Michael Briggs 1935-1986. Faked data on the safety of oral contraceptive preparations taken by millions of women

Overview

Michael Briggs was a British born biochemist who worked at Deakin University in Australia and was regarded as an expert on assessing the safety of oral contraceptives. He was a WHO adviser on the contraceptive pill and its risks especially on biochemical changes that might be used to predict risk. In around 1983, he was accused of research fraud by the chair of the ethics committee at Deakin, Dr Jim Rossiter. Briggs initially replied that these accusations were about trivial inconsistencies and memory lapses but in August 1985 he resigned his position and moved to Spain. He admitted to a Sunday Times journalist (Brian Deer) in an interview published in 1986 that he had committed research fraud and fabricated data. He died in Spain from liver failure shortly after this interview at the age of 51. (Bibliography and available links at the end.)

Career timeline

Briggs was British born and a graduate of Liverpool University from where he went to Cornell University in the USA to undertake postgraduate studies and then moved to Victoria University in Wellington, New Zealand. He claimed to have a PhD from Cornell and a DSc from the University of New Zealand. According to a report in Nature by Dr Jim Rossiter who was chair of the ethics committee at Deakin University for more than a decade, Briggs only spent a relatively short time at Cornell and was awarded an MSc not a PhD. Rossiter does acknowledge that his DSc (usually awarded on the basis of a distinguished publication record) was genuine even though he spent less than three years in New Zealand. From 1966-1970 he worked for the UK research department of the international pharmaceutical company Schering and during this time he was also a visiting professor at the University of Sussex. In 1970 he took up a position as Professor of Biochemistry at the University of Zambia. In 1973 Briggs and his wife Maxine moved to Melbourne Australia where he initially worked at the Alfred Hospital.

In 1977 Briggs became the first Professor of Human Biology and the inaugural head of the science school at the newly formed Deakin University in Geelong in the Australian state of Victoria. Deakin University had its first intake of students in 1977. By the time of his appointment to this post, Briggs had gained an international reputation as an expert on the safety of oral contraceptives particularly about the biochemical markers that might be used to predict the long term safety of these pills and was an adviser to the World Health Organisation about these changes in blood biochemistry. His wife Maxine (nee Staniford) was medically qualified and was a co-author on many of his clinical papers and articles. When I did a literature search for papers by Maxine Staniford, I found just one published before she started publishing with her husband-to-be  and that was a review article which she co-authored in the British Journal of Clinical Practice in June 1967 relating to a particular oral contraceptive. I could find no article relating to oral contraceptives published by Briggs before 1969 and indeed his publication topics prior to this time are extremely diverse, eclectic even, in their subject matter e.g. the chemical composition of fossils and meteorites, effects of feeding urea to cattle, composition measurements on insects, visual pigments of crabs, olfaction (sense of smell), composition of lake water, side effects of a compound called dimethyl sulphoxide etc. So it is possible that his new wife’s interest and expertise in oral contraceptives helped to focus him on oral contraceptives as the future area of his research.

Briggs certainly has a high number of publications to his credit, a recent search using the Scopus search engine generated almost 200 publications that could be attributed to him. In an article in Nature Rossiter suggests that many of his publications were review articles or invited articles and many were published in the proceedings of meetings sponsored by drug companies and some were published in journals owned by pharmaceutical companies. In this 1992 article entitled Reflections of a whistle-blower, Rossiter claimed to have obtained copies of all of the articles listed in Briggs curriculum vitae and he suggests that only three were papers that he considered to be original research published in peer reviewed journals. He further noted that many of those published in prestigious international journals like the Lancet, BMJ and Nature were one page letters or commentaries and he called many of them ephemeral publications. I found 21 publications listed for Briggs that were published in the Lancet between 1968 and 1980 and it is likely that all or almost all of them were less than a single printed page. Seven of these 21 articles were related to vitamin C and at least 6 others were nutrition-related and more than half were published during his four years at the Alfred Hospital in Melbourne.

Briggs work on oral contraceptives

The traditional form of oral contraceptives uses a pill that contains a combination of synthetic hormones that mimic the actions of the natural female hormones of the oestrogen-type and progesterone. Women would normally take these combined pills for 21 days and then have seven pill-free days during which a reduced menstrual period would occur. In recent years there have been efforts to produce effective pills with lower level of the oestrogenic component (low oestrogen pills) to reduce the risks of thrombosis and some pills use just small doses of a progesterone-like compound (mini pill). Other more complex regimens use different doses of hormones during different phases of the cycle either 2 dose levels (biphasic) or three dose levels (triphasic). Much of Briggs research was favourable to one particular progesterone-like compound called levonorgestrel and his work and writings also did much to promote the development and use of triphasic pill regimens; the first triphasic preparations contained levonorgestrel.

