The Doctor’s Surgery
Theodore Dalrymple
There has been an increasing number of reports in the medical journals of the negative results of controlled trials of various treatments. It’s one of the most important advances in medical science of the last two decades – though an inconspicuous and perhaps surprising one.
This is important, because if positive results only of trials are published, misleading impressions of the efficacy of treatments are created. Indeed, until recently the non-publication of negative results was a favourite technique of the drug companies. In part, that explains why so large a proportion of the adult population is now taking antidepressants – that and the ghastliness of life itself, of course.
Another dangerous line of argument in medicine is that ‘it stands to reason’. It stands to reason, for example, that if nutrient x is lacking in disease y, giving a patient nutrient x will prevent or cure his or her case of disease y.
But nature does not always obey human reason, which is always founded on partial knowledge and frequently on false premises. That is why the proof of the curing is in the healing.
There was a recent trial of a cocktail of a drug and two vitamins in a grave condition called septic shock – the collapse of the cardiovascular condition in the presence of severe infection, particularly likely in the old. The trial gave negative results when, theoretically, they might have given positive ones.
Because vitamin C and thiamine (the B vitamin, whose shortage may lead to permanent brain damage in severe alcoholics) are at reduced levels in this condition, and because hydrocortisone reduces the inflammatory response, it was hypothesised by the researchers – and not only by them – that a mixture of all three might improve survival. So they conducted a trial.
The results were disappointing. A slightly higher percentage (34.7 per cent) died with the active treatment than with placebo control (29.3 per cent), but this was not statistically significant. The treatment did not prevent kidney failure, one of the complications of septic shock. It did not reduce the need for artificial ventilation. It had no cognitive benefits (of special interest to the old). It had one or two minor benefits of a temporary nature of no lasting clinical significance. In short, the treatment was a failure.
That would seem to be that, then. What stood to reason didn’t work and no one in the future need waste his or her time, effort or hope by giving these drugs in such a situation. The lesson seems perfectly clear.
As is always the way in medicine, however, things are slightly more complicated. To obtain their final sample of 200 patients who fulfilled all their criteria for entry to the trial, both positive and negative, they had to exclude 4,369 patients with septic shock for one reason or another – to make sure that they compared like with like.
In other words, their results applied only to those patients who were very similar in those selected for the trial, who were only 1 in 22.5 of all patients with septic shock. It would therefore still be reasonable, or at least not unreasonable, for an experienced doctor to say, ‘I have seen this treatment work in many cases, and therefore I am going to use it. The trial is not relevant to the patient I have before me.’
These complexities explain, perhaps, the violence of the recent controversy over the use of hydroxychloroquine in the prevention and treatment of COVID-19. It is always possible to argue that it might not work in these patients at this dose, but it would work in those patients, at that dose.
It is not only of the making of books that there is no end, but also of medical controversies: and yet progress, somehow, takes place.