A variety of approaches have been used by clinical trial sponsors to ensure that monitoring obligations are fulfilled. In the year 2013, the U.S. Food and Drug Administration (FDA) recommended the industry to shift from traditional monitoring to remote and risk-based monitoring to increase efficiency, optimize resources and reduce the costs of clinical trials. Earlier this year, due to the recent coronavirus disease (COVID-19) pandemic, the FDA, European Medicines Agency (EMA) and other regulatory bodies have further encouraged the move, emphasizing that, “If planned onsite monitoring visits are no longer feasible, sponsors should consider optimizing the use of central and remote monitoring programs to maintain oversight of clinical research sites”.
Never before, as in this period of the viral pandemic crisis have had the clinical trial industry experienced the challenges of performing onsite monitoring. Social distancing, travel restrictions and lockdown conditions prevent CRA visits to clinical sites and traditional on-site monitoring may no longer be the most practical or safest form of monitoring. Also, the integrity of clinical trials is affected with more potential for study conduct issues, and general non-compliance. The COVID-19 pandemic has accelerated interest in the remote monitoring approach and the industry has thus embraced newer and better technological solutions to conduct and manage clinical trials in a completely remote and digital mode.
Why Shift from Traditional SDV to remote SDV (rSDV)?
Traditional monitoring tasks are performed in person and on-site.
The main activity of clinical trial monitoring—Source Data Verification—is a process that ensures the integrity of the clinical data and therefore forms a crucial part of the on-site QC process. From a regulatory perspective, it provides evidence that the data collected is true and authentic when submitting to the regulatory bodies. Apart from SDV which forms the main chunk of the onsite tasks, a CRA also performs drug reconciliation, essential documents verification, GCP compliance check, and risk identification and queries resolution; to name a few.
The last few decades and the current pandemic situation have increased the complexity, size, and the number of clinical trials, not only across the industry but also within individual organizations. With this comes the increased pressure of effectively monitoring these trials. Whilst industry leaders are promoting a more risk-based approach for the monitoring of clinical trials, especially with the changes in ICH GCP E6 R2 Addendum (November 2016); newer technologies are now available that enables the efficient SDV of most clinical trial data remotely.
Thus transitioning from onsite SDV to remote SDV is not only the need of the hour but also an opportunity for the research industry to ensure it is well prepared for future crises. Moreover, the rSDV process is cost-effective since it significantly reduces costs related to monitoring visits and associated travel. It also makes monitoring visits less disruptive and more valuable to all the stakeholders since the rSDV process is not conditioned by the need for a simultaneous presence of both CRA and CRC; and the time commitment of the site staff is reduced compared to that of an on-site monitoring visit. The CRA can check multiple sites’ data from a single central location instead of going to a particular site. By this approach, the CRA can review more data in less time while remaining efficient.
Model rSDV Capabilities
SDV mainly focuses on and puts much effort into accurate data transcription from source data to case record form (CRF) and ensuring that both sets of data are congruent. Ensuring the congruency of source data versus CRF improves data quality and integrity. In a remote environment, a basic rSDV model should have the minimum of the following capabilities to support this transition from offline to an online mode.
Streamline remote source data provisioning and aggregation
- Efficient remote SDV (rSDV) is done through scanning of redacted source document PDFs or image files by a site user into a central repository, where they become viewable to an external CRA.
- The system automatically creates subject folders within this central document repository where the site user can upload the source files systematically. Site file records are thus organized so that both the Sponsor/CRO and site team can work efficiently.
- If an rSDV module is integrated with an EDC system, the process becomes more seamless since this serves as a central workstation and the users do not have to toggle between two applications to perform the tasks related to rSDV.
- Validated online portals with audit trails, mobile apps, or other such technologies may serve as a technological platform where rSDV can be performed in a secure environment.
Compliance to both regulatory and privacy requirements
- Both the technological, as well as the procedural solution for the remote source data verification, must comply with the regulatory (ICH GCP and 21 CFR Part 11) and privacy (HIPPA Privacy Rules) requirements.
- The source data must be appropriately redacted and either the system or a process must ensure that no inappropriate subject identifiers were added. Either the clinical site personnel or an independent entity/person that is not part of the study should perform redaction or there should be a technology/automatic program in place where subject identifiers are first electronically de-identified while uploading to an application.
- The system should capture automatic audit trails of all documents and folders in the study and the rSDV module should be validated according to GCPs standards.
- The sponsor should define a procedure for clear identification of personnel (CRA) who is responsible for verification of source data of the subjects.
- The rSDV application should guarantee that access to the database containing the subject’s identifiable data is restricted with controlled access and viewable with read-only rights.
- The application should use advanced cryptography and security protocols in compliance with GDPR, to provide controlled access to the system. The system should capture the audit trail of each user activity.
Incorporate workflow and reporting tools
- The remote SDV application should come with a workflow such that the CRAs can access the clinical site from anywhere, at any time, to review study documents and source data; as well as raise comments on the reviewed documents for the site team to respond.
- The comments raised by the CRA should be appended to all files and documents for the site to review and follow-up. The system should flag the source/study file in case of any open or responded comments to assist the user’s retrieval of information in a time efficient manner.
- The system should have a dashboard for indicators such as
- Missing or expired documents
- Documents flagged for review
- Documents uploaded since the last login
- Documents with open comments
- The system should be able to send automatic notifications to the users for any defined action item.
The feasibility of remote source data verification (rSDV) has been confirmed already in a pilot study titled “Remote Source Document Verification in Two National Clinical Trials Networks” published in 2013 in PLOS ONE.
Today, multiple eClinical technological solutions are available that allow remote management of clinical trials in a complete digital model. We hope that the clinical research industry does not only consider this as a temporary solution to combat an emergent pandemic situation but consider this as an era of the digital modernization of clinical trials.
As a technology enabler, Octalsoft, through its expertise and experience is always ready to support those pharmaceutical companies and CROs who want to undertake a path of digital modernization of clinical research. To request a demo of Octalsoft rSDV module, click here.