Controlling the type I error rate in two-stage sequential adaptive designs when testing for average bioequivalence

Statistics in Medicine
Willi MaurerYing Chen

Abstract

In a 2×2 crossover trial for establishing average bioequivalence (ABE) of a generic agent and a currently marketed drug, the recommended approach to hypothesis testing is the two one-sided test (TOST) procedure, which depends, among other things, on the estimated within-subject variability. The power of this procedure, and therefore the sample size required to achieve a minimum power, depends on having a good estimate of this variability. When there is uncertainty, it is advisable to plan the design in two stages, with an interim sample size reestimation after the first stage, using an interim estimate of the within-subject variability. One method and 3 variations of doing this were proposed by Potvin et al. Using simulation, the operating characteristics, including the empirical type I error rate, of the 4 variations (called Methods A, B, C, and D) were assessed by Potvin et al and Methods B and C were recommended. However, none of these 4 variations formally controls the type I error rate of falsely claiming ABE, even though the amount of inflation produced by Method C was considered acceptable. A major disadvantage of assessing type I error rate inflation using simulation is that unless all possible scenarios for the intende...Continue Reading

References

Aug 1, 1972·Journal of Pharmaceutical Sciences·W J Westlake
Apr 21, 2001·Biometrics·W Lehmacher, G Wassmer
Sep 2, 2004·Biometrics·Werner Brannath, Peter Bauer
Aug 22, 2007·Pharmaceutical Statistics·Diane PotvinRobert A Smith
Feb 11, 2011·Pharmaceutical Statistics·Timothy H MontagueDonald J Schuirmann
Feb 11, 2015·Pharmaceutical Statistics·Cheng ZhengJixian Wang
Mar 27, 2015·Statistics in Medicine·Meinhard Kieser, Geraldine Rauch
Nov 6, 2015·Pharmaceutical Statistics·Jialin XuDonald J Schuirmann

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Citations

Sep 12, 2019·Journal of Biopharmaceutical Statistics·Lin Zhu, Wanjie Sun
Oct 2, 2020·Biometrical Journal. Biometrische Zeitschrift·Eduard MolinsJordi Ocaña
Jul 15, 2020·Pharmaceutical Research·Michał KazaPiotr J Rudzki
Sep 18, 2020·Clinical Pharmacology and Therapeutics·Jieon LeeLiang Zhao
Nov 29, 2020·Clinical Pharmacokinetics·Ryosuke KuribayashiKazunori Takagi

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