Keith Epstein

Research Standards Overseas Vary Greatly

Europeans worry about fraud, sloppy drug experiments

Plain Dealer – December 17, 1996

SERIES: DRUG TRIALS

Third of four articles

With human lives and huge investments at stake, the global pharmaceutical industry has a sense of anxiety over its growing reliance on research from outside the United States, where standards tend to be less strict and widely divergent.

“It’s our little secret. … It’s frightening. I could tell you so many stories. We all can,” said German pharmacologist Joachim Schwarz, whose North Carolina contract research company, Quintiles, runs experiments for drug companies on four continents.

Stephen Lock, former editor of the British Medical Journal and now a research associate at the Wellcome Institute in London, crisscrosses Europe these days, pleading for a renewed devotion to solid science.

He took his message to Cologne, Germany, in March, where mostly European pharmaceutical managers had congregated to learn the latest techniques for stanching the flow of bogus research. Such industry-sponsored training sessions on fraud and misconduct in clinical trials are becoming commonplace.

“Few people outside science realize it, but we’ve reached the point where we must be suspect of any data being submitted. Once, facts were sacred. Now we’ve got to query the facts,” Lock told the gathering.

Iain E. Gillespie, former dean of the University of Manchester Medical School in England, was more blunt. The consequences of sloppy recordkeeping can be as harmful as fraud, he said. “Some people believe there are different degrees of sinfulness,” Gillespie told the gathering. “I subscribe to a more Calvinist view – all sins are serious.”

Within sight of the towering spires of northern Europe’s largest cathedral, the cocktail chatter of the industry insiders turned to confessions of scientific sin.

“We just had a case,” said Klaus-Peter Barth, who had overseen European tests of an anti-allergy medication. “All the patients were invented, every one. It hurts. … Now we have to do [the study] again.”

Peter Brock, medical director for Lederle-Wyeth U.K., offered another account. Without revealing too much, Brock said fraud by two researchers had stalled approvals of six drugs.

“It’s all serious, because … it can have a major impact on safety.”

Nils Axelsen, of the Danish State Serum Institute, related a story about a U.S. drug company that offered a professor a completed paper ready for publication; all he had to do was sign his name.

Robert Donnelly of Janssen-Cilag Ltd. told of an English doctor who altered study dates and birth dates, “using real patients as phantom subjects.” The drug test was designed for older patients who could not climb stairs; one patient turned out to be 16 years old.

What was common knowledge in Cologne is commonly denied in Congress, where the Food and Drug Administration is under attack for taking too long to approve drugs that are developed overseas. Republicans such as Rep. Joe Barton of Texas complain that the FDA is overzealous, and they urge even greater acceptance of drugs developed overseas. Barton has said he doubts there is more fraud and incompetence in Europe than in the United States.

That is not how Frank Wells sees it. In Europe, “nearly every one of us has some experience with fraud,” said Wells, recently retired medical director of the Association of the British Pharmaceutical Industry.

In England, he was the keeper of the “gray list,” a euphemism for the names of suspect researchers – those who broke or bent the rules but against whom no actions were taken. The medical profession polices itself, and in England, blacklists, like the U.S. version maintained discreetly by the FDA, are forbidden.

“It’s all inside Frank Wells’ head,” said Lederle-Wyeth’s Brock. “Now with him retiring, I’m rather concerned that when the gray list is passed on through folklore, our oral tradition, it will be lost.”

In Germany, drug manufacturers turn to “The Man with the Golden Memory.”

Since 1988, this anonymous individual at the Fachgesellschaft der Arzte in der Pharmazeutischen Industrie, the association of pharmaceutical industry physicians, has tracked unreliable and dishonest researchers.

Identities of doctors, firms and products are not public. But the inner circle can find out what it needs to know.

In England, Wells could refer cases to the General Medical Council, a professional association of physicians, which conducts discreet inquiries and revokes medical licenses. Since 1991, the council has disciplined 17 doctors for “serious professional misconduct” in drug research; eight were forbidden to practice medicine.

There is no comparable national system of disciplining medical researchers in the United States. Trade secrecy laws prevent any disclosures about drugs before they are approved; the FDA cannot even confirm that a new-drug application has been filed.

