To overcome the problem of uncertainty in the planning phase of clinical trials, study designs have been proposed that allow for mid-course reestimation of the sample size. Using a study in asthma patients, we illustrate how blind sample size adjustment can be performed in an equivalence trial. Thereby, we demonstrate how the type I error rate can be controlled. Further, we show that the well-known expectation-maximization algorithm-based procedure by Gould and Shih is inappropriate for the purpose of sample size reestimation.
BauerPKöhneK.Evaluation of experiments with adaptive interim analyses. Biometrics.1994;50:1029–1104. Correction in Biometrics. 1996;52:380.
2.
WittesJBrittainE.The role of internal pilot studies in increasing the efficiency of clinical trials. Stat Med.1990;9:65–72.
3.
ShunZYuanWGradyWEHsuH.Type I error in sample size re-estimations based on observed treatment difference. Stat Med.2001;20:497–513.
4.
ShihWJCommentary: Sample size re-estimation—journey for a decade. Stat Med.2001;20:515–518.
5.
ShunZ.Sample size reestimation in clinical trials. Drug Inf J.2001;35.
6.
GouldALShihWJSample size re-estimation without unblinding for normally distributed outcomes with unknown variance. Commun Stat—Theory Methods (B).1992;21:2833–2853.
7.
Committee for Proprietary Medicinal Products (CPMP).Replacement of Chlorofluorocarbons (CFCs) in metered dose inhalation products. CPMP Note for Guidance III/5378/93 Final. Brussels, Belgium: Commission of the European Communities; 1993.
8.
KunkelGSchlaefkeSKoehlerS.Efficacy, safety and acceptance of beclomethasone dipropionate (BDP) administered via a new dry powder inhaler or standard CFC metered dose inhaler in asthma patients. European Respiratory J.1999;14(Suppl 30): 105s (Abstract).
9.
KieserMHauschkeD.Approximate sample sizes for testing hypotheses about the ratio and difference of two means. J Biopharm Stat.1999;9:641–650.
10.
HauschkeDKieserMDilettiEBurkeM.Sample size determination for proving equivalence based on the ratio of two means for normally distributed data. Stat Med.1999;18:93–105.
11.
KieserMFriedeT.Blinded sample size reestimation in multiarmed clinical trials. Drug Inf J.2000;34:455–460.
12.
SandvikLErikssenJMowinckelPRodlandEAA method for determining the size of internal pilot studies. Stat Med.1996;15:1587–1590.
13.
SingerJ.Letter to the editor: A method for determining the size of internal pilot studies. Stat Med.1999;18:1151–1153.
14.
BirkettMADaySJInternal pilot studies for estimating sample size. Stat Med.1994;13:2455–2463.
15.
CPMP Working Party on Efficacy of Medicinal Products.Biostatistical methodology in clinical trials in applications for marketing authorizations for medicinal products. Stat Med.1995;14:659–1682.
16.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.ICH Harmonised Tripartite Guideline: Statistical Principles for Clinical Trials. Stat Med.1999;18:1905–1942.
17.
FriedeTKieserM.A comparison of methods for adaptive sample size adjustment. Stat Med.2001.
18.
ZuckerDMWittesJTSchabenbergerOBrittainE.Internal pilot studies II: Comparison of various procedures. Stat Med.1999;18:3493–3509.
19.
FriedeTKieserM.On the inappropriateness of an EM algorithm based procedure for blinded sample size reestimation. Stat Med.2001.
20.
CoffeyCSMullerKEExact test size and power of a gaussian error linear model for an internal pilot study. Stat Med.1999;18:1199–1214.
21.
DenneJSJennisonC.Estimating the sample size for a t-test using an internal pilot. Stat Med.1999;18:1575–1585.
22.
WittesJSchabenbergerOZuckerDBrittainEProschanM.Internal pilot studies I: Type I error rate of the naive t-test. Stat Med.1999;18:3481–3491.
23.
KieserMFriedeT.Re-calculating the sample size in internal pilot study designs with control of the type I error rate. Stat Med.2000;19:901–911.
