Canine atopic dermatitis clinical trials: study design and methodological considerations.
4 affiliations
- 1Okava Pharmaceuticals, San Francisco, CA, United States.
- 2School of Public Health, University of California, Berkeley, Berkeley, CA, United States.
- 3Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, United States.
- 4University of Florida College of Veterinary Medicine, Gainesville, FL, United States.
Abstract
Canine atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disease affecting up to 15% of dogs, with clinical expression shaped by genetic, environmental, and microbial factors. Although the International Committee for Allergic Diseases of Animals (ICADA) established COSCAD as a core outcome set providing standardized outcome measures for evaluating treatment efficacy, comparatively little attention has been given to the upstream methodological considerations that determine the validity and interpretability of trial results. This narrative review uses a structured methodological framework to examine key sources of random error, bias, confounding, and effect modification that can compromise randomized controlled trials (RCTs) in canine AD. We identify critical parameters requiring careful control in trial design, including food and environmental allergen exposures, seasonality, flea infestation, concurrent bacterial and fungal infections, concomitant therapies, and washout period determination. Historical study protocols, conducted primarily in treatment-naïve dogs with mild-to-moderate disease, are analyzed to illustrate how pivotal registration trials mitigated these sources of error through strict case definitions, medication-specific washout intervals, concomitant therapy restrictions, and rigorous blinding and randomization. We further examine the trade-offs between internal validity and external generalizability, and the growing tension between traditional explanatory trial designs and real-world feasibility in an evolving therapeutic landscape. Synthesizing perspectives from a panel of veterinary dermatology experts, we highlight how disease severity, treatment history, and therapeutic modality should inform eligibility criteria, endpoint selection, and assessment timing. Based on these assessments, we highlight the limitations of applying standardized study design methodologies to such a heterogeneous disease. Applying uniform methodologies to such a heterogeneous syndrome risks obscuring clinically meaningful differences in disease presentation and treatment response. Progress requires flexible, fit-for-purpose study designs that align key methodological elements with the phenotype under investigation, enabling accurate interpretation of treatment effects and more effective therapeutic development.
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BibTeX
@article{klotsman2026canine,
title = {{Canine atopic dermatitis clinical trials: study design and methodological considerations.}},
author = {Michael Klotsman and Sharon K Sagiv and Wayne H Anderson and Domenico Santoro},
journal = {Frontiers in veterinary science},
year = {2026},
month = oct,
doi = {10.3389/fvets.2026.1878714},
url = {https://europepmc.org/article/MED/42921062},
note = {CC BY},
}
RIS
TY - JOUR
TI - Canine atopic dermatitis clinical trials: study design and methodological considerations.
AU - Michael Klotsman
AU - Sharon K Sagiv
AU - Wayne H Anderson
AU - Domenico Santoro
PY - 2026
DA - 2026/10/09
JO - Frontiers in veterinary science
DO - 10.3389/fvets.2026.1878714
UR - https://europepmc.org/article/MED/42921062
AB - Canine atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disease affecting up to 15% of dogs, with clinical expression shaped by genetic, environmental, and microbial factors. Although the International Committee for Allergic Diseases of Animals (ICADA) established COSCAD as a core outcome set providing standardized outcome measures for evaluating treatment efficacy, comparatively little attention has been given to the upstream methodological considerations that determine the validity and interpretability of trial results. This narrative review uses a structured methodological framework to examine key sources of random error, bias, confounding, and effect modification that can compromise randomized controlled trials (RCTs) in canine AD. We identify critical parameters requiring careful control in trial design, including food and environmental allergen exposures, seasonality, flea infestation, concurrent bacterial and fungal infections, concomitant therapies, and washout period determination. Historical study protocols, conducted primarily in treatment-naïve dogs with mild-to-moderate disease, are analyzed to illustrate how pivotal registration trials mitigated these sources of error through strict case definitions, medication-specific washout intervals, concomitant therapy restrictions, and rigorous blinding and randomization. We further examine the trade-offs between internal validity and external generalizability, and the growing tension between traditional explanatory trial designs and real-world feasibility in an evolving therapeutic landscape. Synthesizing perspectives from a panel of veterinary dermatology experts, we highlight how disease severity, treatment history, and therapeutic modality should inform eligibility criteria, endpoint selection, and assessment timing. Based on these assessments, we highlight the limitations of applying standardized study design methodologies to such a heterogeneous disease. Applying uniform methodologies to such a heterogeneous syndrome risks obscuring clinically meaningful differences in disease presentation and treatment response. Progress requires flexible, fit-for-purpose study designs that align key methodological elements with the phenotype under investigation, enabling accurate interpretation of treatment effects and more effective therapeutic development.
SN - 2297-1769
ER -