Tamara Fernández

Marc Ditzhaus, Tamara Fernández, Nicolás Rivera

In this paper we propose a Multiple kernel testing procedure to infer survival data when several factors (e.g. different treatment groups, gender, medical history) and their interaction are of interest simultaneously. Our method is able to deal with complex data and can be seen as an alternative to the omnipresent Cox model when assumptions such as proportionality cannot be justified. Our methodology combines well-known concepts from Survival Analysis, Machine Learning and Multiple Testing: differently weighted log-rank tests, kernel methods and multiple contrast tests. By that, complex hazard alternatives beyond the classical proportional hazard set-up can be detected. Moreover, multiple comparisons are performed by fully exploiting the dependence structure of the single testing procedures to avoid a loss of power. In all, this leads to a flexible and powerful procedure for factorial survival designs whose theoretical validity is proven by martingale arguments and the theory for $V$-statistics. We evaluate the performance of our method in an extensive simulation study and illustrate it by a real data analysis.

Oscar Key, Arthur Gretton, François-Xavier Briol et al.

Model misspecification can create significant challenges for the implementation of probabilistic models, and this has led to development of a range of robust methods which directly account for this issue. However, whether these more involved methods are required will depend on whether the model is really misspecified, and there is a lack of generally applicable methods to answer this question. In this paper, we propose one such method. More precisely, we propose kernel-based hypothesis tests for the challenging composite testing problem, where we are interested in whether the data comes from any distribution in some parametric family. Our tests make use of minimum distance estimators based on the maximum mean discrepancy and the kernel Stein discrepancy. They are widely applicable, including whenever the density of the parametric model is known up to normalisation constant, or if the model takes the form of a simulator. As our main result, we show that we are able to estimate the parameter and conduct our test on the same data (without data splitting), while maintaining a correct test level. Our approach is illustrated on a range of problems, including testing for goodness-of-fit of an unnormalised non-parametric density model, and an intractable generative model of a biological cellular network.

Tamara Fernández, Wenkai Xu, Marc Ditzhaus et al.

We consider settings in which the data of interest correspond to pairs of ordered times, e.g, the birth times of the first and second child, the times at which a new user creates an account and makes the first purchase on a website, and the entry and survival times of patients in a clinical trial. In these settings, the two times are not independent (the second occurs after the first), yet it is still of interest to determine whether there exists significant dependence {\em beyond} their ordering in time. We refer to this notion as "quasi-(in)dependence". For instance, in a clinical trial, to avoid biased selection, we might wish to verify that recruitment times are quasi-independent of survival times, where dependencies might arise due to seasonal effects. In this paper, we propose a nonparametric statistical test of quasi-independence. Our test considers a potentially infinite space of alternatives, making it suitable for complex data where the nature of the possible quasi-dependence is not known in advance. Standard parametric approaches are recovered as special cases, such as the classical conditional Kendall's tau, and log-rank tests. The tests apply in the right-censored setting: an essential feature in clinical trials, where patients can withdraw from the study. We provide an asymptotic analysis of our test-statistic, and demonstrate in experiments that our test obtains better power than existing approaches, while being more computationally efficient.

Tamara Fernandez, Nicolas Rivera, Wenkai Xu et al.

Survival Analysis and Reliability Theory are concerned with the analysis of time-to-event data, in which observations correspond to waiting times until an event of interest such as death from a particular disease or failure of a component in a mechanical system. This type of data is unique due to the presence of censoring, a type of missing data that occurs when we do not observe the actual time of the event of interest but, instead, we have access to an approximation for it given by random interval in which the observation is known to belong. Most traditional methods are not designed to deal with censoring, and thus we need to adapt them to censored time-to-event data. In this paper, we focus on non-parametric goodness-of-fit testing procedures based on combining the Stein's method and kernelized discrepancies. While for uncensored data, there is a natural way of implementing a kernelized Stein discrepancy test, for censored data there are several options, each of them with different advantages and disadvantages. In this paper, we propose a collection of kernelized Stein discrepancy tests for time-to-event data, and we study each of them theoretically and empirically; our experimental results show that our proposed methods perform better than existing tests, including previous tests based on a kernelized maximum mean discrepancy.

Tamara Fernandez, Arthur Gretton, David Rindt et al.

We introduce a general non-parametric independence test between right-censored survival times and covariates, which may be multivariate. Our test statistic has a dual interpretation, first in terms of the supremum of a potentially infinite collection of weight-indexed log-rank tests, with weight functions belonging to a reproducing kernel Hilbert space (RKHS) of functions; and second, as the norm of the difference of embeddings of certain finite measures into the RKHS, similar to the Hilbert-Schmidt Independence Criterion (HSIC) test-statistic. We study the asymptotic properties of the test, finding sufficient conditions to ensure our test correctly rejects the null hypothesis under any alternative. The test statistic can be computed straightforwardly, and the rejection threshold is obtained via an asymptotically consistent Wild Bootstrap procedure. Extensive investigations on both simulated and real data suggest that our testing procedure generally performs better than competing approaches in detecting complex non-linear dependence.

Tamara Fernandez, Nicolas Rivera

Weighted log-rank tests are arguably the most widely used tests by practitioners for the two-sample problem in the context of right-censored data. Many approaches have been considered to make weighted log-rank tests more robust against a broader family of alternatives, among them, considering linear combinations of weighted log-rank tests, and taking the maximum among a finite collection of them. In this paper, we propose as test statistic the supremum of a collection of (potentially infinite) weight-indexed log-rank tests where the index space is the unit ball in a reproducing kernel Hilbert space (RKHS). By using some desirable properties of RKHSs we provide an exact and simple evaluation of the test statistic and establish connections with previous tests in the literature. Additionally, we show that for a special family of RKHSs, the proposed test is omnibus. We finalise by performing an empirical evaluation of the proposed methodology and show an application to a real data scenario. Our theoretical results are proved using techniques for double integrals with respect to martingales that may be of independent interest.

Tamara Fernández, Nicolás Rivera, Yee Whye Teh

We introduce a semi-parametric Bayesian model for survival analysis. The model is centred on a parametric baseline hazard, and uses a Gaussian process to model variations away from it nonparametrically, as well as dependence on covariates. As opposed to many other methods in survival analysis, our framework does not impose unnecessary constraints in the hazard rate or in the survival function. Furthermore, our model handles left, right and interval censoring mechanisms common in survival analysis. We propose a MCMC algorithm to perform inference and an approximation scheme based on random Fourier features to make computations faster. We report experimental results on synthetic and real data, showing that our model performs better than competing models such as Cox proportional hazards, ANOVA-DDP and random survival forests.