Avandia: the holes in "evidence-based" medicine

In a 1664 diary entry, Samuel Pepys noted that he was feeling in unusually good health and wondered why. Was it because he’d taken to wearing a hare’s foot around his neck? Or maybe it was the pill of turpentine he swallowed every morning?

Today we, theoretically, no longer have to wonder about such things. There is a vast clinical trials industry designed to test and prove the efficacy of pharmaceutical cures for our afflictions. Establishing an evidence base is now as central to medicine as democracy is to our politics or credit to banking.

But the fanatical application of any big idea can have destructive consequences. The past few years have seen increasingly vociferous attacks on non-drug remedies, usually lumped together as CAM (complementary and alternative medicine), on the grounds that they lack a proper evidence base. Of course, weeding out ineffective treatments makes sense, but the assault on CAM (particularly homeopathy) by the new puritans of evidence-based medicine has become a dangerous distraction from a much more serious problem: the failings in the regulation of drug-based medicine.

This was highlighted when two reports were published last February. One, from the Commons Science and Technology Committee, concluded after a few days of hearings that: “using money on homoeopathy’s highly diluted remedies could not be justified.” The other came from the finance committee of the US senate and followed a two-year investigation of the drug company GlaxoSmithKline (GSK), makers of Avandia, a drug used to treat diabetes. It, too, reached a damning conclusion—not only about the drug’s safety, but the lengths the company had gone to conceal evidence that the drug raised the risk of heart disease. “GSK executives,” it said, “had attempted to intimidate independent physicians, and focused on strategies to minimise or misrepresent findings.” Yet while the homeopathy ruling made news across Britain, the Avandia story did not—despite the fact that over 550,000 prescriptions were written for it in England alone last year.

For an eye-opening view of the lengths to which a drug company will go keep unfavourable trials out of the public eye and possibly (GSK denies it) manipulate the data from a safety trial so it looks favourable, watch Panorama this evening—A Risk Worth Taking? BBC1, 8.30pm, Monday 6th September. Until we have a proper and effective drug regulatory system, getting worked up about homeopathy is like worrying about litter when there is a killer on the loose.

The senate report was actually the third investigation into the safety of Avandia in three years. In 2007 a large study by Dr Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio, found that the drug was linked to a 43 per cent increase in the risk of having a heart attack. The following year investigators from the FDA estimated that the drug was causing an extra 500 heart attacks per month in the US and urged the company to take it off the market.

At the July hearing, an FDA scientist testified that, in a big trial the company relied on to show the drug was safe, patients who had suffered heart attacks were left out of the results. And a new analysis of Avandia studies by Dr Nissen claimed that as few as 40 people had to take the drug for one to be harmed.

It might be argued that the investigations into Avandia, worrying as the findings were, did at least show the evidence-based system was working. But the alarm was actually raised thanks to an unusual combination of circumstances, without which the problems might never have come to light.

The researcher who carried out the re-analysis of Avandia trials in 2007 (and discovered the raised risk of heart disease) was only able to do so because GSK, unlike other companies, had been forced to make all the data from its trials available online. This was a condition arising from a court case involving another charge: that GSK had concealed the results of a different drug, the antidepressant Seroxat.

Why, then, are champions of evidence-based medicine not directing more of their attention towards the practises of large pharmaceutical companies, instead of going after the practitioners of homoeopathy? The Avandia case, to be fair, has not gone wholly unnoticed in Britain: prescriptions have declined significantly from their height of 1.1m in 2006 because, it seems, doctors are aware of the problem. This raises an interesting question. Who are the doctors practising evidence-based medicine? Those who continue prescribing Avandia because regulators still say its benefits outweigh the risks, or those who have stopped because they believe the evidence shows it is unsafe? In both cases, it seems they are having to make a guess, rather like Pepys and his turpentine.