gms | German Medical Science

62. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie

17.09. - 21.09.2017, Oldenburg

Wilcoxon-Mann-Whitney test for non-inferiority in the presence of death-censored observations – power considerations

Meeting Abstract

  • Irene Schmidtmann - Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Mainz, Deutschland
  • Stavros Konstantinides - Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Mainz, Deutschland
  • Harald Binder - Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Mainz, Deutschland

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie. 62. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS). Oldenburg, 17.-21.09.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocAbstr. 285

doi: 10.3205/17gmds082, urn:nbn:de:0183-17gmds0822

Published: August 29, 2017

© 2017 Schmidtmann et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

In clinical trials the goal may be to establish non-inferiority of a new treatment compared to a standard treatment. We consider a situation where the primary endpoint is quantitative, but the probability of a fatal outcome is non-negligible thus censoring by death may occur if patients die before the quantitative outcome can be determined. Excluding censored patients is likely to introduce bias.

Felker and Maisel [1] have suggested a global rank endpoint for this type of problem. Matsouaka and Betensky [2] provide a formal description for the situation where superiority is to be demonstrated for a quantitative endpoint in the presence of censoring by death. They also derive power and sample size formulae. Without loss of generality, they assume that high values of the quantitative endpoint represent a favourable outcome. Let N the number of patients in the study of whom m patients have died. Then the ranks 1 to m are assigned to those patients who have died, the surviving patients have ranks m +1 to N according to their values of the quantitative endpoint. Using these rank scores, the Mann-Whitney U statistic is computed.

We apply this idea to the non-inferiority situation as described in [3]. Using the fact that the Mann-Whitney U statistic follows an asymptotically normal distribution and applying the Matsouaka and Betensky formulas for mean and variance of the U statistic, we derived a formula for the power of the Wilcoxon–Mann–Whitney test for non-inferiority in the presence of death-censored observations.

We present an application to planning a study in pulmonary embolism and assess the precision of the formula in a simulation study.



Die Autoren geben an, dass kein Interessenkonflikt besteht.

Die Autoren geben an, dass kein Ethikvotum erforderlich ist.

Beitrag wurde parallel eingereicht für CEN-ISBS Vienna 2017 Joint Conference on Biometrics & Biopharmaceutical Statistics.


References

1.
Felker GM, Maisel AS. A Global Rank End Point for Clinical Trials in Acute Heart Failure. Circ Heart Fail. 2010;3:643-646.
2.
Matsouaka RA, Betensky RA. Power and sample size calculations for the Wilcoxon–Mann–Whitney test in the presence of death-censored observations. Statist Med. 2015, 34 406–431
3.
Wellek, S. Testing Statistical Hypotheses of Equivalence and Noninferiority. CRC Press; 2010.