Even before the COVID-19 pandemic began, clinical research teams increasingly had their eye on decentralized trial technology. With the travel restrictions, office closures and other obstacles created by the virus, decentralized trials are even more center stage than before.
Outsourcing-Pharma (OSP) recently spoke with Marina Acosta Enslen (MAE), associate director of clinical management for Rho, about the challenges and opportunities associated with clinical trials, and how trial teams can better work with patients.
OSP: Could you please tell me about the evolution of decentralized trials in the years/months leading up to the pandemic?
MAE: In the months and years leading up to the pandemic, the industry has gradually moved towards the implementation of decentralized clinical trial solutions. These have included ePro solutions, direct data capture, eConsenting, wearables, direct-to-patient IP delivery, and home health care solutions, just to name a few.
Implementation can be challenging, as it frequently involves new technology. Not only do sponsors and CROs need to have the ability to manage the technology (and data, which flows from these solutions), but the adaption may require sites and patients to be more technologically capable and literate. Due to some of these challenges, the industry’s adoption has been slow.
OSP: How has that evolution changed since COVID-19 landed on us?
MAE: COVID-19 has accelerated the pace of implementation of decentralized trials. Protocols are now being developed proactively, keeping decentralized approaches in mind to ensure studies can continue even if areas of the country are shut down due to a resurgence of COVID-19.
OSP: Could you please share how the pandemic has impacted the patient experience?
MAE: Initially, the pandemic impacted the trial patient’s ability to be seen for their study visits on time and, in some instances, to maintain continued access to IP. Sponsors, CROs, and sites pivoted quickly to ensure patients would not lose access to IP, but some subject visits were missed in the first four to eight weeks following the initial pandemic shut down.
Some studies were required to halt recruitment efforts, and some patients that were in screening at the time were ultimately unable to participate. As clinics adjusted to the new normal, clinical trial patients were able to return to clinics for in-person visits and recruitment activities.
With the inclusion of decentralized trial solutions in amended and new protocols, many post-pandemic clinical trial patients may now expect to have fewer on-site visits and may conduct more study visits with research staff via telemedicine visits. They may also spend less time traveling to their site, but more time providing real-time data via special apps on their phone or a study-specific provided device; they may also be asked to wear a device that is capable of capturing data or may even be asked to collect and mail lab samples from home.
OSP: How does changing from brick-and-mortar site visits to decentralized (either in part or in total) benefit sites and sponsors?
MAE: This approach benefits sites and sponsors by increasing their real-time access to data, ability to reach a geographically more diverse population and, in a potential decrease in time and resources needed to capture data, assuming direct data capture technology is included in the decentralized approach. It can also increase the potential trial patient pool, to help enhance and speed up enrollment, as patients may no longer be impeded by geography.
OSP: Similarly, how does that shift benefit patients?
MAE: The shift benefits patients in that it is designed to be patient centric. The patient may no longer have to travel for frequent site visits or miss work to participate. In the rare disease space, a patient that may have been required to travel hundreds of miles for treatment and participation four times a year may now only need to make that journey once. Patients that may have opted out of participating in a clinical trial, due to the multiple challenges of on-site visits, may now have the ability to participate.
OSP: At the outset of the study design stage, how should trial teams take the patient experience/burden/voice into account?
MAE: They should examine their schedule of events and think of it from a patient’s perspective. Is this feasible from a logistical perspective? Is it reasonable? How can the data integrity be maintained while making study participation easier for potential study patients? Ultimately the sponsor will benefit from a study that is easier to recruit.
OSP: In a recent Rho blog post, you state, “The patient must be the central focus of any decentralized solution.” What considerations should trial teams make?
MAE: When clinical sites are closed and/or patients aren’t able to travel to sites, it’s important to consider the following:
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.
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.
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.
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.
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.
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.
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.
Centralized monitoring and data visualized monitoring
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.
OSP: Is there anything else you’d like to tell our readers?
MAE: We are risk adverse in this industry and sometimes change can be daunting. However, embracing change mindfully, while thinking strategically, can ultimately benefit everyone.