Introduction
Paper-based data capture has been the standard in clinical trials since their inception. In the 1990s, the FDA kicked off the digital era in clinical trials with their Computer-Assisted New Drug Application (CANDA)1. Since then, electronic data capture has been incorporated in many aspects of clinical trials, from electronic case report forms (eCRF) to electronic patient reported outcomes (ePRO), and electronic trial master files (eTMF). One area that has been slow to adopt site-based electronic data is laboratory testing.
Below we explore the current technology landscape for investigator sites to interact with central laboratories, positive changes being driven by real-time electronic data capture (RT-EDC), options available, and challenges in implementation.
Current Industry Landscape
The manual and inefficient use of paper for data collection drives a high query rate within the laboratory. Due to transit time from site to lab, queries are typically not generated until 24-48 hours after sample/data collection, delaying the query resolution process. For samples that are batch shipped, this time is even further extended. The average paper based central laboratory query closure rate is estimated at 3 to >7 days compared to <2 days with EDC queries. These delays often lead to downstream impacts for both the sites and sponsors, including holds on lab reports, prolonged data reconciliation, and potentially delayed submission deadlines. The longer the delay in query generation or reconciliation, the higher the chances the data will take longer to confirm.
The Shift to RT-EDC
Key players in the central lab industry have begun to realize the benefits of RT-EDC and are advocating for this method of data collection, whether through their own solution or a vendor provided solution. RT-EDC solutions are becoming more available within the central laboratory space and the benefits are noticeable, including:
- Immediate reduction in query generation (estimates 75% to >98%)
- Faster query closure rates (estimates <2 days)
- Real-time sample & shipment tracking
- Immediate notification of sample collection protocol deviations
- Shipping of samples direct to analyzing labs
- Reduced transit risk and decreased overall shipping costs
Reduced queries coupled with real-time query resolution reduces delays in reporting by providing faster receipt processing at the laboratory. In turn, there can be a quicker turnaround of results and a significant reduction in data cleaning/reconciliation time at the close of a project.
The shift towards RT-EDC within the central laboratory, creating a site-centric model that uses existing portal functionality, provides a more organized method of sample collection and shipment, enhancing site-level efficiencies. Sites no longer spend time identifying the source paper and resolving queries or looking through paper lab manuals – it is all at their fingertips, through the central lab portal. Real-time amendment changes are also implemented more quickly and efficiently at the site level when implemented through an integrated application. All data is contained in one source of information without the need to reconcile between papers and multiple systems.
Current Options and Challenges in Implementation
Industry stakeholders have raised concerns that moving to RT-EDC could burden site teams. We must be careful not to increase the number of portals and logins sites are required to use and assure that RT-EDC systems are designed with investigator site staff in mind. It is important to discuss the value of RT-EDC during the trial planning stages along with providing proper education and training for sites, to ensure they recognize the efficiencies and benefits that RT-EDC can have on their day-to-day operations. To realize the full benefits of RT-EDC there must be 100% adoption on a trial from sites and sponsors, having both electronic and paper options increases the risk of changes to one without the other, increasing queries for this type of reconciliation while minimizing the benefits RT-EDC provides. The shift to RT-EDC has started in the central laboratory space, with several of the large central labs creating their own platform for electronic data,the introduction of 3rd party software companies, and even some sponsors creating their own software, continuing to expand the options available to go electronic and move away from paper requisitions. However, as the options continue to grow, so do the challenges with implementation. The use of a 3rd party or even sponsor driven software, requires additional integration points, additional database setups, and can add touchpoints and changes during an amendment. Using a Central lab-built RT-EDC system, integrated with the collection kits and testing, provides a streamlined option, and reduces the touchpoints necessary to launch a study.
Conclusion
There has been a tangible shift towards electronic data within the central laboratory in recent years, as more sponsors and sites realize the benefits of clean data at the point of collection. Some example case studies have demonstrated a reduction in query rates from 25% (paper) to <5% when switching to electronic requisition. Additionally, reduced queries mean less of the site’s time spent managing queries, with early data showing a drop from 10% of time spent managing queries when using paper, to <3% when using electronic data. Moving away from paper requisitions will enable fully electronic data across the central lab, joining with the already electronic capabilities for query resolution and lab reporting. The reduction in queries and exponential impacts of cleaner data is becoming the industry drivers for the change to implementing digital data capture functionality. Further, utilization of a central laboratories eRequisition can provide advantages over alternative software solutions. Key benefits of a central laboratory eRequisition solution include site centricity, end to end sample management, and single system set up, leading to streamlined access and data integration. Shifting to electronic data will continue to enable cleaner data from the point of collection, driving lower query rates for sites, and reduced data reconciliation time at the close of a study for sponsors. We will continue to see this evolve, eventually shifting to 100% electronic data capture for central laboratories. To get there, we will continue to push the standards towards electronic data, removing paper and enabling sites to shift their focus from closing queries to caring for patients.
1. https://www.appliedclinicaltrialsonline.com/view/evolution-electronic-submissions