Impact of Potential Symptoms and Risks Associated with Acid Sphingomyelinase Deficiency on Patients and Caregivers: A Best-Worst Scaling Study

Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and potentially fatal disease affecting major organs; its symptoms present heterogeneously. Data on the most bothersome symptoms for patients with ASMD types B or A/B and their caregivers or parents are limited. We conducted a survey to quantify the relative impact of potential ASMD symptoms and risks for patients and parents/caregivers. Twenty respondents, recruited via National Niemann-Pick Disease Foundation (United States) and Niemann-Pick United Kingdom, took a preference survey: 11 patients who had a self-reported diagnosis of ASMD types B or A/B and 9 parents who had a child with ASMD types B or A/B. Using object-case best-worst scaling, we explored the most and least bothersome among a set of 15 ASMD symptoms/risks selected based on clinical input and qualitative research with patients and caregivers. In 15 experimentally designed questions containing five items each, respondents ranked the symptoms/risks, irrespective of their experiences with them. Data were analyzed using a conditional multinomial logit model. Patients reported constant abdominal pain, severe pain in bones and joints, and severe fatigue to be the most bothersome potential symptoms or risks, followed by a chance of bleeding in the spleen. The next most bothersome potential symptom was constant shortness of breath. Easy bruising and noticeable abdominal enlargement were among the least bothersome symptoms. The most bothersome symptom for parents was bleeding in the spleen. Patients and parents had similar perceptions of the most bothersome potential symptoms/risks. Despite the small sample size typical of rare disease studies, understanding patient preferences is important for such diseases and can inform shared decision-making.