Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events

R. Bissonnette; L. F. Eichenfield; E. Simpson; D. Thaçi; K. Kabashima; J. P. Thyssen; E. Guttman-Yassky; F. P. Nunes; M. Gamalo; F. Ahmad; M. Kuligowski; K. Sun; C. Pipper; A. W. Christensen; P. D'Angelo; M. Milutinovic; A. Guettner; J. I. Silverberg

doi:10.1111/jdv.18881

Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events

R. Bissonnette^*, L. F. Eichenfield, E. Simpson, D. Thaçi, K. Kabashima, J. P. Thyssen, E. Guttman-Yassky, F. P. Nunes, M. Gamalo, F. Ahmad, M. Kuligowski, K. Sun, C. Pipper, A. W. Christensen, P. D'Angelo, M. Milutinovic, A. Guettner, J. I. Silverberg

^*Corresponding author for this work

Institute of Inflammation Medicine

4 Citations (Scopus)

Abstract

Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

Original language	English
Journal	Journal of the European Academy of Dermatology and Venereology
Volume	37
Issue number	5
Pages (from-to)	976-983
Number of pages	8
ISSN	0926-9959
DOIs	https://doi.org/10.1111/jdv.18881
Publication status	Published - 05.2023

Funding

RB is an advisory board member, consultant, speaker and/or investigator for, and receives honoraria and/or grants from AbbVie, Arcutis, Arena Pharmaceuticals, Aristea, Asana BioSciences, Bellus Health, Bluefin Biomedicine, Boehringer Ingelheim, CARA Therapeutics, Dermavant, Eli Lilly, EMD Serono, Evidera, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, Kyowa Kirin, LEO Pharma, Novan, Pfizer, Ralexar, RAPT, Regeneron, Respivant, Sanofi‐Genzyme, Sienna and Target RWE. RB is also an employee and shareholder of Innovaderm Research. LFE has served as a scientific adviser, consultant, speaker and/or clinical trial investigator for AbbVie, Almirall, Amgen, Arcutis, Arena, Aslan, Dermavant, Dermira, Eli Lilly, Forté, Galderma, Glenmark/Ichnos, Incyte, LEO Pharma, Novartis Pharma AG, Ortho Dermatologics, Pfizer, Regeneron and Sanofi‐Genzyme. DT received honoraria as a consultant, advisory board member or speaker for AbbVie, Almirall, Amgen, Biogen Idec, Bristol‐Myers Squibb, Janssen‐Cilag, LEO Pharma, Eli Lilly, Novartis Pharma AG, Pfizer, Regeneron, Sanofi‐Genzyme and UCB; and has received research/educational grants from AbbVie, LEO Pharma and Novartis Pharma AG. KK received grants from Japan Tobacco Inc., Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Pola Pharma, Procter & Gamble Company, Taiho Pharmaceutical and Torii Pharmaceutical. JPT is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi‐Genzyme; a speaker for AbbVie, Almirall, Eli Lilly, LEO Pharma, Pfizer, Regeneron and Sanofi‐Genzyme; and received research grants from Pfizer, Regeneron and Sanofi‐Genzyme. EG‐Y has received grants or consulting fees from AbbVie, Almirall, Amgen, AnaptysBio, Arena Pharmaceuticals, Asana Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol‐Meyers Squibb, CARA Therapeutics, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Glenmark/Ichnos Sciences, Incyte, Innovaderm, Janssen Biotech, Kao, Kiniksa Pharmaceuticals, Kyowa Kirin, LEO Pharma, Novan, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron, Ralexar, Sanofi‐Genzyme, SATO Pharmaceutical, Siolta Therapeutics, Target PharmaSolutions, UCB and Ventyx Biosciences. FPN is an employee and stockholder of Janssen Pharmaceuticals of Johnson & Johnson. MG is an employee and stockholder of Pfizer. KS is an employee and stockholder of Incyte. CP has received honoraria for lectures from the University of Copenhagen. CP also has unpaid involvement on the board of the Danish Society of Theoretical Statistics and as an Adjunct Professor at University of Southern Denmark. CP is an employee of LEO Pharma A/S. AWC is an employee of LEO Pharma A/S. PD'A is an employee of Innovaderm Research. MM and AG are employees and stockholders of Novartis Pharma AG. JIS received honoraria as a consultant, advisory board member or speaker for AbbVie, Afyx, Arena Pharmaceuticals, Asana, BioMX, Bluefin Biomedicine, Bodewell, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Luna, Menlo, Novartis Pharma AG, Pfizer, RAPT Therapeutics, Regeneron, Sanofi‐Genzyme. ES, FA and MK have no conflicts of interest to declare. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Charlotte Terry (MSc) of Ashfield MedComms, an Inizio company, and funded by Novartis Pharma AG in accordance with Good Publication Practice (GPP 2022) guidelines. 45

