Best Practices to Optimize Remote Monitoring for Decentralized Trials

Remote monitoring can drive more innovative and efficient protocol designs — if optimized well. Learn how remote monitoring works, common options and recommendations for implementation into your decentralized trials.

In a recent global survey of drug developers conducted by the PPD clinical research business of Thermo Fisher Scientific, organizations that use decentralized trials said they expect their usage to jump 24 percentage points by 2024, compared to 2021 levels. Even organizations not yet using decentralized trials anticipate that more than a quarter of their clinical trials will employ this strategy by 2024.

As adoption of decentralized clinical trial models continues to increase, so too does the need for reliable remote data acquisition. With the right systems in place, remote monitoring can enable sponsors to employ more innovative and efficient protocol designs in decentralized trials, reducing both the number of patients studied and the time to complete studies.

The key to success is selecting the right electronic solution for each specific site and trial.

The industry is aligning to digital tools and remote data acquisition in decentralized trials.

In December 2021, the U.S. Food and Drug Administration (FDA) issued draft guidance on digital tools for remote data acquisition in decentralized trials, as a direct result of a shift in the agency’s thinking toward promoting the adoption of decentralized clinical trials. The guidance focuses on ensuring that digital health technologies (DHTs) are:

• fit-for-purpose,
• accurate,
• usable and
• validated.

As suggested by the FDA, successful decentralized clinical trials cannot take place without access to appropriate technologies that enable remote enrollment and patient evaluation, electronic solutions for the collection of assessments, and digital tools that support remote monitoring.

Specifically, systems are needed to support:

• electronic consent (eConsent),
• electronic clinical outcome assessments (eCOAs) generated both during home healthcare visits and by patients as patient-reported outcomes (PROs),
• telemedicine, and
• where needed, long-term follow-ups.

When the right digital technologies are deployed, everyone benefits from alerts and reminders, automatic data checks, and the centralization of data in a single cloud-based application. In addition, with the growing acceptance of multiple device modalities, including wearables like smart watches, there is much more flexibility.

Clinical trial organizers today can implement fit-for-purpose digital solutions like never before, and remote monitoring is becoming the industry standard.

Clinical trial sponsors and contract research organizations (CROs) must ensure that investigator sites follow protocols, good clinical practices (GCPs), standard operating procedures and all relevant regulations.

They must also ensure the protection of patient rights and safety, as well as the accuracy, completeness and verifiability of reported trial data. In fact, monitoring is currently estimated to account for approximately 30% of clinical trial operating budgets.

Protocols incorporating remote monitoring have been growing in use across the industry since the FDA and European Medicines Agency (EMA) published guidelines in 2013 and industry consortium TransCelerate BioPharma established a standardized framework. However, as with decentralized trials themselves, adoption became more widespread in recent years.

Clinical research associates (CRAs) perform source data verification (SDV) and source data review (SDR) to ensure patient safety, data reliability and data quality. During the pandemic, when the work could not be performed at investigator sites, remote monitoring was fast-tracked as a viable alternative to avoid suspension or delay of trial protocols — shielding trial participants and research personnel from risk — and to ensure maintenance of good clinical practice.

Since then, remote monitoring has evolved into the industry standard, with further acceptance by regulatory bodies. In fact, in the initial survey from PPD Digital and Decentralized solutions, 48 of 100 survey respondents rated remote monitoring as one of the top two DCT strategies, tools and platforms with positive impact on trial performance.

A follow-up survey PPD conducted in late 2021 found that 85% of these participants had implemented or planned remote site visits and/or monitoring activities. In addition, 53% rated remote site visits/monitoring at the two highest levels of importance (9 or 10 on a 10-point scale) among implemented or planned strategies, with a similar percentage praising its impact on trial performance.

In total, nearly two-thirds of respondents in the 2021 survey reported using digital and decentralized trial options for their clinical research.

How does remote monitoring work?

Remote monitoring technologies create numerous benefits for decentralized and hybrid trials, including:

• improved communication, tracking and compliance,
• greater flexibility and resilience in the face of challenges,
• better accommodation of adaptive and other new trial designs,
• alignment with growing expectations around real-world data, and
• the management of data generated by wearable technologies.

The key is to implement a system fully capable of meeting the specific needs of the trial. A digital network that connects the sponsor and site system to enable remote monitoring benefits both investigator sites and sponsors.

Here’s a rundown of how remote monitoring enhances planning and effectiveness.

• First, with user-based permissions, the CRA can access needed documentation at any time or location without waiting for approval or needing to travel. Remote monitoring systems also facilitate communication via multiple digital channels.
• Immediate data monitoring facilitates quicker identification and correction of key risks and outliers, as opposed to the retroactive repair and revision of traditional monitoring approaches.
• Compliance is improved by systems that are designed to meet the requirements of the relevant regulations and standards, including controlled access and comprehensive audit trails.
• Automated document routing ensures that everyone involved receives the right documents when needed while avoiding duplication of work.

Tracking site performance and study progress in real time is possible without the need to be on site. And, with digital tools and technologies, repeatable processes are standardized and made more efficient using document templates and centralized storage.

Common Options for Remote Monitoring of Clinical Trials

The approach to remote monitoring can impact its effectiveness. It’s also essential that ownership of data and documents remain with the site to stay in compliance with GCP standards, and that sites have control over monitor access.

