The EMA Speaks: Key Findings from the EMA’s eSource DDC Qualification Opinion for the Busy Layperson


Patient data is the key element that drives clinical research. The clinical research industry is transforming, becoming more adaptable to improve the way data is captured. Regulators are widely accepting the use of various technologies for the benefit of the key stakeholders in clinical research.

eSource is one such technological advancement, with various regulators and agencies starting to recognize the benefits of eSource Direct Data Capture (DDC). The latest of these regulators is the European Medicines Agency (EMA), which recently published a qualification opinion on the use of eSource DDC while conducting clinical trials. The opinion has been adopted by the Committee for Medicinal Products for Human Use (CHMP). Released by the EMA in October 2018, it presents the views of CHMP on the “regulatory acceptability” of eSource DDC and the potential benefits to the whole ecosystem.

The significance of this qualification opinion should not be underestimated. The reservations about eSource DDC that have long pervaded the European clinical research industry have centered largely on the regulatory uncertainty around it, and the EMA has now taken a big step toward clarifying that uncertainty and bringing a technological watershed moment to one of the world’s foremost regions for clinical research. This white paper will discuss key takeaways from the qualification opinion, providing readers the opportunity to learn its most essential components quickly and in a layperson-friendly format, without having to find time to consume the entire opinion in its original form.

 

What is eSource DDC?

Before diving into the key points of the opinion, it’s helpful to define eSource DDC and establish parameters around what constitutes it. “eSource DDC” is defined in the EMA guidance as an electronic application and/or device, such as a tablet, that allows direct entry of clinical source data at the point of care by clinical trial site staff.

eSource DDC can be considered as an evolution of Electronic Data Capture (EDC). However, unlike EDC, eSource DDC allows clinical data to be directly fed into the system, thereby eliminating the need to manually transcribe it into EDC from paper, while allowing real time data validation.

 

Key Takeaways from the Qualification Opinion

 

1. The qualification opinion does not signal an eSource free-for-all

It is worth noting that the EMA opinion is just that – an opinion – and does not supersede applicable national or EU-level requirements governing the use of eSource DDC. It also establishes parameters around what constitutes acceptable eSource DDC in clinical trial environments, such as:

  •  • Alignment with the legal requirement of ICH guidelines on Good Clinical Practice
  •  • Compliance with the EU Clinical Trials Regulation, GDPR, and other EU-centric regulations
  •  • Ability to provide an audit trail of all additions, deletions, and other changes in the system

However, though the EMA takes care to clarify that the opinion does not represent set-in-stone new policy on eSource DDC, the opinion does signal that European regulators are warming up to the use of the technology in clinical trial contexts. In the coming months and years, the opinion could prove to be a preface to more official guidance on eSource usage in clinical trials, or even a new policy mandating its use.

2. The EMA seems to be largely amenable to the use of eSource DDC

The qualification opinion is a positive step towards improving clinical trial efficiency in Europe with eSource DDC. The regulatory body seems to recognize the potential of the technology to make clinical trials more efficient, while maintaining security and compliance.

 

Advantages of DDC recognized in the qualification opinion:

  •          1. Data accuracy

By allowing electronically-captured source data to sync directly to an EDC, eSource DDC helps reduce redundant and duplicate entry of the data, thus reducing the possibility of transcription errors. One can expect the data entered in an eSource DDC tool to be more complete and accurate due to the “alerts” functionality in the technology, which would flag any inconsistencies or missing data to the investigator. Moreover, an eSource DDC system has an audit trail, which is ALCOA+ compliant (ALCOA stands for Attributable/Legible/Contemporaneous/Original/Accurate).

• Attributable: Who entered or modified the data

• Legible: Electronic data and metadata is in human readable form

• Contemporaneous: Time of data entry into the eCRF should be close to the time of clinical activity

• Original: Earliest record and the changes and/or corrections should not obscure prior entities

• Accurate: eCRF should be a valid representation of the source data

According to a pilot study titled “A comparative effectiveness study of eSource used for data capture for a clinical research registry” by Elsevier, eSource produced 0% data quality issues compared to a 9% error rate in case of manual transcription.[1]

[1] www.sciencedirect.com/science/article/pii/S138650561730103X

Multiple studies worldwide have shown that the sites generally feel that eSource has helped them reduce the overall workload. According to an article titled “Data Shows eSource Reduces Site Workload”, 56% of respondents felt that the implementation of eSource DDC reduced their workload. Of these, more than 83% of respondents felt that the edit checks helped in reduced errors, 75% felt data entry was easier, and 78% saw efficiencies in data entry. [1]

 

2. Optimized patient safety and monitoring

These “alerts” and audit trails in eSource DDC could help reduce protocol deviations such as including an ineligible patient in the trial, thus avoiding potential patient safety issues.

