# Multivariate time series approaches to extract predictive asthma biomarkers from prospectively patient-collected diary data: a systematic review

## TL;DR

This systematic review evaluates methods to extract asthma biomarkers from patient-collected diary data and finds that higher variability in diary variables is linked to worse asthma outcomes.

## Contribution

The study systematically reviews multivariate time series approaches for deriving predictive asthma biomarkers from patient-collected diary data.

## Key findings

- Higher variability in diary variables is associated with increased asthma exacerbation risk and poor asthma control.
- Non-parametric methods are increasingly used to analyze complex diary variable behavior.
- Studies often lack robust reporting of model performance and risk of bias.

## Abstract

Longitudinal data are common in asthma studies, to assess asthma progression in patients and identify predictors of future outcomes, including asthma exacerbations and asthma control. Different methods can quantify temporal behaviour in prospective patient-collected diary variables to obtain predictive biomarkers of asthma outcomes. The aims of this systematic review were to evaluate methods for extracting biomarkers from longitudinally collected diary data in asthma and investigate associations between them and patient-reported outcomes (PROs) of patients with asthma.

Systematic review and narrative synthesis.

MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched for studies published between January 2000 and July 2023.

Included studies generated biomarkers from prospective patient-collected peak expiratory flow, symptom scores, reliever use and nocturnal awakenings, and evaluated their associations with asthma PROs, namely asthma exacerbations, asthma control, asthma-related quality of life and asthma severity.

Two independent reviewers used standardised methods to screen and extract data from included studies. Study quality and risk of bias were assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) and the Prediction model Risk Of Bias ASessment Tool (PROBAST), respectively.

24 full-text articles met the inclusion criteria and were included in the review. Generally, higher levels of variability in the diary variables were associated with poorer outcomes, especially increased asthma exacerbation risk, and poor asthma control. There was increasing interest in non-parametric methods to quantify complex behaviour of diary variables (6/24). TRIPOD and PROBAST highlighted a lack of consistent reporting of model performance measures and potential for model bias.

Prospectively patient-collected diary variables aid in generating asthma assessment tools, including surrogate endpoints, for clinical trials and predictive biomarkers of adverse outcomes, warranting remote monitoring. Studies consistently lacked robust reporting of model performance. Future research should use diary variable-derived biomarkers.