The randomised controlled trial (RCT) is widely considered to be the gold standard study for comparing the effectiveness of health interventions. From both a scientific and ethical standpoint, selecting an appropriate target difference is of crucial importance. Given its importance, determination of the target difference, as opposed to statistical approaches to calculating the sample size, has been greatly neglected. A variety of approaches have been proposed for formally determining what an important difference should be (such as the "minimum clinically important difference") though the current state of the evidence is unclear particularly with regards to informing RCT design. This UK MRC funded project sought to provide an overview of the current evidence through three main components: (i) a systematic review of methods for identifying a target difference developed within and outside the health field to assess their usefulness for various forms of RCTs; (ii) a survey of trialists; and (iii) development of a structured guidance document to aid the design of future trials.
The results were:
1. The search identified seven methods were identified – anchor, distribution, health economic, opinion-seeking, pilot study, review of evidence base (RoEB) and standardised effect size; each with important variations in implementation.
2a. 180 responses to the Society of Clinical Trials survey were received representing 13 countries. Awareness of methods ranged from 69 (38%) for health economic method to 162 (90%) for pilot study.
2b. Of the sixty-one surveys sent out to UK trialist groups, thirty-four (56%) responses were received. Awareness ranged from 33 (97%) for the RoEB and pilot methods, to only 14 (41%) for the distribution method. Based upon the most recent trial all bar three groups (30 - 91%) used a formal method.
3. Guidance was developed on the use of each method and reporting of the sample size calculation in a trial protocol and results paper.
The study concluded that there is a clear need for greater use of formal methods to determine the target difference and better reporting of its specification.
Craig Ramsay; email@example.com
Cook JA, Ramsay CR, Vale LD, DELTA group. Guidance on minimally important clinical difference and trial size is needed [letter]. BMJ 2012;343:-D4375.