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Kjetil Røysland

Publications and source records attributed to Kjetil Røysland.

12 recordsLinked to original sources

Robust estimation of occupation probabilities for coarsened multistate processes

We derive augmented inverse probability weighted estimators for occupation probabilities of multistate models under two levels of coarsening; right-censoring and baseline exposure. The key exchangeability assumption for identification is coarsening at random, while allowing for time-varying confounders, but not requiring Markov properties. Using existing techniques from causal inference and missing data literature, the derived estimators have highly desirable robustness and efficiency properties. These properties are demonstrated through both theoretical results, and a simulation study.

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On causal inference with marked point process data

We define dynamic treatment regimes and associated potential outcomes for data described by marked point processes (MPPs). These definitions motivate MPP analogues of the commonly used consistency, exchangeability, and positivity conditions that are sufficient for identifying effects in MPP data structures. The conditions are formulated based on martingale theory, which allows us to derive explicit identifying assumptions for data described by stochastic processes. The definitions and conditions align with well-established discrete-time results in important special cases. Thus, this work bridges the large literatures on survival (event history) analysis with counting processes in continuous time and causal inference with variables in discrete-time. After formulating a set of identification conditions, we derive and characterize marginal g-formulas. The g-formulas are generally different from those studied in related works, though they coincide in important special cases. We relate our findings to previous work on causal inference with (counting) processes, the classical survival literature, and the discrete-time causal inference literature.

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Graphical criteria for the identification of marginal causal effects in continuous-time survival and event-history analyses

We consider continuous-time survival or more general event-history settings, where the aim is to infer the causal effect of a time-dependent treatment process. This is formalised as the effect on the outcome event of a (possibly hypothetical) intervention on the intensity of the treatment process, i.e. a stochastic intervention. To establish whether valid inference about the interventional situation can be drawn from typical observational, i.e. non-experimental, data we propose graphical rules indicating whether the observed information is sufficient to identify the desired causal effect by suitable re-weighting. In analogy to the well-known causal directed acyclic graphs, the corresponding dynamic graphs combine causal semantics with local independence models for multivariate counting processes. Importantly, we highlight that causal inference from censored data requires structural assumptions on the censoring process beyond the usual independent censoring assumption, which can be represented and verified graphically. Our results establish general non-parametric identifiability and do not rely on particular survival models. We illustrate our proposal with a data example on HPV-testing for cervical cancer screening, where the desired effect is estimated by re-weighted cumulative incidence curves.

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Hypothetical Treatment Accelerations: Estimating Causal Effects of Kidney Transplants from Observational Data

Patients with end-stage kidney disease can expect to wait for several years before they receive a transplant, all the while their health deteriorates. How would the survival change if we managed to reduce these waiting times? To provide an answer, we present a continuous-time marginal structural model (MSM) of hypothetical scenarios in which the time until treatment is changed. In these scenarios, the treatment process is defined on a hypothetical time scale where time passes at a different rate compared to the time actually observed. Changing the time of the treatment process corresponds to changing the joint probability distribution, thereby making it possible to identify and estimate hypothetical parameters from observational data using previously developed methodology. We demonstrate this treatment-accelerated MSM using observational data from a Norwegian cohort of elderly patients with kidney failure. This model can potentially be useful to health authorities looking to assess the impacts of reducing the waiting times for organ transplantation in a given patient population.

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Time-dependent mediators in survival analysis: Modelling direct and indirect effects with the additive hazards model

We discuss causal mediation analyses for survival data and propose a new approach based on the additive hazards model. The emphasis is on a dynamic point of view, that is, understanding how the direct and indirect effects develop over time. Hence, importantly, we allow for a time varying mediator. To define direct and indirect effects in such a longitudinal survival setting we take an interventional approach (Didelez (2018)) where treatment is separated into one aspect affecting the mediator and a different aspect affecting survival. In general, this leads to a version of the non-parametric g-formula (Robins (1986)). In the present paper, we demonstrate that combining the g-formula with the additive hazards model and a sequential linear model for the mediator process results in simple and interpretable expressions for direct and indirect effects in terms of relative survival as well as cumulative hazards. Our results generalise and formalise the method of dynamic path analysis (Fosen et al. (2006), Strohmaier et al. (2015)). An application to data from a clinical trial on blood pressure medication is given.

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Transforming cumulative hazard estimates

Time to event outcomes are often evaluated on the hazard scale, but interpreting hazards may be difficult. Recently, there has been concern in the causal inference literature that hazards actually have a built in selection-effect that prevents simple causal interpretations. This is even a problem in randomized controlled trials, where hazard ratios have become a standard measure of treatment effects. Modeling on the hazard scale is nevertheless convenient, e.g. to adjust for covariates. Using hazards for intermediate calculations may therefore be desirable. Here, we provide a generic method for transforming hazard estimates consistently to other scales at which these built in selection effects are avoided. The method is based on differential equations, and generalize a well known relation between the Nelson-Aalen and Kaplan-Meier estimators. Using the martingale central limit theorem we also find that covariances can be estimated consistently for a large class of estimators, thus allowing for rapid calculations of confidence intervals. Hence, given cumulative hazard estimates based on e.g. Aalen's additive hazard model, we can obtain many other parameters without much more effort. We present several examples and associated estimators. Coverage and convergence speed is explored using simulations, suggesting that reliable estimates can be obtained in real-life scenarios.

