And, although it is expensive, sometimes a six-figure investment, a well-developed EDC system significantly reduces paperwork and provides quick and easy access to valuable information.
The process of converting paper clinical report forms into electronic-based data capture is fraught with challenges. The process begins with the initial partnership between a vendor (a company that develops an EDC system and sells the service of building and maintaining study-specific databases) and the sponsor, or organization conducting the clinical trial. A typical scenario often develops as follows: An EDC vendor meets with a sponsor company that is interested in using an EDC system to collect clinical study data. The EDC vendor provides a demonstration of the system. The sponsor describes additional needs not demonstrated in the vendor’s presentation. The vendor confirms the EDC system can meet those needs. The meeting ends with both sides confident their expectations will be met.
When the EDC developer begins working with the sponsor, red flags begin to emerge. The sponsor realizes the system does not meet the needs or functions as expected. The sponsor requests changes to the design of the database either due to a misunderstanding of the system or realization of additional design needs. This leads the vendor to conclude that the sponsor (company) does not really know what it wants.
What started out as a constructive partnership can quickly deteriorate into a contentious relationship. Such conflicts can be avoided if both sides take the steps to ensure they sufficiently communicate their needs and understand the other’s capabilities and requirements. Sponsors need to gain knowledge about the EDC process and be clear in their expectations. Vendors need to understand the clinical trial environment and give sponsors more complex and thorough demonstrations, as well as plenty of hands-on experience with the software prior to developing a database.
The primary problem is that people aren’t speaking the same language. Sometimes an EDC vendor does not have people in-house with clinical experience, and the company sponsoring the trial or the clinical group may not have anyone with prior experience with EDC studies. They may not understand the functions of the EDC system. What the clinical team wants to accomplish could be very different from how that is interpreted and created by database developers.
In a recent study, 58% of 629 participants reported they were currently using EDC in clinical trials in 2009, compared with 13% in 2001. In addition, 95% of respondents indicated they had has some experience with EDC in the past three years, versus 52% in 2001. The survey, “Investigational Site Perspectives on Clinical Trial Information Systems,” was conducted by eClinical Forum, a not-for-profit association of representatives from pharmaceutical and related industries, and by TechTeam Global and other industry associations.
One respondent participating in the survey explained that previously, people shied away from EDC because of the costs, time, and money for development. Etka Wilcox, senior manager of clinical affairs for Ventus Medical, Inc., a Belmont, CA-based manufacturer of sleep therapy devices says that users can see events as they unfold. If someone wants a quick report, they can get it. She says that userscan do things with EDC that they can’t do with paper case report forms or a user's own database.
The EDC market continues to be a dynamic environment. New service providers continue to enter the marketplace with a range of products. Options include adopting open-source systems the sponsor company can build on, hiring application software providers (ASP) that offer the system and the sponsor company builds and manages the database, or a traditional full-service provider that manages the database build and maintenance details.
Benefits of EDC
There are two major efficiencies gained when using EDC. The first is that data are entered into a data collection tool only once. In a paper system, data are entered first on the clinical report form and second by the data entry group into an electronic system. Accordingly, with an EDC system, processing time for data entry is reduced, and transcription errors are less likely.
The second efficiency is that data cleaning begins immediately and does not require the intensive hands-on work of a data management group for processing. For example, data on a demographics page include gender, date of birth, race, and date of consent. A common logic check confirms the date of consent occurred before the data were collected or any test run.
Unlike paper studies, in which the data management group executes the logic checks against data that were collected weeks or months ago, EDC system logic checks are executed when the site enters and submits data, allowing data to be cleaned in real time. This is one of the major efficiencies of an EDC system.
The primary selling point from EDC vendors is quick access to clean data with low operational costs. This is true with proper system selection, development, and management of a study conducted using EDC.
The most important task in an EDC database plan is to be thorough and complete in the initial design. In a paper study, it is easy to add forms or new fields. With many EDC systems, changes or additions to the system are costly and have broader implications to the function of the database and the collection of data. It is much more important to ensure that the initial design is complete. To ensure completeness, representatives from critical groups should give input to design. These critical participants from the sponsor company include the project or program manager, the monitor or clinical research associate, the data manager, and the statistician.
Specifically for medical devices studies, marketing and complaint departments may also have a vested interest in data collected. Particularly for complaints or returns, consideration should be given to consistency between data collected in an EDC system and any electronic system used for the collection of information for complaints and device returns.
In addition to developing electronic entry forms, typically the sponsor can define how system features are used, the logic checks that are implemented, and how user roles and access are identified.
