Quantifying and visualizing site performance in clinical trials

Abstract

BackgroundOne of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol. Intuitively, the historical track record of a site is one of the strongest predictors of its future performance; however, issues such as data availability and wide differences in protocol complexity can complicate interpretation. Here, we demonstrate how operational data derived from central laboratory services can provide key insights into the performance of clinical sites and help guide operational planning and site selection for new clinical trials.MethodsOur methodology uses the metadata associated with laboratory kit shipments to clinical sites (such as trial and anonymized patient identifiers, investigator names and addresses, sample collection and shipment dates, etc.) to reconstruct the complete schedule of patient visits and derive insights about the operational performance of those sites, including screening, enrollment, and drop-out rates and other quality indicators. This information can be displayed in its raw form or normalized to enable direct comparison of site performance across studies of varied design and complexity.ResultsLeveraging Covance's market leadership in central laboratory services, we have assembled a database of operational metrics that spans more than 14,000 protocols, 1400 indications, 230,000 unique investigators, and 23 million patient visits and represents a significant fraction of all clinical trials run globally in the last few years. By analyzing this historical data, we are able to assess and compare the performance of clinical investigators across a wide range of therapeutic areas and study designs. This information can be aggregated across trials and geographies to gain further insights into country and regional trends, sometimes with surprising results.ConclusionsThe use of operational data from Covance Central Laboratories provides a unique perspective into the performance of clinical sites with respect to many important metrics such as patient enrollment and retention. These metrics can, in turn, be used to guide operational planning and site selection for new clinical trials, thereby accelerating recruitment, improving quality, and reducing cost.

Risk-based Monitoring of Clinical Trials: An Integrative Approach

“…Both our own work in discovery, 25 clinical, 26,27 and outcomes research 28 and work in other scientific domains 29 have found that human intuition married to meaningful and actionable visualizations can lead to more optimal outcomes than a purely statistical or computational approach. Our primary goal in designing our RBM solution was to allow clinical staff who may not have formal training in data mining, informatics, or statistics to readily identify patterns in the data, confirm or challenge their assumptions, and make more informed decisions.…”

Changes in key recruitment performance metrics from 2008–2019 in industry-sponsored phase III clinical trials registered at ClinicalTrials.gov

“…Furthermore, demanding protocols could also negatively influence clinical trial site performance, increasing the level of stress for trial site personnel [ 35 ]. High complexity and demanding trial site tasks may impact the performance of clinical trial sites, where low- and non-performing sites are already a challenge for the clinical trial industry [ 11 ]. In an analysis from 2018 conducted by the Boston Consulting Group and KMR Group, data from more than 75000 sites were used to examine site performance and underlying drivers of success.…”

“…Armed with such knowledge, a growing number of pharmaceutical companies and contract research organizations (CRO’s) are working to optimize recruitment for clinical trials through optimizing study designs in order to improve feasibility and ease site and subject participation burden [ 40 ]. The declining productivity of drug development has intensified the interest in digital tools and other technologies that may improve trial efficiency [ 11 ]. In a systematic review and meta analysis from 2019, we found that targeting participants using online remedies was an effective tool for patient recruitment in clinical trials, as online recruitment was superior to traditional in-clinic recrutiment in regards to both time-efficiency and cost-effectiveness [ 41 ].…”

“…From an operational standpoint, the goal is to complete clinical trials as quickly as possible without delays and with the highest data quality [ 11 ]. However, such goals require efficient and high-performing clinical trial sites.…”

Xcellerate Investigator Portal: A New Web-Based Tool for Online Delivery of Central Laboratory Data, Reports, and Communications to Clinical Sites

“…The investigator portal presented here is part of a broader clinical trial management suite, known as Xcellerate, that uses advanced data integration, analytics, and visualization capabilities to improve patient safety, data quality, and protocol compliance throughout the clinical development process and enable greater transparency and oversight of study conduct and performance. 4 – 9 Inspired from previous work in discovery, 10 clinical, 11 , 12 and outcomes research, 13 this solution consists of a number of end-user applications connected to a clinical data repository that supports near-real-time acquisition, mapping, and integration of clinical trial data from any germane source, including laboratory test results, the subject matter of the present work. The Xcellerate Investigator Portal leverages the same architectural and web design principles to provide secure online access to laboratory results, manuals, and training materials through an intuitive interface that enhances user adoption, productivity, and collaboration.…”