Suddenly, medical research doesn’t seem so trustworthy. Three recent high-profile cases have highlighted the problem of fraud in scientific trials. And experts say these are merely symptoms of a much wider malaise. Now a new British watchdog is to be set up to staunch the steady rise of misrepresentation in medical papers. It won’t have legal teeth. It hopes to triumph through advice and cajolery. Will it be enough to restore our confidence?
When Jon Sudbo, a senior Norwegian consultant, reported in The Lancet last October that anti-inflammatory drugs cut the risk of mouth cancer, it caused much optimism. Now he admits that the data, on 980 people, was fake. In December, The New England Journal of Medicine (NEJM) had to issue a caution about a study on the arthritis drug Vioxx, which was withdrawn last year over cardiovascular risks. The journal said that the research material it published in 2000 had omitted to mention that three Vioxx patients had suffered unexpected heart attacks, which would have made the drug look significantly riskier. Add to that the case of the South Korean cloner Woo Suk Hwang, who faked human-embryo studies in the journal Science, and it’s a bad time for research integrity.
Research fraud, by its nature, tries to evade detection. But an idea of its extent comes from an anonymous poll of 3,200 American medical researchers in Nature last year: about a third admitted dubious practices such as changing results and methodology, often under pressure from the organisations funding them.
The medical journals’ front-line against fraudulent studies is peer review, where experts in the same field vet academic papers for publication. But Richard Horton, the editor of The Lancet, argues that peer review can’t stop systematic fabrications such as Sudbo’s. “Peer review is good at picking up poorly designed studies,” he says. “But it is not designed to pick up fabricated research.”
A second line of defence is replication, where studies are repeated to find if they produce the same result. These are gathered together in systematic reviews to get a bigger picture. But an Italian study in the BMJ last month found that even these become swerved: ones that involved commercial funding were much more likely to be poorly compiled.
Fiona Godlee, the editor of the BMJ, admits: “Poor research does get published even in the best journals. But even when dodgy authors are discovered, editors can do little more than reject them, she says. “Blacklisting perpetrators is legally difficult. There is an informal network for swapping information about people we catch, but it would be very hard to make that a formal process because unless their malpractice has been proven in the courts, you could be sued for libel.”
Editors have sought safety in numbers, forming the London-based Committee on Publication Ethics (Cope) in 1997, which investigates about 30 cases a year. The majority are found to be fraudulent. “We’re convinced that it’s the tip of the iceberg,” says its chairman, Dr Harvey Marcovitch, a consultant paediatrician. “We are seeing a rise in cases of dodgy research. Other than fraud, incomplete reporting of results is a big problem and is far more common with pharmaceutically funded studies,” he says.
“When you compare the number of published papers with positive and negative outcomes, you find very few negative ones that are pharmaceutically funded. Bad news gets buried. Trials get started but never see the light of day because they show the wrong outcomes. Vioxx is a good example. If the original trial had revealed those three heart deaths, it could have made an impact on doctors’ prescribing.”
But even if an editor spots a dodgy trial, it’s likely to be published eventually. “Every paper finds a home – if it’s rejected by a prestigious journal it can slide down the pecking order,” says Dr Marcovitch. “The big journals publish only 5 per cent of submissions, but there are tens of thousands of lower-rung journals and many take almost anything. That research can then get picked up by wider, systematic reviews, thus affecting patient care. It ’s disturbing.”
The UK is a latecomer to official fraud prevention. America, Germany and France have for more than ten years had organisations that either investigate fraud or monitor investigations. But no one, it seems, has the perfect model, says Professor Michael Farthing, who is creating Britain’s new watchdog, the UK Panel for Health and Biomedical Research Integrity. He plans to launch it in April. “About 1 per cent of all clinical trials involve a degree of impropriety, which overall is a lot,” he says. The panel aims to foster the proper investigation and punishment of bent researchers by offering training and advice to disciplinary inquiries and keeping an official record of investigations.
These are important, says Farthing, a gastroenterologist and former editor of Gut, because many offenders escape punishment, often because the initial investigation collapses under attack from expert lawyers. Many other investigations fizzle out because of complexity or internal politics. “A lot of cases get past the first stage of investigation, and then we never know what’s happened to them. We want to encourage employers to follow investigations through,” he says.“It’s an embarrassment for the UK that we don’t know how many medical research fraud cases have been investigated or what their outcomes are. While the General Medical Council publishes cases it has investigated, that’s only the tip of the iceberg because it deals only with doctors, not university scientists and non-clinical health researchers.”
The panel is backed financially by the NHS and Universities UK and is supported by the Medical Research Council and the Association of British Pharmaceutical Industries. But Farthing doesn’t want it to have policing powers: “I don’t see it taking on investigations. Other countries have tried that and backed away. We can’t force employers but we want to open them up in this gradual way.” Not everyone is convinced. Dr Richard Nicholson, a paediatrician and the editor of the Bulletin of Medical Ethics, wants it to be made illegal for drug companies to interfere with research results, either by burying negative ones or by cutting trials short if they look promising. “If the original trial for the Aids treatment AZT had gone on for another 30 days, we’d have seen no benefit from it because there were a lot of deaths among those treated in that subsequent period,” he says.
But ultimately, Nicholson argues, fraud will diminish only if we stop “overvaluing medical research” and take the pressure off doctors and researchers to publish. “Medical research hardly ever lives up to its promise. Ten years ago it was predicted that gene therapy would cure many of our genetic diseases by now. Now we know that’s overhyped. It’s the same with stem cells,” he says. “More than half of medical research is not cited even once but people have to get published to get promoted. We’d get much better research if it was left to the few people who are genuinely interested in doing it properly, who aren’t doing it to further their careers.”
Tracking down the fraudsters
Peter Jay is a former police chief who brought the 1980s serial killer Dennis Nilsen to justice. Now he works with drug companies helping them to catch doctors committing research fraud.
Drug companies pay doctors to trial new remedies on their patients, first having obtained their patients’ consent. But unscrupulous medics can consider drug companies fair game, says Jay. They take money to conduct trials and invent fake trial data instead of performing them properly. Jay is the chief executive of MedicoLegal Investigations, a company he set up after working for six years as a fraud investigator for the General Medical Council (GMC).
“If you have 20 patients in a two-year study, there is no reason why you shouldn’t earn £40,000, and there’s nothing to stop you running six to eight studies at a time, so long as you can get it past your employer’s ethics committee,” he says.
“The first drug company case I pursued was in 1991. Until then, companies which had caught doctors fabricating medical-trial results simply stopped using them. That left them free to work for other companies, having learnt how not to get detected so easily. There was always the possibility that a medicine could be licensed on the back of bogus data or a that good drug could be declared unsuitable.”
In 1996 he left the GMC and set up his own company, in partnership with a former head of the Association of British Pharmaceutical Industries (ABPI). “Since then we worked with the ABPI to take 26 doctors through the GMC disciplinary procedure. All but one were found guilty and struck off.”
Jay believes there is now comparatively little fraud in UK drug-company funded trials. “It looks like the message has gone around. But in wider medical research, I suspect that there are many problems because it is not policed successfully,” he says.
“There should be someone out on the loose who can pick up on suspicions and put a case together. This was why Harold Shipman managed to go on so long.”
Rogues' gallery
William Summerlin, of the Sloan-Kettering Institute in New York, claimed that he had carried out a successful skin graft experiment, using black and white mice. He was exposed in 1974 as having daubed a white mouse with a black felt-tip pen.
