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Biggest drug research fraud case in FDA history

Biggest drug research fraud case in FDA history – Food and Drug Administration

Judy Folkenberg

Biggest Drug Research Fraud Case In FDA History

After pleading guilty to pocketing nearly $2 million from pharmaceutical firms for experimental drug tests that he never performed, prominent New Jersey physician Robert A. Fogari was sentenced to four years in prison on Feb. 2. He was also fined $2 million and ordered to make financial restitution to the drug companies he defrauded. After serving his prison sentence, Fogari will be placed on probation for five years.

“This is one of the worst cases I’ve ever seen, and I would not have believed it if I had not seen it,” said Judge Garrett Brown of the U.S. District Court for the District of New Jersey, who presided over the trial. “What you did was worse than dealing in drugs and murder,” he told Fogari. “You betrayed the public trust. Our system of drug testing relies on honesty.”

The judge said the sentence was as compassionate as possible considering the circumstances.

Fogari’s case is believed to be the biggest investigational drug fraud case in the history of FDA, according to Alan B. Lisook, M.D., chief of FDA’s clinical investigations.

At the beginning of his trial last Sept. 27, Fogari, an arthritis specialist, had pleaded not guilty to 20 charges of fraud and obstruction of justice. But seven days into what was expected to be a month-long trial he changed his plea and admitted guilt on four counts: conspiring to falsify drug test data, making two false statements to FDA,

Fogari also admitted that he concealed the deaths of two patients “enrolled” in the bogus drug studies because he wanted to “maintain a favorable impression” with the pharmaceutical companies that had hired him, according to assistant U.S. attorney Paul Weissman, who prosecuted the case. However, Fogari said the deaths were not related to the experimental drugs, and FDA had no evidence to contradict him. (Although Fogari never conducted any formal research, he may have used the experimental drugs in a haphazard fashion.)

Between 1977 and 1985, pharmaceutical companies that were seeking FDA approval for anti-inflammatory arthritis drugs paid Fogari to conduct clinical studies. Payment was based on the number of patients enrolled, the number of office visits, and the number of procedures performed during the study. According to Weissman, Fogari submitted thousands of falsified reports to drug companies.

During the week-long trial, former employees, who were given immunity, testified that Fogari instructed them to list the names of persons who were not enrolled in the study, make up patients, and continue to include patients who had dropped out of the study. Fogari also failed to conduct urine, stool, and blood tests necessary for the study. Under questioning from Weissman, Fogari admitted to forging the signatures of radiologists and other specialists to documents attesting that X-rays and other tests or exams had been performed.

The most damaging testimony came from Patricia Cunningham Czorniewy, a former assistant to Fogari who admitted under questioning that the doctor had pressured her to sign an affidavit falsely stating that she had invented study data. It was after her testimony that Fogari changed his plea from innocent to guilty. Questioned by Weissman, Fogari admitted it was he who falsified all data and that he did not conduct any legitimate research during the entire eight-year period.

Fogari participated as an investigator in at least 18 experimental drug studies for nine drug manufacturers, including Ciba-Geigy, Johnson & Johnson, Warner-Lambert, Pfizer, Upjohn, Syntex, and Merck, Sharp & Dohme. The drugs he was supposed to test included Voltaren, Maxicam, Seldene, and Naprosyn. However, Anthony Panzica, director of FDA’s compliance branch in the Newark district office, emphasizes that the drug manufacturers deleted Fogari’s data from their marketing applications after they were notified of his disqualification. Panzica said that most of the drugs have not yet been approved by FDA, and those that were did not depend on his data for approval.

“His research did not influence decisions to put any drugs on the market,” said Panzica.

Fogari was first investigated by FDA in 1983 after officials at Ciba-Geigy became suspicious because his data were “too perfect,” said Weissman.

