Application of Adaptive Designs – a Review

Abstract

A literature search has been performed to review applications of the adaptive design methodology based on the combination test or conditional error function approach. Some features of the 60 papers identified are summarized, e.g., the specific methodology used, calendar year, country, impact factor of the journal, number of planned and performed stages respectively, stopping for futility boundaries, type of adaptations and others. A selection of the ten recent publications in journals with the highest impact factors is discussed in more detail. Most applications up to now aim at sample size reassessment, the majority of papers is coming from Germany. Although we found that renowned journals allow for sufficient space to present the new statistical methodology in all its necessary details, the general impression is that the presentation of the adaptive designs methodology in applied papers has to be improved. Education and development of standards could help to achieve this.

Adaptive designs undertaken in clinical research: a review of registered clinical trials

“…However, ADs are not widely used routinely in clinical trial research despite the prominence given to them in the statistical literature [2–5]. Initiatives, predominately from a pharmaceutical drug development perspective, have been undertaken to understand and address some of the perceived barriers to the uptake of ADs in routine practice when they are considered appropriate [5–9].…”

Methodological Developments vs. Regulatory Requirements

“…This would be connected with breaking of the rules and like any other misconduct it has to be excluded by a careful documentation of the adaptation. Basically, I agree with the authors that mid-trial sample size reassessment should not be proposed as the standard in clinical trials although most published applications in medicine apply this type of adaptation (Bauer and Einfalt, 2006). Dropping treatment/dose arms because of lack of efficacy and/or toxicity is an important application of adaptive designs.…”

“…There is certainly a need for careful exploration when looking at the limited number of published applications in medicine. The average quality of applying and presenting adaptive designs is rather poor (Bauer and Einfalt, 2006).…”

Can emergency medicine research benefit from adaptive design clinical trials?

“…Bauer and Einfalt21 make recommendations, which we endorse, that the following points should be included in the reporting of an adaptive design: the motivation for using an adaptive trial designthe type of adaptations useda description of the trial that was initially plannedadaptations made to the trial including the reasons for thisestimates and CIs with appropriate adjustments accounting for the adaptive nature of the trial.…”