A dose of realism exposes the heart of the matter

Heart disease is the scourge of the developed world, sending millions to an early grave every year. Small wonder, then, that news of a way of halting and even reversing its deadly course has been seized on by scientists and the media alike.

A study of patients with heart disease has found that high doses of a cholesterol-lowering drug known as a statin can break down the potentially fatty deposits lining the arteries. Over three-quarters of the patients showed some improvement, with the most severe cases showing the biggest

Announced at a meeting of the American College of Cardiology this week, the results have been hailed as a big breakthrough in the fight against this killer disease. Even before the results were unveiled, industry analysts were talking of the implications for AstraZeneca, makers of Crestor, the statin used in the trials. The drug was expected to prove a huge money-spinner for the company, but has so far failed to achieve the expected share of the statin drug market.

AstraZeneca’s share price duly rose a couple of per cent, and may benefit again when the results of the trial are published in a leading medical journal next month. But already some experts are trying to sound a note of caution. They include Professor Peter Weissberg, the medical director of the British Heart Foundation, who points out that while the study was “important”, the trial had been set up to show only the effects on cholesterol levels and fatty deposits. Whether these will translate into reduced risks of heart attack and death remains to be seen.

This will doubtless be the target of future studies. Until the results of these are in, veterans of clinical research like Prof Weissberg can be forgiven for failing to join the celebrations. After all, over the years they have seen countless “breakthroughs” fail to go the distance. And this latest example bears worrying signs of those that fizzle rather than fly. For a start, the drug was used at the highest recommended dosage – but in a trial too small to detect all but the most egregious levels of side-effects. It could yet turn out that Crestor cures one problem, only to replace it with another.

But there is another tell-tale sign of DSS – damp squib syndrome – and one routinely found in supposed breakthroughs in many other fields. Ironically, it centres on the level of surprise that leads to such findings making the media spotlight in the first place.

In the case of Crestor, even the researchers themselves admit to being stunned by the results of the trial. While statins were already known to be capable of slowing the build-up of arterial deposits, few expected them to produce a reduction. The increase in “healthy” cholesterol levels was also a surprise. The research team leader summed up the results as “shockingly positive”.

In other words, the results fly in the face of previous experience with these drugs. Considering there is no shortage of that, and that the new results come from a small trial, the smart money is on this “breakthrough” falling victim to DSS.

That may sound glib, but it has its basis in sophisticated techniques for making sense of new findings. Known collectively as Bayesian methods, they allow new findings to be assessed in the light of extant knowledge – with often salutary consequences.

Take the case of anistreplase, a clot-busting drug hailed in the early 1990s as a breakthrough in the treatment of heart attacks. A small trial conducted in Scotland suggested that early administration of the drug could cut death-rates by an astonishing 50 per cent. This again flew in the face of experience, which had suggested a much more modest level of benefit. Using Bayesian methods to combine that extant knowledge with the trial results, statisticians predicted the real improvement would be about 20 per cent. This has now been confirmed by much larger studies.

Despite their obvious value in making sense of new claims, Bayesian methods are still regarded by some as esoteric. The blame for this must lie with statisticians, who have done a dismal job of making these powerful techniques accessible to a much wider audience – including the business community. After all, even the least mathematical can appreciate the central message: extraordinary claims demand extraordinary evidence.

And while claims of drugs reversing heart disease are certainly extraordinary, evidence extracted from a few hundred patients is anything but.

The writer is visiting reader in science at Aston University, Birmingham

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