Fogari’s sentence angered many patients and former patients. He had a “great following among his patients, and people couldn’t believe what had happened,” said Diane Kolaitis, a compliance officer in FDA’s Newark office. He was known as a kind doctor, and long lines of patients were a familiar sight at his office, according to newspaper accounts.

Fogari can no longer practice medicine since the New Jersey State Board of Medical Examiners revoked Fogari’s medical license as of March 17, according to Deputy Attorney General James F. Lafargue.

Another Case of Fraud

As New Jersey physician Robert Fogari faced trial in the biggest case of fraudulent drug research in FDA’s history (see preceding article), a board-certified urologist pleaded guilty in the U.S. District Court of Massachusetts on charges of faking research data.

On July 14, 1988, Constantine I. Kostas pleaded guilty to one count of making a false statement to a federal agency and one count of mail fraud.

Although he faced a maximum penalty of 10 years in prison and a $500,000 fine, Kostas instead received a one-year suspended prison sentence, was fined $30,000, and was ordered to perform 400 hours of community service.

Miles Pharmaceuticals of West Haven, Conn., had hired Kostas as a clinical investigator to test the drug ciprofloxacin (brand name Cipro) for treating urinary infections. The firm’s officials became alarmed when, during a routine audit, serious discrepancies–such as giving antibiotics instead of Cipro to some patients–were discovered in Kostas’ data. When the firm informed Kostas it intended to conduct a full audit, he confessed that only 15 of the 85 subjects listed in the study had actually received the experimental drug.

In addition, Kostas included in the study patients who did not meet the medical criteria of the research protocol, and he faked results of nonexistent lab tests and office examinations.

Kostas admitted that he thought the study would be easy to conduct, but he had been dogged with problems from the start. The physician said he pressured himself to continue the study and “wouldn’t admit that he couldn’t do it,” according to Ed Warner, assistant regional director for operations for the northeast region. Kostas’ study had no bearing on FDA’s approval of the drug.

According to his probation officer, Kostas fulfills the community service obligations of his sentence by giving physical exams to people who go before court at the Peabody District Court Clinic. He retains his medical license and continues to practice medicine in Peabody, Mass.

Snaring Smugglers

Of Animal Drugs

A former veterinary drug company executive pleaded guilty in January to charges of illegally importing and selling unapproved animal drugs. The plea followed a four-year investigation by FDA, the U.S. Customs Service, and the Justice Department into a nationwide bulk veterinary drug business with international connections. More than 30 tons of animal drugs, with a wholesale value of more than $600,000, were seized in Illinois and Nebraska in connection with the case. The former executive, Jeffrey A. Engel, was president and general manager of Custom Feed Blenders, Fort Dodge, Iowa.

The investigation followed a growing number of complaints from legitimate veterinary drug sources about the availability throughout the country of illegal bulk drugs. Investigators eventually uncovered an illegal path of distribution that reached from Eastern Europe and China, where the drugs were produced, to Canada, then Iowa, and, from there, across the United States. The drugs were smuggled into the United States by tractor-trailer truck, concealed under loads of hay or wood chips, investigators said. The operation began in May 1983 and ended in October 1988, although Custom Feed Blenders closed in the spring of 1986 while under investigation.

Custom Feed Blenders made and distributed drugs for sale to veterinarians, farm supply outlets, and farmers throughout the nation, according to the Justice Department. Engel and the company were linked to the illegal operation in 1984 along with 13 others. They were charged with working together–or, in some cases, separately–to import, manufacture or sell high-potency, unapproved bulk animal drugs, and with making false statements to federal agents.

Others pleading guilty in the case were Rex J. Blunk of Callender, Iowa; Gary Van Dusen of Mississauga, Ontario, Canada; Jon L. Engel of Omaha, Neb., brother of Jeffrey Engel; Timothy J. Hoffman of Omaha; Bradley Langmo and Gregory S. Langmo of Litchfield, Minn.; Ronald L. Nissen of Fort Dodge; James Rhodes of Fort Dodge; Wesley J. Thoreson of Ellsworth, Iowa; Larry Tipton of Winona, Minn.; and Dana Wolf of Fort Calhoun, Neb. As of April 1, Hoffman had been fined $9,000, Thoreson $2,500, and Wolf $4,500. At press time, the others, along with Jeffrey Engel, were awaiting sentencing.

