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.