How to Write First-Rate Protocols for an Atopic Dermatitis Study - Focus: STUDY DESIGN
In recent years, therapeutics for dermatologic conditions have become a subspecialty of growing interest in the Contract Research Organisation (CRO) industry, with clinical research in the area focused on a wide range of skin indications, such as acne vulgaris, psoriasis, and atopic dermatitis.
What is atopic dermatitis?
Atopic dermatitis (AD), also known as atopic eczema, is the most common, long-term type of inflammatory skin disease. Stemming from skin barrier dysfunction, immune alterations, and/or genetic and environmental factors, the condition may occur at any age but usually starts in early infancy.
Insights into study design
Before writing a protocol for AD, it is important to examine the competitive landscape for the indication under investigation and to identify the study drug’s stage of clinical development.
In a Phase 1 study, the safety and pharmacokinetics (PK) of the study drug are evaluated through intensive lab testing, electrocardiograms (ECGs), and vital sign assessments to provide full safety and PK profiles. Biomarker assessments can also offer insight on efficacy in small early phase trials.
In proof-of-concept (POC) and Phase 2 studies, the efficacy endpoint that is the most sensitive or has the greatest power to detect a difference between treatment groups should be selected. In Phase 3 studies, the protocol should be aligned as much as possible with the requirements of regulatory agencies.
Screening time: 30 vs 28 days
A screening period duration of 30 days is recommended in order to allow subjects who are using medications that need to be stopped at least 4 weeks (28 days) prior to baseline to do so within the screening period. Many protocols have a 28-day screening period; however, an extension of 2 days can help decrease the screen failure rate. This general approach can be used for AD clinical trials involving topical or systemic agents.
What is an intraindividual design?
In AD trials with topical products, randomization can be at the level of subjects or be within subjects (ie, intraindividual study).
An intraindividual study involves applying different study products (and/or different concentrations) to several target places on a person’s body. There are many advantages to using an intraindividual design, including a reduction in both inter-subject variability and in the number of subjects required to attain significance.
In a study that was published in November 2019 and in which Innovaderm participated, 40 adult patients had 2 AD lesions of identical severity randomly assigned to crisaborole or a vehicle applied twice daily for 2 weeks. This study involved a biopsy collection and disease severity assessments, including the pruritus numeric rating scale (NRS) of the lesions.
The results revealed significant improvement in the pruritus NRS of the lesions, demonstrating that subjects can effectively differentiate the intensity of itch in 2 different locations. The intraindividual design can therefore be an interesting option when seeking an early read of efficacy, such as whether a topical agent is effective for alleviating itch.
While intraindividual randomized trials have many advantages, they also present several challenges and limitations, which are important to address when writing protocols. Not only should the administration of the study drug take place on site for most cases, but it also requires study personnel, some of whom may need to be unblinded regarding the treatment randomization. As well, the disease severity for eligibility should not be too severe since only discrete lesional areas or lesions are being treated.
Duration of treatment
Lastly, writing a first-rate protocol for a study on AD entails defining the dosage of the study drug and the duration of its treatment. In AD trials, the duration should be between 4 and 8 weeks, which is relatively short. Indeed, AD is a highly symptomatic disease and treatment should demonstrate efficacy quickly to be commercially viable. To learn other tips for writing about treatment duration and key eligibility criteria for a study on AD, click here.
When writing an AD protocol, you must not only have a solid understanding of the indication and what you are measuring, but also keep abreast of related literature. Be it procedures for a study on AD or another skin indication, the best protocols in dermatology are often the simplest, with the goal of bridging a knowledge gap or highlighting something new in the field. Resulting from a strong collaborative effort, a first-rate protocol not only provides a roadmap for better enrollment rates and data quality, but also allows investigators to remain at the forefront of dermatology research.
About the Author
Stéphanie Légaré is a senior clinical scientist at Innovaderm with >10 years’ experience in scientific and medical communication and translational/clinical research. Throughout her career, she has managed several investigator-initiated studies and developed training materials for pharmaceutical and life sciences companies.
✨ To learn best tips for writing about treatment duration and key eligibility criteria for a study on AD, click here.
✨ To learn best tips for writing about clinical assessments and types of endpoints for a study on AD, click here.
✨ For more great tips, watch our webinar on the Art of Protocol Writing in Dermatology.
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