What is eSource?
The Food and Drug Administration (FDA) defines eSource, or electronic source data, as data initially recorded in an electronic format. The TransCelerate eSource workstream further categorizes eSource into the four groups shown below:
*The eSource team recognizes that some technologies may apply to more than one modality and that these modalities will likely evolve over time due to technological advances.
What is the Anticipated Value of eSource?
- Eliminate unnecessary duplication of data
- Reduce the possibility for transcription errors and eliminate transcription of source data prior to entry into an electronic case report form (eCRF)
- Facilitate remote monitoring of data; promote real-time access for data review
- Facilitate the collection of accurate and complete data
Here are some key metrics from several industry projects that quantify the value of eSource:
|Novartis - Memorial Sloan Kettering|
• EHR export -> sponsor data warehouse
• Local lab and vitals domain
|• Manual data entry reduced by 20%
• Query rate reduced by 50%
• Transcription errors 0
|Eli Lilly - Memorial Sloan Kettering & Yale|
• EHR -> EDC
• Local lab domains
|• Data latency reduced from 20.4 to 3.5 days
• Transcription errors reduced from 6.7% to 0
• Site effort reduced by 8 hours/patient/study
• Monitoring activity reduced by 2 hours/patient/study
|Duke University School of Medicine|
• Internal EHR -> internal EDC
|• Time saved 37% total time between traditional EDC vs eSource, 1 FTE, 65% total keystrokes
• Data Quality - 9% error rate to 0
Industry Collaborator References
- Novartis/Memorial Sloan Kettering (1) and Eli Lilly/Memorial Sloan Kettering/Yale (2): SCDM 2018, Session 6 “eSource implementation at Academic and Industry-Sponsored Sites”
- Duke University School of Medicine (3): FDA-CDER 2017, “RADapator Duke University’s Solution for Improved Clinical Research Efficiency”
Major challenges with eSource Adoption
There are several key challenges with eSource adoption.
- Lack of change management
- Acceptance of novel technology solutions that enable eSource and unknown quality and regulatory clarity on the data in these solutions.
- Lack of system interoperability
- Interoperability is referred to by the Institute of Electrical and Electronics Engineers (IEEE) in basic terms as “the ability of a system or a product to work with other systems or products without special effort on part of the customer. Interoperability is made possible by the implementation of standards.”
- Concerns over eSource acceptability as endpoints; lack of clarity from key study stakeholders
- Low risk tolerance in pharma industry
The industry must reach common understandings about novel endpoints, data standards, system validation, and related issues. While technology in itself is not a significant barrier to eSource implementation, interoperability among systems is an enormous challenge to establishing a complete end-to-end electronic health care and research ecosystem.
The TransCelerate eSource Initiative
The TransCelerate eSource Initiative works to alleviate the pain points of the industry to further expedite clinical development. This is done through the advancement of the digitalization of clinical development for patients, sites, and sponsors by:
- Proposing a logical architecture and data flow diagram outlining the needs of the industry
- Working with the standards-setting organization to advance EHR to CDISC mapping to align with global healthcare interoperability trends
- Collaborating with regulators to further understand expectations for submissions
What needs to change to increase eSource adoption? The paper, Accelerating the Adoption of eSource in Clinical Research, a TransCelerate Point of View, describes the desired future state of clinical research where all source data are completely electronic, with an adequate quality that is fully acceptable in clinical trial submissions, from the point of view of TransCelerate member companies. To get to that future state, the paper describes five key challenge areas that need to be addressed before the future state can be obtained.
- Clinical Trial Design, Protocol, and Data Collection
- Automated Data Exchange, Security and Privacy
- New Roles
- Regulatory Alignment
The paper, Technology Considerations for Enabling eSource in Clinical Research: Industry Perspective, provides insights into the technological complexities, operational scope, and the actions required from pharmaceutical industry stakeholders to adopt the eSource framework for clinical research at scale. Crucially, research organizations must consider patterns of anticipated use, the current state of trial operations, and new technologies to ensure that implementation can occur successfully. By adopting a single technical architecture across research sites and organizations, good clinical research practices can be implemented more broadly, across the industry.
The eSource Informatics Reference Guide for Clinical Research Sites provides information on clinical research informatics, the basics of informatics, and possible resources to expand capabilities around interoperability and data exchange for clinical sites. In mid-2018 and into 2019, the TransCelerate eSource team engaged with a Site Advocacy Group (SAG) in collaboration with the Society for Clinical Research Sites (SCRS) for an information gathering exercise via voluntary site survey to discuss challenges and areas for improvement in conjunction with technology use in clinical trials.
Results from the survey and the following discussions showed the inconsistencies between the wider adoption of eSource in the industry and the level of understanding at sites. The eSource Informatics Reference Guide for Clinical Research Sites was developed to provide guidance to sites on their journey to eSource and interoperability readiness.
The objective of the eSource Informatics Continuum is to help study sites determine their readiness for eSource implementation, by identifying their location on the continuum and pathway to increase interoperability. Interoperability is key to the exchange of source data electronically for research. The continuum includes a diagram that shows different varying degrees of interoperability based on clinical informatics, starting with ‘traditional’ data collection, i.e. using paper medical records and paper case report forms (CRFs), and ending with ‘innovative’ data collection, which includes full interoperability and integration between clinical care and clinical research.
In Guidance for Industry Electronic Source Data in Clinical Investigations, eSource is defined as “data initially recorded in an electronic format is considered eSource. This can include information in original records and certified copies of original records of clinical findings, observations, or other activities captured prior to or during a clinical investigation used for reconstructing and evaluating the investigation.” The Site Capability Questionnaire is intended to help capture the site’s use of technology during the site qualification process that is conducted prior to the start of a study. The intent of this form is to facilitate the reduction of any administrative burden on Investigative Sites by collecting information in a consistent way across multiple sponsor companies–reducing the duplicative completion of similar forms across multiple studies.
