The clinical trial landscape is changing rapidly, and one of the things helping to drive this change is eSource (or electronic source) data. eSource is something that we talk about constantly here at IgniteData, but, as a topic with rapid developments happening, it’s worth reviewing what it actually is, and why it’s important to clinical trials and the interoperability of the systems used in them.
Source data in clinical trials
The source data in a clinical trial is the original recording of information to be included in an investigation. This can include classification data on patients, clinical results and observations, or any other data recorded to evaluate the trial. It’s important that the original source of data is recorded and maintained, not least because regulators such as the FDA (in the US) and EMA (in Europe) need to be able to access and review the source data to verify the quality of the trial.
Regulators typically require that source data should be attributable, legible, contemporaneous, original, and accurate (ALCOA). More recently this has been upgraded to ALCOA++, with the addition of the terms ‘complete, consistent, enduring, available and traceable’. In brief, these requirements mean the source data should be:
● Attributable – Data should be attributable to the person generating the data, and information about the originator should be recorded.
● Legible – Data should be maintained in a readable form to allow review in its original context.
● Contemporaneous – Data should be generated or captured at the time of the observation. Information on the date and time of the observation and the permanent save should be recorded, including audit trail.
● Original – Data should be the original first capture of the observation, or a certified copy of the original data.
● Accurate – Data should be an accurate representation of the observations made and any data transfer between systems should be validated to ensure it remains accurate.
● Complete – Data should be a complete representation of the observation made and should be represented in the original context and associated metadata, including audit trail.
● Consistent – Processes such as standardisation, data validation and training should be in place to ensure consistency of the definition, generation/capturing and management (including migration) of data.
● Enduring – Data should be maintained and remain intact through the entire data life cycle, matching any regulatory retention requirements.
● Available when needed – Data should be stored at all times in order to be readily available for review when needed.
● Traceable – There should be an audit trail that follows data through its life cycle, including tracking where and why any changes have been made.
How source data is included in clinical trial data
A case report form (CRF) is a questionnaire covering the data being collected by a sponsor (such as a pharmaceutical company) in a clinical trial. Today, this is typically in a digital format – eCRF – described in FDA guidance as: The eCRF is an auditable electronic record of information that generally is reported to the sponsor on each trial subject, according to a clinical investigation protocol. The eCRF enables clinical investigation data to be systematically captured, reviewed, managed, stored, analyzed, and reported. The eCRF typically sits within an electronic data capture (EDC) software system that is used for collecting and accessing clinical trial data.
eSource: What is it
eSource data is source data that was originally captured in electronic form. Historically, both clinical data used for clinical care and source data (as described above) for clinical trials were captured on paper notes. For clinical trials, this meant a multi-stage process of written notes being transcribed onto CRF or eCRF forms.
Even as electronic systems for patient data (EHRs), and electronic systems for clinical trial data (EDCs) have been developed, the two have, until recently, remained separate. Data recorded electronically in an EHR has been laboriously copied into EDCs, at great effort and cost to those involved in clinical trials.
Now, as systems mature and more and more clinical data is captured electronically, the opportunity for direct use of eSource data in clinical trials – via better interoperability between systems – can no longer be ignored.
Types of eSource
With the seemingly exponential growth of data being captured in electronic form, we sometimes find that the term ‘eSource’ can mean slightly different things to different people in healthcare and the clinical trial industry. Depending on the way the data was captured, it can refer to:
● Direct data capture (DDC) – where data is entered directly onto eCRFs, rather than first being recorded on paper (or other) notes
● EHR-to-EDC – where data that is recorded digitally in a hospital or GP EHR system is transferred electronically into the EDC, rather than being manually transcribed
● Patient reported – data captured directly from patients, e.g. electronic clinical outcomes assessments (eCOA)/electronic patient reported outcomes (ePRO) – where patients report on their outcomes; eConsent form data; and, increasingly, data collected via devices like wearables
● Non-CRF – Data captured from other sources/clinical assessments, such as via central labs, ECG, etc.
