Flexible analytical methods for adding a treatment arm mid-study to an ongoing clinical trial.
It is not uncommon to have experimental drugs under different stages of development for a given disease area. Methods are proposed for use when another treatment arm is to be added mid-study to an ongoing clinical trial. Monte Carlo simulation was used to compare potential analytical approaches for pairwise comparisons through a difference in means in independent normal populations including (1) a linear model adjusting for the design change (stage effect), (2) pooling data across the stages, or (3) the use of an adaptive combination test. In the presence of intra-stage correlation (or a non-ignorable fixed stage effect), simply pooling the data will result in a loss of power and will inflate the type I error rate. The linear model approach is more powerful, but the adaptive methods allow for flexibility (re-estimating sample size). The flexibility to add a treatment arm to an ongoing trial may result in cost savings as treatments that become ready for testing can be added to ongoing studies.
Medical University of South Carolina, Charleston, SC, USA. elmj@musc.edu
Jordan J
JJ
Elm
Yuko Y
YY
Palesch
Gary G
GG
Koch
Vanessa
V
Hinson
Bernard
B
Ravina
Wenle
W
Zhao
D000465:Algorithms; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D016014:Linear Models; D009010:Monte Carlo Method; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome