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GMDS 2012: 57. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie

16. - 20.09.2012, Braunschweig

Blinded and unblinded internal pilot study designs for clinical trials with overdispersed count data

Meeting Abstract

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  • Simon Schneider - Universitätsmedizin Göttingen, Deutschland
  • Heinz Schmidli - Statistical Methodology, Novartis Pharma AG, Basel, Schweiz
  • Tim Friede - Universitätsmedizin Göttingen, Deutschland

GMDS 2012. 57. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS). Braunschweig, 16.-20.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12gmds150

DOI: 10.3205/12gmds150, URN: urn:nbn:de:0183-12gmds1503

Published: September 13, 2012

© 2012 Schneider et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

In the planning phase of a clinical trial with counts as primary outcomes, such as relapses in Multiple Sclerosis (MS), there is uncertainty with regard to the nuisance parameters (e.g. overall event rate, the dispersion parameter) which need to be specified for sample size estimation. For this reason the application of adaptive designs with blinded sample size reestimation (BSSR) are attractive (Cook et al. 2009 [1], Friede and Schmidli 2010 [2]). After a comparison of existing methods we consider in this presentation a modified version of the maximum likelihood method for BSSR for negative binomial data proposed by Friede and Schmidli (2010) [3]. The method works well in terms of sample size distribution and power, if the assumed clinically effect is equal to the true effect. We compare the BSSR approach to an unblinded procedure in situations where an uncertainty about the assumed effect size exists. For practically relevant scenarios we make recommendations when application of the blinded or unblinded procedure are indicated. In addition, results for unbalanced designs previously not considered are shown in a simulation study. The methods are illustrated by a study in Relapsing Remitting MS.


References

1.
Cook RJ, et al. Two-stage design of clinical trials involving recurrent events. Stat Med. 2009;28:2617-38.
2.
Friede T, Schmidli H. Blinded sample size reestimation with count data: Methods and applications in multiple sclerosis. Stat Med. 2010;29:1145-56.
3.
Friede T, Schmidli H. Blinded Sample Size Reestimation with Negative Binomial Counts in Superiority and Non-inferiority Trials. Meth Inform Med. 2010;49:618-24.