Clinical trial trends driving eSource adoption
As well as the sheer scale of the opportunity being presented by the increased amount of data now available in electronic form, there are a number of other trends in clinical trials that make the use of eSource data increasingly attractive:
● Decentralised trials. Increasingly, clinical trials don’t need to be based in just one central trial site. To ensure accessibility and the best sample of patients for a trial, decentralised (or virtual) trials are becoming more and more common. Patients can participate in a trial from home, or via a local clinic without ever having to travel to a central hospital trial site. But this, of course, raises the challenge of how the data from those dispersed patients is collected in one place. Certainly, using paper that is transported and stored in a central place would be cumbersome and costly.
● Larger, more complex trials. Connected to the above point, clinical trials are now conducted on a global scale. They are multi-regional and they are becoming increasingly complex, with more data being collected. Recent studies have shown that, in a typical phase three oncology trial, an average of 3.6 million data points will be generated (three times the data collected by late stage trials 10 years ago).
● Speed of trial execution and completion. Particularly since the Covid-19 pandemic and the fast response that it necessitated, our expectations of clinical trials have changed. Everyone from industry insiders, to the general public at large has seen how quickly clinical trials can be progressed if necessary, and the bar has been set for future trials. eSource data is one of the tools that can be leveraged to help speed up trials to keep up with the demand.
● Real-world data usage. Real-world data (or real-world evidence) is data that has routinely been collected in healthcare, rather than specifically for a clinical trial. This kind of data is increasingly being used, particularly to help inform the design of clinical trials, but the data can only be made use of if it is in an accessible electronic format.
● Changing attitudes to remote work. Again, largely driven by the Covid-19 pandemic, we now have a different attitude to everyone needing to be in the same place at once. Even outside of the decentralised trial format – where patients can participate remotely – Covid-19 meant that new ways of working for the staff involved in clinical trials needed to be found. This has made the use of eSource data even more attractive.
● Increased use of devices. The use of wearables and other devices by patients presents a huge opportunity for clinical trials. Devices capture health data in a digital format so the data is, by nature, eSource. Wearables, therefore, offer an affordable, quick way to collect large amounts of real-time data for clinical trials.
How the regulators feel about eSource
The FDA guidance on eSource issued in 2013 included a clear backing for the use of eSource data. It said:
Capturing source data electronically and transmitting it to the eCRF should:
● Eliminate unnecessary duplication of data
● Reduce the possibility for transcription errors
● Encourage entering source data during a subject’s visit, where appropriate
● Eliminate transcription of source data prior to entry into an eCRF
● Facilitate remote monitoring of data
● Promote real-time access for data review
● Facilitate the collection of accurate and complete data
Meanwhile, the EMA has focused on supporting the use of eSource data by publishing guidance and advice for its use. They published a Reflection Paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials in 2010, a Qualification opinion on eSource Direct Data Capture (DDC) in 2013, and in 2021, published their Draft guideline on computerised systems and electronic data in clinical trials. The Draft guideline replaced the earlier ‘reflection paper’, and covers detailed guidance on considerations such as data protection and audit trails.
Even earlier than this, in 2006, the scene was set (in the US, at least) for regulators taking a positive view of eSource data, when CDISC published Leveraging the CDISC Standards to Facilitate the use of Electronic Source Data within Clinical Trials. This document’s stated purpose was to align multiple factors in the current global regulatory environment to encourage the use of electronic source data (eSource) collection and industry data standards to facilitate clinical and biomedical research for investigators, sponsors and other stakeholders, and shows clearly that a move to eSource data was seen as overwhelmingly positive by that point.
Benefits of eSource to trial sponsors
For clinical trial sponsors like pharmaceutical companies, the benefits of eSource are huge:
● Speeding up clinical trials. Older processes including the duplication of data from physical records into clinical trial systems has historically consumed vast amounts of time and effort. The hours involved in copying and verifying data have represented a significant proportion of the overall time trials take to complete. And this built-in delay has only increased over time. The time from patient visit to re-entry of data for research has increased from an average of 6.9 days to 8.1 days over the past decade. Having eSource data available allows for trials to be completed much more quickly, with the opportunity to take life-changing treatments to market sooner.
