By Deborah Borfitz  

May 16, 2011 | Despite noble efforts by the Clinical Data Interchange Standards Consortium (CDISC) and others to write a rulebook for the exchange of patient-level clinical information between electronic health records (EHRs) and electronic data capture (EDC), interoperability between the two systems is largely a pipe dream. All this obsessing over data will not in any case remedy the budgetary woes of trial sponsors or the exodus of investigators from clinical research. Answers to these most pressing concerns will remain elusive until the focus shifts to the realities of investigators and study coordinators at sites initially capturing the data. 

So says Edward Seguine, formerly an advisory board member of CDISC and CEO of clinical trial planning software FastTrack (acquired three years ago by Medidata) and now president of electronic source record creator Clinical Ink. Relying solely upon EHR data is impractical for clinical research focused on investigational new drugs, excepting oncology studies where all but the new treatment is customary medical care. The proposed clinical research interoperability standard (HITSP IS158), which is intended to serve as the basis for how data within EHR systems can be used to support clinical research, instead “makes the process even more complicated.” 

Critically, of the 37 “use case actions” mapped out for an interconnected environment, 22 have dependencies on systems that don’t exist, says Seguine.  Data monitoring activities, the biggest cost driver of clinical research, are addressed merely by referencing a non-existent Reviewer System or EHRs that magically learn of protocol requirements via a standardized message from another non-existent Protocol Development System. “The [nonsensical] HITSP IS158 standard completely misses the big picture.” 

It’s no coincidence that the United Kingdom, with its nearly 20-year-old national database of patient information, is still unable to tap the data for clinical studies or use its EHR capabilities for direct entry of clinical trial data, says Seguine. Interoperability proponents this side of the pond will point to results of recent Connectathons sponsored by CDISC and IHE (Integrating the Healthcare Enterprise) as “proof that EHR/EDC integration is viable now.” Tellingly, Nextrials is the only participating EDC company and “that’s because this type of staged integration doesn’t fully test all the pieces together and simply ‘assumes’ data exists from non-existent systems,” says Seguine. 

Part of the holdup is CDISC’s close ties to the National Cancer Institute (two current CDISC board members represent NCI), which has resulted in “overly simplistic views about the best approach,” says Seguine. “In contrast to oncology, most other therapeutic areas don’t manifest the same treatment dynamic.” About two-thirds of procedures called for in clinical trial protocols over the last decade have no corresponding medical billing standard, including well-known research instruments such as the Hamilton Depression Rating Scale, says Seguine, who recently co-authored research on increasing protocol complexity. 

Irrespective of therapeutic area, it’s “extremely valuable and easy with today’s technology and business practices” to export from EDC or Clinical Ink’s SureSource solution an HL7 standard document containing study visit data into an EHR so other physicians are aware the patient was involved in a trial, says Seguine. Conversely, “already standardized concepts”—e.g. patient demographics, prior medications, lab results, and medical history—could under certain conditions be imported into research data from an EHR. 

But data-related activities—data entry, database handling, and data clean-up—account for less than 12% of clinical trial budgets, according to Medidata CRO Contractor calculations averaged across phases. Meanwhile, site monitoring and site management consume a whopping 43% of the total. “Other research points out that monitoring [by itself] can be nearly 40% of a large phase III study budget,” says Seguine. “As a result of the convoluted process, project management is over 26% of the total study budget. In any other industry that would be laughable.” 

The Paperless Path  

All of this brings us to the ideals of Clinical Ink, which include getting rid of all the paper that has made clinical research burdensome for sites and unnecessarily expensive for study sponsors. Online portals used to disseminate newer versions of paper documents is tacit acknowledgment that “paper rules the roost,” says Seguine. His goal with the newly minted SureSource is to create a model for how sites collect information that reduces the need for paper-based source documents and thus source data verification (SDV). 

The paper-free world Seguine envisions won’t happen at the hand of Clinical Ink alone. SureSource provides a web portal where study sponsors, monitors, and site users can review electronic source documents remotely as visits happen in real time. But sponsors and sites would also need access to other types of information electronically, including regulatory and informed consent documents as well as clinical trial results for individual participants.  Seguine feels this broader information-sharing environment could be built now using Microsoft’s Sharepoint and Amalga platforms, but require interfaces that are geared toward sites—not data managers—to facilitate the gathering of data and documents.  

Clinical Ink is now working with small biotechnology companies and clinical research organizations to prove the SureSource concept which, if successful, could cut total study costs by 25% or more and produce hundreds of millions of dollars in annual savings for large trial sponsors, says Seguine. The return on investment is calculable based on the number of monitoring visits ($2,500-$5,000 each) and queries related to SDV ($65-$100 per cleaning) that can be eliminated.     

With the untimely passing of Clinical Ink co-founder Tommy Littlejohn in March, the company lost some commercial acceleration as well as a respected peer who befriended everyone he met, says Seguine. During the development of SureSource, Littlejohn provided unfettered access to the 11 sites of Winston-Salem, NC-based PMG Research, Inc. where he served as president and executive medical director. Field testing at the sites ensured data entry into a tablet computer happens in the most expeditious way possible—be it a drop-down list, yes/no checkbox, number scale, image, or handwriting—with the familiar feel of pen and paper. 

The e-source record complements existing data warehousing infrastructures, and ultimately could supplant existing EDC systems that output data statisticians want to analyze, says Seguine. SureSource collects the same information in addition to the source data investigators must document to demonstrate compliance with Good Clinical Practice and patient case history requirements. Importantly, within the source documents study monitors can immediately spot an adverse event that investigators may initially interpret as clinically insignificant. Indeed, the frequency and relevance of interactions between monitors and sites increases even as the number of face-to-face visits decline, he adds. 

Despite new e-source guidance from the U.S. Food and Drug Administration, sites as a rule are not doing direct data entry into EDC because those systems were created to address the needs of data managers and are thus sequentially out-of-sync with how patients get evaluated, says Seguine. “If EDC could be used to capture source data directly in front of a patient, enterprising researchers would have been doing so long ago.  They haven’t because EDC doesn’t meet their needs.”  And so long as doctors have to endlessly toggle between forms, setting off round after round of edit checks, they will continue documenting patient visits on paper.