Consistency of studies spurred swift response

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The three Pill studies which forced the Committee on Safety of Medicines to issue its controversial advice on seven of the most popular oral contraceptive brands, are, as yet, unpublished.

Two of the studies have not been "peer reviewed" - refereed by independent experts - and there is confusion over whether some of the results are final or interim analyses only.

But at the heart of this fierce controversy is one question: was this data enough for the CSM, ahead of every other country with the same information, to advise 1.5 million women that they should consider changing their Pill brands to reduce risk of blood clots?

The Department of Health thinks so. "We were in receipt of three reports which made it imperative to act. All were final analyses. We are not in a position to hold on to such information," a spokesman said yesterday.

Other bodies, including leading scientists, family planning experts and GPs, international drug regulatory authorities, and the drug manufacturers, think the CSM was premature, verging on the irresponsible.

The three epidemiological studies were comparing the risk for cardiovascular side- effects, venous thrombolism (blood clots in the veins), heart attacks and strokes, for women taking "second-generation" oral contraceptives with "third-generation" Pills. The former contain synthetic progestogens, a female hormone called levornorgestrel, norethisterone. The latter, the newly identified higher risk Pills, contain progestogens known as gestodene and desogestrel. These had been shown to have less effect on fats in women's blood than the older Pills, and were therefore deemed safer.

It was preliminary data from a World Health Organisation 17-nation trial, issued in July to all drug regulatory authorities, that the CSM says initially alerted it to an increased risk of blood clots in veins in the legs (known as deep venous thrombosis or DVT) associated with the third-generation Pills. The risk for third-generation Pills was twice that of the second- generation Pills.

The second study was the Transnational (European) Study, by Professor Walter Spitzer, conducted in five countries including the UK.

Early results from the Transnational trial indicate, according to Professor Spitzer, that "all low-dose oral contraceptives continue to be associated with an increased risk of venous thromboembolism. Preparations containing third-generation progestogens appear to have a slightly stronger association . . . than other low-dose preparations".

The final study, which the Department of Health says was the trigger for the CSM's decision, was that of Dr Hershel Jick, Associate Professor of Medicine at Boston University Medical School, and his team.

The team has access to up to 2,100 GP data bases in England and Wales. In May it began analysing data on the cardiovascular risks of third-generation pills, following media reports of problems. It extended its investigations to venous thrombosis and related deaths in July, after the WHO study.