A former Food and Drug Administration official testified today that the maker of the morning-sickness drug Bendectin made false reports to the FDA on tests that produced limb deformities in the fetuses of laboratory animals treated with the drug.
Dr. M. Adrian Gross testified in a lawsuit filed by the parents of a boy who was born blind and with one finger on each hand and one toe on each foot.
Alfred and Louise Lanziotti and their son Anthony, 8, are suing Merrell-Dow Pharmaceuticals of Cincinnati, which Dow Chemical bought from Richardson-Merrell (now Richardson-Vicks) in 1981.
Merrell has estimated that 33 million women worldwide used Bendectin between its introduction in 1956 and when production was halted in June 1983 after a series of lawsuits against the maker. Merrell won FDA clearance for the drug without submitting test data on safety in pregnant animals and with limited clinical test data. The drug was made in two versions, one with two ingredients and one with three; each ingredient had long and widely been used separately.
Gross, a research pathologist and veterinarian, was the FDA's associate director of pre-clinical investigations until 1979, when he joined the Environmental Protection Agency. He is now an EPA senior science adviser.
Today, largely on the basis of his review of previously undisclosed Merrell research notebooks on a test in rabbits, Gross concluded there is no safe dose of Bendectin in either animals or humans. Gross testified about Bendectin tests in which pregnant rabbits were killed so their fetuses could be examined.
In pretrial discovery, plaintiffs' lawyer Thomas R. Kline obtained research notebooks written in August 1963 by lab worker Carol J. Carl who wrote on each page that they were "a true record of work done by me." In turn, her supervisor certified the accuracy of her entries.
Gross, reviewing the notebooks for the jury, testified that 12 of 110 fetuses had one or more limb abnormalities, such as clubbed feet or toes.
Two weeks after Carl signed the notebook pages, Robert E. Staples, the Merrell scientist in charge of the rabbit study, reported the results to his boss, D. E. Holtkamp and recommended "further experimentation" to ascertain "the biological implications."
Not until 1966 -- nearly three years later -- did Merrell disclose the study to the FDA, in a report that mentioned limb anomalies in two fetuses.
In 1980, the FDA convened an outside advisory committee to review the question of whether Bendectin caused birth defects.
Making a new report on the 1963 Staples study, Merrell official J. W. Newberne told the advisory panel four fetuses had limb anomalies.
The panel then found no cause-effect connection between Bendectin and birth defects, although it cited a "residual uncertainty" about some types of deformities.
For more than two years afterward, the official instructions for the drug said: "Studies in rats and rabbits have revealed no suggestion of drug-induced fetal abnormalities at doses of Bendectin up to 90 times the maximum human dose."
During cross-examination, Merrell lawyer Frank Woodside III said Carl had been directed to "over-report anomalies." Woodside also mentioned a second Merrell study purported to cast doubt on Carl's findings.
The drug's most often suspected ingredient is doxylamine succinate, an antihistamine used in certain non-prescription sleeping pills that carry label warnings against use by pregnant women.
A second ingredient was a vitamin. A third, an anti-spasm compound, was dropped from the U.S. formulation in 1976. Whether Louise Lanziotti received the two- or three-component version is unclear.
A crucial issue in the Lanziotti case is precisely when the mother conceived. If it was on March 2, 1977, as Merrell contends, Anthony's birth defects would have occurred before she took Bendectin eight weeks later, on April 28. But if conception took place about 13 days later, as her lawyers contend, the eyes and limbs, of her fetus were in an early developmental stage in which it was possible for chemicals crossing the placental barrier to do harm.
Under an order of Judge Charles R. Weiner, the jury will decide only if Bendectin caused Anthony's birth defects. If needed, a separate trial will be held to determine the damages to be awarded.