TY  - JOUR
TI  - Improper analysis of trials randomised using stratified blocks or minimisation
EP  -  340
AV  - public
Y1  - 2012/02/20/
ID  - discovery1406689
N2  - Many clinical trials restrict randomisation using stratified blocks or minimisation to balance prognostic factors across treatment groups. It is widely acknowledged in the statistical literature that the subsequent analysis should reflect the design of the study, and any stratification or minimisation variables should be adjusted for in the analysis. However, a review of recent general medical literature showed only 14 of 41 eligible studies reported adjusting their primary analysis for stratification or minimisation variables. We show that balancing treatment groups using stratification leads to correlation between the treatment groups. If this correlation is ignored and an unadjusted analysis is performed, standard errors for the treatment effect will be biased upwards, resulting in 95% confidence intervals that are too wide, type I error rates that are too low and a reduction in power. Conversely, an adjusted analysis will give valid inference. We explore the extent of this issue using simulation for continuous, binary and time-to-event outcomes where treatment is allocated using stratified block randomisation or minimisation.
KW  - Antineoplastic Agents
KW  -  Back Injuries
KW  -  Bias (Epidemiology)
KW  -  Breast Neoplasms
KW  -  Carcinoma
KW  -  Computer Simulation
KW  -  Data Interpretation
KW  -  Statistical
KW  -  Deoxyribonucleases
KW  -  Drug Therapy
KW  -  Combination
KW  -  Female
KW  -  Fibrinolytic Agents
KW  -  Humans
KW  -  Interferon-alpha
KW  -  Kidney Neoplasms
KW  -  Liver Cirrhosis
KW  -  Biliary
KW  -  Male
KW  -  Medroxyprogesterone Acetate
KW  -  Penicillamine
KW  -  Pleural Effusion
KW  -  Randomized Controlled Trials as Topic
KW  -  Survival Analysis
KW  -  Tamoxifen
KW  -  Tissue Plasminogen Activator
KW  -  Treatment Outcome
VL  - 31
SP  - 328 
N1  - This is the peer reviewed version of the following article: Kahan, BC; Morris, TP; (2012) Improper analysis of trials randomised using stratified blocks or minimisation. Statistics in Medicine , 31 (4) 328 - 340, which has been published in final form at: http://dx.doi.org/10.1002/sim.4431. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'. 
IS  - 4
SN  - 0277-6715
UR  - http://dx.doi.org/10.1002/sim.4431
JF  - Statistics in Medicine
A1  - Kahan, BC
A1  - Morris, TP
ER  -