Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Nov;13(11):2549-2571.
doi: 10.1007/s13555-023-01038-3. Epub 2023 Sep 25.

Assessing Response in Atopic Dermatitis: A Systematic Review of the Psychometric Performance of Measures Used in HTAs and Clinical Trials

Hannah Penton  1 , Sayeli Jayade  2 , Santhani Selveindran  3 , Marieke Heisen  4 , Christophe Piketty  5 , Liliana Ulianov  5 , Zarif K Jabbar-Lopez  5 , Jonathan I Silverberg  6 , Jorge Puelles  5
Affiliations
Review

Assessing Response in Atopic Dermatitis: A Systematic Review of the Psychometric Performance of Measures Used in HTAs and Clinical Trials

Hannah Penton et al. Dermatol Ther (Heidelb). 2023 Nov.

Abstract

Introduction: Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits.

Methods: A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD.

Results: A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria.

Conclusion: Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.

Keywords: Atopic dermatitis; DLQI; EASI; Health technology assessment; IGA; PP-NRS; Response.

Plain language summary

The assessment of treatment response is important in determining treatment value in atopic dermatitis (AD). This study aimed to identify which outcome measures and criteria are used to determine treatment response in clinical trials and health technology assessments (HTAs). The psychometric performance of identified outcome measures and criteria was then systematically reviewed to understand which perform best in capturing patient-relevant symptoms and treatment benefits in AD. The review identified and included the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and Peak Pruritus Numerical Rating Scale (PP-NRS) as response measures. Lack of consistency in how response is assessed across clinical trials and HTAs makes it difficult for clinicians and payers to compare the efficacies and cost-effectivenesses of different treatments and to make optimal treatment decisions. The review found that content validity (the extent to which a measure covers those symptoms and treatment benefits which are important to patients) was not assessed for EASI and IGA. EASI and IGA are often used to assess response in clinical trials and HTAs, but they miss key elements of the patient-relevant disease impact and treatment benefit, including itch. Treatments leading to improvements in missed symptoms (e.g. itch) will be undervalued using EASI and IGA, decreasing the chances of regulatory approval and reimbursement. Moreover, response criteria used in clinical trials and HTAs are sometimes adopted in prescriber settings. Here, if response assessment does not capture patient-relevant benefit, patients’ access to tailored treatment may be restricted due to the perceived non-response.

PubMed Disclaimer

Conflict of interest statement

Christophe Piketty, Liliana Ulianov, Zarif K. Jabbar-Lopez and Jorge Puelles are employees of Galderma, which funded this research. Hannah Penton, Sayeli Jayade, Santhani Selveindran and Marieke Heisen are employees of OPEN Health, which received consulting fees from Galderma in connection with this study. Jonathan I. Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, and Union, and as a speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; his institution received grants from Galderma, Incyte, and Pfizer.

Figures

Fig. 1
Fig. 1
Definition of overall ratings for each included response measure per psychometric property
Fig. 2
Fig. 2
PRISMA flow diagram
See this image and copyright information in PMC

References

    1. Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66(Suppl 1):8–16. doi: 10.1159/000370220. - DOI - PubMed
    1. Yosipovitch G, Reaney M, Mastey V, et al. Peak pruritus numerical rating scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol. 2019;181(4):761–769. doi: 10.1111/bjd.17744. - DOI - PMC - PubMed
    1. Schmitt J, Csotonyi F, Bauer A, Meurer M. Determinants of treatment goals and satisfaction of patients with atopic eczema. J Dtsch Dermatol Ges. 2008;6(6):458–465. doi: 10.1111/j.1610-0387.2007.06609.x. - DOI - PubMed
    1. Nusbaum KB, Fleischer S, Fleischer AB. Efficacy of biologics and oral small molecules for atopic dermatitis: a systematic review and meta-analysis. J Dermatol Treat. 2021 doi: 10.1080/09546634.2021.1986204. - DOI - PubMed
    1. Schmitt J, Langan S, Williams HC. What are the best outcome measurements for atopic eczema? A systematic review. J Allergy Clin Immunol. 2007;120(6):1389–98. - PubMed