Elsevier

Clinics in Dermatology

Volume 26, Issue 5, September–October 2008, Pages 565-569
Clinics in Dermatology

Comment and controversy
Edited by Stephen P. Stone, MD
Impact of seasonality on conducting clinical studies in dermatology

https://doi.org/10.1016/j.clindermatol.2008.01.016Get rights and content

Abstract

It is generally accepted among dermatologists that certain skin diseases are subject to seasonal influence. This belief, however, is based primarily on anecdotal observation rather than fact-based evidence. To address this controversy, we performed a retrospective analysis of a total of 3931 subjects enrolled in 7 phase 3 clinical trials across the diseases acne, atopic dermatitis, and seborrheic dermatitis and found a seasonal effect to exist in the treatment response of the 3 very common dermatologic diseases studied. To be truly representative of a drug's benefit when the disease is known to be impacted by seasonality, efficacy figures in the package insert should therefore be based on data collected from patients enrolled across all seasons.

Introduction

It is generally accepted among dermatologists that certain skin diseases are subject to seasonal influence. For instance, acne, atopic dermatitis, and seborrheic dermatitis are thought generally to worsen in the colder, winter months and to demonstrate clinical improvement in the summer. This belief, however, is based primarily on anecdotal observation rather than fact-based evidence. Even if these observations reflect reality, they nevertheless may be negatively impacting the timing for conducting controlled clinical trials in these particular disease states. Indeed, that same anecdotal evidence suggests a seasonal variability in clinical trials.1 As a matter of practicality, clinical trials evaluating treatments for certain diseases are most often conducted in the late fall and winter to avoid subjects improving naturally on their own.

The power calculations necessary to optimize clinical trial success require an adequate estimation of treatment effect. For studies enrolling in the spring and summer months, the impact on trial design has been to enroll a greater sample size to differentiate treatment groups. If one could predict the magnitude of variability in treatment difference throughout the year, enrollment could be tailored to minimize the number of subjects required to attain a given outcome. Analyzing past trends would thereby afford sponsors an opportunity to structure future trials more efficiently. Strategic planning and resource allocation would also be optimized if enrollment could be more rationally managed.

This paper is a retrospective analysis of a total of 3931 subjects enrolled in 7 phase 3 clinical trials. The seasons were defined according to patient enrollment dates as described in Table 1. Although these studies were not powered to show seasonal differences, should seasonal differences exist between treatment groups for overall severity of disease, this would be important new learning.

We evaluated percentage differences rather than absolute differences because we believed them to be more meaningful when assessing a seasonality effect. The percentage differential allows for a better estimate of statistical significance over smaller numbers.

The diseases evaluated included acne, atopic dermatitis, and seborrheic dermatitis. The intent of our analysis was to determine the impact, if any, of seasonal enrollment on treatment outcomes and, in so doing, reevaluate the conduct of clinical trials in certain, supposedly seasonally dependent, skin diseases. Our study evaluates whether the season in which a subject participates in a clinical trial has an impact on the treatment outcome. Segmenting the primary outcome measure according to season in which the subject participated offers the opportunity to determine whether future studies in specific dermatologic diseases could be structured to capitalize on seasonal treatment differences.

We furthermore sought to provide the practicing clinician empirical data on why certain diseases respond to therapy better during specific times of the year. An impact of season might allow for more efficacy data to be published in the package insert. With this new learning, better management of these diseases may be facilitated.

Section snippets

Results

Between June of 2002 and April of 2005, 7 phase 3, multicenter clinical trials were performed to evaluate 4 novel therapeutics for the treatment of dermatologic diseases including acne, atopic dermatitis, and seborrheic dermatitis. The total enrollment across all studies was 3931.

Discussion

These 4 studies suggest that a seasonal effect exists in treatment response in 3 very common dermatologic diseases: acne, atopic dermatitis, and seborrheic dermatitis.

Conclusions

We believe these results offer interesting insights to a current controversy regarding the conduct of clinical trials and clinical program design for major sponsors as well as individual investigators in academic centers and the community.

Often, practioners will look across studies to determine if one therapy has better comparative efficacy. Without noting enrollment season, this becomes even more challenging because efficacy results can be inflated or deflated based on when subjects are

Reference (1)

  • A.B. Haidich et al.

    Determinants of patient recruitment in a multicenter clinical trials group: trends, seasonality and the effect of large studies

    BMC Med Res Methodol

    (2001)

Cited by (23)

  • Chemical characterization of riverine sediments affected by wastewater treatment plant effluent discharge

    2022, Science of the Total Environment
    Citation Excerpt :

    Another contribution to the interpretation of the results relies on the usage patterns of PPCPs. Two of the quantified PPCPs are antidepressants and the use of these type of pharmaceuticals does follow seasonality, with higher consumption rates in the winter to treat seasonal affective disorders (Gardarsdottir et al., 2010; Winkler et al., 2019); climbazole is also more used in the winter, when dermatitis crises increase (Weiss et al., 2008). It is thus reasonable to hypothesize that the collection of our samples in the late Spring may have constrained the overall picture on the PPCP burden in the effluents and the dissolution of the potential link of this burden to the contamination of the sediments of recipient ecosystems.

  • Effects of extreme temperatures on childhood allergic respiratory diseases with and without sensitization to house dust mites in Shanghai, China

    2022, Urban Climate
    Citation Excerpt :

    Finally, some measurement variance is unavoidable as an ecological time-series study. Weather conditions and air pollutants information were taken from shanghai monitoring stations, which may not adequately represent personal exposures (Tian et al., 2018; Weiss et al., 2008). This form of measurement error, however, is probably non-differential, biasing impact estimates towards the null (Brenner and Loomis, 1994).

  • Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions

    2015, Journal of Allergy and Clinical Immunology
    Citation Excerpt :

    Beyond molecular changes, basic skin physiology with regard to skin temperature, pH, and TEWL varies in a circadian manner,59 with the worst barrier function and greatest TEWL at night. Circadian timing mechanisms are sensitive to day length and temperature, and skin diseases, such as AD, can change with seasonal changes in day length.60 Skin mast cell responses also have circadian rhythm and might contribute to timing of AD flares.61,62

  • How the skin can tell time

    2009, Journal of Investigative Dermatology
    Citation Excerpt :

    Circadian timing mechanisms are also sensitive to day length and temperature, and therefore circadian clock mechanisms are candidates for the regulation of seasonal phenomena within the skin. Interestingly, several skin diseases do exhibit seasonal change in severity (Weiss et al., 2008). In the future, the availability of mouse models with mutations in genes encoding several clock components may allow the role of the circadian clock in skin biology to be tested.

  • Seasonal Patterns and Trends in Dermatoses in Poland

    2022, International Journal of Environmental Research and Public Health
View all citing articles on Scopus
View full text