SCIENCE: DOCTORING THE EVIDENCE

A scientific degree is no guarantee of honesty. So why, when fraudulent research can allow dangerous drugs onto the market, does it go unpoliced? Roger Dobson reports

IT IS ALMOST three years since the high-flying career of Malcolm Pearce, a leading obstetrician with an impeccable background and a glittering future, came to an abrupt halt.

Over a period of just a few weeks, Dr Pearce was sacked from his job as senior consultant at St George's Hospital in south-west London, found guilty of serious professional misconduct, and struck off the medical register.

His crime? Unlike others who've appeared before the General Medical Council, he was not found guilty of professional incompetence, nor of abusing drugs prescriptions, nor of assaulting his patients. His downfall was scientific fraud.

Dr Pearce claimed in a research paper, published in the British Journal of Obstetrics and Gynaecology, that a 29-year-old woman had given birth to a healthy baby after he had successfully relocated a five-week-old ectopic foetus into her womb. The report excited worldwide interest and gave hope to the thousands of women who are prone to pregnancies that start outside the uterus and end in miscarriage.

But it soon became clear that all was not well. Dr Pearce's patient records had been tampered with, colleagues had mysteriously known nothing of his pioneering research while it was going on, and the mother herself could not be tracked down. It eventually transpired that he had falsified all of his evidence - one of his patients was in fact dead at the time that he said he'd operated on her. The GMC ruled that he had fraudulently claimed to have performed the pioneering operation, and struck his name off the register. Sir Robert Kilpatrick, chairman of the disciplinary committee at the time, voiced a common professional concern when he condemned Dr Pearce: "[This] web of deceit has had incalculable consequences for public confidence in the integrity of research."

Not only does research fraud undermine the credibility of science, it can also have far-reaching consequences for medicine. Falsified clinical trials, for instance, could lead to a drug arriving on the market without any dangerous side- effects being reported.

And further research may also be compromised because there is a necessary assumption that what is already researched and published is correct and honest. Such assumptions are essential - without them as a reliable background, researchers would have to spend much of their time reinventing the wheel.

But since the Pearce case, there have been several further instances of scientific fraud in Britain. Dr Mark Williams, a senior lecturer in Bristol, had his research into care in the community withdrawn when he was struck off after admitting faking statistics. And Dr John And- erton, a senior consultant physician and former registrar of the Royal College of Physicians, was struck off for misconduct during clinical trials of a powerful new anti-angina drug. Instead of recruiting patients for his study, obtaining their consent and registering their progress, he forged their consent papers and made up the data.

Motives for such fraud vary between individuals. Some do it out of greed, others for fame and kudos, and it can also result from the pressures of intense professional rivalry. A few are simply lazy and take short cuts, while others plagiarise the work of others. In one case in the US, a researcher into hamster diseases succeeded in obtaining a federal grant on the back of so-called preliminary data that had simply been copied from a textbook, published in London some 20 years earlier.

"There are two major motives for fraud: money and prestige, getting your name into articles and that kind of thing," says Dr Richard Tiner, medical director of the Association of the British Pharmaceutical Industry. "From our point of view, whatever the motive it is important that it is dealt with, because if a pivotal clinical trial is found to have a fraudulent aspect it may well have a major effect on whether or not the product can go forward on to the market."

But despite the growing problem, Britain, unlike Australia, the US and the Scandinavian countries, has no national agency to police researchers. Here, exposure of fraud is usually left to employers and professional bodies.

And many of these bodies face a dilemma because the exposure of a wrongdoer can taint the institution itself. So there is a suspicion that university labs and commercial agencies have been inclined to deal with perpetrators privately. This used to be commonplace in the US too, but less so since the creation of the Office of Research Integrity (ORI) in 1992 .

"People were put out the back door in the past and sometimes just went on to another institution and nobody ever knew about it. Now we publish our findings so that can't happen any more," says Chris Pascal, acting director of the ORI. Those found guilty of misconduct face the humiliation of having to withdraw all previous papers. They may be banned from getting research grants for three years or more, and they may also have to agree to having all their future papers and grant applications vetted.

Since its inception, the ORI has made more than 80 findings of misconduct among doctors and scientists and has investigated 1,500 cases. In the UK, the General Medical Council has struck off only 10 doctors in around 10 years for the same kind of fraud in medicine.

There are growing calls for a similar national body to police research misconduct in Britain. Richard Smith, the editor of the British Medical Journal, who has written extensively on the issue, says the question has moved on from whether or not there is a problem, to deciding what the best course of action should be.

