Abstract
Electronic data capture (EDC) has emerged as a proven tool for sponsors of clinical trials. Understanding the principles of EDC is more important than ever for clinical data management (CDM) professionals. This chapter reviews the regulations and guidance that currently apply to EDC during pre-production and study start-up, and emphasizes the important role that CDM professionals have in the adoption, development, and improvement of EDC systems.
Introduction
Electronic data management for research emerged in the 1970s and has evolved into a suite of processes and tools to enhance the management, quality control, quality assurance, and archiving of clinical trial research data. In the 1990s the development of electronic data capture (EDC) tools for clinical trials research became more focused. Today, EDC is gaining in popularity, and regulatory agencies are readily accepting submissions in which validated EDC tools are used. EDC systems should be more than just a means to an end and quality EDC systems can be drivers of the entire clinical trial’s information management process. Data managers provide significant value in designing processes to make the transition from paper systems to EDC systems efficient while ensuring data integrity is maintained.
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In the late 1990s, Web-based approaches to clinical data capture were introduced in an effort to gain efficiencies that other industries had realized by moving processes to the Internet. The acronym RDE was subsequently replaced by EDC as data transfer was expedited by Internet technologies rather than FTP, resulting in more frequent and rapid data transfers.5 The introduction of Web-based EDC led to greatly expanded use of decentralized clinical data capture.
Scope
This chapter provides information on the concepts and start-up activities related to EDC systems for companies who are considering transferring some or all processes from traditional paper data collection to EDC. It concentrates on establishing an environment conducive to incorporating EDC technologies into the clinical trial process from the viewpoint of data management. Practices, procedures, and recommendations are proposed for data managers to prepare for and start an EDC system that will properly align electronic data capture technology to support statistical and medical research needs.
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Recommendations for proper study conduct and study closeout using EDC will be addressed in the chapters entitled “Electronic Data Capture—Study Conduct” and “Electronic Data Capture—Study Closeout.” Recommendations for patient diaries and interactive voice response systems (IVRS) will be addressed in future chapters of the GCDMP.
Minimum Standards
Ensure compliance with 21 CFR 11 and consistency with the Food and Drug Administration’s (FDA) Guidance for Industry: Computerized Systems Used in Clinical Trials.2, 3
Stated quality standards should support the utilization of automated data capture, management and archiving.
Ensure requirements are defined for data transfers and integration with other systems.
Software systems validation should be scheduled and completed prior to EDC study implementation.
Ensure user acceptance testing (UAT) is completed prior to implementation and deployment to sites.
Verify training is provided for all users of the EDC systems and that all training is documented and minimum competencies are met.
Verify access to data is limited to authorized individuals.
Determine roles and responsibilities in data review and query management.
Software technical support should be provided to users and a toll free phone number should be available for the help desk.
Ensure sites have access and control of data up to database lock.
Best Practices
Use business process analysts (possibly external, for objectivity) to establish EDC-specific workflow processes and identify required transitions from current processes.
Do not apply paper study processes to studies using EDC.
Identify stakeholders in current processes, as well as additional stakeholders required for new EDC processes.
Plan studies to avoid “last minute” system modifications that introduce errors and complexity to study-specific CRFs.
Develop CRFs or data collection tools with teams of individuals from monitoring, data management, statistics, regulatory affairs, and medical, ensuring adequate attention to the collection of safety data.
Ensure systems are user-friendly and flexible for data entry.
Ensure EDC systems do not restrict answers site staff can provide in a way that introduces bias into the clinical study.
Ensure adequate edit check procedures and query management tools are built into EDC software.
Before the start of a study, conditions (e.g., SDV completed, all queries resolved) for locking forms and/or casebooks should be set according to a set of criteria, such as, all SDV complete, all data review complete, no outstanding queries or missing data exist.
When coding in an EDC environment it is recommended not to display coded terms back to the site user.
Ensure data can be traced from the time of original input through the reporting and analysis files via easily accessible audit trails.
Ensure ease and quality of all data transfers by testing data transfers prior to deployment of EDC systems.
Ensure your EDC system integrates as needed with other databases by testing integrations with your EDC system prior to initiating any trials using the system.
Ensure processes are defined to integrate laboratory and other non-CRF data with data obtained from the CRF.
Ensure all user acceptance tests are documented.
Ensure change control procedures include complete documentation.
Ensure all documentation for use by site staff is adequately reviewed before being provided to site staff.
If 24 x 7 x 365 support is not available, the help desk should cover the work days/times of all regions included in the study.
The help desk should support the minimum number of languages needed to communicate with all users and all languages, including local dialects.
Develop and follow standard operating procedures (SOPs) for electronic data capture, data validation, and data archiving.
Assess current SOPs for potential impact created by EDC workflow processes and update SOPs as necessary.
Include SOP modification time in project plans for EDC implementation.
Assume that both the new workflow and SOPs will be in transition for some period of time as the staff interact with the EDC system following any modification of SOPs.
Identify issues that merit periodic reminders, such as user ID and password security, and schedule recurring reminders
Provide an instruction manual for study workflow processes.
