The collection of data directly into electronic format (eSource) - rather than via paper – and the subsequent clinical study data flow towards tabulations to support submissions for marketing application is being accepted by recent publications from regulatory bodies. These publications provide clarity around strategies and approaches which can be taken to ensure regulatory confidence in eSource data.
In addition guidance on Risk-Based Approach to Monitoring has been published, which encourages centralized monitoring activities remotely accomplished. Collection of accurate clinical trial data is essential for compliance with Good Clinical Practice. There should be no loss of quality when an electronic system is used in place of a paper system. A number of attributes are considered of universal importance to source data and the records that hold those data (1, 5).
In 2011 SGS began the process of implementing an eSource data capture system in its Antwerp, Belgium clinical pharmacology unit. The goal of the project was to increase the efficiency of the unit itself as well as the downstream data analysis. The eSource system provides tools that allow for the collection of data directly into electronic format rather than via paper as well as to help recruit study volunteers quickly, and streamline the complete clinical process. The system also enables SGS to share real-time data with sponsors throughout a study and provides a flexible reporting structure.
In this article SGS will share implementation experiences and lessons learned while replacing paper source at the clinical unit through embedding eSource in all operational processes.
eSource System Details & Advantages
To successfully run a Phase I trial, it is essential to have a clear idea of the trial design framework – how many subjects, time of dosing, what clinical samples and data will be collected and at what time relative to dosing. While the trial protocol presents this information, in only a few hours this framework is captured electronically by the system and used to drive key operations.
The eSource system also includes creation and management of a recruitment database. The system identifies eligible subjects using a set of selection criteria for a trial, and subsequently leverages the candidates to promote participation in trials. The framework schedule is pushed via handheld devices directly to clinical staff at the bedside and provide the ‘what, where, whom and when' information they require to run the trial and to capture the source data electronically.
The use of eSource is key to achieving the full efficiencies of automation at the clinical unit. Checks, time-alerts and tube barcode verification improve quality during collection, and data are available for review in real-time. With even more progressive thinking one can envision using the eSource system as the electronic case report form (eCRF) platform and thus reward the sponsor with important additional efficiencies by eliminating eCRF design and source document verification from the process flow, as well as providing the classic benefits of Electronic Data Capture (EDC) tools.
A crucial challenge to implementing the automated solution in the Phase I unit is accommodating the rapid pace of setup and execution – there are just a few weeks between the protocol being available and the study starting. The automated solutions also need to accommodate a mobile staff. In addition, the diverse data in the eSource system needs to be organized in a manner that satisfies the study protocol and enables the data to be systematically reviewed and analyzed by investigators, other authorized parties. The system has to be validated, a business continuity process is defined, and SOPs and appropriate training for the use of the system must be provided for the staff.
In addition, eSource data collected at the clinical unit requires data transfer agreements between the clinical unit and the sponsor and/or SGS data management centre. Looking at the CDISC standards portfolio, an Operational Data Model (ODM) data export from the eSource system is the most practical choice. However, during this process SGS observed additional data transfer options being requested; including:
- A native eSource database extract. XML knowledge in the pharmaceutical and biopharmaceutical industries is still fairly limited; as a result many companies prefer a native extract from the eSource system in Oracle or SAS file format over ODM XML files to support trial processing and analysis activities
- SDTM datasets in SAS XPT files with an associated define.xml file. The most recent CDISC survey shows that SDTM is being used by 65% of the survey respondents while this is only 25% for ODM
- Custom sponsor data formats. A wide range of custom formats is seen going from the older SDTM 1.1 version and very specific SDTM 1.2 or SDTM 1.3 implementation requirements on the one hand and sponsor defined non-CDISC data tabulations on the other hand
- … and even manual transcription of eSource data into the sponsor’s (e)CRF
Each option has advantages and disadvantages with regards to data availability, effectiveness of processes and ease of getting the clinical data ready for statistical analysis, and each request can be accommodated by the SGS team.
The automated software solution (eSource system) is an accepted alternative for paper trials, and has numerous advantages such as an electronically captured trial design framework which drives the key operations at the clinical floor, increased data quality by checks, time-alerts and tube barcode verification, data are available for review in real-time that allow critical decisions in a timely manner. By introducing different data transfer options based on – preferably - CDISC standards, SGS can deliver data files to the sponsor in custom formats.
Joris De Bondt
Head EDC and Data Standards
- Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials – European Medicines Agency
- Electronic Source Documentation in Clinical Investigations – U.S. Department of Health and Human Services Food and Drug Administration
- Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring - U.S. Department of Health and Human Services Food and Drug Administration
- Computerized Systems Used in Clinical Investigations - U.S. Department of Health and Human Services Food and Drug Administration
- CDISC e-source standard requirements-CDISC (Clinical Data Interchange Standards Consortium) Version 1.0 20 November 2006