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Noninferiority testing in cost-minimization studies: Practical issues concerning power analysis

Published online by Cambridge University Press:  28 March 2006

Mark M. Span ,
Elisabeth M. TenVergert ,
Christian S. van der Hilst  and
Ronald P. Stolk
Mark M. Span
Affiliation:
University Medical Center Groningen, University of Groningen
Elisabeth M. TenVergert
Affiliation:
University Medical Center Groningen, University of Groningen
Christian S. van der Hilst
Affiliation:
University Medical Center Groningen, University of Groningen
Ronald P. Stolk
Affiliation:
University Medical Center Groningen, University of Groningen
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Abstract

Objectives: In cost-minimization studies, it is important to establish noninferiority in the clinical effect of the treatments under investigation. The relationship between the proportion of patients reaching the end point in a study, equivalence limit (δ), and power is investigated in the context of cost-minimization studies with dichotomous clinical end points. Two formulations of the null-hypothesis, absolute and relative formulations of δ, will be explored.

Methods: Sensitivity analysis was performed, in which the effect of the predicted proportions and δ on the power in a noninferiority setting was investigated. The patterns found are discussed in terms of the practical relevance within the cost-minimization framework.

Results: Sensitivity analyses show different patterns of results for both null-hypotheses. The differences in these results originate from the way δ is expressed. By expressing δ as absolute difference, power grows quite fast when sample proportions are smaller than expected. In the case of a proportional δ at small sample proportions, the power to establish noninferiority remains low.

Conclusions: To obtain valid results from a cost-minimization study, care has to be taken to adapt the correct methodology for noninferiority testing in clinical outcomes. Defining δ in terms of absolute differences between treatments can lead to obscured results. Although conservative, the expression of δ as a proportion of the effectiveness of the treatment as usual is found to be closer to clinical practice. The inflated δ, resulting from smaller clinical effects than expected when absolute formulation is applied, thus can be avoided.

Keywords

Medical economicsCost-minimizationNoninferioritySensitivity analysis
Type
RESEARCH REPORTS
Information
International Journal of Technology Assessment in Health Care , Volume 22 , Issue 2 , April 2006 , pp. 261 - 266
Copyright
© 2006 Cambridge University Press

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