June 11, 2021 PAO-06-21-CL-03
While protocols incorporating remote monitoring have been growing in use across the industry since the U.S. FDA and EMA guidelines (2013) and the standardized framework created by the industry consortium TransCelerate BioPharma, the pandemic has acted as catalyst for more widespread adoption.
Before the pandemic, a significant percentage of studies still used traditional forms of monitoring that involved CRAs physically travelling to investigational sites to perform source data verification (SDV) and source data review (SDR) to ensure patient safety, data reliability, and data quality. With the onset of the pandemic, biopharma and biotech organizations faced quarantines, site closures, travel restrictions, lack of access to investigative sites, clinical supply chain interruptions, and disruption due to personnel or trial participants affected by COVID-19. In order to avoid suspension or delay of trial protocols and placing both trial participants and research personnel at risk and to ensure maintenance of good clinical practice, remote monitoring was fast tracked as a viable alternative solution to traditional on-site monitoring.
At the onset of the pandemic in early 2020, the FDA issued further guidance on the conduct of clinical trials and offered permission to consider “optimizing the use of central and remote monitoring programs to maintain oversight of clinical sites.” Sponsors were encouraged to continue to increase remote monitoring, both centralized and decentralized, in order to reduce disruption during the COVID-19 pandemic.
While the FDA provided early recognition of the need for an alternative to traditional on-site monitoring, there was a lack of adoption and accessible infrastructure to allow compliance with the Health Insurance Portability and Accountability Act (HIPPA) and 21 CFR Part 11 to allow access to patients’ records. Without such compliance infrastructure, remote monitoring had to be linked to enhanced centralized monitoring. Centralized monitoring using data analytics can be used to support both traditional on-site and remote monitoring. In some cases, a hybrid approach has been employed to maximize data integrity and patient safety. However, decentralized remote monitoring is rapidly evolving into the industry standard going forward, seeing further acceptance by global regulatory bodies.
Decentralized remote monitoring enhances trial flexibility, making research resistant to disruptions due to pandemics or any other unforeseen natural disasters. The main advantage of a remote approach to monitoring is that it enables monitoring of data in real time. This enables sponsors to employ more innovative and efficient protocol designs (e.g., adaptive designs) to reduce both the number of patients studied and the time to complete studies and accelerate the delivery of innovative medicines available to patients.
There are significant advantages to immediate data monitoring, as key risks and outliers can be readily identified, and corrections can be implemented immediately, driving higher quality. Unlike traditional on-site monitoring, this instantaneous assessment garners a proactive approach as an alternative to retroactive repair and revision. Instead of the need to repeat 10 or 20 tasks for multiple trial participants after the fact, these revisions or repetitions are often significantly reduced before they are necessary in widespread swaths of trial participants.
Due to the intricacies of all the moving parts in clinical trial implementation, sponsors are consistently seeking a “fit-for-purpose” strategy. There are varying tolerance levels when considering whether remote monitoring or a decentralized perspective will be feasible, particularly when global regulations must be considered. At present, sponsors are building decentralized remote monitoring options into protocols and monitoring plans as an alternative option, making it ready for times needing flexibility. With the ease of use and implementation of today’s platforms, decentralized remote monitoring can be offered midstream during an ongoing study; however, the benefits of a decentralized remote monitoring solution are maximized when employed from the start of a study.
A clinical trial management system (CTMS) plays an important role in ensuring that all members of the clinical research team work together from a remote standpoint. CTMS provides the means for assimilation of the data. Data Analytics/Centralized Monitoring teams provide targeted data visualizations and analytics to the clinical research team so the CRAs are fully informed of which investigator sites and data to prioritize and what actions still need to be completed to drive compliance, mitigate any risk factors, and ensure proper oversight and regulatory compliance.
Decentralized remote monitoring enhances trial flexibility, making research resistant to disruptions due to pandemics or any other unforeseen natural disasters. The main advantage of a remote approach to monitoring is that it enables monitoring of data in real time.
An aspect that differentiates PPD in the industry is the sheer number of projects our teams have successfully implemented. For example, the number of trials incorporating a remote SDV/SDR strategy currently exceeds 200 across several countries, including several COVID-19 clinical trials. PPD’s breadth of experience is vast and distinguished against other organizations when it comes to risk analysis, monitoring efficiency, speed, and optimization of SDV/SDR conducted in a given study.
PPD not only possesses the ability to tap into multiple available platforms —rather than being locked into a single SDV tool — but the capacity to adapt to changes in the platforms themselves and work with platform partners globally. In addition, our teams utilize other available novel tools to increase clinical study protocol effectiveness. These tools can produce significant cost savings over the long term, presenting a strong opportunity cost for sponsors. Our global operations are cross-functional, driven by quality input from the outset. Data privacy, legal considerations, and risk management are of paramount importance.
We are proud to have a robust track record with a network of experienced CRAs. These are individuals who have years of providing high-quality monitoring services and are very familiar with the clinical research sites and staff. As a result of the pandemic, a new regional infrastructure has emerged of quality individuals who have adapted not only to working remotely — but working remotely in a risk-based SDV/SDR-type environment. It has improved efficiency and flexibility, since fewer resources are needed to achieve the same output. The right individual can now do things simultaneously when previously it would involve several people in multiple locations doing tasks concurrently.
PPD continues to develop dynamic protocols for sponsors so that amendments are unnecessary. With the implementation of decentralized remote monitoring, PPD can promote all-around safety: for CRAs, the clinical research sites, patients, and all others involved.
When evaluating the appropriate CRO for a clinical trial involving remote monitoring, there is a tug of war between what a sponsor wants in the present moment and anticipation of what they might need in the future, should the research progress or the approach shift. PPD differentiates itself by its ability to deliver on both those wants and needs for different kinds of trials in different ways, being adaptable and flexible – carefully considering possible abrupt changes, such as those recently thrust upon the industry in the wake of the COVID-19 pandemic.
PPD remains ahead of the innovation curve. Versatility, adaptability, and the ability to flex various models that can be pivoted rapidly position PPD as the leading choice to support today’s clinical trials.
Amber Lee is responsible globally for PPD’s in-country site startup, monitoring and support teams, as well as those for clinical functional service partnerships and centralized monitoring. Lee joined PPD in 2006 and has more than 30 years of experience in operational delivery and has held roles at AstraZeneca, GlaxoSmithKline, Merck, Lipha and Wyeth, as well as academic positions at the University of Southampton, U.K., and the University of Wellington, New Zealand. Om addition, Lee has a wide array of therapeutic experience, including women’s health, circulatory, hematology/oncology, infectious diseases, neuroscience and endocrine/metabolic. Lee earned a Diploma of Clinical Science from the University of Wales and a Bachelor of Nursing from the University of Southampton, U.K. She is a registered general nurse.