The Case for Controls: Identifying outbreak risk factors through case-control comparisons

TL;DR

This paper advocates for using case-control hypothesis testing as a robust epidemiological framework to identify outbreak risk factors, enhancing predictive and preventive strategies.

Contribution

It introduces a structured case-control approach for outbreak investigation, emphasizing hypothesis testing and multidisciplinary interrogation for better outbreak prevention.

Findings

Case-control framework improves outbreak risk factor identification.

Iterative multidisciplinary interrogation aids in discovering key outbreak factors.

Applying this approach promotes evidence-based outbreak response strategies.

Abstract

Investigations of infectious disease outbreaks often focus on identifying place- and context-dependent factors responsible for emergence and spread, resulting in phenomenological narratives ill-suited to developing generalizable predictive and preventive measures. We contend that case-control hypothesis testing is a more powerful framework for epidemiological investigation. The approach, widely used in medical research, involves identifying counterfactuals, with case-control comparisons drawn to test hypotheses about the conditions that manifest outbreaks. Here we outline the merits of applying a case-control framework as epidemiological study design. We first describe a framework for iterative multidisciplinary interrogation to discover minimally sufficient sets of factors that can lead to disease outbreaks. We then lay out how case-control comparisons can respectively center on pathogen(s), factor(s), or landscape(s) with vignettes focusing on pathogen transmission. Finally, we consider how adopting case-control approaches can promote evidence-based decision making for responding to and preventing outbreaks.