In 2016, a survey was conducted among TransCelerate member companies to understand the sponsor landscape around eSource at that moment in time, as the initiative’s intent is to facilitate the industry’s movement toward optimal usage of electronic data sources. This paper describes the results of that survey. The survey indicates that member companies had begun taking steps to leverage current eSource technologies and prepare for optimal utilization of electronic data sources already at that time. The most important factors related to the successful implementation of devices/apps based on experience in conducted studies are shown below.
The TransCelerate eSource Initiative continues to evaluate the technology, regulatory, standards, and health care landscape to support the goal of improving global clinical science and global clinical trial execution.
TransCelerate surveyed technology companies, including CROs providing technology, to better understand the capabilities available at that time (2016/2017), their plans for eSource space, and perceived barriers to greater adoption. It is clear from the survey results that the technologies needed to support the various eSource modalities are mature. However, the approach to implementing eSource is fragmented.
- Figure: Factors contributing to successful studies with clients
- Figure: Stated Return on investment (ROI) measures
The results are a vital input that will help shape forthcoming TransCelerate proposals for best practices for industry-wide utilization of electronic data collection tools and methods. While the technology itself is not a significant barrier to eSource implementation, interoperability among systems is an enormous challenge to establishing a complete end-to-end electronic health care and research ecosystem.
Addressing interoperability constraints is a necessary enabler of achieving the desired future state – global implementation of eSource. The Data Standards and Mapping Team, an initiative of the eSource Technology and Standards team, is piloting new techniques, applying standards, and leveraging innovative technology platforms to remove these constraints. In partnership with Health Level Seven (HL7), the team is working toward bridging the gap between CDISC and HL7 standards, harmonizing the existing standards, and advancing the maturity of HL7® FHIR® for use in clinical research.
Why is mapping important? Data standards and interoperability are key enablers for eSource. As the data for clinical trials becomes less about collecting protocol-defined data points, and more about using data from patient records and other electronic sources (e.g., devices and apps), electronic interoperability and consistent use of data standards become paramount.
Our approach is to:
- Channel our efforts around solving a use case
- Connect across entities/resources, to confirm the completeness
- Test draft mappings in an environment that simulates real interactions
We focus on three objectives:
- Produce a quality product that can be adopted as a standard,
- Help Sponsors make sense of FHIR messages, and
- Help Sites (and their vendors) understand the requirements for setting up FHIR and sharing data with Sponsors
Mapping Process and Deliverables:
- Goals: define the narrative/use case, describe the data flow, identify relevant standards and templates (e.g., CDISC, TransCelerate templates, regulatory mandates)
- Goals: develop mappings between FHIR and standards identified in the definition component
- Goals: develop code for transformation; identify and facilitate changes to FHIR resources, etc. (when applicable)
- Goals: define the implementation guide or alternative guidance document/white paper (when applicable)
eSource Use Cases:
|Extract lab data from Site local EHR to Sponsor clinical data system||Available data is made accessible for a Study with reduced latency and effort|
|Develop and refine the FHIR resource for Adverse Events (maturity 0)||Common representation of Adverse Event data facilitates exchange and reporting|
|Extract the protocol schedule of activities and integrate with the patient calendar||Study participant is able to incorporate study activities into their existing calendar and better manage time|
|Receive and apply Real World Evidence (RWE) updates to the study database as new or changed data is recorded in the EHR or received from patients||Scalable and automated indication of EHR data from Sites where patients participating in a Study receive care|
Lab Data Use Case: The use of local labs, where each lab may have distinct processes and data collection systems, introduces the need for a standardized structure for the exchange of laboratory data. Without standard guidance to utilize in data transfer, data are inconsistently exchanged, in a variety of formats, increasing the burden on both the site and the research sponsor. This may increase cost, complexity, and timelines for clinical trials. FHIR provides an effective standard for sites and sponsors to utilize in exchanging clinical research laboratory data.
For illustration purposes only
To address this need, we developed a mapping to assist sponsors in understanding how the HL7 FHIR® format (an interchange standard emerging in many EHR systems) relates to their existing CDISC standards for transmitting laboratory from sites to sponsors. This solution could have the potential to decrease costs and timelines in the exchange of information between sites and sponsors. The Mapping and Standards team partnered with HL7’s Biomedical Research and Regulation (BR&R) Working Group to deliver an FHIR Implementation Guide that contains the mapping process deliverables and provides requirements to Sites who seek to share data via FHIR. The deliverables have been published on the HL7 website: http://hl7.org/fhir/uv/cdisc-lab/2019Sep/
In Optimizing the Use of Electronic Data Sources in Clinical Trials, The Landscape, Part II, non-Case Report Form (CRF) data are defined as data which include collection and transfer of data in electronic format from internal clinical trial sponsor sources (e.g., specialty laboratories) or external vendors (e.g., laboratory results, imaging, ECG, randomization, drug accountability) into clinical research data repositories/warehouses without entering the data on a CRF. Although sponsors must collect and retain this data, there is currently no applicable industry guidance. Well-thought-out practices and procedures for the collection and retention of non-CRF data are crucial to maintaining data accuracy and integrity. To guide the development of such practices and procedures, this paper outlines certain high-level best practices related to handling and managing non-CRF data. These are high-level suggestions, as the purpose is to share learnings to enable more efficient, effective use, and/or adoption of eSource. The suggestions can and should be tailored to each company’s individual circumstances. These considerations can also help companies to address or reduce challenges that they have encountered and/or to initiate discussions to help improve processes.