Reprint
Exposed: the bogus work of Professor Briggs
The Sunday Times, 28 September 1986.
Professor Michael Briggs, an eminent British scientist, faked major research on leading brands of contraceptive pill now taken by 10m women around the world.
An investigation by BRIAN DEER
DEAKIN UNIVERSITY lies just outside the small town of Geelong, an hour’s train journey west of Melbourne on Australia’s south coast. Road traffic is light and the squat, modern buildings of student, arts and science blocks barely disturb the peaceful Victoria countryside. It is not the sort of place where one expects to find major research going on.
But it was to Deakin’s little campus that Professor Michael Briggs came in 1976. His background was beyond reproach. The British scientist had a string of publications on the contraceptive pill. To Fred Jevons, Deakin university vice-chancellor, he was the sort of academic who might put the university on the map.
“It was Briggs who really started to get research going, and who built up the school of sciences into what it is today,” says Jevons. “He brought funds from drug companies to buy equipment for students to work with. Personally, he was charming and we often had dinner together.”
Briggs, now aged 51, assumed the post of professor of human biology and head of the sciences school. His teaching duties were extensive, mainly coaching Ph.D students in biochemistry. But he was also able to continue work he had begun in Zambia four years previously on one of the most remarkable series of research publications that has ever been produced.
Under his authorship, or jointly with his wife, Dr Maxine Briggs, he produced over 10 years some 55 research papers, and almost as many detailed reports in letters to science or medical journals. Most were on various aspects of contraceptive safety. Briggs’s particular speciality was in subtle blood chemistry changes that might predict long-term risks from the pill.
He was also a special adviser to the World Health Organisation and was often seen at European or American gatherings of endocrinologists – the hormone specialists who dominate contraceptive science. At these meetings he brought a new prestige to Deakin University, and, among senior hormone researchers, won a tremendous personal regard.
It was around 1982, however, that the warmth of his reception began to decline by degrees. Briggs was not alone in the scientific areas on which he wrote. Rivals began to wonder about some of his results. Not only were a number of his findings questioned, but so were the means by which he so swiftly published them.
“It was incredible, unbelievable, the things he was reporting,” says Dr Bryan Hudson, who lives in Melbourne, and who was at the time president of both the Royal Australasian College of Physicians and the International Society of Endocrinology. “Our professional colleagues abroad were saying they simply did not believe that he could do major studies in the way that he described.”
*****
CONCERN over the long-term risk of the contraceptive pill has been rising during its 25 years in use. Few doctors doubt that health hazards exist, and product information supplied to them is required to point this out. What remains in doubt is what balance can be struck between risks and benefits.
The incidences of cervical and breast cancers among pill users have been raised, doubted and raised again. Just as important are the connections feared by doctors between taking the pill and the development later in life of heart attacks, strokes and raised blood pressure. These are grouped together as vascular disease.
Since the pill’s introduction, research findings in this area have been important in leading to a progressive reduction in the hormone content of the contraceptive pill to reduce the risk. In 1969, the British government’s safety watchdog said that the hormone oestrogen should be reduced. In 1977, a study by the Royal College of General Practitioners led to efforts to cut the other hormone in pills, progestogen.
But cuts in hormone content can only be pursued to the point where the pill remains effective. Because taking the pill also affects menstruation, settling a regular cycle through hormone control, varying the chemical content of pills can also cause erratic, breakthrough bleeding.
The hopes of many researchers for further reducing the risk of vascular disease were raised with the discovery by the West German pharmaceutical giant Schering AG of a new way of preparing pills, delivering three varying doses of hormones over the menstrual cycle.
Although other products make competing claims, these pills, known as “triphasics”, and containing the synthetic progestogen levenorgestrel, have been extensively promoted by drug companies as an even safer form of contraceptive pill, in an attempt to bring increasingly sceptical women to use oral contraception.
“Trinodial – the lowest ever monthly hormone dose to provide reliable contraceptive protection,” declares a typical advertisement in the medical press. That one was placed by the American drug company Wyeth, which makes the Schering product under license. It goes on to offer: “Minimal breakthrough bleeding, while minimal interference with metabolism points to increased safety.”