● Improved accuracy in clinical trial data. Duplicating data from one format to another introduces the potential for errors and omissions. With data being recorded as eSource, the potential is opened up for clinically-validated data to be directly transferred into clinical trial systems for use in the trial, meaning more accurate data and higher quality trials overall. A Duke University trial, for example, found that the use of eSource to collect demographic data improved data quality from a 9% error rate to 0%.
● Ability to monitor trials remotely. The review of source data recorded on paper records typically includes multiple site visits by investigators and/or the transportation of physical records back and forth between sponsor and site. With eSource, trials can be monitored largely remotely, with vastly reduced need for on-site visits. When Covid-19 struck, this also had unforeseen benefits, by facilitating social distancing for staff involved in monitoring trials.
● Reduced need to maintain physical records. Going back to the need for source data to be ‘Available’ and ‘Traceable’, the transportation and storage of source data (including audit trails) in paper form comes with its own cost and logistical challenges. The shift towards eSource means data storage moves to servers or cloud storage – with all the efficiencies in space and costs that this brings.
Benefits of eSource to hospitals
The benefits that trial sponsors see also translate into benefits for hospitals and other study sites. With improved speed and accuracy, sites can conduct more trials to improve their revenue streams, and free up valuable staff time, including clinicians being able to spend more time with patients. Remote monitoring and reduced storage needs for record-keeping mean more efficient use of space and resources. And, the streamlining of processes mean that the hospital and trial sponsor can develop better, mutually beneficial relationships.
As well as these benefits, having clinical data that is recorded in digital form should lead to better care for patients – whether they are part of a clinical trial or not. With intelligent systems, eSource data can be used to trigger alerts on patient care. And, by removing delays in data being transferred between systems, better, faster clinical decisions can be made for patients in trials.
Just as there are different definitions of ‘what is eSource’, the definition of what it means to be eSource-ready, can vary, depending on what the ultimate goal is.
For IgniteData, what eSource means to us is a powerful way to transform the way clinical trials are run. eSource, combined with greater interoperability between EHRs and EDCs, means trials can be run more quickly and efficiently, with greater accuracy and improved outcomes for patients. Hence, our version of eSource readiness is one that facilitates the transfer of data from EHR-to-EDC (see ‘Types of eSource’ above). In brief, this entails:
● The site operating a modern EHR system
● The EHR system holding quality, accurate data
● The EHR system being HL7 FHIR-enabled
● The data in the EHR being configured and mappable to an EDC system
● People and processes being in place that ensure all of the above, and allow for the oversight of connected systems.
How ‘eSource ready’ is the industry now?
Hospitals employing a modern EHR system is, of course, the biggest and most easily definable tracker of the state of play when it comes to eSource readiness in hospitals. On that point, adoption globally has varied, but seen a considerable uptick over the last few years. The US leads the way – as of 2018, 98% of hospitals in the US had an EHR system in place, or planned to install one. While other countries may not be quite as advanced as this, a study of hospitals in China, for example, showed that between 2007 and 2018, adoption of EHRs rose from 18.6% to 85.3%.
Definitive up-to-date information on where adoption of EHRs currently sits in the US and UK is hard to come by, but anecdotally, this figure – globally – is only increasing. One recent survey of clinical trial sites also found that 45% of sites adopted new electronic systems due to COVID, so we can glean from this that the journey to digitisation will continue at pace.
We’ve seen a considerable shift in the industry over the last few years, with the key players waking up to the value of eSource, and the need for the industry, as a whole, to work in unison to support increased adoption. Clinical trial sponsors, for example, are looking at ways they can support hospitals with technology rollouts. And hospitals are seeing how implementing eSource technology not only allows them to make advances in how they conduct trials, but also in how they deliver patient care.
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