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Statistical Issues and Limitations in Personalized Medicine Research with Clinical Trials

Author

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  • Rubin Daniel B.

    (Food and Drug Administration)

  • van der Laan Mark J.

    (University of California - Berkeley)

Abstract

We discuss using clinical trial data to construct and evaluate rules that use baseline covariates to assign different treatments to different patients. Given such a candidate personalization rule, we first note that its performance can often be evaluated without actually applying the rule to subjects, and a class of estimators is characterized from a statistical efficiency standpoint. We also point out a recently noted reduction of the rule construction problem to a classification task and extend results in this direction. Together these facts suggest a natural form of cross-validation in which a personalized medicine rule can be constructed from clinical trial data using standard classification tools and then evaluated in a replicated trial. Because replication is often required by the FDA to provide evidence of safety and efficacy before pharmaceutical drugs can be marketed, there are abundant data with which to explore the potential benefits of more tailored therapy. We constructed and evaluated personalized medicine rules using simulations based on two active-controlled randomized clinical trials of antibacterial drugs for the treatment of skin and skin structure infections. Unfortunately we present negative results that did not suggest benefit from personalization. We discuss the implications of this finding and why statistical approaches to personalized medicine problems will often face difficult challenges.

Suggested Citation

  • Rubin Daniel B. & van der Laan Mark J., 2012. "Statistical Issues and Limitations in Personalized Medicine Research with Clinical Trials," The International Journal of Biostatistics, De Gruyter, vol. 8(1), pages 1-20, July.
    • Handle: RePEc:bpj:ijbist:v:8:y:2012:i:1:n:18
    DOI: 10.1515/1557-4679.1423
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    References listed on IDEAS

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    1. Yingqi Zhao & Donglin Zeng & A. John Rush & Michael R. Kosorok, 2012. "Estimating Individualized Treatment Rules Using Outcome Weighted Learning," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 107(499), pages 1106-1118, September.
    2. Baqun Zhang & Anastasios A. Tsiatis & Eric B. Laber & Marie Davidian, 2012. "A Robust Method for Estimating Optimal Treatment Regimes," Biometrics, The International Biometric Society, vol. 68(4), pages 1010-1018, December.
    3. Bartlett, Peter L. & Jordan, Michael I. & McAuliffe, Jon D., 2006. "Convexity, Classification, and Risk Bounds," Journal of the American Statistical Association, American Statistical Association, vol. 101, pages 138-156, March.
    4. Rubin Daniel B & van der Laan Mark J., 2008. "Empirical Efficiency Maximization: Improved Locally Efficient Covariate Adjustment in Randomized Experiments and Survival Analysis," The International Journal of Biostatistics, De Gruyter, vol. 4(1), pages 1-42, May.
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    1. I Díaz & O Savenkov & K Ballman, 2018. "Targeted learning ensembles for optimal individualized treatment rules with time-to-event outcomes," Biometrika, Biometrika Trust, vol. 105(3), pages 723-738.
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    3. Cui, Yifan & Tchetgen Tchetgen, Eric, 2021. "On a necessary and sufficient identification condition of optimal treatment regimes with an instrumental variable," Statistics & Probability Letters, Elsevier, vol. 178(C).
    4. Zhen Li & Jie Chen & Eric Laber & Fang Liu & Richard Baumgartner, 2023. "Optimal Treatment Regimes: A Review and Empirical Comparison," International Statistical Review, International Statistical Institute, vol. 91(3), pages 427-463, December.

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