experts say, is that if Duchesnay does bring Bendectin back, it may be the drug maker least likely to be sued. Many judges have made it clear that they will no longer allow Bendectin cases in their courts.

''Unless there is new evidence supporting the causal relationship between Bendectin and birth defects, lawyers are going to be reluctant to bring cases because they will fear that judges won't allow their experts on the stand,'' said Michael Gottesman, a Georgetown law professor who argued for the Bendectin plaintiffs before the Supreme Court.

As for the drug's safety, Mr. Nace said, ''In my mind, there is no question that Bendectin causes birth defects.'' He added that every time he saw a young person with missing fingers or a shortened arm or club feet, he thought of the drug. ''I want to walk up to them and say, 'Did your mother take Bendectin?' '' he said.

While Mr. Nace says he shudders to think that Bendectin may return, obstetricians say they welcome it.

Dr. Charles Lockwood, chairman of the department of obstetrics and gynecology at New York University School of Medicine, said he had seen large numbers of pregnant women whose lives were made miserable by nausea and vomiting.

''We try all sorts of different remedies,'' Dr. Lockwood said. ''We've literally tried everything from acupuncture bands, which don't seem to work, to fairly aggressive medications that are psychoactive.'' For example, Dr. Lockwood said, he sometimes prescribed Reglan, a drug that controls nausea but also makes women drowsy. ''The amount you have to give to have an effect tends to make them sleepy all day long,'' he said.

Dr. Scialli said one of his pregnant patients recently got Bendectin from Canada because she was afraid to take other drugs whose safety in pregnancy had not been as well studied.

In desperation, a few doctors say they tell women essentially to make their own Bendectin. The ingredients, an antihistamine and vitamin B6, are available over the counter.