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Publication

On null hypotheses in survival analysis

Pal Christie Ryalen, Mats Julius Stensrud
2019
Journal paper

Abstract

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. As an illustration, we apply our tests to evaluate the effect of adjuvant chemotherapies in patients with colon cancer, using data from a randomized controlled trial.

Official source

https://infoscience.epfl.ch/record/280939?ln=en

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2018

In multiple testing problems where the components come from a mixture model of noise and true effect, we seek to first test for the existence of the non-zero components, and then identify the true alternatives under a fixed significance level

\alpha

. Two parameters, namely the fraction of the non-null components

\varepsilon

and the size of the effects

\mu

, characterise the two-point mixture model under the global alternative. When the number of hypotheses

m

goes to infinity, we are interested in an asymptotic framework where the fraction of the non-null components is vanishing, and the true effects need to be sizable to be detected. Donoho and Jin give an explicit form of the asymptotic detectable boundary based on the Gaussian mixture model under the classic calibration of the parameters of the mixture model. We prove the analogous results for the Cauchy mixture distribution as an example heavy-tailed case. This requires a different formulation of the parameters, which reflects the added difficulties. We also propose a multiple testing procedure based on a filtering approach that can discover the true alternatives. Benjamini and Hochberg (BH) compare the observed

p

-values to a linear threshold curve and reject the null hypotheses from the minimum up to the last up-crossing, and prove the false discovery rate (FDR) is controlled. However, there is an intrinsic difference in heavy-tailed settings. Were we to use the BH procedure we would get a highly variable positive false discovery rate (pFDR). In our study we analyse the distribution of the

p

-values and devise a new multiple testing procedure to combine the usual case and the heavy-tailed case based on the empirical properties of the

p

-values. The filtering approach is designed to eliminate most

p

-values that are more likely to be uniform, while preserving most of the true alternatives. Based on the filtered

p

-values, we estimate the mode

\vartheta

and define the rejection region

\mathscr{R}(\vartheta, \delta)=\left[ \vartheta -\delta/2, \vartheta +\delta/2 \right]

such that the most informative

p

-values are included. The length

\delta

is chosen by controlling the data-dependent estimation of FDR at a desired level.

EPFL2021

\alpha