Marshall R, Collins A, Escolar M, Jinnah HA, Klopstock T, Kruer M, Videnovic A, Robichaux-Viehoeve A, Swett L, Revicki D, Bender R, Lenderking W. Development of a Clinical Outcomes Assessment (COA) in Pantothenate-Kinase Associated Neurodegeneration (PKAN): item generation and clinimetric properties. Presented at the 2017 International Congress of Parkinson’s Disease and Movement Disorders; June 8, 2017. Vancouver, Canada. [abstract] Mov Disord. 2017 Jun; 32(suppl 2).

OBJECTIVE: To develop a clinical outcome assessment (COA) scale that measures key aspects of functioning and daily living in patients with pantothenate kinase-associated neurodegeneration (PKAN) for use in research, clinical, and regulatory settings.

BACKGROUND: PKAN is an autosomal recessive, neurodegenerative disorder with dominant dystonia, caused by a defective PanK2 enzyme, the rate-limiting step in Coenzyme A production. Fosmetpantotenate is under development as a replacement therapy. There are no validated rating scales in PKAN. A COA scale that assesses activities of daily living (ADL) in patients with PKAN from the patient’s and caregiver’s perspective was needed for use in clinical trials and for regulatory submissions.

METHODS: A conceptually driven, iterative, content-development process generated items for the scale, using the well-validated Unified Parkinson’s Disease Rating Scale (UPDRS) Part II as a starting reference. The PKAN-ADL scale was then administered by telephone interview to caregivers (n=25) and patients (n=1) twice over approximately two weeks, along with scales to assess construct validity: the Neuro-QoL mobility and dexterity item banks; the HUI2/3P-4 attributes Speech, Dexterity, Ambulation, and Pain; and the Stroke Aphasia Depression Questionnaire (SADQ).

RESULTS: Based on expert and caregiver opinion and clinical experience with the UPDRS II as relevant to PKAN, a 12-item PKAN-ADL scale was developed to capture multiple domains of daily function.

The PKAN-ADL scale demonstrated excellent internal consistency (alpha = 0.94) and excellent test-retest reliability between two interviews (ICC = 0.98). Only a few items had ceiling or floor effects (> 30%). The PKAN-ADL demonstrated good construct validity with the Neuro-QoL item banks (all rs > 0.90) and all HUI2/3P-4 attributes (r > 0.48). Divergent validity was demonstrated with the SADQ-10 (r = 0.04).

CONCLUSIONS: The PKAN-ADL scale was shown to have acceptable content validity for research in PKAN. The reliability of the scale is very good and findings provide evidence of construct validity. Overall results support the use of this scale as a COA in clinical trials for PKAN.