The goal attainment scale in primary mitochondrial disease: Construct validity and lessons learned from a randomized...

Area of Science:

• Mitochondrial disease research
• Clinical trial methodology
• Patient-reported outcomes

Background:

• Primary mitochondrial diseases (PMD) are rare, heterogeneous disorders affecting oxidative phosphorylation, with diverse symptoms.
• Current outcome measures for adults with PMD lack consensus on reflecting function, activities, and participation.
• The Goal Attainment Scale (GAS) offers a personalized approach, but its validity and standardization in trials require investigation.

Purpose of the Study:

• To assess the construct validity of the Goal Attainment Scale (GAS) in a clinical trial for adults with primary mitochondrial diseases (PMD).
• To compare GAS with the Canadian Occupational Performance Measure (COPM) and other outcome measures.
• To provide guidance for the standardized application of GAS in future PMD trials.

Main Methods:

• Retrospective analysis of data from a Phase IIA cross-over trial of sonlicromanol (KH176) in 18 adult m.3243 A>G patients.
• Categorization of GAS goals using the World Health Organization International Classification of Functioning, Disability and Health (ICF).
• Evaluation of GAS validity through comparison with other outcome measures and assessment of implementation quality using 17 criteria.

Main Results:

• GAS goals primarily focused on fatigue or lack of energy (85%).
• GAS demonstrated weak to moderate negative correlations with fatigue (Checklist Individual Strength) and depression (Beck Depression Inventory-II) measures.
• Moderate correlations were found between GAS and COPM scores; limited correlations with other measures like the 6-min walk test.
• Only 35% of GAS implementation criteria were fully met, indicating suboptimal application.

Conclusions:

• GAS shows preliminary construct validity for capturing patient-relevant changes in fatigue and depressive symptoms in adults with PMD.
• GAS demonstrated limited overlap with conventional outcome measures, highlighting its unique patient-centered focus.
• Suboptimal implementation necessitates standardized methodology and further validation for GAS to be a robust outcome measure in PMD trials.