But these new products raise questions of their own. Besides the absolute levels of oestrogen and progestogen, the proportions in which they are combined and the manner by which they are artificially synthesised are also of key concern. And in this area of science, there was no more important researcher than Professor Michael Briggs.
“First it was the GPs who moved over to the triphasics, and eventually we in the family planning clinics began to be impressed,” says Dr Fleur Fisher, of the National Association of Family Planning Doctors, and a community physician in the north of England. “We looked at Briggs’s studies when we made that decision.”
*****
MONEY is usually the first big problem for any scientific inquiry, but Briggs easily overcame that hurdle. In the 1960s, he had been UK research director for Schering Pharmaceuticals in Sussex, and was able to raise research grants from Schering AG, its West Berlin-based parent. The Schering group has subsidiaries in 19 countries and an annual turnover of more than £1.6 billion.
Schering AG’s contraceptive pill formulations are also sold under a licensing agreement by the Pennsylvania-based Wyeth, a subsidiary of American Home products, the world’s biggest producer of sex hormones, holding nearly a quarter of the international market. Wyeth, too, contributed heavily when Briggs passed round the hat.
With the money sorted out, Briggs pressed on with the work. Among his most important papers from Deakin University were Recent Biological Studies in Relation to Low Dose Hormonal Contraceptives, published in 1979; progestogens and Mammary Tumours in the Beagle Bitch, published in 1980; and Comparative Metabolic Effects of Oral Contraceptives Containing levonorgestrel or Desogestrel, published in 1983.
Of particular interest is a series of investigations reporting the effects on blood metabolism in a large sample of women using the pill over six, 12 and 18 months. This series culminated in his very widely quoted paper, Implications and Assessment of Metabolic Effects of Oral Contraceptives, published in 1981, and still the biggest such study in the literature.
*****
BUT much of the research work as described and presented by Briggs never took place. He did not do tests on which the papers appeared to present results, some of his reported tests were impossible to conduct, and , in one paper he wrote up a study of dogs that he had not done.
In a four-hour interview in Spain, Briggs admitted to The Sunday Times that he had collected from other people unpublished, small-scale findings and generalised them into apparently big and convincing trials. He refused, however, to reveal from where he got this data. “If I tell you who organised the studies you will know who is involved,” he said. “I still know a lot of them personally and I’m not prepared to drop people in it.”
Although Briggs believed his deceptions would not be exposed, he underestimated the errors that he built into the work. First, he failed to allow the right length of time for the recruitment of subjects for the studies. Pill researchers have always had trouble persuading suitable women to take part, yet Briggs found it strikingly straightforward.
In a key series of papers, he presented findings on more than 80 women who were under 30 years old, within 10% of ideal body weight, who did not smoke and were taking no medicines, who had never used the pill and who were prepared to fast overnight before attending, for 18 months, monthly hospital interviews and blood tests. The timing of his papers also suggests that virtually none of the women dropped out.
Second, the investigations Briggs was conducting were of great breadth and sophistication. His ostensible task – to find out just what was happening in the blood of women who took the pill demanded tests for up to 16 different possible changes in proteins. Doctors believe some of these changes are strongly implicated in raising the risk of heart disease and stroke.
But Deakin University did not have the elaborate and costs equipment for the work Briggs had described, and he gave no indication of where the tests had been performed.
Another query was raised over where Briggs had obtained one of the hormone products, desogestrel, which was not licensed for use in Australia, but for which he published results.
In one paper, tables contradicted the text, and in another a measurement technique used for human subjects relied on a standard meant for sheep. A third, a paper reporting work with beagle dogs, could not have been done as Briggs claimed because there are no beagles at Deakin.
Under pressure from complaints brought by specialists at Deakin and in Melbourne, vice-chancellor Jevons questioned Briggs, who made a number of checkable claims. But Briggs went to law, using a procedural point to block a university investigation. After attempting to support him, Jevons finally changed his mind.
