Saturday August 12, 2006
Look, I feel sorry for the six men who swelled up “like the Elephant Man” on TGN1412. The interim report is out now, and it has a lot of sensible suggestions about the mechanics of that kind of trial, but it got me thinking: if you wanted to be actuarial about this, and count up the pain and death caused by research shortcomings, where would you find the most tragedy?
How about duff studies? Tardive dyskinesia is a horrible and disabling movement disorder, a side-effect of schizophrenia treatment. A 1996 review looked at 500 studies of 90 treatments for it: not one provided useful data, they all either had too few patients or were too brief. That’s 500 duff studies, while patients continued to suffer, with no outcry, and no regulatory response: I could fill the page with similar examples.
But perhaps that’s too esoteric for our tragedy ledger. How about unnecessary research, through absent mindedness, or the greed of drug companies? By the mid-1970s it was pretty clear, from many well performed trials, that taking antibiotics after bowel surgery reduced your chances of getting an infection afterwards. And yet we continued to perform trials well into the 80s: half the patients were exposed to a placebo, and the risk of painful infection and death.
Meanwhile drug companies squander research money, effort, and patients’ goodwill on “me-too” drugs, minor variations on a theme that are unlikely to bring new benefits, except to shareholders. These “me-too” drugs are often tested in small studies, often comparing them against placebo, to ensure a positive result instead of giving them a fairer fight against their best competitors. Where are the regulators then?
Meanwhile, stand this wastage up against trials that were not done, because they wouldn’t make any money for anyone. Eclampsia is estimated to cause 50,000 maternal deaths worldwide each year, and the best treatment by a huge margin is cheap, unpatented, magnesium sulphate: not the expensive anti-convulsants that were used for many decades.
And yet, although magnesium for eclampsia had been used since 1906, its position as the best treatment was only established in 2002, with the help ofthe World Health Organisation: there was no commercial interest in the research question, because the majority of deaths are in the developing world, and because there’s no money for anyone in magnesium sulphate. Millions of women have died of eclampsia since 1906, many of them avoidable.
Now, I have a comfortable life, I profit from global inequality as much as the next man, I recognise that it’s too much to ask that we dismantle capitalism, increase state funding of trials, and ensure that research effort is deployed according to need and not company profit. But what about the easy stuff? Publication bias, for example, and companies who sit on disappointing findings, still pollutes the research evidence: and a compulsory clinical trials database, suggested decades ago, would solve the problem in one sweep. While no one has swelled up “like the Elephant Man”, they’ve been treated inadequately on the basis of a distorted evidence base: where are the regulators there?
I can identify with six blokes my age in intensive care. But if we spread our remit a bit wider and start looking at the body count, we might find the big stories are elsewhere.
Evidence and tardive dyskinesia. Soares K, McGrath J, Adams C. Lancet. 1996 Jun 15;347(9016):1696-7.
If you enjoy this kind of thing you should buy “Testing Treatments: Better Research For Bettter Healthcare”, written for a popular audience by Evans, Thornton and Chalmers.