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Good organization and technological support are needed to bring the benefits of electronic data capture to a clinical trial.
Many professionals involved in the execution and management of clinical trials see electronic data capture as a tool that can enhance the quality of data obtained during a trial. In addition to high data quality, EDC offers another benefitreal-time access to data. Both project managers and clinical research associates can benefit from such access during the trial. EDC allows managers to track and analyze the project progress in terms of deliverables and milestones, and to control the project budget with less time and effort. Using EDC means having real-time access to current project status and on-the-spot ability to generate accurate, up-to-date reports. Hierarchical reporting structures, the availability of the CRA, and time zones no longer need frustrate project managers.
Those familiar frustrations may be replaced by new ones, however, unless project managers and CRAs plan for the problems that can arise when EDC is implemented. Based on the challenges that I have encountered on EDC projects, I offer some issues to anticipate.
Changes in workflow
The workload in an EDC study is distributed over time differently than it is when paper CRFs are used. In EDC projects, the start-up phase is more challenging than it is in conventional paper case report form (CRF) projects. Getting started on EDC trials requires up-front planning and training in addition to software and capital equipment selection.
Project managers must keep in mind that data management tasks, such as database setup or programming of validation checks, must be completed by the time of site initiation, and sufficient time has to be planned for CRA training. Such planning requires intense collaboration with the departments involved, but will definitely pay off during the project life.
Unlike managers, who must plan for more work at the start of a study, CRAs will find that the use of EDC will result in a more balanced workload from site initiation through recruitment phase, and from the last subjects last visit to database lock.
Training. An EDC study requires more time at study start for training. Familiarizing site personnel with an electronic case report form (eCRF) will take as much time as it does to familiarize them with a paper CRF.
In addition to study-specific training on the protocol, CRAs will need to acquire basic computer skills and become familiar with the monitoring tools available on the system. CRAs also will have to be familiar with basic computer tasks and solutions in order to provide training to site personnel assigned to the study after initiation.
Monitoring. With both a correctly functioning system and appropriately trained on-site personnel, CRAs will discover that using EDC leads to positive changes to the work on site. Having direct access to the data at their sites, CRAs can determine the workload they can expect at their next monitoring visit. The direct access to site data will help CRAs plan visits in accordance with recruitment and performance of the site, thus resulting in more efficient visits. Data can be reviewed for quality purposes before the monitoring visit, and queries can be generated and ideally resolved by site personnel before the visit. When the CRA arrives on site, he or she can perform source data verification on clean data. Certainly the time required for source data verification will remain the same. But appropriate validation checks and automatic queries will significantly improve data quality and reduce the number of queries.
These changes will reduce the time the CRA spends on site and also the number of monitoring visits, subsequently resulting in less travel time.
The time savings on activities associated with the use of paper CRFs is also significant. Paper CRFs require printing, distribution, collection, and tracking. Using EDC, CRAs are spared the need to retrieve pages of CRFs and/or data clarification requests, separate originals and copies, complete tracking logs, pack and send originals to data management, and search for missing pages.
Visit follow-up activities, such as sending reminders to the site and generating reports, will be simplified because basic information is available on the system and will not have to be duplicated.
Despite these potential benefits when an EDC study goes well, technical difficulties can quickly cause an EDC study to fall behind schedule. In the last six years I have had the opportunity to experience a variety of platforms and software applications, and both vendors and sponsors solutions. Most projects in which I was involved were multinational, multicenter trials in both Western and Eastern Europe, Australia, and Southeast Asia. Entering the world of EDC meant dealing with a variety of new challenges.
Because my first EDC projects took place at familiar and experienced sites, my team had validated historical data on the expected recruitment rate and data reliability to allow an estimate of the projects duration. Prestudy visits covered technical and information technology issues, and the investigators were asked to provide detailed information regarding technical status. Hardware and equipment were individually tailored for all sites.
Inadequate technical infrastructure. After this initial halcyon period, we found that in reality, the majority of sites had problems with technical infrastructure that led to unexpected delays in study start-up. Some sites had no Internet access on the wards, in the departments, or in the treatment rooms where subjects were actually evaluated. Where local equipment was used, auditing local hardware and software was necessary to determine the need for upgrade and updates. This raised contract and confidentiality issues.
Some hospital telecommunication systems did not allow direct dialing to numbers outside the clinic, and when connections could be made, lines sometimes broke down.
Procedural problems. Once sites were set up and initiated, a new set of unexpected issues arose. Staff persons at sites working offline often missed entering data. Sometimes this happened because, for insurance purposes, sites stored laptops in locked cupboards with restricted access.
Sometimes data were entered on time but not actually transferred because setting up a communication line (that is, unplugging phones or fax machines in use during the regular working hours) presented too many difficulties.
On-line systems were often not accessible or were otherwise unacceptably slow.
Unavailability of help. Even if the technical infrastructure was satisfactory, users often had difficulty solving problems with the system. Navigation through eCRFs was time-consuming, and the help desk not always available. Investigators faced with frozen screens simply gave up. Those sites that already had experience with more user-friendly systems refused to tolerate a step backwards.
Staff rejection of EDC. As a result of these problems, site personnel were reluctant to enter data, instead waiting for the study monitor to complete the eCRF. Data were never completely available for the project manager or the CRA. The information captured in the system represented only a fraction of the data available on site. Consequently, CRAs spent more time on site for monitoring and made more monitoring visits. More contacts were also necessary to motivate the site staff.
The rejection of the EDC system led to a declining recruitment rate and extension of the project duration. Additional efforts and costs were necessary to select and initiate new sites.
Time for source data verification was actually doubled by using a worksheet as well as eCRFs and subject records. Far more inconsistencies were found, of course, and more time had to be spent on clarifying those. Queries relating to data inconsistencies tended to remain unresolved over time, therefore accumulating.
Furthermore, CRF insufficiencies had to be compensated for by comments, and eCRFs were not adjusted to reflect protocol amendments. Additional paper CRFs were introduced halfway through the study. This meant additional working hours for everybody involved, and enormous unexpected logistic efforts.
Ongoing site personnel changes and reduced use of and practice with the system resulted in a need for repeated training sessions. In short, our teams assumption that monitoring visits would require less time once the first visits were done was proven wrong.
Solving the problems
Faced with challenges like these, both project managers and CRAs must respond. To keep their teams motivated and the project on schedule, project managers must be prepared to help sites overcome technical obstacles. CRAs, for their part, must get used to changes in their duties.
Project managers. Only if site personnel accept the EDC system will project managers and CRAs have the opportunity to reap the benefits EDC can offer. Investigator and initiation meetings are an opportunity to demonstrate to investigators, study coordinators, and study nurses the potential for the reduction in the number of queries and the gain in time for all involved in the performance of the study. The message must be clear that the industry is not abusing site personnel as data entry staff.
This message must be backed up with adequate technical support. Providing a user-friendly CRF and equipment that can transmit data at an acceptable line speed is crucial.
CRAs. Our working environment demands from us a capability to adapt to new electronic systems. CRAs will have to get used to the overlap of data management tasks, to source data verification and consistency checks on a screen, and to data listings, that is, cross-references for site payments, sample logs, and so on.
It is also sometimes necessary to accept navigating through eCRFs that are not user friendly, and working with unsatisfactory monitoring tools.
Getting the full value of EDC
EDC potentially offers more than just high-quality data. The added value for project managers and CRAs comes with appropriate monitoring tools, validation, and consistency and plausibility checks.
Provided that sufficient thought is given to the initial expenditure on planning, training, software, and capital equipment selection, the cost of EDC can be recouped many times over in more efficient and effective project control, leading to faster project completion.