“I think this was the first time in history that the law was used to stop a scientific investigation,” says Jevons, now an emeritus professor at Deakin. “That was the turning point for me. I defended him up until then.”
*****
BY THIS time, however, Briggs’ work had managed to penetrate medical literature, even though none of his results of any real importance on contraception has been published in a major medical or science journal. Instead, his key work appeared substantially through the medium of drug-company sponsored books.
These publications, essentially transcripts of specially-arranged symposia, provide a quick, cheap, but poorly-vetted means of issuing new research to doctors. Briggs’s work therefore acquired “respectability” through symposia in Madrid; in San Francisco, financed by Schering; and in Leuvens in Belgium financed by Wyeth.
Had Briggs offered his findings to one of the major medical or scientific journals, which normally employ panels of experts to “referee”, or vet papers, suspicions might have been aroused that would have caught him out. But the eminent editors of the symposia proceedings could not have had the time or the resources to make any rigorous inquiries of Briggs.
“The editor can’t go and check whether the laboratory equipment existed or the patients existed,” says Professor Max Elstein, who edited the San Francisco proceedings, and who chaired another symposium last week in Chicago. “You rely on the scientific integrity of the person who supplies the data.”
Despite these difficulties, and the consensus in medicine and science that symposia proceedings should not been given too much weight, they were submitted by drug companies to national licensing authorities and were extensively used to promote brands of pills to doctors. In Wyeth promotions, still being distributed in Chicago last week, Briggs’s material is used to authenticate important safety claims.
Promotions directly to family doctors have also been dominated by references to Briggs’s work. “No significant lipid impact up to 18 months of use,” declares a Wyeth worldwide advertising campaign, quoting a Wyeth symposium paper.
*****
WHEN Briggs quit Deakin a year ago and retired to a villa in the south of Spain, the university council ruled that this was not an admission of guilt. “No charge or complaint is proved against professor Briggs,” declared Mr Justice Ashe, the chancellor, accepting the resignation. “Nothing adverse to his reputation has been established and no inferences to him should be drawn.”
This was not, however, the verdict of the international scientific community. Last October, a special meeting was held in West Berlin, solely to discuss Briggs. British doctors agreed that researchers should no longer use his findings. They believe that the deceptions discovered in his work are so serious that earlier papers, relating to many more contraceptive products, must now be re-examined.
“What is clear is that we must not now trust any of the earlier work that he did,” says Dr John Guillebaud, director of the Margaret Pyke family planning centre in London, who attended the Berlin discussion. “The reviews and letters are all right, but we can’t accept the research.”
However, these have remained private decisions. Although the charges against Briggs are common knowledge at a senior level in the pharmaceutical industry and among researchers on the pill, most of those who know have been unwilling to tell the tale. “I’m sorry, I can’t help you any further,” said Guillebaud. “Not in my position.”
No suggestion of complicity by the drug companies has been made – indeed Briggs often acknowledged the firms that supplied products for his tests. Wyeth International said last week that, although it had financed Briggs, it was “supporting” rather than “sponsoring” his research. proposals for studies came from Briggs, not the company.
Schering AG said it never doubted his work. “Professor Briggs had a very high rank in the medical community. He was consultant for oral contraception to the World Health Organisation for many years. He has published extensive work. He was looked upon as a real authority in the field,” sys Dr Ursula Lachnit-Fixson, head of Schering’s hormone research and inventor of triphasics. “We have no reason whatsoever to doubt that his work has been done correctly.”
*****
WHEN we first pulled up outside Briggs’s new home in Marbella it was clear such an arrival by a newspaper was the sort of event he had long feared.
Despite a series of admissions, he denies that the matter is of any significance. The results he produced were similar to those of other researcher, he tells us, and the link between blood chemistry changes and long-term illness was still a matter of medical speculation. It was not his fault that so much had been made of his work.
“What am I supposed to do?” he said, during one of several moments when he almost broke down. “In any case, can’t you leave her out of it?” he added, nodding towards his wife, who shared much of his work. “It’s me, really, you are interested in.”
Two years later…
Research reveals birth pill risk for 2m British women
The Sunday Times, September 18 1988.
