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Statistical decisions and the interim analyses of clinical trials

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Abstract

This paper analyzes statistical decisions during the interim analyses of clinical trials. After some general remarks about the ethical and scientific demands of clinical trials, I introduce the notion of a hard-case clinical trial, explain the basic idea behind it, and provide a real example involving the interim analyses of zidovudine in asymptomatic HIV-infected patients. The example leads me to propose a decision analytic framework for handling ethical conflicts that might arise during the monitoring of hard-case clinical trials. I use computer simulations to show how the framework can assist in reconciling certain ethical conflicts. The framework is partial, lacking the precision of a complete systematization of statistical monitoring procedures in practice.

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Notes

  1. Note, however, that alternative approaches to the discussion of the ethics of stopping rules can be found in Cannistra [5] and Buchanan and Miller [6]. No attempt is made to compare them in this article.

  2. P((y 2 − y 1) ≥ 4|H0) = 0.058, computed according to the joint probability distribution. E.g., P((y 2 = 7, y 1 = 3)|H0) = (0.117)2 = 0.014.

  3. cc is a loss that can be conceptualized in different ways. For my purposes, it can be understood as the “cost” of having a patient subjected to a new treatment, when that treatment is no better than standard treatment.

  4. Weighted-loss = (loss)*(probability of taking that action).

  5. (0.48 + 10.06)/2 = 5.27, and once divided by 0.17, I reach the multiplicative loss factor of 31.

References

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Acknowledgments

I thank Julian Reiss, David Teira, Jan Vandenbroucke, Teddy Seidenfeld, Jesús Zamora-Bonilla, Scott Anderson, Alan Richardson, the audiences at the philosophy of medicine roundtable at Erasmus University Rotterdam, and the European Philosophy of Science in Amsterdam, for helpful discussion and feedback. Earlier version of this work was also presented at a conference in Toronto (HAPSAT) of which I am also thankful. I am most grateful to Paul Bartha, Hubert Wong, and two anonymous reviewers for their many useful comments, discussions, and criticisms. This work was supported by the department of philosophy at UBC and an earlier travel grant from the Canadian Institute of Health Research (IHSPR).

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  1. Department of Philosophy, University of British Columbia, 1866 Main Mall E370, Vancouver, BC, V6T 1Z1, Canada

    Roger Stanev

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Stanev, R. Statistical decisions and the interim analyses of clinical trials. Theor Med Bioeth 32, 61–74 (2011). https://doi.org/10.1007/s11017-010-9170-9

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