Strategies for Virtual and Decentralized Study Designs
In the wake of the COVID-19 health crisis, studies need solutions to remediate disruptions and ensure continuity of support for sites and patients participating in research. Understanding how to incorporate technologies and strategies that decrease the reliance upon brick and mortar sites and ‘bring the study to the patient’ for conducting research is critical across all phases of drug development in today’s challenging environment.
Recently, Jersino Jean-Mary, Executive Director, European Late Stage Operations Team, and Aaron Berger, Executive Director, North American Late Stage Operations Team, shared their thoughts on how the pandemic is impacting clinical trials and post-approval research, and ways that the industry is working together to get patients the access they vitally need to novel therapies.
Traditional study designs are no longer practical due to the burdens on the healthcare system and restrictions in travel caused by the pandemic. What solutions are you incorporating into study designs that allow for data collection in this new paradigm?
Aaron Berger: A transformation was already occurring in the trial landscape and the global health crisis has accelerated this movement which touches most domains of study design and execution. From direct-to-patient digital recruitment strategies, patient-generated data collection technology, remote monitoring and source document verification, telehealth-enabled study visits and in-home nursing visits, we are seeing widespread integration of these solutions into study designs across the drug development continuum.
Jersino Jean-Mary: Our clients’ goals have always been to bring new therapies to market to ensure therapies reach patients and provide live-saving treatments as quickly as possible. The evolved clinical landscape we find ourselves in today provides an opportunity to reach patients more effectively and collect data utilizing technology to ease the burden on both patients and health care providers. The solutions we’re incorporating that include virtual study designs through remote / virtual monitoring, more efficient utilization of electronic medical records (EMRs), real-world evidence (RWE) data compilation, data warehousing and registries, are driving efficiencies to shorten development timeframes for our clients. With our telehealth and in-home nursing services, we support our patients by easing their burden in adhering to therapies and ensuring higher patient compliance in data collection. These integral changes will be around for years to come.
How do you ensure good clinical practice (GCP) obligations are met for ongoing studies?
Berger: In late March, shortly after the outset of the health crisis, the FDA issued Guidance on Conduct of Clinical Trials of Medicinal Products during COVID-19 Public Health Emergency¹. This document was issued to provide guidance to sponsors in meeting their obligations to assure the safety of trial participants and maintain GCP compliance. The guidance document suggests that sponsors consider alternative methods for safety assessments, such as phone contacts, virtual study visits and alternate site data collection. In addition, the guidance contemplates best practices for remote monitoring of data as well as electronic consent and signature processes. GCP obligations still need to be adhered to, but the delivery, safety and monitoring of the study will need to adapted.
Jean-Mary: General regulatory and protocol guidelines must be followed to ensure patient safety – regardless of how the study is adapted into the current landscape. We are still diligently training sites on study procedures/protocols and GCP, though we’re now training them more virtually utilizing electronic training platforms and local resources to effectively conduct virtual Site Initiation Visits (SIVs). In addition, we continue to closely monitor the activity and output of sites in adherence with GCP principles, again conducted virtually and utilizing fit-for-purpose technology. We have seen this change as an opportunity to employ a true risk-based monitoring approach, allowing for a more focused real-time data review and better assessment of data trends around protocol deviations, adverse events, missing data, quality of data. All of these could have profound impact on the results of a given study.
What technologies do you use to ensure that you are conducting virtual monitoring in a compliant way?
Berger: In the March Guidance, FDA provided specific options that would be considered acceptable to support the conduct of remote source document verification:
- Sites can provide a “secure remote viewing portal that would permit site staff to provide access to the sites’ study documentation and/or trial participants’ source documents for study monitors review”. We are finding that several of the site EMR platforms are enabling functionality that meets these requirements.
- Site upload of certified copies of source records to a sponsor-controlled electronic or cloud-based repository contains appropriate security controls. We are deploying 21CRF compliant technologies that meet these standards.
By adopting these approaches, we closely replicate the conduct of the monitoring visit and conduct the essential function of source document verification in a virtual ‘data monitoring room’. In addition, the virtual monitoring experience is further supported by video conferencing with Investigators and Study Coordinators, as well as review of the eTMF, which was already widely adopted prior to the health crisis.
Jean-Mary: Telecommunication technology enables our monitoring team and study staff to meet virtually to ensure sites are complying with protocol and study guidelines. In addition, our proprietary technologies, like our EDC platform, are tailored to support virtual monitoring. In combination with these platforms, we are able to review drug accountability, patient-informed consent, source documents in a virtual setting with technology platforms we have access to, as well as meet with Principle Investigators (PIs) and study staff. In-person monitoring may still have a place in the future of clinical studies; however, we see it with less frequency. Moving forward as an industry, we could take a more pragmatic approach to monitoring by implementing a true risk-based approach where there only a percentage of on-site monitoring sites are conducted annually, supplemented with virtual or remote monitoring as the standard. This would seem to be a more efficient option for consideration.
