Introduction
In March 2020, New York City became the epicenter of the COVID-19 pandemic, and “The New York State on PAUSE” executive order effectively closed all non-essential businesses statewide. In order to mitigate the public health burden, most ongoing clinical trials visits were suspended, or needed to rapidly shift to home visits only. Nationwide, between December 1, 2019 and July 1, 2020, 1473 clinical trials were suspended, terminated, or withdrawn with a reported reason that explicitly mentioned COVID-19. At the same time, all available resources were focused on the initiation of COVID-19-related studies which, as of November 18, 2021, included 1557 new studies.
Patients with rare diseases often have complex multisystem disorders that are challenging to manage and lack optimal treatment options Clinical trials are vital in developing therapeutics for this vulnerable population and exploring better therapies. Most patients enrolled in clinical trials and their caregivers require substantial support from the study team given the intricacies of trial participation.
Very few established centers are equipped to conduct clinical trials for rare diseases. Traditional clinical trial models often involve multiple onsite visits, and may require lengthy travel to the study sites, further increasing the patient burden in this group. The difficulties in delivering healthcare during the pandemic complicated the operations of clinical trials for rare diseases even further.
The Clinical Trials Office in the Department of Genetics and Genomic Sciences (GGS CTO) at Icahn School of Medicine at Mount Sinai located in New York City conducts over 45 research studies focused on rare inherited disorders. To overcome the challenges posed by the Covid-19 pandemic in executing clinical studies, GGS CTO adopted a Hybrid Decentralized Clinical Trial (DCT) model executed using digital health tools like telemedicine as well as other strategies including use of mobile health care providers to assist with trial-related functions. The experiences and perspectives of this office are presented.
Methods
Principal Investigators and Clinical Research Coordinators GGS CTO at Mount Sinai, New York were interviewed regarding their experience with the ongoing clinical trials. Participants were asked to share their experiences with the Hybrid DCT model, difficulties with implementation, and modifications made to operating procedures to meet the pandemic challenges. The impact of these modifications on the clinical trial endpoints and subject recruitment and retention were also documented.
Results
Issues related to the pandemic included delays in subject recruitment, screening, and enrollment, delayed availability of investigational product (IP) and testing supplies, concerns over missing/delayed procedures including physical examination, delays in meeting timelines and on occasion, a complete halt of operations. Study protocols were modified to remove procedures that involved exposure to aerosolized particles such as pulmonary function tests, to protect subjects and staff from spreading or contracting Covid-19.
The Hybrid DCT model increased recruitment, reduced barriers to participation, and enhanced subject engagement. It reduced costs for subjects and sponsors. Electronic consenting optimized the enrollment process. Wearable devices/ apps improved subject monitoring and reduced the number of required on site visits. Deployment of mobile health professionals for home visits, IP administration and collection of laboratory data was extremely valuable to maintain the work flow in this context.
Challenges included reporting and managing adverse events (AEs), ensuring appropriate investigator oversight, maintaining subject confidentiality, data collection from home health professionals, storing IP and implementing remote monitoring. Issues related to delays in shipping IP, inadequacy of study supplies and scarcity of trained mobile health professionals have been the most difficult hurdles to overcome.
Conclusion
The pandemic has highlighted the need for innovations in work flow in the conduct of clinical trials. The Hybrid Decentralized Clinical Trial model was successful in maintaining study work flows in a safe and effective manner. Rapid adoption of digital health for clinical research was shown to be possible and we expect this hybrid model of conducting trials to be adopted long-term. This will help reduce the high participant burden which comes with in person visits associated with a more traditional clinical trial approach. Limiting onsite visits and increasing the availability of home visits may increase diversity in enrollment, adherence, and subject retention. Telemedicine is a practical resource not only in patient care but also in the research setting and is an effective way to maintain investigator oversight. The scope of DCTs may be restricted in some situations involving early phase trials with limited safety data until appropriate procedures are in place to identify, assess, and adequately treat AEs. However, in our experience, the hybrid DCT model was found to be a useful tool in broadening initiatives and promoting patient- centricity in clinical research.