Comparative Analysis of Group Sequential Designs Tests for Randomized Controlled Clinical Trials: A Model Study on Two-Sided Tests for Comparing Two Treatments

Mehmet Ali Sungur, Emine Arzu Kanik

.

DOI: 10.4236/ojs.2012.21007                

Abstract

Clinical trials are usually long term studies and it seems impossible to reach all required subjects at the same time. Performing interim analyses and monitoring results may provide early termination of trial after obtaining significant results. The aim of this study is comparing group sequential tests in respect to advantage of sample size reduction and early termination. In this study, 4 test types used in group sequential designs were compared with fixed sample size design test and each other. Comparisons were done according to two-sided tests for comparing two treatments. In this sense, 1080 models were performed. In models, 2 different Type I errors, 2 different powers, 5 different analysis groups, 6 different effect sizes and 9 different variances selections were considered. All test types increased the maximum sample size in different manner, compared with fixed sample size design. Each test had different critical values to reject H0 hypothesis, at the same type I error rate and number of analyses conditions. Selection of test type used in group sequential designs depends on a few characteristics, as reducing sample size, early termination and detecting minimal effect size. Test performance is highly related with selected Type I error rate, power and number of analyses. In addition to these statistical characteristics, researchers should decide test type with respect to other trial conditions as the issue of trial, reaching subjects easy or not and importance of early termination.

Keywords

Group Sequential Designs; Group Sequential Test Types; Interim Analysis; Monitoring

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	D. L. DeMets, “Sequential Designs in Clinical Trials,” Cardiac Electrophysiology Review, 1998, Vol. 2, No. 1, pp. 57-60. doi:10.1023/A:1009954810211
[2]	S. C. Chow and J. P. Liu, “Design and Analysis of Clinical Trials: Concepts and Methodologies (Wiley Series in Probability and Statistics),” 2nd Edition, Wiley-Blackwell, Hoboken, 2004.
[3]	P. C. O’Brien, “Data and Safety Monitoring,” In: P. Armitage and T. Colton, Eds., Encyclopedia of Biostatistics, Vol. 2, 2005, pp. 1362-1371.
[4]	R. Aplenc, H. Zhao, T. R. Rebbeck and K. J. Propert, “Group Sequential Methods and Sample Size Savings in Biomarker-Disease Association Studies,” Genetics, Vol. 163, 2003, pp. 1215-1219.
[5]	C. Jennison and B. W. Turnbull, “Group Sequential Methods with Applications to Clinical Trials,” Chapman & Hall/CRC, Boca Raton, 2000.
[6]	M. Mazumdar and A. Liu, “Group Sequential Design for Comparative Diagnostic Accuracy Studies,” Statistics in Medicine, Vol. 22, No. 5, 2003, pp. 727-739. doi:10.1002/sim.1386
[7]	M. Mazumdar, “Group Sequential Design for Comparative Diagnostic Accuracy Studies: Implications and Guidelines for Practitioners,” Medical Decision Making, Vol. 24, No. 5, 2004, pp. 525-533. doi:10.1177/0272989X04269240
[8]	B. Tasdelen and E. A. Kanik, “The Formulae and Tables to Determine Sample Sizes for Classical Hypothesis Tests,” University of Mersin School of Medicine Medical Journal, Vol. 4, 2004, pp. 438-446.
[9]	S. C. Chow, J. Shao and H. Wang, “Sample Size Calculations in Clinical Research,” Marcel Dekker, Inc., New York, 2003.
[10]	J. M. Lachin, “Sample Size Determination,” Armitage P., Colton T. (Ed.), Encyclopedia of Biostatistics, Wiley, Second Edition, United Kingdom, 2005, Vol. 7, pp. 4693- 4704.
[11]	E. Lakatos, “Sample Size Determination for Clinical Trials,” In: P. Armitage and T. Colton, Eds., Encyclopedia of Biostatistics, Vol. 7, 2005, pp. 4704-4711.
[12]	H. H. Muller and H. Schafer, “Adaptive Group Sequential Designs for Clinical Trials: Combining the Advantages of Adaptive and of Classical Group Sequential Approaches,” Biometrics, Vol. 57, No. 3, 2001, pp. 886-891. doi:10.1111/j.0006-341X.2001.00886.x
[13]	T. G. Karrison, D. Huo and R. Chappell, “A Group Sequential, Response-Adaptive Design for Randomized Clinical Trials,” Controlled Clinical Trials, Vol. 24, No. 5, 2003, pp. 506-522. doi:10.1016/S0197-2456(03)00092-8