RANDOMISATION IN CLINICAL TRIALS – EFFECTIVE AND ETHICAL SOLUTION

Abstract

Randomised controlled clinical trials (RCTs) produce the most reliable evidence about the effects of clinical care. In surgical trials, lack of surgeons’ individual equipoise (state of genuine uncertainty about treatment arms) appears to be one of the greatest obstacles. Collective equipoise based on present or imminent controversy in the expert medical community has been proposed as a solution (Freedman, 1987), but could be applied only at the beginning of a trial to a general trial question.

We developed a system that quantifies collective uncertainty among a group of surgeons for an individual clinical case. After a successful pilot study the system was introduced as an independent project within the UK Heel Fracture Trial. The expert panel included 10 surgeons from 8 hospitals. Anonymous clinical data of potentially eligible consecutive cases including CT and X-ray images was published on a secure online forum after 6 weeks follow up clinic to avoid interference with clinical course. Surgeons registered in the panel estimated the probability that the patient would be better or worse by various degrees with operative treatment.

30 clinical cases have been analysed, including 6 bilateral fractures (otherwise excluded). 86.7% could be recommended for inclusion in the trial, compared to 43.3% recruited out of this series in the actual trial. Lack of individual uncertainty within the panel was present in every case.

The system not only has a potential to improve recruitment in surgical RCTs, but provides ethically sound grounds to offer or otherwise a patient participation in a trial. Surgeon’s individual equipoise dilemma and responsibility is shared with colleagues. Cases that otherwise will be excluded can be evaluated with broader inclusion criteria. The system is easy to use, cheap and reliable. Limitations include surgeons’ compliance and time lapse (at least 48 hours) for voting to be completed.