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

@article{Schuirmann2005ACO, 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}, year={2005}, volume={15}, pages={657-680} }

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…

## 1,644 Citations

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## References

SHOWING 1-8 OF 8 REFERENCES

A new procedure for testing equivalence in comparative bioavailability and other clinical trials

- Mathematics
- 1983

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

- MathematicsJournal of Pharmacokinetics and Biopharmaceutics
- 2005

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.

- MathematicsBiometrics
- 1981

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

- MathematicsJournal 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.

- BiologyBiometrics
- 1984

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