Comply With the New EMA CT-C19 Remote Source Data Verification (rSDV) Guidance

And Avoid Undue Burden on Patients and Sites

On February 4, 2021, the European Medicines Agency (EMA) issued CT-C19 guidance v4, an update on the management of clinical trials during the COVID-19 pandemic. Given the impact of COVID-19 on clinical trials and participants, the guidance acknowledges that standard clinical trial conduct may need to be adjusted to enable research to continue.

Accommodations must be made for trial participants entering self-isolation or quarantine with limited access to public spaces, including trial sites, to minimize the risk of spreading infection. Health care professionals prioritizing immediate, patient-care activities also need special consideration.

As a solution, the guidance introduces flexibility and procedural simplifications intended to preserve clinical trial integrity; protect the rights, safety, and wellbeing of trial participants; and safeguard clinical trial staff. Member states are encouraged to “mitigate and slow the disruption of clinical research in Europe during the public health crisis” by implementing the guidance to the maximum possible extent.

“Changes should be well balanced and proportionate, taking into account in particular the legitimate interest of trial sites in avoiding further burden in terms of time and staffing during the COVID-19 pandemic.”

EMA-Issued CT-C19 Guidance v4, Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) Epidemic

CT-C19 Guidance for rSDV and Audits Is Nuanced and Specific

While the guidance addresses a variety of activities, such as the completion of trial assessments, the provision of investigational drugs, ongoing recruitment, reconsenting and so on, two sections stand out: modifications for remote source data verification (rSDV) processes and audits.

 A risk-based approach is recommended to reassess sponsor oversight responsibilities, such as monitoring and quality assurance activities. Temporary, alternative and proportionate mechanisms of oversight should be instituted as required to balance appropriate oversight with the extra burden incurred for sites.

Sites are then responsible for reporting results of adjusted monitoring and review measures and their impact to sponsors. And once the pandemic abates, sponsors are responsible for robust follow-up monitoring to rectify and document the impact of the reduced monitoring.

“Data subject to remote source data verification are likely to require re-monitoring, in particular if it was based on pseudonymised documents, which cannot be considered as source documents, and considering that remote monitoring is expected to only have focused on the most critical information.”

EMA-Issued CT-C19 Guidance v4, Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) Epidemic

Though the authors repeatedly admonish sponsors to avoid overburdening already stressed sites and PIs, the suggested adaptations for rSDV to ensure trial participant safety, data integrity, and personal data protection in the time of COVID seem complex and time- and labor-intensive. That is, if data is collected via standard EDC or on paper records.

An Integrated eSource Data Capture Solution Removes the Burden

An excellent alternative, in this situation, would be Clinical Ink’s Lunexis™ eSource Direct Data Capture Solution. With this system, unlike with standard EDC systems, 85% of clinical trial data is entered directly into the electronic record during the patient visit. The clean, digitized data is then uploaded to a portal in real time, ready to be reviewed remotely.

Such an approach to data collection eliminates time-consuming and error-prone transcription steps and edit checks. There is no paper and no transcription, so no source document verification (SDV) is needed. These major efficiencies eliminate quantities of work under normal circumstances, delivering better quality data for less labor, with reduced timelines. Under the above pandemic guidance, our eSource approach would make a highly fraught task relatively simple.

Consider the below comparison of possible activities to adjust for data collection and verification during the current health crisis using a standard paper or EDC system versus an eSource system, as developed and implemented by Clinical Ink.

Comparison of Activities to Satisfy New Pandemic Guidance for Monitoring and rSDV

(Reference EMA CT-C19 Section 11 & Annex 1)

With Standard Data Collection Methods, Such as EDC and Paper Records With eSource Direct Data Capture
  • Cancel or postpone on-site monitoring visits, depending on urgency and site staff availability
  • Consider limited, targeted on-site monitoring for higher-risk clinical sites
  • Delay source data verification and audits, if possible
  • Adapt on-site monitoring plan to make greater use of alternative measures
  • Monitor continuously, as usual, via a fully remote, centralized review of integrated data collected into the eSource ecosystem and apply rSDR (remote source data review)
How to accomplish rSDV, where justified under the new guidance:
  • Focus on critical primary efficacy and important safety data
  • Only include secondary efficacy data when not placing undue burden on site staff
  • 85% of source data is captured directly into the digital record at the moment of creation and does not need transcription, and has real-time edits and validations applied as the data are being directly captured
  • Remainder of data sources can be approached as per guidance and can even be scanned and uploaded to the patient record and SDV’d remotely
  • Additional, general benefits include continuing, higher quality clinical trial data; faster timelines; prompt issue recognition and mitigation; and savings through efficiency and reduced monitor time and travel
Meet with investigators to determine feasibility of:
  • Sharing pseudonymized copies of trial documents with monitor, electronically
  • Providing direct, controlled access only to participants’ EMR
  • Site team facilitating video review of medical records — no copies or images allowed

Not needed with eSource DDC.
Ensure (jointly with PI) the protection of trial data and patients’ personal data, even if pseudonymized:
  • Document risk assessment of critical SDV needs to ensure only necessary data is accessed
  • Consult with data protection officer (DPO) and PI at each site to determine feasibility of security
  • Submit amendment to ethics committee and/or national competent authority (NCA) as required
  • Ensure secure internet connections, secure computers, and privacy for data sharing

Not needed with eSource DDC.
Describe remote monitoring process in new protocol applications or amendments:
  • Inform each trial participant to verify they have no objection to having their records reviewed remotely

Not needed with eSource DDC.
Where redaction is necessary:
  • Monitor must submit written request for specific participant’s trial records
  • Site staff create copies, second person does QC to ensure complete redaction of identifiers
  • Monitors must securely destroy paper and digital redacted document copies after accessing securely and provide certificate of destruction
  • As soon as visits resume, monitor should verify that the pseudonymized data matches that of participant with related code

Not needed with eSource DDC.
For video review of records, consider:
  • Video quality must be adequate for reliable legibility and viewer visual health
  • Secure video conferencing app is required
  • Video review is labor intensive for site staff

Not needed with eSource DDC.


Why Stress Site Staff More? It’s Completely Unnecessary With eSource

Clinical Ink’s integrated eSource direct data capture solutions enable companies to largely avoid the issue of rSDV by minimizing the amount of data that needs to be reviewed in that way.

Rather than jumping through hoops to adjust or suspend and later revisit on-site monitoring, sponsors can implement our Lunexis™ eSource solution. Teams will enjoy a seamless transition to ongoing, remote, near-real-time review of electronically collected clinical trial data while protecting investigative sites from a myriad of extra hurdles that would be unwelcome at the best of times.

Industry and regulators are encouraging practical solutions to continue important research during the global crisis without placing any undue burden on site staff. With our eSource solution, sponsors and monitors can log in, look at most data remotely without ever having to bother sites, review it, and be done. It’s that simple.

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