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.22-19 Dermatology

Access to Document

10.1111/jdv.18881

Cite this

Bissonnette, R., Eichenfield, L. F., Simpson, E., Thaçi, D., Kabashima, K., Thyssen, J. P., Guttman-Yassky, E., Nunes, F. P., Gamalo, M., Ahmad, F., Kuligowski, M., Sun, K., Pipper, C., Christensen, A. W., D'Angelo, P., Milutinovic, M., Guettner, A., & Silverberg, J. I. (2023). Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events. Journal of the European Academy of Dermatology and Venereology, 37(5), 976-983. https://doi.org/10.1111/jdv.18881

@article{b507d48f427b4db2bb51e17dfc898316,

title = "Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events",

abstract = "Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.",

author = "R. Bissonnette and Eichenfield, \{L. F.\} and E. Simpson and D. Tha{\c c}i and K. Kabashima and Thyssen, \{J. P.\} and E. Guttman-Yassky and Nunes, \{F. P.\} and M. Gamalo and F. Ahmad and M. Kuligowski and K. Sun and C. Pipper and Christensen, \{A. W.\} and P. D'Angelo and M. Milutinovic and A. Guettner and Silverberg, \{J. I.\}",

note = "Publisher Copyright: {\textcopyright} 2023 European Academy of Dermatology and Venereology.",

year = "2023",

month = may,

doi = "10.1111/jdv.18881",

language = "English",

volume = "37",

pages = "976--983",

journal = "Journal of the European Academy of Dermatology and Venereology",

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Bissonnette, R, Eichenfield, LF, Simpson, E, Thaçi, D, Kabashima, K, Thyssen, JP, Guttman-Yassky, E, Nunes, FP, Gamalo, M, Ahmad, F, Kuligowski, M, Sun, K, Pipper, C, Christensen, AW, D'Angelo, P, Milutinovic, M, Guettner, A & Silverberg, JI 2023, 'Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events', Journal of the European Academy of Dermatology and Venereology, vol. 37, no. 5, pp. 976-983. https://doi.org/10.1111/jdv.18881

TY - JOUR

T1 - Estimands for atopic dermatitis clinical trials

T2 - Expert opinion on the importance of intercurrent events

AU - Bissonnette, R.

AU - Eichenfield, L. F.

AU - Simpson, E.

AU - Thaçi, D.

AU - Kabashima, K.

AU - Thyssen, J. P.

AU - Guttman-Yassky, E.

AU - Nunes, F. P.

AU - Gamalo, M.

AU - Ahmad, F.

AU - Kuligowski, M.

AU - Sun, K.

AU - Pipper, C.

AU - Christensen, A. W.

AU - D'Angelo, P.

AU - Milutinovic, M.

AU - Guettner, A.

AU - Silverberg, J. I.

PY - 2023/5

Y1 - 2023/5

N2 - Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

AB - Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

UR - https://www.scopus.com/pages/publications/85148914312

U2 - 10.1111/jdv.18881

DO - 10.1111/jdv.18881

M3 - Scientific review articles

C2 - 36652273

AN - SCOPUS:85148914312

SN - 0926-9959

VL - 37

SP - 976

EP - 983

JO - Journal of the European Academy of Dermatology and Venereology

JF - Journal of the European Academy of Dermatology and Venereology

IS - 5

ER -

Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

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