BREVE RELAZIONE SU Randomized Controlled Trial gentilmente concessa da: Stefano Mazzon U.O. Medicina Fisica e Riabilitazione - ULSS 8 Asolo (TV)

Randomized Controlled Trial La più affidabile forma di evidenza scientifica, in quanto elimina i bias (pregiudizi, caso, recupero spontaneo, effetto Hawthorne). randomizzata Suddivisione della popolazione da studiare in due gruppi (omogenei) in maniera randomizzata (casuale): Gruppo - Trattamento vs Gruppo - Controllo Le variabili esterne agiscono allo stesso modo sia nel gruppo di trattamento che nel gruppo di controllo. Gruppo controllo = placebo o altro trattamento (problemi etici)

Trial singlo-cieco: il ricercatore conosce i dettagli del trattamento, il paziente no (si elimina abbastanza l’effetto placebo - Hawthorne) Trial doppio-cieco: sia l’esaminatore sia il paziente non conoscono i dettagli del trattamento, ovvero chi appartiene al gruppo controllo (si elimina l’effetto placebo - Hawthorne). I drop-out dovrebbero essere < 15% (es. pz. peggiorati possono abbandonare)

Tests statistici appropriati. p < 0.05 non necessariamente significa evidenza clinica … NNT: Number Needed to Treat = numero di pazienti da trattare per prevenire un evento negativo. La misura migliore è la differenza tra i due gruppi. NNT = inverso della differenza Es.Gruppo Trattamento: 45% in meno di eventi negativi Gruppo Controllo:20% in meno di eventi negativi NNT = 1 / 0.25 = 4

Un po’ di storia… Ben Cao Tu Jing. (Atlas of Materia Medica). Song Dynasty ( ), “ It was said that in order to evaluate the effect of genuine Shangdang ginseng, two persons were asked to run together. One was given the ginseng while the other ran without. After running for approximately three to five li [equivalent to 1500 to 2500 meters], the one without the ginseng developed severe shortness of breath, while the one who took the ginseng breathed evenly and smoothly.”

Treatment of burns with onions and comparison with another treatment; observations made between October 1537 and the end of 1538 Ambroise Paré, Oeuvres 1575, p 359 “I applied onions to one half of his face and the usual remedies to the other. At the second dressing I found the side where I had applied the onions to have no blisters nor scarring and the other side to be all blistered; and so I planned to write about the effects of these onions….”

Comparison of two treatments of gunshot wounds. Ambroise Paré, Oeuvres 1575 p 358 line 7ff “…oil of elderberry …knowing that such treatment could be extremely painful for the wounded… …to apply a digestive made of egg yolk, oil of roses and turpentine … …I found those on whom I had put the digestive dressing feeling little pain from their wounds which were not swollen or inflamed, and having spent quite a restful night. But the others, to whom the oil of eldelberry had been applied, I found fevered, with great pain and swelling around their wounds….

The rules of logic are inadequate for judging the influence of a given medication in an equally given disease and for classifying the medications recommended for this same disease according to their influences. The principles of the law of large numbers are strictly applicable to therapeutic research and they alone can furnish the solution of important problems. A therapeutic law ensuing from the comparison of a small number of observations may be so far from the truth that it merits no degree of confidence in any case. To be able to decide in favour of one treatment method over another, it is not enough for the method to yield better results; the difference found must also exceed a certain limit, the extent of which is a function of the number of observations.

Il “padre” degli studi randomizzati controllati Il “padre” degli studi randomizzati controllati