Quite many health interventions such as surgical procedures to improve patient health in chronic conditions are already very effective. This means that superiority of a novel procedure is extremely hard to show as a) there is very little to improve by controlling certain baseline variables and b) there may not even be a room for improvement if average group result is ready 90-95% of the maximum value ie. in quality of life questionnaires. This is especially the case if the rationale of the study is that minimally clinically important difference should be achieved in the group level.

A realistic assumption is that a novel intervention may improve group level outcomes few points if outcome is measured at 0-100 point interval scale. What is even more realistic is that this difference may very well be due to lower number of outliers in the primary outcome, ie. lower number of patients with poor outcome, ie. <50 points in the 0-100 scale where >90 is considered is âhealedâ of good outcome. Lower proportion of poor outcome may result in few points higher group mean and also smaller dispersion.

I wonder if there is any basis to use this approach when planning for primary outcome in a RCT. A novel approach may not result to MCID but it may very well reduce the dispersion and result to lower number of patients with poor outcome. I have not managed to find clinical studies which would have used this approach. My initial impression is that this approach should involve comparison of variances as a pimary outcome because that utilizes continuous outcome. Alternative option is to compare proportions but this would require arbitrary dichotomization of the outcome variable, ie. <50 points is considered poor. Usually there is no universal definition what is a poor outcome when QoL or other patient reported outcome measures are used. Equivalence approach does not seem feasible since at least for me that has negative connotation regarding the novel intervention (aiming to equivalence but assuming superiority in terms of poor outcomes).

So my question is that has there been studies using heterogeneity of variance as a primary outcome or is there other methodological aspect to consider in a clinical situation which I described (aiming to reduce number of outliers).