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The additive hazard estimator is consistent for continuous-time marginal structural models

Marginal structural models (MSMs) allow for causal analysis of longitudinal data. The MSMs were originally developed as discrete time models. Recently, continuous-time MSMs were presented as a conceptually appealing alternative for survival analysis. In applied analyses, it is often assumed that the theoretical treatment weights are known, but these weights are usually unknown and must be estimated from the data. Here we provide a sufficient condition for a class of continuous-time MSMs to be consistent even when the weights are estimated, and we show how additive hazard models can be used to estimate such weights. Our results suggest that the continuous-time weights perform better than IPTW when the underlying treatment process is continuous. Furthermore, we may wish to transform effect estimates of hazards to other scales that are easier to interpret causally. We show that a general transformation strategy can be used on weighted cumulative hazard estimates to obtain a range of other parameters in survival analysis, and demonstrate how this strategy can be applied on data using our R packages ahw and transform.hazards.

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On null hypotheses in survival analysis

The conventional nonparametric tests in survival analysis, such as the log-rank test, assess the null hypothesis that the hazards are equal at all times. However, hazards are hard to interpret causally, and other null hypotheses are more relevant in many scenarios with survival outcomes. To allow for a wider range of null hypotheses, we present a generic approach to define test statistics. This approach utilizes the fact that a wide range of common parameters in survival analysis can be expressed as solutions of differential equations. Thereby we can test hypotheses based on survival parameters that solve differential equations driven by cumulative hazards, and it is easy to implement the tests on a computer. We present simulations, suggesting that our tests perform well for several hypotheses in a range of scenarios. Finally, we use our tests to evaluate the effect of adjuvant chemotherapies in patients with colon cancer, using data from a randomised controlled trial.

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Dynamic path analysis - A useful tool to investigate mediation processes in clinical survival trials

When it comes to clinical survival trials, regulatory restrictions usually require the application of methods that solely utilize baseline covariates and the intention-to-treat principle. Thereby a lot of potentially useful information is lost, as collection of time-to-event data often goes hand in hand with collection of information on biomarkers and other internal time-dependent covariates. However, there are tools to incorporate information from repeated measurements in a useful manner that can help to shed more light on the underlying treatment mechanisms. We consider dynamic path analysis, a model for mediation analysis in the presence of a time-to-event outcome and time-dependent covariates to investigate direct and indirect effects in a study of different lipid lowering treatments in patients with previous myocardial infarctions. Further, we address the question whether survival in itself may produce associations between the treatment and the mediator in dynamic path analysis and give an argument that, due to linearity of the assumed additive hazard model, this is not the case. We further elaborate on our view that, when studying mediation, we are actually dealing with underlying processes rather than single variables measured only once during the study period. This becomes apparent in results from various models applied to the study of lipid lowering treatments as well as our additionally conducted simulation study, where we clearly observe, that discarding information on repeated measurements can lead to potentially erroneous conclusions.

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Counterfactual analyses with graphical models based on local independence

We show that one can perform causal inference in a natural way for continuous-time scenarios using tools from stochastic analysis. This provides new alternatives to the positivity condition for inverse probability weighting. The probability distribution that would govern the frequency of observations in the counterfactual scenario can be characterized in terms of a so-called martingale problem. The counterfactual and factual probability distributions may be related through a likelihood ratio given by a stochastic differential equation. We can perform inference for counterfactual scenarios based on the original observations, re-weighted according to this likelihood ratio. This is possible if the solution of the stochastic differential equation is uniformly integrable, a property that can be determined by comparing the corresponding factual and counterfactual short-term predictions. Local independence graphs are directed, possibly cyclic, graphs that represent short-term prediction among sufficiently autonomous stochastic processes. We show through an example that these graphs can be used to identify and provide consistent estimators for counterfactual parameters in continuous time. This is analogous to how Judea Pearl uses graphical information to identify causal effects in finite state Bayesian networks.

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A martingale approach to continuous-time marginal structural models

Marginal structural models were introduced in order to provide estimates of causal effects from interventions based on observational studies in epidemiological research. The key point is that this can be understood in terms of Girsanov's change of measure. This offers a mathematical interpretation of marginal structural models that has not been available before. We consider both a model of an observational study and a model of a hypothetical randomized trial. These models correspond to different martingale measures -- the observational measure and the randomized trial measure -- on some underlying space. We describe situations where the randomized trial measure is absolutely continuous with respect to the observational measure. The resulting continuous-time likelihood ratio process with respect to these two probability measures corresponds to the weights in discrete-time marginal structural models. In order to do inference for the hypothetical randomized trial, we can simulate samples using observational data weighted by this likelihood ratio.

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Symmetries in projective multiresolution analyses

We give an equivariant version of Packer and Rieffel's theorem on sufficient conditions for the existence of orthonormal wavelets in projective multiresolution analyses. The scaling functions that generate a projective multiresolution analysis are supposed to be invariant with respect to some finite group action. We give sufficient conditions for the existence of wavelets with similar invariance.

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