The Food and Drug Administration has barred a leading heart specialist from testing drugs in humans because he reported false evidence of success in patient experiments at a Veterans Administration hospital.
The FDA said Dr. Wilbert S. Aronow "repeatedly or deliberately" violated agency rules for four years at the VA Medical Center in Long Beach, Calif., mainly in testing a Pfizer drug on victims of congestive heart failure. The FDA also told the drug firms sponsoring his studies that it will not accept his data.
The case is one of the most important in a wave of phony medical testing that is raising new concerns in federal health agencies, which rely heavily on such data to help them determine a drug's safety and effectiveness.
At the National Institutes of Health, staff official Mary L. Miers said that until about 1980 cases of phony medical research by NIH grantees came up rarely, "perhaps once every other year."
Since then, she said, such cases "are cropping up so often they can't be dealt with as isolated events."
Aronow was the latest of seven physicians to sign a new type of "consent agreement" when he pledged last October to test no investigational drugs unless he gets specific permission from the FDA commissioner.
Last year the FDA ruled eight physicians ineligible to receive "investigational" drugs, which are either new chemical entities or marketed drugs proposed for new uses.
But there were criminal prosecutions last year as well.
In one, a federal judge in Philadelphia approved a plea-bargain agreement under which obstetrician-gynecologist Harvey M. Levin will go to prison for fraudulent human drug testing.
Levin pleaded guilty to two of 19 counts in an indictment, admitting that he fabricated results in eight tests of painkillers and sent them to the FDA via the drugs' five manufacturers.
The companies, which paid him $140,000 over 4 1/2 years, are Ortho and McNeil Laboratories, owned by Johnson & Johnson; Bristol Laboratories; Sterling Winthrop Research Institute, and Pennwalt.
Aronow's prominence, however, makes his case stand out. He was one of the FDA's outside advisers for six years in the 1970s, is a past president of the VA Association of Cardiologists, has published more than 200 scientific papers, is an adviser to 21 professional journals and has been a consultant to numerous federal and state agencies, the American Medical Association's Department of Drugs and the American Heart Association.
Aronow did "a vast number" of drug studies, and some were "heavily relied upon by industry in support of claims of efficacy," an FDA official said in records obtained under the Freedom of Information Act.
The case began in mid-1979, after Pfizer gave the FDA Aronow's report on a study of the proposed use in congestive heart failure of Minipres (prazosin), which already was on the market as a drug to lower blood pressure.
The pivotal importance of the prazosin study led to an audit by the FDA's Clinical Investigations Branch, which also got word that Aronow's results had struck an FDA medical officer as too good to be true. Similarly, scientific investigator Doralie L. Segal said that case reports she found "not believable" led to the Levin plea bargain.
FDA officials approached Aronow cautiously, telling him only that they wanted to look at his records. Upset, Aronow telephoned a high FDA official.
Sobbing, he volunteered that he had "fudged" chest X-ray reports from his studies of prazosin and two other drugs, but insisted "that that was the only aberration," the official said in a memo.
Aronow, 51, told a reporter that he had "dedicated my entire life to the public good" and has "never done anything dishonest . . . . If I did something wrong, my conscience couldn't take it."
The FDA said his case reports claimed that heart enlargement and lung congestion vanished after treatment with the Pfizer drug, as shown by successive chest X-rays. But FDA audits revealed that in only one of 10 series of X-rays did Aronow's reports agree fully with the interpretations of the hospital's radiologist and of a FDA-retained Yale expert.
In studies of Minipres and four other drugs, Aronow discarded "most of the raw data" while failing "to maintain adequate and accurate case histories," the FDA said. It also cited "serious discrepancies" between hospital records and his sometimes handwritten case reports.
The FDA also alleged that Aronow deviated from the approved testing plan by including certain patients whose medical conditions should have excluded them.
At a 5 1/2-hour informal conference with the FDA, held at Aronow's request in September, 1980, he pleaded repeatedly not to be disqualified.
"I would be destroyed," he said. He blamed his troubles partly on 100-hour work-weeks and on his failure "to exercise adequate supervision" over younger research physicians. But the FDA's auditor said the research physicians never saw his case reports, and none worked for him throughout the four-year period at issue, 1974-1978.
Aronow also blamed the "extreme emotional distress" generated by learning that he faced an FDA inspection.
Near the end of the conference, Dr. Alan B. Lisook, chief of clinical investigations, questioned the quality of "the workings of the VA hospital," saying that "they would almost seem to be such that research should not be conducted there."
He told Aronow: "Records are lost, records are unavailable, notes are written by interns which you cannot believe because they are at odds with what your cardiac fellows say. I am concerned that your records at the hospital are not worth a damn, is what I hear you saying."
By contrast, Dr. Frederic A. Wyle, a top hospital official, said in a 1980 letter in the FDA record that Aronow was "invaluable"and did "more than any other individual to 'put the Long Beach VA Medical Center on the map.' "
Aronow resigned in July from the VA hospital, where he was chief of cardiovascular diseases for nine years, and from the University of California at Irvine, where he was a professor of medicine, and became director of cardiovascular research at Creighton University Medical School in Omaha.
The resignations came nearly three years after the VA's inspector general obtained a copy of a preliminary FDA investigative report. A VA spokesman now says that the agency "was considering an official administrative inquiry."