Analyzing longitudinal clinical trial data with nonignorable missingness and unknown missingness reasons
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.
If you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
As the access to this document is restricted, you may want to look for a different version under "Related research" (further below) or search for a different version of it.
References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- 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.
- 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.
- 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.
- 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.
- 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.
When requesting a correction, please mention this item's handle: RePEc:eee:csdana:v:56:y:2012:i:5:p:1287-1300. See general information about how to correct material in RePEc.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: (Zhang, Lei)
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
If references are entirely missing, you can add them using this form.
If the full references list an item that is present in RePEc, but the system did not link to it, you can help with this form.
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your profile, as there may be some citations waiting for confirmation.
Please note that corrections may take a couple of weeks to filter through the various RePEc services.