Most EDC systems come with a standard suite of reports. However, additional reports may be required for study oversight and management. Most, if not all, EDC vendors provide custom reporting in addition to standard reports. As with database development, the design of reports should be well considered and clearly specified at the beginning of the study.
Another consideration for medical devices is importing and storing data or images collected external to the database. It is critical to confirm with the EDC vendor that external files can be associated with subjects. File size limits should also be discussed because they could influence study management.
Timelines and Changes
Once the sponsor has provided final documents for the design of the database, most EDC vendors will quote four to six weeks for building the database. The EDC system timeline can vary depending on several key factors. Some of these factors include the following:
- Number of visits.
- Number of unique forms.
- Number of logic checks.
Although it still means a shorter time frame than paper forms, the EDC process may take longer than expected, particularly as changes are made. Of course, it is important to realize that requested changes take more time and money. That is why having a good project manager on the EDC side is key.
Roles and Responsibilities on an Active Study
A major difference between EDC and paper studies is the change in the roles and responsibilities of the investigational site and sponsor. The sponsor’s primary role is to study the oversight’s activities, the clinical research associate’s activities, and the data manager’s activities.
The sponsor monitors study conduct and identifies site-specific problems using the EDC system's report and tracking tools. It is important to ensure that the EDC system can provide these tools. A standard report should include metrics on subject enrollment, data entry completion, and query volume and query aging reports. It should also monitor the number of subjects completed, frozen, and locked.
The clinical research associate can remotely access the EDC system to review study activities and progress, manage site visits, and monitor data. Additional responsibilities when using EDC include generating manual queries and freezing clean data. Freezing clean data in the EDC system prevents data changes by the site and shortens the time for database lock at the end of the study.
The role of the data manager shifts to an oversight role of reviewing data entry and monitoring activities and confirming query resolutions. The data manager corroborates that all study-related activities are completed prior to database lock and is responsible for locking subjects and the database.
Many of the difficulties that may be encountered when using EDC are dependent on the system used. Because there are many EDC vendors on the market, sufficient time should be spent reviewing the services of specific vendors. Common pitfalls are as follows:
- EDC vendor and system do not meet the sponsor’s needs.
- Insufficient time spent on development.
- Insufficient time spent on testing the system.
- Insufficient metrics reports.
- Delays in data entry or query resolution.
Sponsors need sufficient interaction with the EDC system in the beginning. Later testing is also critical to the success of the system. EDC vendors need to provide enough concrete functionality detail in their demonstrations for the sponsor to fully understand how the system can be used.
It’s one thing to watch a demonstration of how the system works, but a user is highly unlikely to absorb all of the information necessary to understand full functionality. Instead, they need hands-on experience and time to play with the system to gain confidence and skill in using it.
Typically the same participants who give input in the design should also be involved in the user acceptance testing of the database, although some groups may have limited participation. Be warned, user acceptance testing is an intensive process. The first round of testing usually takes three days—more for a complex database. In subsequent cycles of tests, it’s important to recheck system function to ensure that changes or corrections do not have unintended effects.
It is best to develop test cases that specifically verify database function and logic checks. Test cases and results of their execution serve as documentation of the validation process. Documentation also assists the EDC project managers, programmers, and developers in resolving problems more efficiently.
Checks and Balances
It’s important to schedule a meeting with all testing participants and the EDC representatives who are responsible for addressing corrections. Problems should be discussed so that there is no miscommunication or misunderstanding. When using an EDC system, it is essential to document decisions and changes, as well as the reasons for those changes. Changes may be requested by the sponsor or suggested by the vendor to improve the functionality of the EDC system. In both cases, changes should be documented during both the design process and the testing process.
It is also crucial for the meeting minutes to document decisions and the reasons behind those decisions so they can be shared and reviewed by all parities for insight and clarification. They should also clearly indicate the expected follow-up on all action items.
Documenting, testing, accepting changes and deadlines, involvement in the design, and understanding possible pitfalls and challenges are critical steps in the EDC process. Sponsors need to be clear about what they want from an EDC system, and vendors must demonstrate that an EDC system can meet a sponsor’s needs. Ideally, the two parties will become true partners, working together to identify their processes, requirements, and expectations throughout the relationship. In this way, back-end surprises will be reduced, and the project implementation is likely to end with two satisfied stakeholders. The time and costs associated with an EDC can be recouped if the final product meets the stakeholder’s needs for efficient and accurate clinical trial management.
Melody Lashlee is the director of clinical data management at Advance Research Associates Inc. (Mountain View, CA).