Three common options for remote monitoring of clinical trials are:

• Sponsor-driven remote monitoring was initially the most common pathway, requiring software solutions that integrate with existing site technologies and workflows.
• In recent years, we’ve seen the rise of site-managed electronic investigator site file (eISF) platforms, connected to the sponsor’s electronic trial master file (eTMF). These platforms align with both site processes and sponsor needs, enable proactive improvement of workflows, and can be used for multiple studies. Sponsors benefit from the use of a single platform for all sites and studies, as well as streamlined monitoring activities that do not disrupt site workflows or otherwise burden sites.
• Another more recent option is site-driven remote monitoring and eISF management. Sponsors are often willing to fund development of such solutions because of the benefits: greater efficiency and cost savings, enhanced productivity leveraging existing processes, real-time access for greater oversight and transparency, better communication and collaboration with electronic document exchange, central data access for better tracking and trending, and reduced compliance risks. It is also possible to use a single platform across all studies at the site.

Regulatory Considerations for Remote Monitoring of Clinical Trials

A key consideration for remote monitoring is compliance with relevant regulations and requirements at the local, national and international levels, following the established hierarchy of authority and compliance.

It begins with the patient and the need for informed consent forms, then proceeds to expectations established through clinical trial agreements, site-established standard operating procedures, institutional polices, and regulations across local, national and international authorities.

Only when sites have alignment across stakeholders, processes and policies can they be considered remote-monitoring capable.

Sites must consider the broadest applicable regulations and expectations when updating policies and procedures. Clinical trial organizers and sponsors should reference existing regulations and other requirements in internal policies and procedures to demonstrate compliance.

A particularly critical one is compliance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule regarding sharing protected health information (PHI): The patient must sign a waiver of HIPAA authorization to remotely share PHI with monitors. Often, institutional review boards embed the waiver of HIPAA authorization into their informed consent form template.

Similar concerns exist with respect to global regulatory requirements. While there are some differences, the key concern is coordinating plans in conversation with local regulatory bodies.

Risk-Based Remote Monitoring for Decentralized Clinical Trials

Both the FDA and the EMA expect risk-based approaches to remote monitoring.

Risk-based monitoring (RBM) is a “more targeted, strategic approach that takes advantage of increased connectivity and advances in data analytics” and “streamlines and optimizes error detection, which may facilitate the replacement of some or all on-site monitoring visits.” It is also part of risk-based quality management (RBQM).

There are five key components of RBM:

1. Use of key risk indicators (KRIs)
2. Centralized monitoring
3. Off-site/remote-site monitoring
4. SDV
5. SDR

RBM can be targeted or triggered. Targeted RBM focuses on certain data points, sites and events determined during the trial planning stage to have the most risk. Thus, validating them should provide the best value for time and resources invested. Triggered RBM occurs in response to specific events that create the need for detailed monitoring.

Unlike SDV and SDR, which focus on past events, the goal of RBM is to examine present data and future trends through real-time monitoring and predictive modeling.

Benefits of RBM include:

• improved trial execution in the form of more effective monitoring,
• improved trial quality,
• greater patient safety and
• increased efficiency.

These benefits have become more apparent in the past two years. However, data suggest that RBM affords as high a level of effectiveness as traditional on-site monitoring.

Best Practice Recommendations for Remote Monitoring Implementation

A well-defined strategy for remote monitoring includes planning and design, process tracking, reviews, and assessments. The strategy should be updated to promote best practices, ensuring alignment with study sponsors and promoting effective communication.

Choosing the approach that best fits the workflows and needs of the site is paramount, as is the right monitoring platform. In addition, the use of a clinical trial management system (CTMS) helps to ensure that all members of the clinical research team work together.

Frequent, regular meetings enable ongoing discussions between sponsors, CROs, central and supporting offices, and vendors to proactively address any concerns or issues.

Revision of remote monitoring plans should be expected, keeping in mind the long-term benefits of this approach: increased efficiency, reduced costs and higher data quality.

Key Capabilities Needed in a Remote Monitoring Partner

When evaluating the appropriate partner for a clinical trial involving remote monitoring, sponsors must consider present needs – and anticipate what they might need in the future, should the research progress or the approach shift.

To enable trial success, biotech and biopharma organizations should look for a CRO that has proven itself to be adaptable and flexible, capable of remote monitoring success across different trials and indications.

The PPD clinical research business of Thermo Fisher Scientific has been involved in the successful implementation of more than 200 trials incorporating a remote SDV/SDR strategy across several countries and offers deep experience in risk analysis, monitoring efficiency, speed and optimization of SDV/SDR conducted in each study. Remote monitoring is performed by a network of experienced CRAs with a track record of excellent performance.

With access to multiple platforms, PPD is able to meet the specific needs of clients. PPD’s capacity to adapt to changes in the platforms themselves enables work on an ongoing basis with platform partners globally.

When implementing decentralized remote monitoring, it’s important to choose a CRO partner that can promote all-around safety: for CRAs, the clinical research sites, patients and all others involved.

PPD remains ahead of the curve and is committed to furthering novel digital solutions, including those for efficient and effective remote monitoring.