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. 2011 Sep;21(5):971-91.
doi: 10.1080/10543406.2011.590922.

Joint modeling of multiple longitudinal patient-reported outcomes and survival

Laura A Hatfield  1 , Mark E Boye, Bradley P Carlin
Affiliations

Joint modeling of multiple longitudinal patient-reported outcomes and survival

Laura A Hatfield et al. J Biopharm Stat. 2011 Sep.

Abstract

Researchers often include patient-reported outcomes (PROs) in Phase III clinical trials to demonstrate the value of treatment from the patient's perspective. These data are collected as longitudinal repeated measures and are often censored by occurrence of a clinical event that defines a survival time. Hierarchical Bayesian models having latent individual-level trajectories provide a flexible approach to modeling such multiple outcome types simultaneously. We consider the case of many zeros in the longitudinal data motivating a mixture model, and demonstrate several approaches to modeling multiple longitudinal PROs with survival in a cancer clinical trial. These joint models may enhance Phase III analyses and better inform health care decision makers.

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Figures

Figure 1
Figure 1
Predictive model comparison statistics for models fit to mesothelioma data. Means and 95% posterior credible intervals are shown.
Figure 2
Figure 2
Posterior means and 95% equal-tail credible intervals for parameters governing probability of non-zero PRO (β0, top row) and mean of non-zero PRO (β1, bottom row). Credible intervals that exclude the null value of 0 are shaded darker. Circles represent effects on cough, triangles for effects on dyspnea.
Figure 3
Figure 3
Posterior means and 95% equal-tail credible intervals for parameters governing hazard of progression (β2). Credible intervals that exclude the null value of 0 are shaded darker. Effects in models joint with cough are plotted as circles; models with dyspnea are triangles.
Figure 4
Figure 4
Observed outcomes (zeros plotted as stars) according to individual probability of non-zero score (u0i) and non-zero score mean (u1i) in a model of cough and progression-free survival.
Figure 5
Figure 5
Estimated cumulative hazard functions and 95% confidence intervals for the treatment group, pemetrexed plus best supportive care (BSC), and BSC alone group (left panel). The right panel displays simple estimates (circles, plotted at time period midpoint) with 95% confidence intervals (dashed lines) of treatment effect on progression-free survival (PFS).
See this image and copyright information in PMC

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