A stochastic mixed effects model to assess treatment effects and fluctuations in home-measured peak expiratory flow and the association with exacerbation risk in asthma
Artikel i vetenskaplig tidskrift, 2022

Home-based measures of lung function, inflammation, symptoms, and medication use are frequently collected in respiratory clinical trials. However, new statistical approaches are needed to make better use of the information contained in these data-rich variables. In this work, we use data from two phase III asthma clinical trials demonstrating the benefit of benralizumab treatment to develop a novel longitudinal mixed effects model of peak expiratory flow (PEF), a lung function measure easily captured at home using a hand-held device. The model is based on an extension of the mixed effects modeling framework to incorporate stochastic differential equations and allows for quantification of several statistical properties of a patient's PEF data: the longitudinal trend, long-term fluctuations, and day-to-day variability. These properties are compared between treatment groups and related to a patient's exacerbation risk using a repeated time-to-event model. The mixed effects model adequately described the observed data from the two clinical trials, and model parameters were accurately estimated. Benralizumab treatment was shown to improve a patient's average PEF level and reduce long-term fluctuations. Both of these effects were shown to be associated with a lower exacerbation risk. The day-to-day variability was neither significantly affected by treatment nor associated with exacerbation risk. Our work shows the potential of a stochastic model-based analysis of home-based lung function measures to support better estimation and understanding of treatment effects and disease stability. The proposed analysis can serve as a complement to descriptive statistics of home-based measures in the reporting of respiratory clinical trials.

Författare

Jacob Leander

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

AstraZeneca R&D

Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik

Mats Jirstrand

Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik

Ulf Eriksson

AstraZeneca R&D

Robert Palmér

AstraZeneca R&D

CPT: Pharmacometrics and Systems Pharmacology

21638306 (eISSN)

Vol. 11 2 212-224

Hierarkiska mixed effects-modeller av dynamiska system

Stiftelsen för Strategisk forskning (SSF) (AM13-0046), 2014-04-01 -- 2019-06-30.

Stiftelsen för Strategisk forskning (SSF) (AM13-0046), 2019-09-01 -- 2020-06-30.

Ämneskategorier

Lungmedicin och allergi

Sannolikhetsteori och statistik

DOI

10.1002/psp4.12748

Mer information

Senast uppdaterat

2022-04-05