In England, a doctor who is accused of research misconduct can be summoned to a court-martial-like proceeding before a panel of eight physicians.

Last March, they summoned Geoffrey Fairhurst to a room at the General Medical Council’s headquarters in London, where oil portraits of famous doctors stare from high walls. Fairhurst was a prominent family doctor in a town outside Liverpool.

The council also summoned his patients and pharmaceutical company employees. From her wheelchair, Constance Mary Jerram related how she had seen Fairhurst for 12 years. He had treated the 73-year-old widow’s arthritis and bronchitis and monitored her blood pressure.

“He called me by my first name,” she told the panel from her wheelchair. “I was happy to go to him. I trusted him.”

Then, one day last year, she recalled, another physician made a house call – and it wasn’t to check her health. The doctor asked Jerram to examine a piece of paper from Fairhurst’s files.

She studied the signature on the paper.

“Constance Jerram,” she read.

It wasn’t her writing.

She was shown another piece of paper.

Again, not her writing. “No, no,” she said, “I never signed this.”

Jerram had been placed in an experiment sponsored by Glaxo Pharmaceuticals UK. The company was trying to assess the safety of a new blood-pressure drug.

“No, I’ve never consented,” Jerram told the council judging Fairhurst. “Dr. Fairhurst never asked me to be in any trial or test.”

It turned out that between 1988 and 1993, the doctor conducted three clinical trials for Glaxo, Merck, Sharp & Dohme and Leo Laboratories Ltd. There was no evidence the companies, which arranged to pay Fairhurst up to $900 per patient, were aware of any lack of consent.

“He put me on these heart tablets,” recalls 75-year-old Harry Noble. “I thought he knew it was good for me. But it was experimental. The drug hadn’t even come to market.” When Noble found out, “I just couldn’t believe it. He’d been my doctor for 30 years. I trusted him. He was like a friend, really.”

Fairhurst’s nurse said the doctor didn’t tell his patients they were in research for fear they would refuse to participate. He said, “It’s the kiss of death to recruitment,” the nurse told the panel in London.

She also testified to back-dating echocardiograms for the doctor.

A handwriting expert suggested patients’ signatures had been forged on consent forms.

Fairhurst’s lawyer argued the doctor had been treated unfairly and was the victim of a partner’s ambitions to take over his practice and research opportunities.

The testimony about Fairhurst’s activities appalled the board, which found him “guilty of serious professional misconduct” and drummed him out of the medical profession.

“Trust lies at the heart of the medical profession,” the chairman, Sir Donald Irwin, admonished. “You have repeatedly behaved dishonestly and have betrayed the trust placed in you by your patients … by involving them in pharmaceutical trials without their knowledge.

“You have undermined the reputation of the medical profession and damaged the confidence of the public in the integrity of scientific research. Your behavior has not only been dishonorable but has also placed the welfare of patients at risk.”

“I feel as if I’d been violated,” says Jerram. “All doctors should ask permission first of the patient. When you stop to think about it, that’s only right and proper. It’s not very complicated. It’s just common sense and common decency.”

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Related stories:

In the Name of Healing Doctors infused a solvent also used as a gasoline additive into Laura Michalski’s abdomen. Within hours, she died. Eight years later, her family learned it had been an experiment.

“They Used Our Kids as Guinea Pigs.” Medical research records show the U.S. government is still in the business of conducting and paying for clinical trials on unsuspecting Americans.

Foreign Tests Don’t Meet U.S. Criteria The cycle of hype, hope and heartbreak surrounding clinical trials has become a chronic condition in the global pharmaceutical industry, which now initially tests two-thirds of all products for Americans overseas. The experiments often involve fraud, concealed side effects, improvised experiments and human rights abuses.

Living Proof: U.S.-Run Study Gave Ugandans Dummy Pills Instead of Treatment American researchers let tuberculosis worsen, unchecked by an effective drug, in a control group of 500 Ugandans with HIV, as they charted its deadly progression. Some thought “placebo” was a medication that would help them. In the U.S, the practice would have been unethical.

U.S. Medical Researchers Flout Rules Around World On nearly every continent, the U.S. government and its clinical trials partners have hidden risks and undertaken medical experiments without legally required  agreements to avoid human rights abuses.