An example of his support for the use of levonorgestrel is a paper that he published in 1983 in the Journal of Reproductive Medicine in which he compares the effect of four different low dose oestrogen pills on measures of blood lipids and measures of the blood clotting factors over 12 monthly cycles of taking these pills. For one of the non-levonorgestrel products all of the subjects had stopped taking the product within five months, for the other two there were apparently adverse effects upon blood lipid measures (including total cholesterol) and upon 6 measures of blood clotting; the levonorgestrel product, however, had little or no effect upon these 10 risk factors and this clearly suggest its superiority in terms of potential health risk.

Accusations of research misconduct surface

In the early 1980s, there was disquiet amongst other specialists in the field about how Briggs could manage to recruit so many subjects who were ideally suited for his studies when others working in the field found this to be a difficult and time-consuming task. This disquiet reached Dr Rossiter, who as Chair of the ethics committee at Deakin approached the chancellor of the university in October 1983 to suggest that some sort of investigative action by the university was warranted to consider a portfolio of evidence that he had generated. He later recommended that a committee of inquiry should be set up. The chancellor (Justice Austin Asche) refused this request and suggested that Rossiter should write to Briggs making his concerns known and giving him a chance to allay any suspicions. Briggs eventually replied to Rossiter’s second request for him to answer the accusations being made against him but Rossiter considered this reply an inadequate reply to the criticisms (this letter is reproduced in full in Rossiter’s 1992 article in Nature). Eventually Rossiter and some of his colleagues made formal complaints to the university vice-chancellor. These two formal complaints listed a number of accusations against Briggs and these are summarised below.

• Relating to a 1979 paper on oral contraceptives and plasma protein metabolism and a 1980 paper on the metabolic effects of oral contraceptives containing different doses of levonorgestrel:
  • That Briggs had not recruited the stated number of women from the sources stated in the papers
  • That not all of the complex laboratory analyses in the paper could have been carried out in the way that was claimed in the papers.
• Relating to a 1980 paper comparing the effects of a compound called desogestrel with another compound:
  • Desogesterol was not available in Australia at that time and Briggs had no licence to import it
  • Briggs received money from the manufacturer of desogestrel into a private account for making the results of his studies available to them.
• In two papers published with his wife Maxine in 1980 and 1981:
  • A total of 291 volunteers with strict inclusion criteria were said to have been used but it is alleged that no such number existed and the studies were not carried out to the extent stated, if at all
  • No ethical approval for these studies had been given by the University Ethics Committee
  • The measurement of blood constituents were claimed to have been made at two hospitals but were not carried out at these hospitals and it is alleged they were not carried out at all
• In another 1980 paper published with his wife on the development of a triphasic oral contraceptive:
  • Measurements of hormone levels (FSH and LH) were said to have been carried out by a Dr K Fotherby and they were not carried out by Dr Fotherby.
• In a 1980 paper using beagle dogs:
  • Briggs claimed that progesterone receptor measurements were made at Huntingdon laboratories in the UK but they were not carried out there.

The initial inquiry set up to investigate the Briggs affair was abandoned because it was referred to a high court judge who ruled that the initial complaint against Briggs was “improperly founded”. A second committee of inquiry was set up following a re-drafting of complaints against Briggs but because Briggs resigned from the university in 1985 the inquiry did not continue. In 1988, a working party chaired by a member of the university council Margery Ramsay produced an 80 page report into the Briggs affair and its implications for Deakin University inquiry procedures.

Dr Rossiter claims in his Reflections of a whistle-blower article that following the submission of his first complaint he was subject to a campaign of harassment and intimidation as summarised below.

• 200 threatening, obscene or silent phone calls; many at night
• Letters containing obscene allegations about his private life
• Expressions of doubt about his sanity from a psychologist on the Deakin staff which he believes adversely affected his private medical practice
• Attempts to remove him as chair of the ethics committee at Deakin
• Attempts to blame him for leaking details of the affair to a journalist (he says that in fact the confidential files had been removed from his locked office).

