The COVID-19 pandemic has accelerated the implementation of decentralized (also referred to as virtual, remote, or hybrid) solutions for clinical trials. In addition to keeping your clinical trials on-track during the pandemic, decentralized solutions can often provide the following added benefits:
1) An improved patient experience (i.e. reduced burden and increased engagement)
2) Lower barriers to patient recruitment
3) Increased patient retention and lower drop-out rates
4) Higher data quality
Our teams have helped many sponsors navigate and implement decentralized solutions for their clinical trials and programs. This includes providing recommendations for the level of decentralization required (e.g. a fully virtual trial or a hybrid approach), as well as the development of strategic plans for remote and central monitoring, technology integration, IP management, and site and patient engagement.
Based on our experience, we believe that the best decentralized solutions are patient-centric, customized, and rooted in a robust Risk-Based Quality Management (RBQM) framework, as specified by the E6R2 guidance.
Below we will discuss some considerations for successfully implementing decentralized solutions:
Risk Analysis - A formal risk analysis is the foundation for implementing a decentralized solution. A data-driven RBQM process that allows you to identify and evaluate risks early, monitor those risks and provide insights to make adjustments throughout your trial is essential. A robust RBQM process led by an experienced CRO will help determine the type of decentralized solution needed for your clinical trial (e.g. fully virtual or hybrid). It will also help you make decisions around the most appropriate use of monitoring strategies, including risk-based monitoring, central monitoring, off-site monitoring and targeted source data verification (TSDV), as well as provide insight into other critical considerations for subject safety and data integrity.
Patient Centricity and Study Logistics - The patient must be the central focus of any decentralized solution. This includes considerations for safety, engagement, and study logistics. When clinical sites are closed and/or patients aren’t able to travel to sites, it’s important to consider the following:
1. Remote consenting – We have consulted with IRBs to implement remote informed consent processes that meet regulatory requirements. It’s important to have this process in place before starting a decentralized clinical trial. If your trial started prior to the pandemic, you may need to update and re-consent subjects based on necessary changes made to trial design in regard to subjects visits and even potentially for the remote review of subject data.
2. Remote Recruitment and Enrollment Processes – Discussions regarding the digital management of recruitment and enrollment should be held with the clinical sites at the feasibility and qualification stage. Ongoing conversations with clinical sites and any vendors (if used) should continue through the site activation period to ensure sites are prepared to begin recruitment and enrollment activities as soon as they are initiated. If implemented and managed well, these remote processes have the potential to increase patient engagement and overall retention.
3. Telemedicine Visits – Many of our sites have implemented telemedicine visits to evaluate subject safety throughout a decentralized trial. Telehealth is the use of digital information and communication technologies, such as computers and mobile devices, that allow patients to access health care services remotely. In a telemedicine visit, the clinical site staff connect with the patient via phone or web conference to assess new and/or ongoing adverse events and any changes to the patient’s medications.
4. Home Health Care – A common home health care solution we have implemented pairs a trained Home Health Care medical professional with patients for in-person evaluations. The patient chooses a time and location that is convenient, and during the appointment, the Home Health Care professional performs safety procedures, such as blood collection and vital sign review and evaluation. It’s important to note that clinical sites might not immediately embrace home health solutions because of a perceived lack of control of the patient’s care. We have had success by addressing these concerns with the sites and investigators early in the process to ensure buy-in and support.
5. Lab Draws – It’s important not to overlook a local laboratory as an option for certain blood collections. Allowing a patient to have blood draws done at a lab closer to the his or her home, can reduce patient burden. We have also partnered with a vendor that provides the patient the ability to collect blood, urine, saliva and stool samples in their own home and send it directly to the lab for analysis.
6. Direct to patient (DTP) Investigational Product (IP) shipments – We have developed strategies for the dispensation of IP, such as home delivery or use of courier services for shipment of IP directly to patients’ homes. To ensure IP maintains a specific temperature in transit, our shipping partners use a controlled temperature shipper and a temperature tracking device.
7. Off-Site Monitoring – We have implemented many types of off-site monitoring processes to meet the needs of specific decentralized clinical trials. These solutions have included customized approaches to and levels of risk-based monitoring, off-site monitoring and targeted site data verification (TSDV). The right combination of these solutions for your clinical trial will depend on the risks identified in the RBQM process, along with the status of your clinical trial or program (e.g. a new study that has not begun yet versus a study that has been on-going and needs to implement a decentralized solution partway through), and the level of access to your clinical sites.
8. Centralized Monitoring and Data Visualization – Remote evaluation of clinical data (e.g. centralized monitoring) is a critical component of any decentralized solution, and it becomes more important as direct access to clinical sites and patients is reduced. Centralized monitoring is used to identify trends in the clinical data, including information pertinent to site management activities and data related to safety events. Our teams have the centralized monitoring tools to identify key quality and risk indicators early and monitor them throughout the study to provide actionable and timely insights that will help manage your decentralized clinical trial.
Technology – Technology is a key component of most decentralized solutions. At Rho, we have implemented eCOA and ePRO solutions, along with devices and wearables that capture data directly from patients. Technology solutions have the potential to significantly reduce patient burden and increase patient engagement if implemented properly. It’s important to map out a strategy early in the process, which includes robust plans for site and patient training. It’s also important to ensure that the CRO you’re working with has developed strong partnerships with any technology vendors they bring to the table.
Continuous Assessment - Any decentralized solutions during this pandemic must be both customized and agile. The conditions at research sites and patient availability has been shifting rapidly and will continue to be uncertain for the foreseeable future. This means that it’s even more important to have a decentralized approach that’s grounded in a robust RBQM framework, which can provide data and triggers to determine when a shift in approach is necessary.
Updating Study Plans/Protocols – To document potential changes to your decentralized strategy, make sure to update study plans and protocols throughout your trial or program. Study plans include the project management plan, clinical monitoring plan, and the statistical analysis and data management plans, among others. Updating plans and protocols, will ensure compliance and result in reliable data that supports endpoints.
In conclusion, we’d like to emphasize that decentralized solutions are not one-size fits all. The right solution for your trial or program needs to be determined and managed using a robust RBQM process, which will identify risks upfront and monitor them throughout and let you know when changes need to be made. And a reliable CRO partner is critical to implementing a decentralized solution that will help you realize all the advantages and benefits of a truly decentralized approach.
Marina Acosta Enslen, Associate Director, Clinical Management is a diversely skilled clinical research professional with 20 years of experience across Phase 1 through 4 studies. Prior to joining Rho, Ms. Acosta Enslen has held positions in the areas of clinical monitoring, site level study coordination, site start-up, and clinical study management. Ms. Acosta Enslen has extensive experience working on regional and global HIV, Oncology, Acute Pain and Vaccine clinical trials. Nearly half of her career has been focused in HIV/AIDS research working on NIH and industry funded clinical trials.