A comparison of the Two One-Sided Tests Procedure and the Power Approach for assessing the equivalence of average bioavailability

  title={A comparison of the Two One-Sided Tests Procedure and the Power Approach for assessing the equivalence of average bioavailability},
  author={Donald J. Schuirmann},
  journal={Journal of Pharmacokinetics and Biopharmaceutics},
  • Donald J. Schuirmann
  • Published 1 December 1987
  • Mathematics
  • Journal of Pharmacokinetics and Biopharmaceutics
The statistical test of the hypothesis of no difference between the average bioavailabilities of two drug formulations, usually supplemented by an assessment of what the power of the statistical test would have been if the true averages had been inequivalent, continues to be used in the statistical analysis of bioavailability/bioequivalence studies. In the present article, this Power Approach (which in practice usually consists of testing the hypothesis of no difference at level 0.05 and… 
Equivalence tests for ratio of means in bioequivalence studies under crossover design
There are several problems concerning the statistical definition of average bioequivalence provided by the U.S. Food and Drug Administration. We proposed a ratio of means based on the original
Bioequivalence: An overview of statistical concepts
The value of testing two one-sided null hypotheses of non-equivalence at a significance level of 0.05, and the importance of estimating a 90% confidence interval of the ratio (test/reference) of mean AUC and C m a x values, and of the difference between mean T m a X values, are now recognized and form the current standards for BE.
An approximate approach to sample size determination in bioequivalence testing with multiple pharmacokinetic responses
An approximate method for sample size determination is suggested, which can also provide the type II rate for each of NI and NS hypotheses, and is flexible to allow extension from one pharmacokinetic response to determination of the sample size required for multiple PK responses.
Testing bioequivalence for multiple formulations with power and sample size calculations
It is shown that given the same overall type I error and power, a BE crossover trial designed to test multiple formulations simultaneously only requires a small increase in the total sample size compared with a simple 2 × 2 crossover design evaluating only one test formulation.
Testing the equivalence of treatments in a two-period crossover design setting occurs often in the pharmaceutical industry. These studies usually compare the rate and extent of absorption of two
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We consider the comparison of two formulations in terms of average bioequivalence using the 2 × 2 cross‐over design. In a bioequivalence study, the primary outcome is a pharmacokinetic measure, such
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The purpose of bioequivalence (BE) trial is to show that the test (T) and the reference (R) products can produce similarity bioavailability, and then show therapeutically equivalence. There are three
Sample Size Determination for a Three-Arm Equivalence Trial of Normally Distributed Responses
The test statistics and the power function for the ratio of mean differences hypothesis and the required sample size for a three-arm clinical trial are derived and compared by the traditional mean difference equivalence test.
A Novel Approach to Testing for Average Bioequivalence Based on Modeling the Within-Period Dependence Structure
A general linear model approach that incorporates the within-subject covariance structure for making inferences on mean areas and is a cost-effective, viable alternative to the traditional method with superior inferential properties is proposed.
Asymptotic properties of the two one-sided t-tests – new insights and the Schuirmann-constant
Abstract The two one-sided t-tests (TOST) method is the most popular statistical equivalence test with many areas of application, i.e., in the pharmaceutical industry. Proper sample size calculation


A new procedure for testing equivalence in comparative bioavailability and other clinical trials
The problem of testing for equivalence in clinical trials is restated here in terms of the proper clinical hypotheses and a simple classical frequentist significance test based on the central t
A new statistical procedure for testing equivalence in two-group comparative bioavailability trials
A simple t-test procedure for these hypotheses has been devloped that is more powerful than the methods based on usual and symmetric confidence intervals, and an example is given, including the method for sample size determination.
Comparison of different methods for decision-making in bioequivalence assessment.
It is thought that the use of symmetrical confidence intervals alone can be misleading and it is recommended that the posterior probabilities and densities, or at least the shortest confidence intervals, be given.
An exact confidence interval from untransformed data for the ratio of two formulation means
  • Charles Locke
  • Mathematics
    Journal of Pharmacokinetics and Biopharmaceutics
  • 2005
A method for obtaining an exact confidence interval for a rather general model is described for a test formulation and a standard formulation compared in an experiment with a two period crossover design.
On testing for bioequivalence.
A new method is proposed and compared to three previously suggested techniques for statistical analysis of bioequivalence trials and yields practical suggestions regarding statistical tests.
Bioequivalence testingneed to rethink
  • Biometrics
  • 1981
The design and analysis of comparative blood-level trials
  • Lea and Febiger, Philadelphia,
  • 1973