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Analyzing longitudinal clinical trial data with nonignorable missingness and unknown missingness reasons


  • Xie, Hui


Longitudinal clinical trials are often plagued by nonmonotone missingness due to both patient dropout and intermittent missingness. Standard analysis assumes that missingness is ignorable. Because the assumption can be questionable, the sensitivity of inferences to alternative assumptions about missingness needs to be evaluated. This need arises in the analysis of a longitudinal prostate cancer quality-of-life (QoL) clinical trial dataset, in which nonmonotone missingness occurs. The choice of the missing data model is studied in the analysis. A local sensitivity analysis method is then applied to analyze the dataset and to investigate the changes in parameter estimates in the neighborhood of the ignorable model. One advantage of the method is that it surmounts computational difficulty and completely avoids evaluating the high-dimensional integrals in the likelihood due to nonmonotone missingness. Another is that it can be implemented using the standard software without excessive additional computation. The method is especially advantageous for large clinical datasets for which alternative approaches can become computationally prohibitive. In addition, the analysis demonstrates the importance of exploiting information on reasons for missingness. When such information is unavailable for some missingness and therefore the missingness types (i.e., dropout versus intermittent missingness) are unknown, a bound analysis is proposed, combined with genetic algorithms, to account for unknown missingness types. The analysis demonstrates the usefulness of the method as a general approach to evaluating the sensitivity of standard analysis to nonignorable nonmonotone missingness in clinical trials.

Suggested Citation

  • Xie, Hui, 2012. "Analyzing longitudinal clinical trial data with nonignorable missingness and unknown missingness reasons," Computational Statistics & Data Analysis, Elsevier, vol. 56(5), pages 1287-1300.
  • Handle: RePEc:eee:csdana:v:56:y:2012:i:5:p:1287-1300
    DOI: 10.1016/j.csda.2010.11.021

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    References listed on IDEAS

    1. Sotto, Cristina & Beunckens, Caroline & Molenberghs, Geert & Kenward, Michael G., 2011. "MCMC-based estimation methods for continuous longitudinal data with non-random (non)-monotone missingness," Computational Statistics & Data Analysis, Elsevier, vol. 55(1), pages 301-311, January.
    2. Gad, Ahmed M. & Ahmed, Abeer S., 2006. "Analysis of longitudinal data with intermittent missing values using the stochastic EM algorithm," Computational Statistics & Data Analysis, Elsevier, vol. 50(10), pages 2702-2714, June.
    3. Stijn Vansteelandt & Andrea Rotnitzky & James Robins, 2007. "Estimation of Regression Models for the Mean of Repeated Outcomes Under Nonignorable Nonmonotone Nonresponse," Biometrika, Biometrika Trust, vol. 94(4), pages 841-860.
    4. Yi Qian, 2007. "Do National Patent Laws Stimulate Domestic Innovation in a Global Patenting Environment? A Cross-Country Analysis of Pharmaceutical Patent Protection, 1978-2002," The Review of Economics and Statistics, MIT Press, vol. 89(3), pages 436-453, August.
    5. John Copas & Shinto Eguchi, 2001. "Local sensitivity approximations for selectivity bias," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 63(4), pages 871-895.
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