Tuesday, June 19, 2007

Clinical trials, asparagus & the placebo effect

For a hedgehog (who is really a fox) there is a particular joy in academic journals. It is so easy to be diverted by something which has nothing to do with the subject you are supposed to be researching - at least if you are doing it the old fashioned bound volume way, in a library

And so I once read, in the Proceedings of the Royal Society (I think), of the scientific investigations carried out in London on the original Siamese Twins. As a way of testing whether they had independent digestive systems, investigators fed asparagus to one twin. Then smelt the urine of each. As far as I recall, only one urine sample displayed the characteristic odour which is imparted by the vegetable

On another occasion I read one of those end of term articles which the BMJ used to carry in July & August. A group of SHOs had investigated the prevalence of the asparagus phenomenon, whose very existence was in dispute. They found that some people were indeed affected in this way. But estimates of prevalence were confounded by the fact that the population can also be divided into those who can & those who cant detect the smell with their own olfactory organs

All this by way of another sideways approach to my subject

New research has just been reported - the placebo effect does exist! It has a real biological basis or precursor! Our old friends, endorphins, released when you think something will do you good. From what I read in the press, the question of how that belief is engendered was not addressed in this study

I have long thought that, if there is a placebo effect, there should also be a nocebo effect. If you believe it will do you harm, it will. Or even if you just dont expect it will do you any good, it wont. Presumably with biological bases too

And so, can the population also be divided according to which - placebo or nocebo - they are susceptible to? Optimists or pessimists? Those who believe it only does you good if it tastes nasty, il faut souffrire pour etre belle. And those who believe a spoonful of sugar is required. That comfortable feet do more for your inner beauty than painful killer heels?

The effect on the gold standard for clinical trials could be profound. As I understand it, part of the reason for taking the placebo-controlled, randomised, double blind trial as the gold standard was the observation of a hierarchy of size of effect. Observational trials reported the biggest effect, & so on down to the double blind. So this must be the undisputed effect of the drug, right?

Well, perhaps, But then along comes fully informed consent. Suddenly the patient knows he might be getting only a dummy. This can surely, only increase the size of or even induce the nocebo effect. An otherwise effective drug fails to work its magic