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Andrew C. Titman

Publications and source records attributed to Andrew C. Titman.

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Time-dynamic inference for non-Markov transition probabilities under independent right-censoring

In this article, weak convergence of the general non-Markov state transition probability estimator by Titman (2015) is established which, up to now, has not been verified yet for other general non-Markov estimators. A similar theorem is shown for the bootstrap, yielding resampling-based inference methods for statistical functionals. Formulas of the involved covariance functions are presented in detail. Particular applications include the conditional expected length of stay in a specific state, given occupation of another state in the past, as well as the construction of time-simultaneous confidence bands for the transition probabilities. The expected lengths of stay in the two-sample liver cirrhosis data-set by Andersen et al. (1993) are compared and confidence intervals for their difference are constructed. With borderline significance and in comparison to the placebo group, the treatment group has an elevated expected length of stay in the healthy state given an earlier disease state occupation. In contrast, the Aalen-Johansen estimator-based confidence interval, which relies on a Markov assumption, leads to a drastically different conclusion. Also, graphical illustrations of confidence bands for the transition probabilities demonstrate the biasedness of the Aalen-Johansen estimator in this data example. The reliability of these results is assessed in a simulation study.

math.ST

Subgroup analysis of treatment effects for misclassified biomarkers with time-to-event data

Analysing subgroups defined by biomarkers is of increasing importance in clinical research. In some situations the biomarker is subject to misclassification error, meaning the true subgroups are identified with imperfect sensitivity and specificity. For time-to-event data, it is improper to assume the Cox proportional hazards model for the effects with respect to the true subgroups, since the survival distributions with respect to the diagnosed subgroups will not adhere to the proportional hazards assumption. This precludes the possibility of using simple adjustment procedures. Instead, we present a method based on formally modelling the data as a mixture of Cox models using an EM algorithm for estimation. An estimate of the overall population treatment effect is obtained through the interpretation of the hazard ratio as a concordance odds. Profile likelihood is used to construct individual and simultaneous confidence intervals of treatment effects. The resulting confidence intervals are shown to have close to nominal coverage for moderately large sample sizes in simulations and the method is illustrated on data from a renal-cell cancer trial.

stat.ME