Confirmatory psychometric evaluation of the axillary sweating daily diary: a validated patient-reported outcome measure to assess axillary hyperhidrosis sweating severity

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Confirmatory psychometric evaluation of the axillary sweating daily diary: a validated patient-reported outcome measure to assess axillary hyperhidrosis sweating severity

Presenters: Glaser DA1,1 Hebert AA2, Fehnel S3, DiBenedetti D3, Nelson L3, Drew J4, Pariser DM5

Affiliations: 1Saint Louis University, St. Louis, MO; 2UTHealth McGovern Medical School at Houston, Houston, TX; 3RTI Health Solutions, Research Triangle Park, NC; 4Dermira, Inc., Menlo Park, CA; 5Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA

Background/Objective: Hyperhidrosis affects an estimated 4.8 percent of the United States population; approximately three-quarters of patients experience negative psychological effects, with anxiety and depression occurring over

3.5?times more frequently in people with hyperhidrosis than in people without it. Despite high prevalence and burden of disease, few disease-specific outcome measures are available. The Hyperhidrosis Disease Severity Scale (HDSS) is widely used in clinical studies and well understood in clinical practice; however, it does not conform to current regulatory standards for patient-reported outcome (PRO) measures used to support product approvals and labeling. The four-item Axillary Sweating Daily Diary (ASDD) and a child-specific two?item version (ASDD-C) for use in patients between 9 and 16 years of age were developed according to current regulatory standards. The ASDD/ASDD-C axillary sweating severity item (Item 2) was specifically developed for use as an endpoint in clinical trials in support of approval and labeling (and also as a useful clinical parameter). In addition to the ASDD, patients 16 years of age or younger were asked to complete six Weekly Impact Items designed to assess the impact and bother of hyperhidrosis on daily activities and a single?item Patient Global Impression of Change (PGIC) to assess overall change in sweating severity. Initial psychometric evaluation of the ASDD was conducted using data from a Phase II study of topical glycopyrronium tosylate (GT; formerly DRM04), an investigational treatment for primary axillary hyperhidrosis in patients nine years of age or older; results have been previously reported and provide preliminary support for the use of this measure to evaluate the efficacy of axillary hyperhidrosis treatment in clinical trials. In this study, we aimed to confirm and extend the psychometric evidence supporting ASDD/ASDD-C axillary sweating severity item (Item 2) based on pooled data from two Phase III clinical trials of GT: ATMOS-1

(DRM04-HH04; NCT02530281) and ATMOS-2 (DRM04-HH05; NCT02530294)

Methods: ATMOS-1 and ATMOS-2 were Phase III, multicenter (ATMOS-1: sites in the United States and Germany; ATMOS-2: sites in United States), parallel-group, four-week, double-blind clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to GT or vehicle. Eligible patients were at least nine years of age (patients <16 years were only recruited at United States sites) and had primary axillary hyperhidrosis for at least six months, with gravimetrically measured sweat production of at least 50mg per five minutes in each axilla, ASDD/ASDD-C axillary sweating severity item (Item 2) score 4 or above, and Hyperhidrosis Disease Severity Scale (HDSS) Grade 3 or 4. ASDD/ASDD-C Item 2 responses and sweat production were assessed in two age groups (?9 years and ?16 years). ASDD/ASDD-C items were scored as a weekly average of daily responses; at least four days of daily data were required for analysis. Weekly Impact Items and PGIC were included to evaluate construct validity. Potential floor and ceiling effects and nonresponse bias were evaluated based on both summary statistics and graphical techniques. Test-retest reliability was evaluated through the computation of intraclass correlation coefficients (ICCs) between Week 3 and Week 4; a value of at least 0.70 was considered acceptable. Construct validity was evaluated at Week 4 based on correlations between ASDD/ASDD-C Item 2 and ASDD items related to the impact and bother of sweating (Items 3 and 4, respectively), HDSS, sweat production, and other PRO measures, as available. All statistical tests were two-tailed using a type I error rate of one percent (?=0.01).

Results. The pooled Phase III study population (n=697) included 665 patients who were at least 16 years of age and 32 patients aged 9 to 15 years of age. The response distribution for the ASDD/ASDD-C axillary sweating severity item (Item 2) demonstrated no floor or ceiling effect and no nonresponse bias. Construct validity was supported by strong correlations between ASDD Item 2 and the ASDD items addressing the impact and bother of axillary sweating (Items 3 and 4, respectively).

Test-retest reliability was supported by ICCs of 0.93 for both age subgroups, which is well above the 0.70 criterion and within the confidence interval (CI) of the Phase II estimate of 0.91 (95% CI: 0.87, 0.94. The ASDD/ASDD-C Item 2 responsiveness, or ability to detect change in sweating severity, was demonstrated by large effect sizes and correlations that were within the expected range for the change in ASDD/ASDD-C Item 2 and the change in the gravimetric measures of sweat production.

Conclusion: The current study confirms and extends the psychometric evidence supporting the

ASDD/ASDD?C as a new PRO measure developed according to current regulatory standards. The psychometric findings presented here continue to support use of the ASDD/ASDD-C axillary sweating severity item (Item 2) as an endpoint in assessing the efficacy of treatments for patients with axillary hyperhidrosis.

Funding/Disclosures: This study was funded by Dermira, Inc. Dee Anna Glaser is a consultant and investigator for Dermira, Inc. Adelaide A. Herbert is a consultant for Dermira, Inc. and employee of the University of Texas Medical School, Houston, which received compensation from Dermira, Inc. for study participation. Dana DiBenedetti, Lauren Nelson, and Sheri Fehnel are employees of RTI Health Solutions. Janice Drew is an employee of Dermira, Inc. David M. Pariser is a consultant and investigator for Dermira, Inc.