Table 4.

Quality of life measures and cognitive screening measures in ALS

Tool	Description	Strengths	Limitations	Recommendations for best use in a clinical trial
ALSAQ-40 [52, 53]	40-item disease specific HRQoL. Many items similar to ALSFRS-R	A validated ALS-specific HRQoL measure developed in accordance with FDA PRO guidance	40 items may be too impractical for use in a clinical trial due to increased patient burden	Use as secondary endpoint Use in addition to a function measure to provide extra sensitivity in more severe disease
ALSAQ-5 [54]	5-item measure generated from the ALSAQ-40	Provides a quick measure of HRQoL with minimal patient burden	Shorter instrument lacks measurement precision of larger measures	Use when HRQoL is an exploratory endpoint May be a valid alternative to the ALSAQ-40 (i.e., reduced patient burden, costs)
ALSSQOL-20 (ALSSQOL-SF) [55]	20-item disease specific measure of global QOL reduced from the larger ALSQOL	Short administration time suitable for clinical use	Use is better in clinical care Focus is more on global QoL than HRQoL Only 2 bulbar items	Use in an interventional study to determine treatment effect if combined with an HRQoL measure
EQ-5D Self-report [56–58]	5-items on mobility, self-care, usual activities, pain/discomfort, anxiety/depression plus a self-report of current health	Quick, easy to complete Well validated measure very commonly used in clinical trials	Quick snapshot of patient’s current state of health but not specific to ALS	Use when a health economics outcome is required or if general HRQoL is a secondary or exploratory endpoint
WHOQOL-BREF [59]	Recently validated, self-reported 26-item generic measure of QoL. Domains include physical health, social relationships, and environment	Quick, easy to complete High compliance reported in ALS Available in 19 different languages High reliability and construct validity Enables comparisons between ALS conditions and general population Interval level measurement (Rasch)	Social domain showed an unsatisfactory fit to the Rasch model Generic measure, may not capture QoL items specific to ALS patients Limited use data in ALS patients Limited longitudinal validity data	Use for parametric analysis and for comparison with other conditions or general populations
Neuro-QoL [24]	Short form measures of functioning, ADLS Self/proxy report, 6–8 items	Very well developed and validated function and ADL measures (FDA PRO guidance) in a population of patients with neurodegenerative diseases including ALS	Not feasible to include all the individual measures to assess overall functioning Limited validity data in ALS specific populations	Another HRQoL option to the ALSAQ-20 Select the appropriate function / symptom measure for highest treatment impact Secondary or exploratory measure of HRQOL to supplement a primary function measure
PROMIS-10 Global Health [24, 60]	Self-reported short form generic Global Health measure of mental and physical health	Well developed and validated Simple, easy to administer Provides mental and physical health scores	May be too general for use in an ALS population when other disease specific HRQoL measures exist Limited validity data in ALS specific populations	Use for quick global measure of HRQoL rather than disease specific for ALS (secondary or exploratory measure) Can be used in collaboration with NeuroQoL measures (fatigue)
ALS Cognitive Behavior Screen (ALS-CBS) [63–65]	Clinician assessed, 10-item cognitive section and 18-item, caregiver-rated behavioral section to identify patients who have cognitive or behavioral changes suggestive of frontal temporal dementia (FTD)	Validated against neuropsychological tests Can distinguish between cognitively impaired and non-impaired patients Accommodates decline in motor functioning Caregiver/self-reported behavior section Administration time < 10 min	Requires health professional for assessment of cognitive section which incurs added expense Test–retest not established Does not assess language or social cognition Behavioral component may not capture mild behavioral change	Use as initial screening of cognitive or behavioral changes within the population that might affect assessment of disease severity and progression and potentially confound response to therapy
Edinburgh Cognitive and Behavioral ALS Screen (ECAS) [61, 66–68]	ECAS-cognitive screen comprises 16 items divided into ALS-specific subscale and a non-ALS-specific subscale. ECAS-behavioral screen includes 5 domains of behavior	Validated against a battery of neuropsychological tests Can provide early identification of cognitive and behavioral changes Accommodates decline in motor functioning Assesses language and social cognition, may be suitable for patients with bulbar disability	Guidelines prefer that a neuropsychologist administer or supervise ECAS administration (added expense) 45 min + administration time Behavioral component requires interviewing the caregiver May not be feasible in clinical trials due to increased patient burden	Use for screening cognitive or behavioral changes that might affect assessment of ALS disease severity and progression and potentially confound response to therapy Use when decline in functioning in more severe ALS patients may be confounded by neuropsychological impairment that could be related to FTD