Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework

Abstract

Background and objectives: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework.

Methods: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage.

Results: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework.

Discussion: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.

Figure 1. PRISMA Flow Diagram of Included Studies

ALS = amyotrophic lateral sclerosis; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PROM = patient-reported outcome measure.

Figure 2. Comprehensive Conceptual Framework of Health-Related Quality of Life in Amyotrophic Lateral Sclerosis (QuALS)

Ovals with a solid line indicate where the concept covered by a subtheme was originally included in the EQ Health and Wellbeing instrument (EQ-HWB) framework. This includes subthemes that have incurred minor changes (e.g., to the title to include additional aspects or reframe the concept). Ovals with a dashed line indicate a new concept for amyotrophic lateral sclerosis that was added as a result of extraction or Patient and Public Involvement and Engagement (PPIE) feedback. An asterisk indicates a subtheme that was amended specifically as a result of PPIE feedback.

Figure 3. Proportion of PROMs Assessing the 3 High-Level Domains of HRQoL

ALS = amyotrophic lateral sclerosis; HRQoL = health-related quality of life; PROM = patient-reported outcome measure.