Verify all users have documented training prior to being granted access to the system.
Create a training environment in which users can practice, and create training cases as examples that are pertinent to the study.
Provide a “Train the Trainer” program for clinical research associates (CRAs), data managers or others to be able to provide training to sites.
Provide training customized to each user’s role. A study coordinator may need in-depth training of most system functions, while users with read only access may need minimal instructions.
Document all training for trial master files as well as site files.
Integrate metrics on process and cost/benefit into the EDC process to enable better EDC versus non-EDC comparisons and comparisons across EDC technologies
CRF specifications should be finalized prior to finalization of edit check specifications, although development of both should be performed concurrently.
Differences Between EDC and Paper-based Studies
Four important areas that differ between EDC and paper-based studies are the manner in which data will be collected, the timeline necessary to prepare for the study, the manner in which collected data will be verified, and disaster recovery planning.
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Accompanying the DRP should be a Business Continuity Plan (BCP) that guides continuation of a study during the recovery of failed systems. Depending on the number of EDC vendors and contract research organizations (CROs) used by the sponsor, the BCP may be included in the EDC project’s data management plan, or exist separately as a plan applicable to all EDC projects. The BCP should identify alternative processes in the event the EDC system becomes temporarily or permanently unavailable. For example, a project may revert to faxing paper CRFs and queries. The BCP should also establish the process by which sites will be informed of EDC system downtime, and the alternative method for collecting data while the system is unavailable.
EDC Deployment Considerations
Considerations for deployment of an EDC system should be taken into account at the organization level and used when researching, interviewing and assessing EDC vendors. Considerations for this step in the EDC process fall into three main categories:
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The timing and delivery of exports is important, therefore the process for exporting and delivery of data should be robust and flexible.
Integration
Utilizing EDC has added complexity to data integration needs. Data managers must now understand how data collected or maintained outside an EDC system will be used, who will use it, and for what purpose it will be used. Knowing the answers to these questions will determine the path integration efforts must follow. In the event data integration does not occur as expected, a clearly defined roll-back plan should be established. To ensure project goals are met, the data manager must articulate these needs to technical or IT staff in clear terms. This section discusses considerations for various types of data integration that data managers may encounter during an EDC study.
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As new technological tools are developed constantly, it is important to be mindful of other systems that may need to be integrated with an EDC system. In addition to the integrations discussed above, data managers should be aware of the need to also integrate an EDC system with coding, IVRS, and reporting tools other than SAS.In the future, electronic health records (eHR) may also become an important consideration.
International Study Considerations
EDC systems are routinely used in international studies. The role of data managers in international EDC trials is similar to the role played in paper studies. However, planning is critical if the deployment of CRFs and hardware is to be completed prior to the first site initiation. Data management must work with clinical research to understand language needs of the CRF or any components of the CRF. Issues to consider include the following:
Ascertain whether the local language can be used in a multi-national study. Many coordinators speak more than one language. Data management may avoid unnecessary work by asking this simple question or challenging the status quo in this area.
Plan early for CRFs that must be programmed in multiple languages. Significant lead time is required to translate CRFs and verify translations.
If applicable, ensure hardware deployment timelines are increased. Country specific laws may delay shipments significantly.
Establish a plan to manage time zone differences, especially in relation to time and date stamping.
Ensure hardware and software can be used at study sites, and that sites are prepared to use the tools that will be deployed to them.
Develop a plan to manage system upgrades, which is particularly important if the system is being used 24 hours a day.
Consider the wording of manual queries to ensure they will be understood by speakers of other languages.
Consider issues posed by language barriers to staff training. For example, investigator meetings could provide simultaneous translation for all languages spoken by participants, a train the trainer strategy could be employed, or training materials could be translated into the users’ native languages.
System and Vendor Assessments
For most organizations, moving to EDC is a significant decision, with an effect that is not limited to only data management. When launching an EDC system assessment, stakeholders from different parts of the organization are needed to develop the requirements checklist. Included in the requirements checklist should be:
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A global study with numerous sites, complicated and varied forms, and new users represents an opposite example. Use of an outside help desk could provide advantages, such as covering additional time zones and languages without taxing internal resources. Moreover, external help desk agents are typically evaluated on performance of help desk ticket resolutions, and will have a vested interest in being courteous to users. However, they will not be able to address clinical-related questions, which will need to be forwarded to internal resources.
Vendor SLAs and Performance Reports
When using an external vendor, the sponsor must emphasize the writing and managing of service level agreements for performance. A contract should be established between the sponsor and vendor providing help desk services (such as the EDC vendor or other outsourced agency). This contract and/or SLA should include, but is not limited to, the following identified functions and associated costs:
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The main point to remember at this time is that technical support for end users is crucial to the success of your move to EDC. Ensure that your first level of help desk coverage is available to all users, has enough language coverage to accommodate your sites and that the hours of support are sufficient for your user community.
