Development, Evaluation of a Clinical Staging System for ALS
Development, Evaluation of a Clinical Staging System for ALS
Background Staging of disease severity is useful for prognosis, decision-making and resource planning. However, no commonly used, validated staging system exists for amyotrophic lateral sclerosis (ALS). Our purpose was to develop an ALS staging system (ALS Milano-Torino Staging) that captures the observed progressive loss of independence and function.
Methods Clinical milestones in ALS progression were defined by loss of independence in four key domains on the ALS Functional Rating Scale (ALSFRS): swallowing, walking/self-care, communicating and breathing. Stages were defined as follows: stage 0, functional involvement but no loss of independence on any domain; stages 1–4, number of domains in which independence was lost; and stage 5, death. Staging criteria were applied to patients enrolled in a Quality of Care in ALS (QOC) study; endpoints included function (ALSFRS), quality of life (QOL; Short Form-36) and health service costs. Between-stage transition probabilities were assessed in the QOC study and in a second clinical study of lithium carbonate in ALS.
Results 70/118 (59.3%) participants in the QOC study progressed to higher stages of disease at 12 months compared with their baseline stage. Functional (ALSFRS) and QOL measures were inversely related to disease stage. Health service costs were directly related to increasing disease stages from 0 to 4 (p<0.001). Probabilities for transitioning from a given stage at baseline in both studies were usually greatest for the next highest stage.
Conclusions The proposed ALS Milano-Torino Staging system correlates well with assessments of function, QOL and health service costs. Further studies are warranted to validate this system.
Amyotrophic lateral sclerosis (ALS) is an idiopathic neurodegenerative disease that affects motor neurons, typically leading to death within 3 years of symptom onset. ALS is characterised by a progressive loss of functions such as speech, swallowing, mobility and respiration. Functional rating scales such as the ALS Functional Rating Scale (ALSFRS) and ALSFRS–Revised (ALSFRS-R) are useful to measure functional decline and have been used to evaluate treatment effects on function in clinical trials. However, ALSFRS/ALSFRS-R may not fully capture the functional characteristics of later-stage ALS progression and there is no agreed-upon threshold at which a change in ALSFRS/ALSFRS-R score is viewed as an important transition point in functional status.
Definition of discrete stages of disease progression based on such clinical milestones can be a useful tool for prognosis, therapeutic decision-making, assessment of quality of care and resource allocation. A staging system also allows patients and caregivers to understand the disease and its clinical course better. In the case of ALS, a valid staging system should correlate with ALS disease progression and demarcate meaningful differences in quality of life (QOL) and economic burden. Although staging systems for ALS have been proposed, currently there is no commonly used system. The lack of a validated staging system for ALS makes it difficult to quantify the degree of clinical, socioeconomic or QOL impact of a therapeutic intervention.
We sought to develop an ALS staging system that captures the observed progressive loss of independence and function and to apply it to the evaluation of patients' clinical outcomes, QOL and costs in ALS.
Abstract and Introduction
Abstract
Background Staging of disease severity is useful for prognosis, decision-making and resource planning. However, no commonly used, validated staging system exists for amyotrophic lateral sclerosis (ALS). Our purpose was to develop an ALS staging system (ALS Milano-Torino Staging) that captures the observed progressive loss of independence and function.
Methods Clinical milestones in ALS progression were defined by loss of independence in four key domains on the ALS Functional Rating Scale (ALSFRS): swallowing, walking/self-care, communicating and breathing. Stages were defined as follows: stage 0, functional involvement but no loss of independence on any domain; stages 1–4, number of domains in which independence was lost; and stage 5, death. Staging criteria were applied to patients enrolled in a Quality of Care in ALS (QOC) study; endpoints included function (ALSFRS), quality of life (QOL; Short Form-36) and health service costs. Between-stage transition probabilities were assessed in the QOC study and in a second clinical study of lithium carbonate in ALS.
Results 70/118 (59.3%) participants in the QOC study progressed to higher stages of disease at 12 months compared with their baseline stage. Functional (ALSFRS) and QOL measures were inversely related to disease stage. Health service costs were directly related to increasing disease stages from 0 to 4 (p<0.001). Probabilities for transitioning from a given stage at baseline in both studies were usually greatest for the next highest stage.
Conclusions The proposed ALS Milano-Torino Staging system correlates well with assessments of function, QOL and health service costs. Further studies are warranted to validate this system.
Introduction
Amyotrophic lateral sclerosis (ALS) is an idiopathic neurodegenerative disease that affects motor neurons, typically leading to death within 3 years of symptom onset. ALS is characterised by a progressive loss of functions such as speech, swallowing, mobility and respiration. Functional rating scales such as the ALS Functional Rating Scale (ALSFRS) and ALSFRS–Revised (ALSFRS-R) are useful to measure functional decline and have been used to evaluate treatment effects on function in clinical trials. However, ALSFRS/ALSFRS-R may not fully capture the functional characteristics of later-stage ALS progression and there is no agreed-upon threshold at which a change in ALSFRS/ALSFRS-R score is viewed as an important transition point in functional status.
Definition of discrete stages of disease progression based on such clinical milestones can be a useful tool for prognosis, therapeutic decision-making, assessment of quality of care and resource allocation. A staging system also allows patients and caregivers to understand the disease and its clinical course better. In the case of ALS, a valid staging system should correlate with ALS disease progression and demarcate meaningful differences in quality of life (QOL) and economic burden. Although staging systems for ALS have been proposed, currently there is no commonly used system. The lack of a validated staging system for ALS makes it difficult to quantify the degree of clinical, socioeconomic or QOL impact of a therapeutic intervention.
We sought to develop an ALS staging system that captures the observed progressive loss of independence and function and to apply it to the evaluation of patients' clinical outcomes, QOL and costs in ALS.
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