2021 journal article
Mapping of critical events in disease progression through binary classification: Application to amyotrophic lateral sclerosis
JOURNAL OF BIOMEDICAL INFORMATICS, 123.
author keywords: Disease progression; Timing of critical events; Binary classification; Amyotrophic lateral sclerosis; Prognosis; Kaplan-Meier analysis
MeSH headings : Amyotrophic Lateral Sclerosis; Disease Progression; Humans; Prospective Studies; Speech; Walking
TL;DR:
A novel binary classification approach to map scale scores into disease tollgates to describe disease progression leveraging standard/modified Kaplan-Meier analyses is developed and demonstrated by estimating progression pathways in amyotrophic lateral sclerosis.
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3. Good Health and Well-being
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16. Peace, Justice and Strong Institutions
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Source: Web Of Science
Added: November 1, 2021
The progression of many degenerative diseases is tracked periodically using scales evaluating functionality in daily activities. Although estimating the timing of critical events (i.e., disease tollgates) during degenerative disease progression is desirable, the necessary data may not be readily available in scale records. Further, analysis of disease progression poses data challenges, such as censoring and misclassification errors, which need to be addressed to provide meaningful research findings and inform patients.We developed a novel binary classification approach to map scale scores into disease tollgates to describe disease progression leveraging standard/modified Kaplan-Meier analyses. The approach is demonstrated by estimating progression pathways in amyotrophic lateral sclerosis (ALS). Tollgate-based ALS Staging System (TASS) specifies the critical events (i.e., tollgates) in ALS progression. We first developed a binary classification predicting whether each TASS tollgate was passed given the itemized ALSFRS-R scores using 514 ALS patients' data from Mayo Clinic-Rochester. Then, we utilized the binary classification to translate/map the ALSFRS-R data of 3,264 patients from the PRO-ACT database into TASS. We derived the time trajectories of ALS progression through tollgates from the augmented PRO-ACT data using Kaplan-Meier analyses. The effects of misclassification errors, condition-dependent dropouts, and censored data in trajectory estimations were evaluated with Interval Censored Kaplan Meier Analysis and Multistate Model for Panel Data.The approach using Mayo Clinic data accurately estimated tollgate-passed states of patients given their itemized ALSFRS-R scores (AUCs > 0.90). The tollgate time trajectories derived from the augmented PRO-ACT dataset provide valuable insights; we predicted that the majority of the ALS patients would have modified arm function (67%) and require assistive devices for walking (53%) by the second year after ALS onset. By the third year, most (74%) ALS patients would occasionally use a wheelchair, while 48% of the ALS patients would be wheelchair-dependent by the fourth year. Assistive speech devices and feeding tubes were needed in 49% and 30% of the patients by the third year after ALS onset, respectively. The onset body region alters some tollgate passage time estimations by 1-2 years.The estimated tollgate-based time trajectories inform patients and clinicians about prospective assistive device needs and life changes. More research is needed to personalize these estimations according to prognostic factors. Further, the approach can be leveraged in the progression of other diseases.