The BEAT-CF Causal Model: A model for guiding the design of trials and observational analyses of cystic fibrosis exacerbations

TL;DR

The paper introduces the BEAT-CF causal model, a Bayesian network designed to guide clinical trial design and analysis for cystic fibrosis exacerbations, integrating expert knowledge to improve understanding and management.

Contribution

It presents a novel causal model (DAG and Bayesian network) for CF exacerbations, developed with expert input, to inform trial design and causal inference in CF management.

Findings

Developed a DAG capturing CF exacerbation pathophysiology

Provided a transparent framework for trial design and analysis

Enabled causal inference in CF exacerbation studies

Abstract

Loss of lung function in cystic fibrosis (CF) occurs progressively, punctuated by acute pulmonary exacerbations (PEx) in which abrupt declines in lung function are not fully recovered. A key component of CF management over the past half century has been the treatment of PEx to slow lung function decline. This has been credited with improvements in survival for people with CF (PwCF), but there is no consensus on the optimal approach to PEx management. BEAT-CF (Bayesian evidence-adaptive treatment of CF) was established to build an evidence-informed knowledge base for CF management. The BEAT-CF causal model is a directed acyclic graph (DAG) and Bayesian network (BN) for PEx that aims to inform the design and analysis of clinical trials comparing the effectiveness of alternative approaches to PEx management. The causal model describes relationships between background risk factors, treatments, and pathogen colonisation of the airways that affect the outcome of an individual PEx episode. The key factors, outcomes, and causal relationships were elicited from CF clinical experts and together represent current expert understanding of the pathophysiology of a PEx episode, guiding the design of data collection and studies and enabling causal inference. Here, we present the DAG that documents this understanding, along with the processes used in its development, providing transparency around our trial design and study processes, as well as a reusable framework for others.