Validity and power considerations on hypothesis testing under minimization

Minimization, a dynamic allocation method, is gaining popularity especially in cancer clinical trials. Aiming to achieve balance on all important prognostic factors simultaneously, this procedure can lead to a substantial reduction in covariate imbalance compared with conventional randomization in small clinical trials. While minimization has generated enthusiasm, some controversy exists over the proper analysis of such a trial. Critics argue that standard testing methods that do not account for the dynamic allocation algorithm can lead to invalid statistical inference. Acknowledging this limitation, the International Conference on Harmonization E9 guideline suggests that 'the complexity of the logistics and potential impact on analyses be carefully evaluated when considering dynamic allocation'. In this article, we investigate the proper analysis approaches to inference in a minimization design for both continuous and time-to-event endpoints and evaluate the validity and power of these approaches under a variety of scenarios both theoretically and empirically. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

[1]  Kari Lock Morgan,et al.  Rerandomization to improve covariate balance in experiments , 2012, 1207.5625.

[2]  Mikel Aickin,et al.  A Simulation Study of the Validity and Efficiency of Design-Adaptive Allocation to Two Groups in the Regression Situation , 2009, The international journal of biostatistics.

[3]  B. Efron.  Forcing a sequential experiment to be balanced , 1971 .

[4]  S. Pocock,et al.  Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. , 1975, Biometrics.

[5]  L. Kaiser.  Dynamic randomization and a randomization model for clinical trials data , 2012, Statistics in medicine.

[6]  N. Birkett,et al.  Adaptive allocation in randomized controlled trials. , 1985, Controlled clinical trials.

[7]  Michael Proschan,et al.  Minimize the Use of Minimization with Unequal Allocation , 2011, Biometrics.

[8]  Jun Shao,et al.  A theory for testing hypotheses under covariate-adaptive randomization , 2010 .

[9]  Nitin R. Patel,et al.  Constructing exact significance tests with restricted randomization rules , 1988 .

[10]  D P Byar,et al.  The effect of stratified randomization on size and power of statistical tests in clinical trials. , 1978, Journal of chronic diseases.

[11]  C B Begg,et al.  Treatment allocation methods in clinical trials: a review. , 1985, Statistics in medicine.

[12]  R. McHugh,et al.  Analysis of accrual randomized clinical trials with balanced groups in strata. , 1978, Journal of chronic diseases.

[13]  G. Pond,et al.  Statistical issues in the use of dynamic allocation methods for balancing baseline covariates , 2011, British Journal of Cancer.

[14]  Yevgen Tymofyeyev,et al.  Preserving the allocation ratio at every allocation with biased coin randomization and minimization in studies with unequal allocation , 2012, Statistics in medicine.

[15]  D R Taves,et al.  Minimization: A new method of assigning patients to treatment and control groups , 1974, Clinical pharmacology and therapeutics.

[16]  L. J. Wei,et al.  The Adaptive Biased Coin Design for Sequential Experiments , 1978 .

[17]  M A Proschan.  On the distribution of the unpaired t-statistic with paired data. , 1996, Statistics in medicine.

[18]  R. L. Prentice,et al.  Exponential survivals with censoring and explanatory variables , 1973 .

[19]  F. Hu,et al.  Asymptotic properties of covariate-adaptive randomization , 2012, 1210.4666.

[20]  M Zelen,et al.  The randomization and stratification of patients to clinical trials. , 1974, Journal of chronic diseases.

[21]  Lee-Jen Wei,et al.  A Class of Designs for Sequential Clinical Trials , 1977 .

[22]  Mikel Aickin,et al.  Randomization, balance, and the validity and efficiency of design-adaptive allocation methods , 2001 .

[23]  R. Simon,et al.  Restricted randomization designs in clinical trials. , 1979, Biometrics.

[24]  Richard Simon,et al.  Using Randomization Tests to Preserve Type I Error With Response-Adaptive and Covariate-Adaptive Randomization. , 2011, Statistics & probability letters.

[25]  Damian McEntegart,et al.  Weighted re‐randomization tests for minimization with unbalanced allocation , 2013, Pharmaceutical statistics.

[26]  B W Brown,et al.  Sequential treatment allocation procedures in clinical trials--with particular attention to the analysis of results for the biased coin design. , 1986, Statistics in medicine.

[27]  Feifang Hu,et al.  Testing Hypotheses of Covariate-Adaptive Randomized Clinical Trials , 2015 .

[28]  Julia Brown,et al.  Minimization—reducing predictability for multi‐centre trials whilst retaining balance within centre , 2005, Statistics in medicine.

[29]  A. Forsythe,et al.  Validity and power of tests when groups have been balanced for prognostic factors , 1987 .

[30]  C B Begg,et al.  The impact of treatment allocation procedures on nominal significance levels and bias. , 1987, Controlled clinical trials.