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Bias and Conditioning in Sequential Medical Trials

Published online by Cambridge University Press:  01 January 2022

Cecilia Nardini  and
Jan Sprenger
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Abstract

Randomized controlled trials are currently the gold standard within evidence-based medicine. Usually they are monitored for early signs of effectiveness or harm. However, evidence from trials stopped early is often charged with bias toward implausibly large effects. To our mind, this skeptical attitude is unfounded and caused by the failure to perform appropriate conditioning in the statistical analysis of the evidence. We contend that conditional hypothesis tests give a superior appreciation of the obtained evidence and significantly improve the practice of sequential medical trials, while staying firmly rooted in frequentist methodology.

Type
General Philosophy of Science
Information
Philosophy of Science , Volume 80 , Issue 5 , December 2013 , pp. 1053 - 1064
Copyright
Copyright © The Philosophy of Science Association

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Footnotes

†

The authors would like to thank the senior and junior members of the FOLSATEC PhD program, as well as David Teira and the PSA audience. Jan Sprenger would also like to thank the Netherlands Organization for Scientific Research (NWO) for supporting this research through Veni grant no. 016.104.079.

References

Bassler, Dirk, et al. 2010. “Stopping Randomized Trials Early for Benefit and Estimation of Treatment Effects.” Journal of the American Medical Association 303:1180–87.Google ScholarPubMed
Berger, James O. 2003. “Could Fisher, Jeffreys and Neyman Have Agreed on Testing?” Statistical Science 18:1–12.CrossRefGoogle Scholar
Berger, James O., Boukai, Ben, and Wang, Yinping. 1997. “Unified Frequentist and Bayesian Testing of a Precise Hypothesis.” Statistical Science 12:133–60.CrossRefGoogle Scholar
Berger, James O., Brown, Lawrence D., and Wolpert, Robert L.. 1994. “A Unified Conditional Frequentist and Bayesian Test for Fixed and Sequential Simple Hypothesis Testing.” Annals of Statistics 22:1787–1807.CrossRefGoogle Scholar
Berry, Scott M., Carlin, Bradley P., and Connor, Jason. 2010. “Bias and Trials Stopped Early for Benefit.” Journal of the American Medical Association 304:156.CrossRefGoogle ScholarPubMed
Cox, David. 1958. “Some Problems Connected with Statistical Inference.” Annals of Mathematical Statistics 29:357–72.CrossRefGoogle Scholar
Cumming, Geoff, and Finch, Sue. 2005. “Inference by Eye: Confidence Intervals and How to Read Pictures of Data.” American Psychologist 60:170–80.CrossRefGoogle ScholarPubMed
Food and Drug Administration. 2010. “Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials.” http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071072.htm.Google Scholar
Goodman, Steven N. 1999. “Toward Evidence-Based Medical Statistics.” Pt. 1, “The P Value Fallacy.” Annals of Internal Medicine 130:995.CrossRefGoogle Scholar
Goodman, Steven N. 2007. “Stopping at Nothing? Some Dilemmas of Data Monitoring in Clinical Trials.” Annals of Internal Medicine 146:882.CrossRefGoogle ScholarPubMed
Goodman, Steven N., Berry, Donald, and Wittes, Janet. 2010. “Bias and Trials Stopped Early for Benefit.” Journal of the American Medical Association 304:157.Google ScholarPubMed
Kiefer, Jack. 1977. “Conditional Confidence Statements and Confidence Estimators.” Journal of the American Statistical Association 72:789–808.Google Scholar
Lau, Wan-Yee, et al. 1999. “Adjuvant intra-Arterial Lipiodol-Iodine-131 for Resectable Hepatocellular Carcinoma: A Prospective Randomised Trial.” Lancet 353:797–801.CrossRefGoogle Scholar
Mayo, Deborah G. 1996. Error and the Growth of Experimental Knowledge. Chicago: University of Chicago Press.CrossRefGoogle Scholar
Mayo, Deborah G., and Kruse, Michael. 2001. “Principles of Inference and Their Consequences.” In Foundations of Bayesianism, ed. Corfield, David and Williamson, Jon, 381–421. Dordrecht: Kluwer Academic.CrossRefGoogle Scholar
Montori, Victor M., et al. 2005. “Randomized Trials Stopped Early for Benefit: A Systematic Review.” Journal of the American Medical Association 294:2203–9.Google ScholarPubMed
Moyé, Lemuel A. 2008. “Bayesians in Clinical Trials: Asleep at the Switch.” Statistics in Medicine 27:469–82.CrossRefGoogle Scholar
Mueller, Paul S., et al. 2007. “Ethical Issues in Stopping Randomized Trials Early because of Apparent Benefit.” Annals of Internal Medicine 146:878–81.CrossRefGoogle ScholarPubMed
Nardini, Cecilia. 2013. “Monitoring Clinical Trials: Benefit or Bias?” Theoretical Medicine and Bioethics 34:259–74.CrossRefGoogle ScholarPubMed
Pocock, Stuart, and White, Ian. 1999. “Trials Stopped Early: Too Good to Be True?” Lancet 353:943–44.CrossRefGoogle ScholarPubMed
Royall, Richard. 1997. Statistical Evidence: A Likelihood Paradigm. London: Chapman & Hall.Google Scholar
Seidenfeld, Teddy. 1981. “On After-Trial Properties of Best Neyman-Pearson Confidence Intervals.” Philosophy of Science 48:281–91.CrossRefGoogle Scholar
Sprenger, Jan. 2009. “Evidence and Experimental Design in Sequential Trials.” Philosophy of Science 76:637–49.CrossRefGoogle Scholar
Wald, Abraham. 1947. Sequential Analysis. New York: Wiley.Google Scholar
Worrall, John. 2007. “Evidence in Medicine and Evidence-Based Medicine.” Philosophy Compass 2:981–1022.CrossRefGoogle Scholar
Worrall, John 2008. “Evidence and Ethics in Medicine.” Perspectives in Biology and Medicine 51:418–31.Google ScholarPubMed