Larske M Soepnel, Shane A Norris, Khuthala Mabetha, Molebogeng Motlhatlhedi, Nokuthula Nkosi, Stephen Lye, Catherine E Draper
A qualitative analysis of community health worker perspectives on the implementation of the preconception and pregnancy phases of the Bukhali randomised controlled trial
PLOS global public health
clinical trials often involve form interim monitoring determine futility planned trial completion many options interim monitoring exist eg alphaspending conditional power nonparametric based interim monitoring methods also needed account complex trial designs analyses upstrap one recently proposed nonparametric method may applied interim monitoring upstrapping motivated case resampling bootstrap involves repeatedly sampling replacement interim data simulate thousands fully enrolled trials pvalue calculated upstrapped trial proportion upstrapped trials pvalue criteria met compared prespecified decision threshold evaluate potential utility upstrapping form interim futility monitoring conducted simulation study considering different sample sizes several different proposed calibration strategies upstrap first compared trial rejection rates across selection threshold combinations validate upstrapping method applied upstrapping methods simulated clinical trial data directly comparing performance traditional alphaspending conditional power interim monitoring methods futility method validation demonstrated upstrapping much likely find evidence futility null scenario alternative across variety simulations settings three proposed approaches calibration upstrap different strengths depending stopping rules used compared obrienfleming group sequential methods upstrapped approaches type error rates differed 17 expected sample size 222 lower null scenario alternative scenario power fluctuated 157 lower 02 higher expected sample size 015 lower proofofconcept simulation study evaluated potential upstrapping resamplingbased method futility monitoring clinical trials tradeoffs expected sample size power type error rate control indicate upstrap calibrated implement futility monitoring varying degrees aggressiveness performance similarities identified relative considered alphaspending conditional power futility monitoring methods