In patients with systemic mastocytosis (SM), the biweekly total symptom score (TSS) of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) is reliable and has demonstrated the ability to differentiate among disease subgroups.
A prospective, observational, noninterventional study was conducted that used an online survey of US patients with indolent systemic mastocytosis (ISM) or smoldering systemic mastocytosis (SSM) who had completed patient-reported outcome evaluations over 15 days. Findings from the analysis were published in Orphanet Journal of Rare Diseases.
Unlike individuals with other types of SM, those with ISM typically have a normal or near-normal life-expectancy, although they often experience severe, life-limiting symptoms. Similar symptomatology has been observed among patients with ISM and those with SSM, but individuals in the latter subgroup have a higher burden of mast cells. Limited therapeutic options are available for patients with SM, with no treatments having been approved to date for those with ISM.
Recognizing that the need exists for well-defined, reliable patient-reported outcome questionnaires to evaluate clinical benefits associated with ISM treatments, the researchers developed the ISM-SAF. In the current study, they sought to conduct an exploratory psychometric assessment of scores generated by the tool regarding score variability, reliability, missingness, distribution, and construct-related validity in an effort to support the trustworthiness of ISM-SAF scores.
Further, they sought to determine an ISM-SAF TSS cutoff value that could differentiate patients with moderate to severe disease symptoms from those with less severe symptoms. In this manner, the ISM-SAF could screen patient eligibility for clinical studies designed to evaluate improvement according to a minimum level of symptom severity.
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One hundred three participants with a self-reported diagnosis of ISM or SSM were enrolled in the study. Overall, 81.6% of the cohort were female and 98.1% were White. The mean patient age was 50.2±12.6 years.
The analysis populations comprised 2 patient cohorts: (1) all patients who self-reported a diagnosis of ISM or SSM (“Self-Reported Diagnosis Cohort”; n=45) and (2) the subset of participants who provided a validated diagnosis of SSM or ISM through medical documentation (“Medically Documented Diagnosis Cohort”; n=58).
All participants completed the ISM-SAF on a daily basis as an electronic diary. A subset of individuals who exhibited no changes in the Patient Global Impression of Severity from day 1 to day 15 was used to assess the test-retest validity of ISM-SAF scores.
Results of the study revealed that psychometric analysis backed the trustworthiness of the biweekly TSS, which proved to be reliable (intraclass correlation coefficient [ICC], >0.9); to be construct-valid; and to possess the ability to differentiate among clinically distinct patient populations based on the Patient Global Impression of Severity, the 12-Item Short-Form Health Survey, and the Mastocytosis Quality of Life Questionnaire (P <.001).
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According to receiver operating characteristic analyses, a biweekly TSS of 21 to 28 should be sufficient for defining patients who report experiencing the most severe symptoms of ISM.
The authors concluded, “A [cutoff] value of 28 is a conservative threshold that can be used for screening purposes in future clinical studies to identify patients with at least moderate severity of ISM symptoms.”
Shields AL, Taylor F, Lamoureux RE, et al. Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF©) and determination of a threshold score for moderate symptoms. Orphanet J Rare Dis. 2023;18:69. doi:10.1186/s13023-023-02661-1