"The institutions don't have enough experience to deal with these situations. And they face terrible conflicts of loyalties in exposing one of their own as fraudulent. A national body should take the lead in defining research misconduct, developing procedures for processing accusations, and ensuring that institutions comply with them," he says.

Richard Smith's fear is that without such a body, the exposure of scientific fraud will be left to whistleblowers and a collection of conscientious professional bodies, academics, and employers. But these investigations are too important to be left to chance.

It has also been suggested that one reason why research fraud has had a relatively low profile in Britain is the popular belief that all scientists are genuinely dedicated to the search for truth. It is time that this misplaced trust is abandoned, writes Dr Drummond Rennie in the British Medical Journal.

"It would help if we were all to stop registering shock and recognise that the bestowal of a scientific or medical degree is not accompanied by a guarantee of honesty. The only useful approach is to assume that a certain proportion of our colleagues will plagiarise, fabricate and falsify their evidence." !

In most cases the fraudsters are turned in by colleagues, and Chris Pascal says that the American experience is that it tends to be the younger scientists who blow the whistle on colleagues. Only one case has been found where the whistleblower acted in bad faith - he gave the researcher the false data himself and then turned in his boss for using it.

One estimate based on experience in Denmark, is that if the UK had a similar policing agency to that operating in Scandinavia there would be around 100 cases a year for it to investigate.

CASE STUDIES

DR MALCOLM PEARCE's report on ectopic pregnancy attracted worldwide attention when it was published.

Dr Pearce, one of Britain's leading obstetricians, purported to show that he had relocated an ectopic pregnancy and suggested that his pioneering treatment would improve the prospects for women worldwide suffering recurrent miscarriages.

But when quizzed about the research, he was unable to produce notes, patient consent forms or even any patients. It was also found that he had illegally altered records in an attempt to present a patient.

Pearce did not attend the GMC's three-day hearing in the summer of 1995 when he was struck off. His head of department, Professor Geoffrey Chamberlain, although not involved, had co-signed his initial report and resigned as president of the Royal College of Obstetricians and Gynaecologists.

Sir Robert Kilpatrick, then chairman of the disciplinary committee, said, "Scientific fraud is dangerous. Medical knowledge worldwide is developed at least in part on the published results of previous research."

DR MARK WILLIAMS was struck off by the General Medical Council for research fraud, and a seminal piece of research, which may have influenced the design of Care in the Community, was withdrawn by his co-author.

In Dr Williams' study, 181 severely disabled adults were interviewed in 1989 and underwent a physical assessment. A year later, he re-interviewed by phone those who had been found to have un-met needs, to see whether those needs were now being met.

But alarm bells began to ring when Williams was struck off after admitting falsifying statistics in another research paper. The GMC also heard that 43-year-old Williams had lied about his qualifications in order to get the post of Senior Lecturer in Public Health Medicine at Bristol University.

Inquiries into the community-care research after the GMC verdict discovered that only a third of the 181 people could remember the original visit, and not one could recall the telephone follow-up.

DR JOHN ANDERTON, a consultant and former registrar of the Royal College of Physicians, was struck off last year. He admitted a charge of serious professional misconduct and the General Medical Council was told that he had forged a number of consent forms for patients supposedly involved in clinical trials of amlodipine, a new anti-angina drug made by Pfizer. He also invented all of his echocardiographic data.

Dr Anderton was paid pounds 42,000 to conduct the trial and Pfizer, whose staff detected the fraud, said they had lost pounds 250,000 as a result of his behaviour.

At the hearing, Dr Jeremy Lee-Potter, then chairman of the GMC's professional conduct committee, said: "Dishonesty by doctors participating in such trials is not only thoroughly discreditable in itself, but is also a potential source of danger for patients."

DR THEREZA IMANISHI-KARI was, for almost a decade, at the centre of America's most notorious alleged fraud case, involving major universities, Congress and the CIA. She has now been cleared of misconduct, but was criticised for sloppy record-keeping and for allowing research "rife with errors" to be published.

In 1986, she published findings which showed that genetically engineered mice produced a range of altered antibodies. The discoveries attracted worldwide attention, but a month after publication Margot O'Toole, a junior researcher, suspected data had been fabricated.

Congress launched an investigation. The CIA was called in to examine lab records and analyse Kari's handwriting, and found they did not match the alleged results.

In 1994, the Office of Research Integrity decided that she had intentionally and deliberately fabricated experimental data. After her appeal she was cleared of misconduct and plans to continue her career in research.