The ability to sync data directly from an eSource DDC platform to an eCRF also drastically reduces the amount of double data entry – a process that is vulnerable to data entry errors as data is transcribed from paper source documents to the eCRF – performed in a study. This renders source data verification (SDV), which constitutes a significant portion of monitoring efforts, largely unnecessary. With less paper transcription and less time spent on SDV, both site staff and monitors can optimize their workflow away from logistics and toward more meaningful tasks. The EMA opinion estimates that eSource DDC can reduce the amount of SDV by 38%, noting that this allows “Monitors time to look at other documents on site and spend more time with the study team.”

 

3. Physical security

The EMA notes that eSource DDC provides better physical security to the collected source data, compared to paper. Data collected using eSource DDC is not generally vulnerable to the risks of damage, destruction, or loss that paper-based source data faces. From the qualification opinion: “The major risks to paper files such as fire or flood are not as significant a concern for source data in eSource DDC systems due to the electronic nature of the original source and due to the inbuilt back-up functionality, which is standardly available in these types of applications.” eSource DDC can also encrypt and securely back up the data across multiple geographies. Moreover, using eSource DDC provides better flexibility in terms of long-term storage and retrieval.

In one of their pilot trials, Novartis performed the technical due diligence and ensured that all disaster recovery and business continuity controls were in place. This included maintaining data storage redundancy and an appropriate contractual agreement with the vendor.

4. Improved transparency and traceability or data compliance

When it comes to the regulatory side of things, the opinion notes that while compliance with EU-centric regulations is not a given, it is certainly feasible: “If [eSource DDC] can be designed to meet all requirements for ICH source data and (national) requirements regarding the EMR maintenance, then it could be compliant.” Under regulations such as ICH GCP and GDPR, privacy of the research subjects is of the utmost importance. eSource DDC can be fully compliant with ICH GCP and GDPR regulations if the patient data is pseudonymized before handing over to the sponsor and non-pseudonymized for the EHR, and if the sponsor is not given any remote access to the patient-identifying data.

Moreover, if the DDC platform adheres to the above guidelines for compliance, data from a clinical trial that uses an eSource DDC system can be submitted in support of a Marketing Authorisation Application (MAA) for a medicine.

Novartis, in its eSource DDC trial, made the “investigator site staff” the only party with “write” access to the data entered into the eSource DDC forms. Other parties such as “sponsor monitors” and “sponsor or CRO data managers” were given limited read access to the database. Thus, these parties could just add queries to the protocol defined CRF data forms.

 

3.   Benefits of eSource DDC for key stakeholders

 

4.   Perceived limitations of eSource DDC:

Change management:

Being a relatively new technology, eSource DDC tools may need significant amount of training that may have to be imparted to various parties such as site staff, sponsors and monitoring staff, etc. Furthermore, there may be challenges with respect to acceptance of the system by the site staff. However, once the training is complete and the eSource DDC tool is accepted, it can lead to potential time and cost savings in terms of streamlined processes.

 

Alignment of Medrio’s eSource solution with EMA opinion:

 

The US FDA published eSource guidelines in 2013 highlighting the aspects of data capture, data review, and record retention by various entities related to a clinical trial such as sponsors, CROs, and investigators. By publishing guidelines on the use of eSource DDC, EMA seems to be following the footsteps of the US FDA.

Given the advantages of implementing eSource, this is encouraging to see, and could alleviate some of the regulatory uncertainty that surrounds new technologies. As stakeholders continue to look for ways to reduce costs and improve the accuracy of data collection, eSource DDC provides a framework for how new technologies can be implemented in clinical trials in Europe.

Medrio, a leading provider of e-clinical technology, realized these benefits of eSource early on, and has had its eSource solution on the market for the past several years. In addition to complying with FDA guidelines, it’s now clear that Medrio’s eSource solution is well-aligned with the guidelines and benefits described in the EMA’s qualification opinion of eSource DDC:

  • Medrio’s eSource solution provides the ability to capture data electronically at the source and sync it with the Medrio EDC solution.
  • It also provides features such as eliminating SDV, real-time site monitoring and tracking.
  • Medrio’s eSource solution ensures data quality and patient safety with real-time notifications.
  • It ensures security and privacy of the health data by keeping it password-protected.