Executive Dir, Lead Epidemiologist Moderna Devon, Pennsylvania, United States
Background: Propionic acidemia (PA) and methylmalonic acidemia (MMA) are ultra-rare metabolic disorders1 where metabolic decompensation events (MDEs) may occur periodically, characterized by acute exacerbations of symptoms with hyperammonemia and/or/ metabolic acidosis, and usually often are triggered by infection, catabolic events, protein overload, or certain drugs.1 There is no validated measure of MDE severity in PA or MMA. Delphi surveys involve structured consensus-building with experts and are often used in healthcare research.2 Objective: To develop an MDE severity score in PA and MMA. Design/Methods: Five clinicians (US, n=3; Italy, n=1; Spain, n=1) experienced in treating patients with PA and MMA participated. In Round 1, clinicians provided vignettes describing different MDE severity levels in PA, rated the importance of factors associated with MDE severity (from 0 =“not at all important” to 5=“extremely important”), selected the three most important factors, and provided severity level definitions for each factor. Clinicians confirmed if their responses would also apply in the context of MMA. In Round 2, clinicians provided feedback on a proposed scale drafted based on Round 1 results. Round 2 was ongoing at the time of submission. Results: In Round 1, the most important factors for assessing MDE severity in PA, based on mean importance ratings, were elevated level of care during hospitalization (mean [standard deviation]: 4.8 [0.4]), extent of medical procedures needed to maintain control (4.8 [0.4]), and lab values (4.4 [0.5]) presenting signs/symptoms (3.8 [0.4]), medications/diet modification needed to maintain control (3.8 [1.3]), and presence of acute organ damage (3.8 [1.3]). Similarly, cIn round 2, clinicians most frequently selected extent of medical procedures needed to maintain control (n=4, 80%), elevated level of care during hospitalization (n=3, 60%), and lab values (n=3, 60%) as the three most important factors. Nearly all clinicians (75-100%) confirmed their responses would not change for MMA.
Conclusion(s): This study describes the development of a clinician tool to standardize measurement of MDE severity in patients with PA and MMA. The Delphi methodology helped achieve consensus on the most important factors for assessing MDE severity. The measure could be used in clinical trials or wider practice. Further validation of this measure is planned.
