Development of an Investigator Global Assessment of Severity in Propionic Acidemia
Author(s)
Longo N1, Sikirica V2, Grunewald S3, Moshkovich O4, Dionisi-Vici C5, Vockley J6, Bellenger MA4, de las Heras J7, Banerjee G8, Schwartz EJ4
1University of Utah, Salt Lake City, UT, USA, 2Moderna, Inc., Cambridge, MA, USA, 3Metabolic Department, Great Ormond Street Hospital NHS Foundation Trust and Institute of Child Health, NIHR Biomedical Research Centre (BRC), University College London, London, UK, 4ICON Insights, Evidence and Value, Raleigh, NC, USA, 5Division of Metabolic Diseases, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy, 6University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 7Hospital Universitario Cruces, Biobizkaia Health Research Institute and University of the Basque Country, Bilbao, Spain, 8Moderna, Inc., Watertown, MA, USA
Presentation Documents
OBJECTIVES: To develop an Investigator Global Assessment of Severity (IGA-S) in propionic acidemia (PA).
METHODS: A pre-survey questionnaire was disseminated to clinicians experienced in treating patients with PA. It included questions on their patients’ characteristics, important factors for assessing PA severity, impact of intercurrent events on metabolic decompensation events (MDEs), core signs/symptoms, lab results/biomarkers, and treatments. This informed an iterative two-round online Delphi survey in which six clinicians were asked to rate importance of factors in evaluating PA severity, on a scale from 1=not at all important to 5=extremely important, select three most important factors, assess the likelihood of the factors to change with treatment, and provide severity level definitions. The IGA-S was drafted based on the Delphi findings and refined during follow-up discussions with the clinicians.
RESULTS: Clinicians were based in the US (n=2), UK (n=2), Italy (n=1), and Spain (n=1). Following the second-round survey, the most important factors for evaluating PA severity were frequency of MDEs (mean [standard deviation]: 5.0 [0]), duration of MDEs (4.3 [1.2]), age of onset (4.2 [0.4]), biomarkers/lab values (3.7 [0.5]), cognitive impairment (3.5 [0.5]), and dietary restrictions (3.0 [1.3]). Clinicians selected frequency of MDEs (n=4, 67%) and age of onset (n=2, 33%) as the single most important factors. Follow-up discussions with the clinicians refined the items as: age of disease onset, frequency of MDEs, duration of MDEs, indicators of MDEs, long-term disease burden, and dietary restrictions. Items have weighted scoring reflecting their relative importance.
CONCLUSIONS: This study developed the first IGA-S for use in PA, allowing for standardization of severity ratings from the clinician's perspective. Delphi methodology helped achieve clinician consensus on those factors most important in evaluating PA severity. The IGA-S may be used as an assessment in clinical trials in PA or as an anchor for the psychometric validation of other measures in PA.
Conference/Value in Health Info
Value in Health, Volume 26, Issue 11, S2 (December 2023)
Code
CO67
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Rare & Orphan Diseases