Abstract
It is the aim of most active control trials to show that the treatment(s) under investigation is (are) not inferior to the reference by more than a prespecified clinically irrelevant amount. In the situation of a multiarmed trial with more than one test treatment it may be required that noninferiority of all these groups to the reference be demonstrated. Alternatively, it may by sufficient to prove noninferiority of at least one of the test treatments to the reference. These clinical questions correspond to the concepts of global and partial noninferiority. For both scenarios test procedures are given for the situation that the noninferiority margin is expressed as a proportion of the unknown reference mean.
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References
Windeler J, Trampisch H-J. Recommendations concerning studies on therapeutic equivalence. Drug Inf J. 1996;30:195–199.
Rohmel J. Therapeutic equivalence investigations: Statistical considerations. Stat Med. 1998;17:1703–1714.
Bristol BR. Clinical equivalence. J Biopharmaceut Stat. 1999;9:549–561.
Berger RL. Multiparameter hypothesis testing and acceptance sampling. Technometrics. 1982;24:295–300.
Sasabuchi S. A multivariate one-sided test with composite hypotheses determined by linear inequalities when the covariance matrix has an unknown scale factor. Memoirs of the Faculty of Science, Kyushu University, Series A, Mathematics. 1988;42:9–19.
Fieller E. Some problems in interval estimation. J Roy Stat Soc, Series B. 1954;16:175–185.
Roy SN. On a heuristic method of test construction and its use in multivariate analysis. Ann Math Stat. 1953;24:220–238.
Marcus R, Peritz E, Gabriel KR. On closed testing procedures with special reference to ordered analysis of variance. Biometrika. 1976;63:655–660.
Dunnett CW, Tamhane AC. Step-down multiple tests for comparing treatments with a control in unbalanced one-way layout. Stat Med. 1991;10:939–947.
Hochberg Y, Tamhane A. Multiple Comparison Procedures. New York, NY: John Wiley; 1987.
Bedotto JE, Gay RG, Graham SD, Morkin E, Goldman S. Cardiac hypertrophy induced by thyroid hormone is independent of loading conditions and beta-adrenoceptor blockade. J Pharmacol Experimen Therapeutics. 1989;248:632–636.
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Hauschke, D., Kieser, M. Multiple Testing to Establish Noninferiority of k Treatments with a Reference Based on the Ratio of Two Means. Ther Innov Regul Sci 35, 1247–1251 (2001). https://doi.org/10.1177/009286150103500421
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DOI: https://doi.org/10.1177/009286150103500421