Ben Goldacre, The Guardian, Saturday 26 March 2011
Every now and then, very occasionally, a government will do something awesomely good. The budget contains plans for a new unified Health Research Regulatory Agency to streamline the regulations on clinical trials, and so make them cheaper and easier to run.
It’s motivated, disappointingly, by a desire to make the UK a more attractive location for commercial clinical trials. But this is the first time that a government has shown signs of seriously addressing one the most serious ethical problems in medicine: the harm done to patients by ethics committees and regulators.
At present there is a bizarre paradox in medicine. When there is no evidence on which treatment is best, out of two available options, then you can choose one randomly at will, on a whim, in clinic, and be subject to no special safeguards. If, however, you decide to formally randomise in the same situation, and so generate new knowledge to improve treatments now and in the future, then suddenly a world of administrative obstruction opens up before you.
This is not an abstract problem. Here is one example. For years in A&E, patients with serious head injury were often treated with steroids, in the reasonable belief that this would reduce swelling, and so reduce crushing damage to the brain, inside the fixed-volume box of your skull.
Researchers wanted to randomise unconscious patients to receive steroids, or no steroids, instantly in A&E, to find out which was best. This was called the CRASH trial, and it was a famously hard fought battle with ethics committees, even though both treatments – steroids, or no steroids – were in widespread, routine use. Finally, when approval was granted, it turned out that steroids were killing patients.
Only a trial could give us this information. Head injury is common. Patients died unnecessarily while we waited for this trial to be approved.
But it wasn’t just the delay to getting the trial approved. Many research sites insisted on getting written consent for randomisation from a relative of the unconscious patient, just because it was a trial, even though the treatments were exactly what the patients would have received in normal practice, while unconscious, without a relative’s consent. On average, treatment in these centres was delayed by 1.2 hours.
Does a delay harm patients? Of course. And this week, after a paper in the Lancet, for the first time we have quantitative data showing how patients are harmed by ethics committees’ insistence on these delays.
The CRASH-2 trial showed that giving a drug called tranexamic acid reduces the number of deaths for trauma patients with severe bleeding in A&E. What’s more, as you’d expect – since they’re bleeding to death – the sooner it’s given the better.
A one hour delay while you get consent for an unconscious patient in this situation reduces the number of patients helped by tranexamic acid from 63% to 49%.
This doesn’t just harm those individual patients, although we should be clear: it really harms those patients. More than that, if the benefits of a treatment in the real world are attenuated in a trial, because of a delay introduced by the demands of ethics committees, then the trial gives the wrong answer. We incorrectly conclude that an effective treatment is ineffective, and it is abandoned, when it could have saved lives.
These kinds of outcomes are disastrous. Furthermore, it has taken medical researchers to expose them. As the Lancet authors explain, with no small touch of huff: “the lethal effects we have shown might have been found decades ago had the research ethics community accepted a responsibility to provide robust evidence that its prescriptions are likely to do more good than harm.”
Of course there is a role for ethics committees. Of course we don’t want an army of Dr Mengele’s let loose on patients. Of course there will be disagreement on details. But I simply don’t believe that most patients hearing the stories I’ve just told – replicated around the country – would welcome the acts of the ethics committees. The government’s new announcement this week should hasten change, and if you ever get sick, you might be grateful.
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The CRASH trial:
This was an extraordinary piece of work. At the end of the trial, where the head injuries were pretty bad (a quarter of the people died), it turned out there were two and a half extra deaths for every one hundred people treated with steroids.