How do you recruit patients in a virtual setting?
Berger: Direct-to-patient recruitment strategies have been utilized for years, including advertising, social media, use of prescription claims and lab data to target patients. These tactics drive patients to a web-screener or call center for eligibility confirmation, telehealth-enabled PI interaction and routing to an eConsent platform. A significant benefit to this approach is that the recruitment of patients is not restricted to the geographic areas that are within proximity to brick and mortar sites. This can be a significant advantage when conducting studies in rare diseases.
Jean-Mary: When recruiting for studies more virtually, it is even more important to ensure the visuals and tools utilized are clear, concise, easy-to-use, and engaging. It’s also key that the outreach is done via different modalities, through multiple channels, and directed to patients as well health care providers. We have produced more educational and recruitment materials, videos, and platforms for virtual trials which focus on providing several ways to pre-screen and enroll through multiple channels, such as text and web screeners. Call centers, mobile messaging, and digital assistant programs are also important for maintaining communication with potential and enrolled study participants. A key consideration is that all outreach is done in adherence with global data protection / privacy regulations, something that we have successfully navigated as communication is conducted more remotely.
How are you designing studies that rely less on the patient going to the site?
Berger: UBC has an existing virtual research, patient engagement and in-home nursing platform that rapidly allows our clients to transform traditional clinical protocol into virtualized study designs. We understand how a pandemic impacts the ability to collect critical insights essential to successful studies. We educate our clients on solutions and strategies to incorporate remote and virtual technologies into their study design.
Jean-Mary: For several years, UBC has been lock-step with the evolution of the clinical landscape, focused on direct-to-patient outreach and leveraging technology to ease the burden on both patients and health care providers. This thinking was in place prior to the COVID-19 pandemic and we have just enhanced the implementation of our services in the design and conduct of our studies. At the subject level, we have increasingly implemented into study designs a variety of data collection services that incorporate a mix of home health nursing to perform lab sample collection, drug administration, and routine assessments, telehealth virtual study visits, patient-generated data collection (including ePRO / eCOA), as well as virtual assistant and text messaging platforms. At the site level, the design focus has been on minimizing the number of data collection timepoints on studies, incorporating a virtual monitoring model via telecommunication technology, and practical measures such as delaying on-site monitoring or conducting additional days-on-site during windows where they are being allowed.
What strategies do you use to drive patient engagement and retention in a virtual or decentralized study design?
Berger: There are a variety of challenges in keeping patients enrolled and engaged throughout a study, and having a completely virtual trial comes with its own challenges. In order to mitigate patient drop off and ensure adherence to trial timelines, we are utilizing mobile messaging platforms and virtual assistants to support the trial from start to finish. From eligibility, consent, scheduling, enrollment, education and reminders, we are ensuring that the patient has the best possible experience in the study and is guided every step of the way through automated conversational intelligence.
Jean-Mary: Given the inherent challenges with engagement and retention in these times, UBC strongly believes that driving and maintaining interest starts with the simplification of study designs and their operational deployment. This includes streamlining data collection, providing effective training, disseminating engaging materials, and generally optimizing the study experience for participants. We also note that it’s vital to enhance the value of study participation for patients and health care providers. These include educational websites containing dynamic content and information, text/email engagement, and use of mobile app technologies. These involve having surveys and PROs completed remotely via patients’ own mobile devices or utilizing virtual assistant technology that travels with patients throughout study participation, providing reminders of things they need to do from a data collection standpoint to ensure quality data required for regulatory submission and review.
What are some of the key takeaways the industry should be thinking about moving forward in a virtual or decentralized study format as impacted by the current public health crisis?
Berger: Drug development is at an inflection point for disruption through the utilization of direct-to-patient and digital strategies that will modernize and accelerate the way we gather critical data and insights needed for regulatory decisions and beyond.
Jean-Mary: The technologies and strategies we just discussed from virtual monitoring to patient engagement are here to stay and are not just the future of research. UBC and the entire industry remain committed to accelerating research so our clients can continue to prove the safety, efficacy and value of critical therapies to ensure treatment gets into the hands of patients in a more efficient manner.
The COVID-19 pandemic continues to cause major disruptions to the continuity of biopharmaceutical companies’ research and development efforts. From consulting on virtual or decentralized study design and execution, to independent and confident therapy administration, through post-marketing safety requirements, UBC is the full-service partner to help you overcome the challenges posed by the pandemic – regardless of where you are in the product development lifecycle.
To learn how how to plan, prioritize and educate internal partners as you help your company enter the world of decentralized trials, download UBC’s Decentralized Research Playbook to uncover the key considerations today.