Regulatory aspects on EDC systems

Investigator-independent copy of the data

There is regulatory concern whether data collection in the EDC systems of today meets the requirement of a contemporaneous, certified copy that is not under the exclusive control of the sponsor. The requirement originates from the EMA eSource reflection paper: EMA/INS/GCP/454280/2010 “Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials” (June 2010).
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The FDA also explains this requirement on Electronic Source Data: “Guidance for Industry – Electronic Source Data in Clinical Investigations” (September 2013).
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Both the EMA and the FDA have stated publicly that the EMA eSource reflection paper and the FDA eSource guidance are equivalent to each other and place the same requirements on clinical trial data, and that any differences between formulations in the documents are merely due to the different judicial climates that the authorities must cater to in Europe and the US.

The requirement was also further emphasized with the recent update of GCP (June 2017).
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Before explaining how Viedoc assures an independent, contemporaneous copy of the data, one should understand how data has been recorded historically and what led to this requirement. With that background in mind, one will see that the requirement is more accurate today than ever.

How the data collection process has changed over the years

In the past, before ICH-GCP was established, CRFs consisted of a single, master copy – on paper. Thus, tracking changes and data edits was practically impossible. When ICH-GCP was introduced it required that a copy of the data should be kept at the investigators’ site, and the original at the sponsor. The No Carbon Required (NCR) CRF was developed to ensure an exact copy of the CRF. The NCR CRF consisted of three papers: one white (the original, normally sent to the data management department for performing data entry), one yellow (the sponsor’s copy), and one pink (the investigators’ copy, which stayed at the site).

Although the NCR CRF was indeed an improvement, the process to complete, collect, transfer and enter the CRF data at the sponsor was very time consuming (especially if the ink from the white copies didn’t bleed through to the yellow ones – a constant problem requiring clarification). To get faster access to data and to decrease the number of errors/clarifications, Remote Data Entry (RDE) systems were developed. In these systems, investigators, nurses, and study coordinators entered data directly at the site. The RDE systems were installed locally on a computer and data was periodically transferred to the sponsor. While the RDE systems had their own shortcomings: deployment, installation, support, usability and cost, this was certainly an improvement over the slow, fallible, and messy paper records. A copy of the data was also always available on the local RDE machine used for data entry.

Soon after the internet opened for general use, web-based EDC software was introduced. This improved the data entry process even further, as sites could simply use their own computers and send data directly to the main database. The EDC landscape has continued to evolve, and today data is available as soon as the investigator hits save, and data can be reviewed, queried, clarified, locked and signed off almost instantly (i.e., in real time).

Regulations state that the archiving of eCRF data is the responsibility of the investigator. The current practice of archiving is to burn a PDF copy of the data on DVDs or Blu-rays and then mail the disc to the site. The investigator must then approve and verify that this disc does indeed contain the data that was entered. The problem with this approach is that the disc doesn’t contain a copy of the originally-entered data but rather a print-out (essentially a screenshot) of the database in the form of a PDF. Regulators from governing bodies around the world have variously been uncertain that such copies truly reflect reality (i.e., match what was physically entered/approved by the site).

How is Viedoc different?

Viedoc provides a contemporaneous PDF copy of the data at the same time as the data is saved. Moreover, the data is not stored on a server under the sole control of the sponsor, but within Viedoc’s servers, where the investigator can access it at any time (the legal equivalent of storing it at the investigator site). Alternatively, generating PDFs at a later date (which is done by many other EDC systems) means that they are not contemporaneous, and thus do not fulfil this requirement.

Furthermore, the requirement applies to all data within the eCRF – not just a subset of data, (e.g., what some consider “eSource”). Because Viedoc provides contemporaneous capture of the entered data on PDFs at the time of data entry, the sponsor does not need to involve other systems in the capture and archiving of source data that is entered or transcribed to the eCRF.

For more information on Viedoc’s regulatory compliance, please contact us.