Personalized Predictions from Population Level Experiments: A Study on Alzheimer's Disease

TL;DR

This paper introduces the synthetic nearest neighbors (SNN) estimator to infer individual patient outcomes from population-level RCT data, addressing missing data issues in Alzheimer's clinical trials and enabling personalized predictions.

Contribution

The paper presents SNN, a novel, interpretable method for imputing missing data and predicting patient outcomes, advancing personalized medicine in clinical trial analysis.

Findings

SNN outperforms standard methods in Alzheimer's Phase 3 trial data

SNN effectively imputes missing outcomes due to treatment discontinuation

SNN enables personalized outcome predictions under various missing data scenarios

Abstract

The purpose of this article is to infer patient level outcomes from population level randomized control trials (RCTs). In this pursuit, we utilize the recently proposed synthetic nearest neighbors (SNN) estimator. At its core, SNN leverages information across patients to impute missing data associated with each patient of interest. We focus on two types of missing data: (i) unrecorded outcomes from discontinuing the assigned treatments and (ii) unobserved outcomes associated with unassigned treatments. Data imputation in the former powers and de-biases RCTs, while data imputation in the latter simulates "synthetic RCTs" to predict the outcomes for each patient under every treatment. The SNN estimator is interpretable, transparent, and causally justified under a broad class of missing data scenarios. Relative to several standard methods, we empirically find that SNN performs well for the above two applications using Phase 3 clinical trial data on patients with Alzheimer's Disease. Our findings directly suggest that SNN can tackle a current pain point within the clinical trial workflow on patient dropouts and serve as a new tool towards the development of precision medicine. Building on our insights, we discuss how SNN can further generalize to real-world applications.