Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis

Amy S. Paller; Gil Yosipovitch; Stephan Weidinger; Dana DiBenedetti; Diane Whalley; Abhijit Gadkari; Isabelle Guillemin; Haixin Zhang; Laurent Eckert; Jingdong Chao; Ashish Bansal; Chien Chia Chuang; Dimittri Delevry

doi:10.1007/s13555-022-00804-z

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis

Amy S. Paller^*, Gil Yosipovitch, Stephan Weidinger, Dana DiBenedetti, Diane Whalley, Abhijit Gadkari, Isabelle Guillemin, Haixin Zhang, Laurent Eckert, Jingdong Chao, Ashish Bansal, Chien Chia Chuang, Dimittri Delevry

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Introduction: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6–11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. Methods: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6–11 years with severe AD. These included test–retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. Results: The Worst Itch Scale consisted of two items asking about ‘worst itching’ experienced ‘last night’ and ‘today’. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. Conclusions: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6–11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3–4-point change in the Worst Itch Scale score. Trial Registration: NCT03345914. [MediaObject not available: see fulltext.].

Original language	English (US)
Pages (from-to)	2839-2850
Number of pages	12
Journal	Dermatology and Therapy
Volume	12
Issue number	12
DOIs	https://doi.org/10.1007/s13555-022-00804-z
State	Published - Dec 2022

Funding

Amy Paller has served as an investigator for AbbVie, AnaptysBio, Eli Lilly, Incyte, Janssen, Krystal Biotech, Regeneron Pharmaceuticals, Inc. and UCB; as a consultant with honorarium for AbbVie, Acrotech, Almirall, Amgen, Amryt Pharma, Arcutis Biotherapeutics, Arena Pharmaceuticals, Azitra, BioCryst, BiomX, BMS, BridgeBio, Castle Creek Biosciences, Catawba Research, Eli Lilly, Exicure, Gilead, Incyte, Janssen, Johnson & Johnson, Kamari Pharma, LEO Pharma, Novartis, OM Pharma, Pfizer, Pierre Fabre, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, Seanergy and UCB; and on data and safety monitoring boards with AbbVie, Abeona, Bausch Health, Galderma and Novan. Gil Yosipovitch has served as an advisory board member for Arcutis and Galderma, BELLUS Health, Eli Lilly, Kiniksa Pharmaceuticals, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and Trevi Therapeutics; and received research grants from Eli Lilly, Kiniksa, LEO Pharma, Novartis, Pfizer and Sanofi-Regeneron Pharmaceuticals, Inc. Stephan Weidinger has received institutional research grants from LEO Pharma, L’Oréal, Pfizer and Sanofi; has served as consultant and/or lecturer for AbbVie, Almirall, LEO Pharma, Lilly, Pfizer, Regeneron Pharmaceuticals Inc. and Sanofi; and is involved in performing clinical trials with many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and atopic eczema. Dana DiBenedetti and Diane Whalley are employees of RTI Health Solutions, which received funding for the conduct of interviews and psychometric evaluation from Regeneron Pharmaceuticals, Inc. Abhijit Gadkari was an employee at Regeneron Pharmaceuticals, Inc. at the time of the study, may have held stock and/or stock options in Regeneron Pharmaceuticals, Inc. and is a current employee at Novartis Pharmaceuticals. Isabelle Guillemin was an employee at Sanofi at the time of the study, may have held stock and/or stock options in Sanofi and is current employee at IQVIA. Haixin Zhang, Jingdong Chao, Ashish Bansal and Dimittri Delevry are employees and shareholders of Regeneron Pharmaceuticals, Inc. Laurent Eckert and Chien-Chia Chuang are employees at and may hold stock and/or stock options in Sanofi. The study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The journal Rapid Service Fee was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.

Keywords

Atopic dermatitis
Clinically meaningful
Dupilumab
Numerical rating scale
Paediatric
Pruritus
Psychometric
Responder threshold
Validation

ASJC Scopus subject areas

Dermatology

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10.1007/s13555-022-00804-z

Cite this

Paller, A. S., Yosipovitch, G., Weidinger, S., DiBenedetti, D., Whalley, D., Gadkari, A., Guillemin, I., Zhang, H., Eckert, L., Chao, J., Bansal, A., Chuang, C. C., & Delevry, D. (2022). Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis. Dermatology and Therapy, 12(12), 2839-2850. https://doi.org/10.1007/s13555-022-00804-z

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keywords = "Atopic dermatitis, Clinically meaningful, Dupilumab, Numerical rating scale, Paediatric, Pruritus, Psychometric, Responder threshold, Validation",

author = "Paller, {Amy S.} and Gil Yosipovitch and Stephan Weidinger and Dana DiBenedetti and Diane Whalley and Abhijit Gadkari and Isabelle Guillemin and Haixin Zhang and Laurent Eckert and Jingdong Chao and Ashish Bansal and Chuang, {Chien Chia} and Dimittri Delevry",

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year = "2022",

month = dec,

doi = "10.1007/s13555-022-00804-z",

language = "English (US)",

volume = "12",

pages = "2839--2850",

journal = "Dermatology and Therapy",

issn = "2193-8210",

publisher = "Springer Verlag",

number = "12",

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Paller, AS, Yosipovitch, G, Weidinger, S, DiBenedetti, D, Whalley, D, Gadkari, A, Guillemin, I, Zhang, H, Eckert, L, Chao, J, Bansal, A, Chuang, CC & Delevry, D 2022, 'Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis', Dermatology and Therapy, vol. 12, no. 12, pp. 2839-2850. https://doi.org/10.1007/s13555-022-00804-z

TY - JOUR

T1 - Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis

AU - Paller, Amy S.

AU - Yosipovitch, Gil

AU - Weidinger, Stephan

AU - DiBenedetti, Dana

AU - Whalley, Diane

AU - Gadkari, Abhijit

AU - Guillemin, Isabelle

AU - Zhang, Haixin

AU - Eckert, Laurent

AU - Chao, Jingdong

AU - Bansal, Ashish

AU - Chuang, Chien Chia

AU - Delevry, Dimittri

PY - 2022/12

Y1 - 2022/12

N2 - Introduction: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6–11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. Methods: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6–11 years with severe AD. These included test–retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. Results: The Worst Itch Scale consisted of two items asking about ‘worst itching’ experienced ‘last night’ and ‘today’. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. Conclusions: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6–11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3–4-point change in the Worst Itch Scale score. Trial Registration: NCT03345914. [MediaObject not available: see fulltext.].

AB - Introduction: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6–11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. Methods: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6–11 years with severe AD. These included test–retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. Results: The Worst Itch Scale consisted of two items asking about ‘worst itching’ experienced ‘last night’ and ‘today’. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. Conclusions: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6–11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3–4-point change in the Worst Itch Scale score. Trial Registration: NCT03345914. [MediaObject not available: see fulltext.].

KW - Atopic dermatitis

KW - Clinically meaningful

KW - Dupilumab

KW - Numerical rating scale

KW - Paediatric

KW - Pruritus

KW - Psychometric

KW - Responder threshold

KW - Validation

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U2 - 10.1007/s13555-022-00804-z

DO - 10.1007/s13555-022-00804-z

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AN - SCOPUS:85140394859

SN - 2193-8210

VL - 12

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JO - Dermatology and Therapy

JF - Dermatology and Therapy

IS - 12

ER -

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis

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