Detailed Help Desk Planning
Once an EDC vendor is selected, roles and responsibilities of the help desk staff and the sponsor’s staff must be established. Consideration should be given to the number of help desk staff available. The number of studies conducted by the sponsor will determine the number of help desk staff required and indicate whether help desk services should be provided by an external party. If only a small number of studies require support, it may be feasible for the sponsor to provide help desk support with internal staff. The timeframe during which users should be able to contact the help desk must be considered. Typically, 24/7 coverage is not required unless the EDC system is deployed globally. When the help desk is provided by an external organization, service level agreements should be established concerning the timeframe in which each call will be answered, as well as any other metric your organization feels is important.
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To be effective, the help desk managing tier 1 support must be able to successfully communicate with all system users. Clinical studies are frequently multilingual and it cannot be assumed that all users will be conversant in English. Several options are available when determining how multiple language needs will be addressed. One option is for the help desk to fully support any and all languages with on-site support staff. Another, more frequently used option, is for the help desk to support several of the more common languages with on-site staff and to make use of a translation service to provide access to translators fluent in languages less likely to be needed. If providing multilingual help desk support is not possible, CDM representatives should discuss this issue with the CRO local to the international site. In many cases, monitoring staff may be fluent in local languages and can handle certain types of support.
Gap Analysis between Existing SOPs and EDC Requirements
It is critical to determine how implementation of an EDC system will require changes in the sponsor’s current set of SOPs and other controlled documentation. Identifying these gaps is an effort of technical and clinical operations that must be shared among all stakeholders.
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Perform and document a process flow evaluation addressing all study team members in the workflow, communication plan, information flow, and reports.
Perform an evaluation of required staff and their skill sets as compared to required resources.
Metrics and Performance Targets
Ideally, performance targets set for EDC projects will be based on the sponsor’s foundational reasons for switching to EDC. These targets should represent the first level objectives for EDC projects. The next set of objectives can be developed during rollout of the EDC solution and should include feedback from all stakeholders.
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In addition to a project plan, create a flow chart that outlines each report deliverable and the person responsible for approving that report design.
Schedule meetings to review and obtain feedback on reports to be used during the study.
Determine the metrics important to the study and design reports to capture these metrics.
If the study involves a CRO, consider what reports will be required from the CRO.
Define CRO performance requirements and design a report to track performance of and provide feedback to the CRO.
CDM Deliverables During Study Start-up
The following section concerns CDM deliverables during the start-up phase of an EDC study, including CRFs, edit checks, and coding.
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Data management should work with the pharmacovigilance and drug safety group to determine how data coding should be handled. For drug safety and clinical trials, coding should be handled centrally by data management. Alternatively, coding can be coordinated between drug safety and data management.
During the CRF development process, all data fields to be coded should be identified.
The capability of the EDC system to support coding should be understood. If the EDC system cannot handle coding, data management should establish a process to code study data on the back-end database.
If the EDC system is capable of handling coding, the sponsor should decide whether the user should be able to see coded terms or only the reported verbatim terms.
Ensure the clinical team understands who will be proposing terms for coding failures. For each study, it is recommended the data manager handles this activity.
The coding team should review the design of electronic CRFs to ensure optimization for coding purposes. For example, CRFs frequently provide menus for the coordinator to enter terms. The medical coding team can assist with development of these menus so that available terms will code appropriately.
Site Evaluation and Qualification
The process for initiating an EDC study is not just a matter of the sponsor selecting an EDC vendor that meets certain business requirements. The sponsor must also consider the pricing model, management, deployment, and implementation of the vendor’s EDC system. The sponsor is responsible for ensuring that sites are assessed and qualified to use hardware and software required by the EDC system. Site evaluation and qualification by the sponsor and EDC vendor must occur during start-up activities and must be seamless, especially when EDC is being implemented at a site for the first time.
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Good clinical practices advise that site assessments be completed, including current trends and practices. These assessments are performed to ensure that, prior to study initiation, sites selected for a study are completely prepared to enroll patients. Although site assessments are not required, not assessing a site could be very costly—a site may have qualified patients and learn that they do not have the equipment and/or knowledge to enter patients correctly within an EDC system. Learning this too late would be detrimental to the site, study, and sponsor. Hardware and broadband provisioning can be undertaken by the sponsor, CRO, or can be outsourced to a 3rd party provider that specializes in this area.
End User Preparation
This section concerns activities that should be conducted before the study begins to ensure staff are prepared to use the EDC system.
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- Self-study: reading materials, e-learning materials, using sample forms in a training environment
Training environments that provide training exercises with examples that are generic or customized to the study-specific workflow
Web-based instruction or demonstration
Face-to-face training: Conduct training for users in a central training facility, such as investigators’ meetings or other centralized training meetings
Recommended Standard Operating Procedures
- EDC Design Specifications
- System Setup, Installation and Support
- EDC Training
- Medical Coding
- Data Collection and Handling
- Data Backup, Recovery, and Contingency Plans
- Data Review and Validation
- Prequalification Requirements including 21 CFR Compliance
- User Access Creation, Modification and Revocation
- Systems and Hardware Security
- Guidelines for Outsourcing with Vendors/Vendor Management
- Handling External Data
- Coding Medical and Clinical Terms
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