A former Food and Drug Administration official testified at a civil trial today that G. D. Searle & Co., the pioneer maker of oral contraceptives, gave the FDA "false" and "misleading" information about the adverse effects of the hormonal pills on animal livers.
Dr. M. Adrian Gross, a veterinarian who was the agency's associate director for preclinical investigations, based part of his testimony on a November 1966 Searle report to the FDA on a two-year study of 200 female rats treated with Enovid. Enovid went on sale in 1960 as the first approved birth control pill.
The report said that liver enlargement due to benign growths, called cysts, were found in only five of 28 rats -- those on a high dose of Enovid -- and that "liver tissue was otherwise mostly unremarkable."
Actually, Gross testified, Searle's own data revealed cysts in 10 rats that received high doses of Enovid -- plus one in 43 on a medium dose, and three of 42 on a low dose.
Gross also faulted a 1969 report made for Searle by Hazleton Laboratories Corp. of Vienna because it claimed that an 88-week and 99-week rat liver study of Searle's Ovulen birth control pills "did not clearly cause liver damage." He said the study data showed that Ovulen "continuously damaged" the rats' livers.
Hazleton did the study under a contract with Searle, which submitted it to the FDA after Dr. Robert G. McConnell, then Searle's director of pathology and toxicology, had "corrected Hazleton's draft," Gross testified.
Gross has been a private expert witness for Constance Bailey, 46, who is suing Searle for compensatory and punitive damages in Howard County Circuit Court. She claims she has experienced severe liver damage caused by the Searle birth control pills.
Mark J. Brand, a spokesman for Searle, refused to comment on the allegations. "We will stand on the arguments our lawyers say in court," he said. "The plaintiffs will not be able to prove the validity of their case."
Brand said in a telephone interview that he is aware of no similar lawsuits against Searle and added: "We have from the beginning said that when used in accordance with the patient prescribing information, it is a safe and effective form of contraception."
Donald P. Nielsen, president of Hazleton, said he was unaware of the specific study mentioned in Gross' testimony, although he confirmed that Gross in 1974 did review certain studies the labs had done for Searle in the mid-1960s.
Gross, who has testified for three days, is to be cross-examined Monday.
Bailey's liver has enlarged to about 24 times normal size and is said by doctors consulted by her lawyers to be possibly the largest liver found in a human being.
She weighs 211 pounds, a gain of about 60 pounds since 1963, when her doctor prescribed Enovid following the birth of her second daughter.
The lawsuit, filed by Bailey, a circuit judge's secretary in Anne Arundel County, and her husband, Jerry, says that her physician later switched to Ovulen, which the FDA approved in 1966. Enovid and Ovulen contain mestranol, an estrogen also found in certain other makes, and a progestin.
In 1984, 180,000 retail prescriptions of Enovid and 1.3 million prescriptions of Ovulen were filled, according to market surveys cited by Dr. Sidney M. Wolfe, director of the Public Citizen Health Research Group.
In 1972, after nine years on the pills, physicians told Constance Bailey that her liver was enlarged, and she stopped using the pills. An examination of her liver tissue revealed polycystic liver disease, in which tiny cysts proliferate. Her lawyers say that because of the enormous enlargement of her liver more recently, tissue cannot be taken from it to test for possible malignancy.
In his opening statement for the Baileys last week, Milwaukee lawyer George A. Kersten told a jury of eight women and four men that the plaintiffs' evidence will show that Searle falsified, concealed and "threw away" adverse animal liver data to win FDA marketing approval and to prevent issuance of adequate warning to physicians and women.
Searle's attorney, William L. Richmond of Chicago, flatly denied charges of impropriety and associated Constance Bailey's disease with a birth defect.
He emphasized the polycystic liver disease has been reported in the 19th century -- many decades before the advent of oral contraceptives -- and occurred in numerous people who never have taken the drugs.
The FDA knows of no problems with any of the studies carried out on oral contraceptives, a spokeswoman said yesterday.
The trial proceeded at a slow pace this week because of frequent defense objections to Kersten's questions and Gross' answers, and because of numerous conferences at the bench with Judge Robert F. Fischer.
Gross, who left the FDA in 1979 to become a senior science adviser to the Environmental Protection Agency, is for many reasons, a pivotal witness.
He is analyzing numerous hitherto undisclosed Searle documents that Kersten and his co-counsel, Joel Katz of Baltimore, obtained in five years of pretrial discovery. In the mid-1970s, in addition, Gross led an FDA investigation of Searle animal data on non-contraceptive drugs. This led to a grand-jury investigation in Chicago that ended without a poll of the jurors as to whether to return indictments.
In the 200-rat Enovid study, 57 of the animals died. Gross stressed that animals that die in a study are "the most important" because their organ tissues have the most to reveal about the drug under test. But, he testified, Searle's records show that the liver tissues of 54 of the 57 rats were not saved for examination.
In a handwritten July 1966 memo, Searle's Dr. McConnell said the livers of the Enovid-treated rats "were clearly more damaged" than the livers of the untreated controls.
Gross pointed out that neither this nor other adverse liver findings were in the report sent to the FDA four months later or in Searle's agency-approved 1968 prescribing instructions for physicians.
The report said that autopsies at the end of the two-year study showed no increase or decrease in liver weight. Gross said his analysis of Searle's data showed "significant" weight increases at all dosage levels and a probability of less than one in one billion that the cause could have been anything but the drug.
Searle's main study to support its application to sell Ovulen was in rats fed components of the pill. In a report to the FDA in November 1963, Searle said that none of the 19 female rats on heavy doses of Ovulen developed liver abnormalities. Searle's records showed instead that 12 did, Gross testified.