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http://orcid.org/0000-0003-0231-9747
Abstract
Abstract
The COVID-19 pandemic has greatly impacted dermatology clinical trial operations due to mandated governmental and institutional shut-downs and newly implemented restrictions. During this unprecedented time, measures should be taken to maintain research conduct compliance while also ensuring the safety of trial staff and participants. Herein, we underscore the challenges facing dermatology trials during the COVID-19 pandemic, and offer strategies to maintain compliant and safe conduct.
Introduction
The unprecedented spread of COVID-19 has led to a multitude of reactionary strategies for viral containment, including mandated quarantines and social distancing (1). Dermatology clinic operations have been drastically impacted. The disruption of clinical trials, in particular, may have far-reaching and long-lasting ramifications. The pandemic has impacted innumerable patients, sponsors, research monitoring entities, trial staff, and investigators. Our query of clinicaltrials.gov (on March 28 2020) yielded 891active trials for ‘skin’ conditions that started on or after January 2019. Herein, we provide considerations and recommendations for compliant and safe conduct of dermatology trials during the global COVID-19 pandemic.
Trial logistics
Determining current government, institution, and Institutional Review Board (IRB) COVID-19 policies for trial performance is essential to ensuring safety and compliance. Some institutions have suspended all in-person trial visits, some have implemented modified protocols, and others may require additional approvals for certain visits. In circumstances when suspension of trials is not mandatory, the principal investigator’s (PI’s) discretion can be used to determine which trials should continue. Trials should be prioritized if study discontinuation may cause harm to the participants. Trials studying conditions with high morbidity and/or mortality, such as those involving severe inflammatory dermatoses or advanced/high-grade cutaneous oncology, should also be given greater weight. Studies that do not provide an immediate clear benefit for participants (e.g. mechanistic or descriptive studies) are best placed on hold. Collecting data on primary study outcomes should take precedence over secondary and adjunctive outcome measures.
For ongoing trials, availability of resources and supplies should be confirmed due to COVID-related delays and shortages. Delivery services and central laboratories should be contacted in advance for updated operational schedule. Sites can consider pre-ordering additional supplies and investigational products (IP) to guarantee enough stock if the supply chain may be interrupted.
For large research centers, consideration should be given to dividing the research group into teams that perform necessary in-person tasks on alternating days to minimize COVID exposure and cross-contamination. Team composition can include one investigator and one research coordinator. Researchers who are at greater risk of developing severe complications from COVID-19, including older adults and those with existing serious health conditions (2), may be assigned to remote tasks. Table 1 outlines a list of practical considerations for conducting trials during the COVID-19 pandemic.
Table 1. Practical recommendations for clinical trials during the COVID-19 pandemic.
Trial participants
All study patients should be notified if their participation may be modified due to COVID-19. Dermatology as a specialty is uniquely poised to have study patients engage in virtual visits as PIs may still be able to use scoring systems to evaluate outcomes. For all participants, but especially for those in higher risk categories, conducting visits virtually via privacy-compliant platforms (e.g. Zoom, VSee) when possible may be the safest option. Permission may need to be obtained from a regulatory body, monitoring organization, or sponsors beforehand. To limit in-person visits, consideration should be given to obtaining approval from the sponsor to mail IP to patients.
For those trials that require continued in-person visits, participant risk stratification can assist with making determinations on appropriateness of continuing study participation. For participants of trials involving immunosuppressive or immunomodulator study drugs for conditions where alternate agents are available, investigators may opt to have certain at-risk participants discontinue the trial to reduce risk of contracting COVID-19 (3). Different strategies may be utilized to optimize in-person study visits including: (1) schedule the study visit during clinic off-hours to minimize exposure risk to both research staff and participant; (2) perform exam room disinfection procedures before and after visits; (3) discourage study participants from using public transportation; and (4) remind participations to notify the trial team immediately if symptoms suggestive of COVID-19 infection develop, so the visit can be re-scheduled and participants can seek appropriate treatment. Finally, thorough documentation should be collected on any pandemic-related alterations of study procedures/performance, so that their impact on study outcomes can be analyzed (4).
Conclusion
In this challenging time of the COVID-19 pandemic, investigators should perform clinical trials in a safe, compliant, and ethnical manner. The suggestions provided in this perspective are general considerations that may be adapted to individual locations, studies, and participants based on their unique needs. Refer to local drug agencies, such as the US Food and Drug Administration (FDA) (5) or the European Medicine Agency (EMA) (6), for the most up-to-date guidance. Further explorations are needed to determine the best strategies for modifying research conduct during times of widespread communicable disease.
| Component of clinical trial | Practical considerations |
|---|---|
| Facility |
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| Supplies |
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| Research team |
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| Participants |
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CDC, Centers for Disease Control; COPD, Chronic Obstructive Pulmonary Disorder; CRA, Clinical Research Associate; FDA, Food and Drug Administration; EMA, European Medicine Agency; IRB, Institutional Review Board.
Disclosure statement
VYS is a stock shareholder of Learn Health, and has served as an advisor, investigator, and/or speaker for Sanofi Genzyme, Regeneron, AbbVie, Burt’s Bees, Dermira, Eli Lilly, Novartis, Pfizer, Galderma, Leo Pharma, SUN Pharma, Menlo Therapeutics, GpSkin, and Skin Actives Scientific. There was no financial transaction for the preparation of this manuscript. EKC and JLH report no conflicts of interest.
References
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