Adaptive nested case-control

An adaptive nested case-control study embeds a case-control comparison within a defined cohort and incorporates pre-specified interim decision rules that allow modifications — such as control-to-case ratio adjustment or biomarker sub-sampling revision — based on accumulating data, without compromising the study's validity or inflating type I error. The design combines the efficiency of the nested case-control framework with the flexibility of adaptive methodology to optimise resource use when exposure assessment is costly.