Attempts were made to remove him as Chair of the University Ethics Committee and to completely alter the composition of this committee but these were ultimately unsuccessful. In 2003, Rossiter was awarded a “Doctor of the University” for his distinguished service to Deakin from 1978-88 and for his contribution to the University in the field of research ethics. This has echoes of the Chandra case-study where the whistleblower was eventually honoured by a prize named after her, years after she felt that she had suffered professionally for her whistleblowing at Memorial University in Canada.

After his resignation from Deakin in 1985, Briggs moved to Marbella on the Costa del Sol in Spain. There is a widespread assumption that some of the money donated by drug companies to sponsor his research activities was used for personal gain. He was tracked down in 1986 by A Sunday Times journalist Brian Deer who conducted a four hour interview with him in Spain. Two articles written by Deer appeared in the Sunday Times in September 1986 under the headlines “The pill: professor’s safety tests were faked” and “Exposed the bogus work of Professor Briggs”. In these articles Deer highlights how important the published work of Briggs was in producing re-assurance about the safety of certain oral contraceptive preparations especially those containing levonorgestrel and the part they played in persuading the licensing authorities to make these products available. Briggs appears to have effectively confessed to the most serious claims of scientific misconduct during his interview with Deer. He admitted:

• Pretending to organise studies of the effects of oral contraceptives which he had not done
• Reporting important studies with beagle dogs which had never been performed
• Including complex biochemical measurements in his papers without being able to state where these analyses had been conducted.

The impact of Briggs work

Deer goes on to discuss how pharmaceutical companies financed the publication of Briggs’ findings in book form and then disseminated these widely to doctors who would be prescribing oral contraceptives.  There is the suggestion that Briggs work may have continued to be used in promotional material for certain oral contraceptives for some time after strong and persuasive doubts about the veracity of his findings were being aired. Briggs died at the end of 1986 i.e. about 3 months after his Sunday Times interview and just 16 months after his flight from Australia.

By the time of his death in the late 1980s, oral contraceptives containing levonorgestrel dominated the UK market and about 2 million women were taking various preparation based on this substance with perhaps 15 million women across the world taking these products. These products were popular because they were good at preventing so-called “breakthrough bleeding” during the cycle and were said to promote a sense of wellbeing and improved libido.  The work of Briggs certainly played an important part in the popularity of these products by suggesting that they induced less negative effects on blood parameters that would increase health risks.  In 1988, a major study looking at the relative risks associated with taking nine different formulations of pill was published under the direction of Professor Victor Wynn in London (Crook et al 1988). Contrary to the falsified findings of Briggs, this study based on data from 1400 healthy women showed that levonorgestrel preparations generally caused more rather than less adverse metabolic changes as compared to other non-levonorgestrel containing formulations. The implication of these findings was that women should be switched to oral contraceptive formulations that did not contain levonorgestrel. This study suggested that the preparation which came out best from these measurements of risk factors was one which contained desogestrel; the compound that Briggs was accused of publishing data about before it was available in Australia.  Other non-levonorgestrel preparations also performed almost as well as desorgestrel according to the parameters measured by Crook and colleagues.

It is impossible to say how many women might have been harmed by the bogus research of Professor Briggs all one can say that his research helped to promote products that were used by millions of women and which turned out to probably not be the safest oral contraceptive option.

Bibliography

Rossiter, EJR (1992) Reflections of a whistle-blower. Nature 357, 434-6. Full access to this article requires a payment but non-academics can get a summary here.

Staniford, M and Taylor, AF (1967) A review of an oral contraceptive, lyndiol 2.5. British Journal of Clinical Practice 21, 293-6. No free online access.

Briggs, MH (1983) A randomised prospective study of the metabolic effects of four low-oestrogen oral contraceptives. Journal of Reproductive Medicine 28, 92-9. Abstract only available from here.

Deer, B (1986) The pill: Professor’s safety tests were faked. The Sunday Times 28^th September 1986. Available from here.

Deer, B (1986) Exposed: the bogus work of Professor Briggs. The Sunday Times 28^th September 1986. Available from here.

Crook, D, Godsland, IF and Wynn, V (1988) Oral contraceptives and coronary heart disease: modulation of glucose tolerance and plasma lipid risk factors by progestins. Americal Journal of Obstetrics and Gynecology 158, 1612-20. Access to full article requires payment but non-academics can see an abstract here.

Deer, B (1988) Research reveals birth pill risk for 2M British women. The Sunday Times 18^th September 1988. Available from here.