Data Management
Case Report Forms
Syreon provides sponsors with the option of electronic or paper-based data collection formats.
> Hard Copy: Syreon employs hard-copy case report forms provided by the study sponsor for paper-based studies, or develops these internally as required. Syreon will design the content and format of the CRFs as well as coordinate the printing, collation and distribution of CRF binders. Paper-based patient reported data forms, for quality of life and resource utilization evaluation, along with business reply envelopes, are also provided as required for individual studies.
> Electronic Case Report Forms: Syreon ClinStream™ electronic case report forms (eCRFs) are designed to ensure ease and efficiency of operation, and are programmed to encompass a broad range of online point of entry quality assurance checks, detecting potential errors at the point of entry and facilitating the collection of clean data. Online CRF completion guidelines are provided but rarely required due to the intuitive simplicity of ClinStream™ eCRF design. More details on Syreon's EDC capability are provided in Section 9 of this document.
Database Design
Syreon employs Clintrial™ version 4.4 running on an Oracle platform, the industry-standard information platform for biopharmaceutical and related industries. The database has full audit trail capacity, allowing immediate review of access and modification logs for full accountability of the status of each data element over time in accordance with industry regulations.
Data Processing and Quality Assurance
Syreon ensures the highest level of data quality through the use of stringent electronic and manual data validation checks, complemented by the extensive clinical knowledge and experience of its data management staff. This integrated approach reduces the mean cycle time for data receipt and processing from days to hours, and reduces clinical errors and queries. Syreon provides a detailed Data Validation Document (DVD) describing the nature and frequency of data checks and crosschecks for completeness, logic, timeliness, errors or inconsistencies. When detected, data errors or inconsistencies are addressed immediately with the site in the form of a data query.
Data is validated when all manual, logic and intuitive checks by data management personnel have been completed and source document verification performed by the study monitors (if required). Syreon may generate queries based on the monitor's queries produced during the source document verification process. A formal database lock procedure is employed at the end of each study. The data management process and validation are subject to regular QC checks in accordance with stringent SOPs. The Manager of Quality Assurance ensures compliance with internal and external regulations, and audit of all critical activities is conducted regularly to provide assurance that quality is built into the system in compliance with SOPs.
Data Coding
Syreon codes medications using the WHO Drug Dictionary and adverse events and co-morbid conditions using MedDRA. Syreon holds a current license for both dictionaries and can provide documentation upon request. Sponsors must also have a current license for MedDRA and WHO under the licensing terms for these coding dictionaries. Coding is performed by Coding Specialists and is also automated following the first assignment of a code to a particular term for consistency and efficiency. Regular listings of code assignment are performed as part of an ongoing QC program for detection and correction of inconsistencies. Syreon will use a sponsor's modified coding dictionary upon request.
Serious Adverse Events
Syreon's role in the handling of Serious Adverse Events is defined in consultation with each sponsor, and can include conjoint responsibilities for reporting and communication with the sponsor's Regulatory Team, reconciliation of SAE information against the AE page, direct reporting to regulatory authorities or a combination of these options. Syreon adapts its role according to sponsor requirements.
> Data reported on the SAE and AE forms must meet one of the three main criteria of matching, consistency or plausibility in the reconciliation process. Failure to meet these criteria results in a query to the site which must confirm the correct response and recommend whether the Safety Database requires an update or change.
> The sponsor's Safety Department may provide listings to Syreon for review and reconciliation of data against that reported in the adverse events CRF. Syreon works with the Safety group to determine the optimum frequency for such data sharing.
> Syreon notifies the sponsor immediately upon receipt of any adverse reactions that are checked as serious or unanticipated in the CRF to ensure that the Safety group has received the SAE form (providing them the opportunity to follow up with the site if the report is missing). No reconciliation is required in this situation.
Data Export
Data can be exported at specified time points throughout the duration of the study, as well as following the completion of final validation and all database lock procedures. Data is exported in a format that is readily accessible and allows navigation and access for manipulation, normally in SAS. At a Sponsor's request, Syreon will review and program a Sponsor's internal specifications for export naming conventions during the construction of the database, ensuring smooth integration of the data into the Sponsor's global database at the end of the study. Options include text-delimited format or Microsoft Excel. SAS files can be generated and exported by Syreon as required for the study. The audit trail from the database can also be exported in a range of formats that are widely and easily accessible, and which do not require sophisticated software or training to use. Clintrial™, the core database employed by Syreon, cannot be exported due to licensing issues, but the database specifications can be provided on request at the beginning and end of each study.
Data Archive
Syreon provides sponsors with the option for return of all essential documents at the end of the study for long term archiving in accordance with regulatory requirements at the sponsor's facility, or long term, secure off-site storage arranged by Syreon may be included as a pass-through cost in the study budget.
Data Export and Archiving
Electronic data (i.e. the study database) can be exported in a number of formats, including SAS tables (programmed by database panel), excel or tab-delimited files. If required, Syreon can adapt the naming conventions for the database at the time of programming to adapt to the Sponsor's format to allow ease of integration of the data within the Sponsor's internal or Global databases. This requirement must be specified at the time of the contract or Request for Proposal. Export includes database audit trails.
All essential documents are returned to the Sponsor following completion of the study for long term storage in accordance with applicable national regulations and ICH guidelines unless otherwise specified at the time of the contract or the Request for Proposal by the Sponsor. Syreon can make arrangements for secure, long term storage of data, as required for each study.
Investigative sites participating in EDC studies are provided with a copy of their sites data and the associated audit trail on CD.