What is wrong with using the MID?
The primary motivation for considering the MID when setting the assumed benefit is the notion that this will help to ensure that the trial can determine whether a meaningfully important benefit exists. Chuang-Stein et al. [However, there is a more fundamental problem than choosing the wrong numerical value for the assumed benefit based on the MID. Although the primary aim of the sample size calculation is to ensure that the trial will generate sufficient information, a fundamental requirement is that the calculation must be For example, suppose we set the sample size based on an assumed benefit to 4 units, reflecting our best estimate for the true benefit. If indeed, the true benefit is near 4 units, then the true power of the trial will match the target power. Now suppose that a 1-unit benefit is considered important. We should be satisfied that our trial likely will yield reasonably strong evidence that the intervention provides an important benefit and proceed using this sample size. We should not change the assumed effect to 1 unit; that would increase the sample size by a factor of 16 and result in an overpowered (and potentially a too-large-to-be-feasible) trial. Conversely, suppose that the minimum important benefit is 8 units. We should acknowledge that the trial is highly unlikely to show that the intervention produces a meaningful benefit and simply abandon the trial. We should not change the assumed effect size to 8 units; this would decrease the calculated sample size by a factor of 4 and result in an underpowered trial that even more surely will not show a meaningful benefit. Any attempt to reconcile discrepancies in judgments between what is important and what is realistic (e.g., by taking the minimum or an in-between value) to obtain a value for the assumed benefit conflates the goal of ensuring sufficient information with the requirement that the calculation be valid and leads to a sample size that addresses neither. This argument does not imply that only one value for the realistic benefit should be considered, given the uncertainty about the true benefit, but judgments about what is an important benefit should not be used to inform judgments about what is a realistic benefit.