By Brian Deer, Social Affairs Correspondent.
FAMILY doctors are to be urged to switch more than 2m British women from their current brands of contraceptive pills, after a scientific investigation which suggests that the most popular pills available carry the greatest health risks.
The pills, which all contain the synthetic hormone levonorgestrel, include leading brands Microgynon, Eugynon, Ovran, Ovranette, Trinordial and Logynon, which currently dominate the British oral contraceptive market. Worldwide, more than 15m women are believed to be taking this type of pill.
Doubts about the levonorgestrel pills have circulated among scientists and doctors for the last two years, after The Sunday Times revealed that important research publications, purporting to show the relative safety of the products, was fabricated.
Now, the gap left in the medical literature by the exposure of the fraud is to be filled by research which shows the pills to be more likely to cause heart disease and other cardiovascular problems than other brands available.
The new research was carried out in Britain on behalf of the American government’s National Institutes of Health, and is the largest investigation of its type ever undertaken independently of drug firms.
The £500,000 research project was led by Professor Victor Wynn, whose team at the Cavendish clinic in north London studied more than 1,400 healthy women taking nine different formulations of pill.
Wynn has been a leading authority on contraceptive safety for more than 20 years. His team measured complex changes in the blood, which are now regarded as key indicators of whether a person is likely to develop cardiovascular diseases. Across a range of measurements, they found that women taking levonorgestrel pills were in significantly greater danger.
The implications for women now taking the pill are likely to be far-reaching. Professor Wynn is currently recovering from illness, but his staff said that family doctors should be alerted to the increased risks which they believe are posed by the levonorgestrel pills.
“These are significant effects that we have found. Here we have the basis for a major shift in prescribing,” said Dr Ian Godsland, a senior biochemist in Wynn’s team and co-author of the research.
More women are taking levonorgestrel pills than any other type of oral contraceptive, after a marketing campaign in the medical profession by their multinational manufacturers. The firms involved are Schering AG of West Berlin and the Philadelphia-based company, Wyeth.
In recent years, the two companies have particularly encouraged doctors to prescribe their so-called “triphasic” levonorgestrel pills, which deliver a smaller quantity of the synthetic hormone. These “low-dose” pills also fared badly in the research.
It was also the triphasics that became the centre of an investigation by The Sunday Times. This revealed that Professor Michael Briggs, a British scientist and a former senior staff member of Schering, faked a series of papers which appeared to refute links between the pills and heart disease.
His work, carried out at Deakin University in Australia, was financed by Schering, which also paid for the results to be published and distributed to doctors worldwide. The company denied knowledge of the deceptions and, after our inquiries, deleted Briggs’s work from its literature.
Schering said this weekend that it did not contest Wynn’s findings at present, and that it is not currently promoting levonorgestrel pills. The company said that it is now recommending to doctors that they consider Femodene, a new oral contraceptive containing a different hormone.
Dr Peter Longthorne, medical director of Schering’s UK subsidiary, said: “We do not know what the implications of this study are in a clinical setting. It is an interesting finding and I do not think we can draw a definitive conclusion at this stage.”
Wynn’s method was to examine more than 30 aspects of blood metabolism in more than 1,400 women. They were a random sample, with an average age of 28. The most worrying sign he detected was a decline in an element in blood known as HDL2, which is believed to protect women against heart disease.
The pill which fared best in the investigation was Marvelon, which contains a hormone called desogestrel, rather than the suspect levonorgestrel. Very closely behind this were pills containing small amounts of norithisterone, such as Brevinor, Minovlar and Loestrin.
General practitioners and doctors in family planning clinics may wish to switch women to these pills, but this will not be easy. Levonorgestrel-containing contraceptives are popular because they are good at preventing “breakthrough bleeding” and because the hormonal changes can in many cases promote a sense of well-being and improved libido.
Dr John Guillebaud, medical director of the Margaret Pyke centre for family planning in London, said that he wanted further research on the alternatives to levonorgestrel before he would advise women to change. “It is not that these pills have suddenly become dangerous, but that from the laboratory studies it appears that the others are better,” he said.