arXiv subjects

Judith ter Schure

Publications and source records attributed to Judith ter Schure.

4 recordsLinked to original sources

arXiv2026

ALL-IN meta-analysis for flexibility and validity in prospective and retrospective evidence synthesis

ALL-IN meta-analysis was developed and first applied during the COVID-19 pandemic. While this setting inspired its name, ALL-IN can also benefit non-pandemic circumstances. Conventional meta-analysis loses its coverage when updated repeatedly over time and when the decisions to initiate new trials and synthesize them depend on the results within the meta-analysis (accumulation bias). ALL-IN meta-analysis is anytime-valid. In its simplest form, ALL-IN meta-analysis stays familiar to run and read based on forest plots with confidence intervals that are wider than standard ones. Within collaborative prospective meta-analysis, the payoff is flexibility and speed, with fast sharing of individual participant data or harmonized aggregate data. Outside of this setting, the payoff is validity, when the decisions that shape the evidence (when to stop trials and whether new ones start) are typically outside the control of the meta-analyst. On the one hand, ALL-IN meta-analysis becomes inefficient when there is a maximum sample size or a stopping rule that the meta-analyist can control. On the other hand, it enables adaptations for any evidence synthesis to halfway become living, prospective or even real-time on interim trial results, without complicating the statistics.

stat.AP↗

arXiv2026

Adaptive clinical trials based on design-optimal e-values with automatic curtailment: An application to single-arm trials with binary data

The e-value is gaining traction as a robust alternative to p-values and Bayes factors for quantifying statistical evidence. e-values are a promising method for adaptive clinical trials due to their anytime-validity: e-values ensure type I error rate control at any stopping time, facilitating repeated interim analyses, complex stopping rules, and valid inference under protocol deviations. The e-value literature focuses mostly on asymptotic optimality; however, sample sizes in clinical trials are often limited. To this end, we investigate e-value-based designs with finite-horizon optimality for single-arm multi-stage clinical trials with binary data. This setting is relevant in early-phase cancer trials, but it also facilitates an accessible introduction to the betting interpretation of e-values, which we use to construct e-values that either (1) maximize statistical power, or (2) minimize the expected sample size, with or without constraints on the minimum power. We construct these designs through (constrained) dynamic programming based on the currently observed e-value, the maximum sample size, and the pre-specified significance level. Using exact calculations, we show that, next to robustness, e-value-based designs can provide competitive operating characteristics to standard (non-)adaptive designs with and without futility stopping and outperform growth-rate-optimal e-values in finite samples. In addition, small e-values automatically indicate trial continuation is futile, e.g., an e-value of zero indicates the impossibility of an efficacy conclusion. Hence, e-value-based designs provide a viable alternative to the current state-of-the-art in single-arm binary trials, warranting extension to other adaptive clinical trial settings such as multi-arm multi-stage and response-adaptive designs.

stat.ME↗

arXiv2025

ALL-IN meta-analysis: breathing life into living systematic reviews and prospective meta-analyses

Science is justly admired as a cumulative process ("standing on the shoulders of giants"), yet scientific knowledge is typically built on a patchwork of research contributions without much coordination. This lack of efficiency has specifically been addressed in clinical research by recommendations against avoidable research waste and for living systematic reviews and prospective meta-analysis. We propose to further those recommendations with ALL-IN meta-analysis: Anytime Live and Leading INterim meta-analysis. ALL-IN provides meta-analysis based on e-values and anytime-valid confidence intervals that can be updated at any time - reanalyzing after each new observation while retaining type-I error and coverage guarantees, live - no need to prespecify the looks, and leading - in the decisions on whether individual studies should be initiated, stopped or expanded, the meta-analysis can be the leading source of information without losing validity to accumulation bias. The analysis design requires no information about the trial sample sizes or the number of trials eventually included. So ALL-IN meta-analysis can be applied retrospectively as well as prospectively, to evaluate the evidence once or sequentially. Because the intention of the analysis does not change the validity of the results, the results of the analysis can change the intentions ('optional stopping' and 'optional continuation' based on the results so far). On the one hand: any analysis can be turned into a living one, or even become prospective and real-time by updating with new trial data and including interim data from trials that are still ongoing - without any changes in the cut-offs for testing or the method for interval estimation. On the other hand: no stopping rule needs to be enforced for the analysis to remain valid, so a prospective meta-analysis can be a bottom-up collaboration [...]

stat.ME↗

arXiv2019

Accumulation Bias in Meta-Analysis: The Need to Consider Time in Error Control

Studies accumulate over time and meta-analyses are mainly retrospective. These two characteristics introduce dependencies between the analysis time, at which a series of studies is up for meta-analysis, and results within the series. Dependencies introduce bias --- Accumulation Bias --- and invalidate the sampling distribution assumed for p-value tests, thus inflating type-I errors. But dependencies are also inevitable, since for science to accumulate efficiently, new research needs to be informed by past results. Here, we investigate various ways in which time influences error control in meta-analysis testing. We introduce an Accumulation Bias Framework that allows us to model a wide variety of practically occurring dependencies, including study series accumulation, meta-analysis timing, and approaches to multiple testing in living systematic reviews. The strength of this framework is that it shows how all dependencies affect p-value-based tests in a similar manner. This leads to two main conclusions. First, Accumulation Bias is inevitable, and even if it can be approximated and accounted for, no valid p-value tests can be constructed. Second, tests based on likelihood ratios withstand Accumulation Bias: they provide bounds on error probabilities that remain valid despite the bias. We leave the reader with a choice between two proposals to consider time in error control: either treat individual (primary) studies and meta-analyses as two separate worlds --- each with their own timing --- or integrate individual studies in the meta-analysis world. Taking up likelihood ratios in either approach allows for valid tests that relate well to the accumulating nature of scientific knowledge. Likelihood ratios can be interpreted as betting profits, earned in previous studies and invested in new ones, while the meta-analyst is allowed to cash out at any time and advise against future studies.

stat.ME↗