We suggest a wild bootstrap resampling technique for nonparametric inference on transition probabilities in a general time-inhomogeneous Markov multistate model. We first approximate the limiting distribution of the Nelson-Aalen estimator by repeatedly generating standard normal wild bootstrap variates, while the data is kept fixed. Next, a transformation using a functional delta method argument is applied. The approach is conceptually easier than direct resampling for the transition probabilities. It is used to investigate a non-standard time-to-event outcome, currently being alive without immunosuppressive treatment, with data from a recent study of prophylactic treatment in allogeneic transplanted leukemia patients. Due to non-monotonic outcome probabilities in time, neither standard survival nor competing risks techniques apply, which highlights the need for the present methodology. Finite sample performance of time-simultaneous confidence bands for the outcome probabilities is assessed in an extensive simulation study motivated by the clinical trial data. Example code is provided in the web-based Supplementary Materials.

Statistical inference in competing risks models is often based on the famous Aalen-Johansen estimator. Since the corresponding limit process lacks independent increments, it is typically applied together with Lin's (1997) resampling technique involving standard normal multipliers. Recently, it has been seen that this approach can be interpreted as a wild bootstrap technique and that other multipliers, as e.g. centered Poissons, may lead to better finite sample performances, see Beyersmann et al. (2013). Since the latter is closely related to Efron's classical bootstrap, the question arises whether this or more general weighted bootstrap versions of Aalen-Johansen processes lead to valid results. Here we analyze their asymptotic behaviour and it turns out that such weighted bootstrap versions in general possess the wrong covariance structure in the limit. However, we explain that the weighted bootstrap can nevertheless be applied for specific null hypotheses of interest and also discuss its limitations for statistical inference. To this end, we introduce different consistent weighted bootstrap tests for the null hypothesis of stochastically ordered cumulative incidence functions and compare their finite sample performance in a simulation study.

This paper introduces new effect parameters for factorial survival designs with possibly right-censored time-to-event data. In the special case of a two-sample design it coincides with the concordance or Wilcoxon parameter in survival analysis. More generally, the new parameters describe treatment or interaction effects and we develop estimates and tests to infer their presence. We rigorously study the asymptotic properties by means of empirical process techniques and additionally suggest wild bootstrapping for a consistent and distribution-free application of the inference procedures. The small sample performance is discussed based on simulation results. The practical usefulness of the developed methodology is exemplified on a data example about patients with colon cancer by conducting one-and two-factorial analyses.

The Mann-Whitney effect is an intuitive measure for discriminating two survival distributions.Here we analyze various inference techniques for this parameter in a two-sample survival setting with independent right-censoring, where the survival times are even allowed to be discretely distributed. This allows for ties in the data and requires the introduction of normalized versions of Kaplan-Meier estimators from which adequate point estimates are deduced. Asymptotically exact inference procedures based on standard normal, bootstrap-and permutation-quantiles are developed and compared in simulations. Here, the asymptotically robust and -under exchangeable data -even finitely exact permutation procedure turned out to be the best. Finally, all procedures are illustrated using a real data set.

Factorial survival designs with right-censored observations are commonly inferred by Cox regression and explained by means of hazard ratios. However, in case of non-proportional hazards, their interpretation can become cumbersome; especially for clinicians. We therefore offer an alternative: median survival times are used to estimate treatment and interaction effects and null hypotheses are formulated in contrasts of their population versions. Permutation-based tests and confidence regions are proposed and shown to be asymptotically valid. Their type-1 error control and power behavior are investigated in extensive simulations, showing the new methods’ wide applicability. The latter is complemented by an illustrative data analysis.