English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

In adaptive clinical trials, the conventional end-of-trial point estimate ofa treatment effect is prone to bias, that is, a systematic tendency to deviatefrom its true value. As stated in recent FDA guidance on adaptive designs, itis desirable to report estimates of treatment effects that reduce or removethis bias. However, it may be unclear which of the available estimators arepreferable, and their use remains rare in practice. This paper is the second ina two-part series that studies the issue of bias in point estimation foradaptive trials. Part I provided a methodological review of approaches toremove or reduce the potential bias in point estimation for adaptive designs.In part II, we discuss how bias can affect standard estimators and assess thenegative impact this can have. We review current practice for reporting pointestimates and illustrate the computation of different estimators using a realadaptive trial example (including code), which we use as a basis for asimulation study. We show that while on average the values of these estimatorscan be similar, for a particular trial realisation they can give noticeablydifferent values for the estimated treatment effect. Finally, we proposeguidelines for researchers around the choice of estimators and the reporting ofestimates following an adaptive design. The issue of bias should be consideredthroughout the whole lifecycle of an adaptive design, with the estimationstrategy pre-specified in the statistical analysis plan. When available,unbiased or bias-reduced estimates are to be preferred.

Point estimation for adaptive trial designs II: practical considerations and guidance