In addition, Heinz G. Dall of Ossining, N.Y., and Robert M. Clack of Pittsfield, III., were charged with 25 counts of illegally importing and distributing animal drugs. They pleaded not guilty after being indicted last November by a federal grand jury in Cedar Rapids, Iowa, and are awaiting trial.

Two businesses dealing in the smuggled veterinary medicines–International Manufacturing and Sales of Omaha, Neb., and Zetapharm Corp., New York–were charged with misbranding and adulteration of animal drugs since the drugs were made under conditions that presented no assurance as to their safety or strength. International Manufacturing has been fined $40,000. Fines of up to $100,000 to $250,000 per count are possible.

The unapproved animal drugs included amprodlium, carbadox, chloramphenicol, chlortetracycline, dimetridazole, ipronidazole, levamisole, nitrofurazone, oxytetracycline, potassium penicillin, rifampin, spectinomycin, tetracycline hydrochloride, tylosin, and other antibiotics. Unapproved drugs pose a threat to an animal’s health because their safety and effectiveness have not been scientifically, determined. They may also endanger humans if they leave cancer-causing or otherwise toxic drug residues in meat, milk or eggs from feed animals.

The nationwide investigation is continuing, with more charges expected.

Blood Bank Put on Notice

The American Red Cross Blood Services Center in Albany, N.Y., almost lost its FDA license last March because of continuing problems that led to the release of more than 300 units of potentially contaminated blood–most of which were transfused. The most critical problem was that hepatitis testing was done incorrectly for nearly five months because the center’s employees had failed to recognize an inappropriate computer setting. To date, retesting of the 112 donors who gave the blood in question has not shown any hepatitis contamination.

Numerous problems with the Red Cross regional blood banking operations over the past several months had prompted FDA to step up its inspections of the centers. Indeed, in 1988, the agency visited every FDA-regulated blood bank. During the Albany center inspection, from May 2 to June 6, an investigator from FDA’s Buffalo district found a number of deficiencies–notably, the distribution of blood components from five units that hadn’t been properly tested for AIDS (acquired immune deficiency syndrome) virus antibodies. The donors are being retested and, so far, all tests have been negative.

Meanwhile, FDA had been working with the Red Cross to remedy such serious deficiencies. On Sept. 14, 1988, the Red Cross signed an agreement to monitor its centers more tightly, to establish uniform blood collection standards that would include improved employee training procedures and auditing procedures, and to analyze computer hardware and software as a further measure to prevent the release of unsuitable blood.

FDA conducted a follow-up inspection of the Albany center from Dec. 6, 1988, to Jan. 18, 1989, to see what changes were in place. Shortly before the inspection, however, the manufacturer of the automated test equipment had conducted a routine check and noticed the computer was in the wrong mode. The center immediately informed FDA. The agency’s subsequent investigation confirmed the error and found significant problems in the blood bank’s hepatitis testing, including: . Faulty procedures that caused inaccurate test results from July 12 to Dec. 2, 1988. . Lack of complete instructions for performing hepatitis testing with automated equipment. . Failure of supervisors or managers to review original test results so as to ensure technicians were using the correct procedure. . Some test records that were incomplete or improperly filed.

In a letter dated Feb. 14, 1989, FDA advised the American Red Cross national headquarters that it would revoke the Albany center’s license unless the center promptly submitted a plan to bring blood handling procedures into accord with FDA standards and regulations. The Albany Red Cross submitted such a plan on March 1, 1989, and FDA is reviewing it.

COPYRIGHT 1989 U.S. Government Printing Office

COPYRIGHT 2004 Gale Group