Search arXivSearch

arXiv · 2307.06552

Learn-As-you-GO (LAGO) Trials: Optimizing Treatments and Preventing Trial Failure Through Ongoing Learning

Abstract

It is well known that changing the intervention package while a trial is ongoing does not lead to valid inference using standard statistical methods. However, it is often necessary to adapt, tailor, or tweak a complex intervention package in public health implementation trials, especially when the intervention package does not have the desired effect. This article presents conditions under which the resulting analyses remain valid even when the intervention package is adapted while a trial is ongoing. Our results on such Learn-As-you-GO (LAGO) studies extend the theory of LAGO for binary outcomes following a logistic regression model (Nevo, Lok and Spiegelman, 2021) to LAGO for continuous outcomes under flexible conditional mean model. We derive point and interval estimators of the intervention effects and ensure the validity of hypothesis tests for an overall intervention effect. We develop a confidence set for the optimal intervention package, which achieves a pre-specified mean outcome while minimizing cost, and confidence bands for the mean outcome under all intervention package compositions. This work will be useful for the design and analysis of large-scale intervention trials where the intervention package is adapted, tailored, or tweaked while the trial is ongoing.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ante Bing, Donna Spiegelman, Daniel Nevo, Judith J. Lok. 2023-07-13. Learn-As-you-GO (LAGO) Trials: Optimizing Treatments and Preventing Trial Failure Through Ongoing Learning. https://arxiv.org/abs/2307.06552

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Generalised Covariances and Correlations

The covariance of two random variables measures the average joint deviations from their respective means. We generalise this well-known measure by replacing the means with other statistical functionals such as quantiles, expectiles, or thresholds. Deviations from these functionals are defined via generalised errors, typically induced through identification or moment functions. As a normalised measure of dependence, a generalised correlation is constructed. Replacing the common Cauchy--Schwarz normalisation by a novel Fréchet--Hoeffding normalisation, we obtain attainability of the entire interval $[-1, 1]$ for any given marginal distributions. We uncover favourable properties of these new dependence measures and establish consistent estimators. The families of quantile and threshold correlations make it possible to measure local dependence and give rise to function-valued distributional correlations, exhibiting the entire dependence structure. Quantile correlations also lead to tail correlations, new measures of tail dependence, closely related to and refining classical coefficients of tail dependence. Finally, we construct summary covariances (correlations), a class of regional or global dependence measures, which arise as (normalised) weighted averages of distributional covariances. We retrieve covariance, Pearson and Spearman correlation as special cases. The usefulness of our new dependence measures is illustrated on demographic data from the Panel Study of Income Dynamics.

stat.ME

Compressive Bayesian non-negative matrix factorization for mutational signatures analysis

Non-negative matrix factorization (NMF) is a popular tool for dimensionality reduction, especially for count matrices. However, inferring an appropriate number of factors is challenging. Existing approaches based on information criteria or nonparametric sparsity-inducing priors tend to be computationally burdensome or highly sensitive to prior choices. Moreover, theoretical properties of the posterior distribution of Poisson NMF parameters endowed with shrinkage priors remain under-explored. This paper introduces a novel Bayesian NMF method that automatically infers the number of factors while also incorporating information on the latent factors from previous studies. This is achieved using compressive hyperpriors, which are hierarchical priors that make the sample-specific weights of unneeded factors concentrate near zero in the posterior. We provide novel distribution theory for posterior inference to elucidate this shrinkage mechanism, both in finite samples and asymptotically. We apply our method to mutational signatures analysis in cancer genomics, in simulations and on real data from breast cancer. Compared to state-of-the-art alternatives, our method is more robust to mild overdispersion and improves detection and estimation of signatures aligned with prior information.

stat.ME

On Relative Cumulative Residual Information Measure and Its Applications

We develop a relative cumulative residual information measure (RCRI) that aims to quantify the divergence between two survival functions. The dynamic relative cumulative residual information (DRCRI) measure is also introduced. We establish some characterization results under the assumption of the proportional hazards model. Additionally, we obtained the non-parametric estimators of RCRI and DRCRI measures based on the kernel density type estimator for the survival function. The effectiveness of the estimators are assessed through an extensive Monte Carlo simulation study. We consider data from the third Gaia data release (Gaia DR3) to demonstrate the use of the proposed measure. For this study, we have collected epoch photometry data for the objects Gaia DR3 4111834567779557376 and Gaia DR3 5090605830056251776. RCRI-based image analysis is conducted using Chest X-ray data from the publicly available dataset.

stat.ME