How should the realistic benefit be determined?
As summarized in the DELTAAll of the foregoing concerns are valid, but ultimately, a value for the realistic effect must be chosen. This judgment should be made through thoughtful consideration of the trial context and all available evidence—information should not be discarded simply because it is not “ideal.” For example, the risks of adopting a treatment effect estimate from a pilot study because it has large uncertainty notwithstanding, it would be counterproductive to ignore this information altogether. Because different sources, types, and amounts of information may need to be considered, each with uncertain levels of relevance, developing a universally applicable synthesis process may not be practical. However, identifying such a process is not as important as ensuring that whatever process is undertaken, it considers the task thoroughly and is reported transparently (as advocated in the DELTAIt is not reasonable to expect that trial designers are able to choose with confidence a single value for the assumed benefit, so a range of values should be considered. But again, for the results to be meaningful, this range must reflect realistic values, not what values are considered important. When insufficient evidence is available to judge what would be a realistic assumed benefit, an adaptive trial design incorporating sample size re-estimation would be appropriate, rather than attempting to fix a sample size based on an assumed benefit which may be far from the truth.