INTRODUCTION: Hyperhidrosis is estimated to affect 4.8% of the US population or 15.3 million Americans.1 Approximately three-quarters of patients experience negative impact on their psychological functions.1 Anxiety and depression are over 3.5-times more common among hyperhidrosis sufferers.2 Despite the high prevalence and impact of hyperhidrosis, few disease-specific measures for outcomes are available. While the Hyperhidrosis Disease Severity Scale (HDSS) has been widely used in clinical studies, this measure does not conform to FDA standards for patient-reported outcome (PRO) measures that can be used to support product approvals and labeling.3 The Axillary Sweating Daily Diary (ASDD) was developed in consultation with FDA and in consideration of the PRO guidance to measure the severity of axillary hyperhidrosis and its impact on daily activities for patients ≥16 years. A child-specific version of the instrument (ASDD-C) was similarly developed for assessment of sweating severity in patients ≥9 to <16 years of age.
METHODS: A preliminary ASDD item pool was drafted based on clinical expertise and literature review. These items were then refined based on iterative sets of qualitative interviews with patients (21 adults and 8 children) with axillary hyperhidrosis. Of the 4 items that comprise the ASDD, Item 2 assessed sweating severity and was specifically validated as an outcome measure for use as a primary endpoint in clinical trials. As such, this item was the focus of the psychometric evaluation using data from a phase 2 study of DRM04, an investigational treatment for primary axillary hyperhidrosis (DRM04-HH02, NCT02129660; N=102). Item 1 assessed the presence of underarm sweating and was a ‘gatekeeper’ question for Item 2 (ie, when Item 1 is answered “no,” Item 2 is skipped and scored as zero). Exploratory items included Item 3 to assess activity impairment and Item 4 to assess symptom bothersomeness. Two additional items (Items 5 and 6) assessed weekly and overall impact of treatment, respectively, and were included to evaluate construct validity. Standard methods were used to evaluate floor/ceiling effects, nonresponse bias, test-retest reliability, construct validity, and responsiveness. ASDD Item 2 was scored as a weekly average of daily responses; at least 4 days of daily data were required for analysis.
RESULTS: ASDD Item 2 demonstrated no floor/ceiling effect or nonresponse bias. Test-retest reliability was supported by an interclass correlation coefficient (ICC) of 0.91. The pattern of correlations between this measure and other efficacy measures collected in the phase 2 study supported construct validity, and known groups validity was demonstrated based on HDSS rating and gravimetric measurement of sweat production. The utility of ASDD to detect change in sweating severity was demonstrated by a large effect size (-2.2) and strong correlations between the change in Item 2 and comparator change scores.
CONCLUSIONS: Taken together, the rigorous development and validation of Item 2 of ASDD support the use of this measure to evaluate the efficacy of axillary hyperhidrosis treatment in clinical trials.
