Euphoria over EHR/EDC Interoperability May be Misplaced

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. 


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    We agree with Ed that relying solely upon EHR data is impractical for clinical research focused on investigational new drugs. We also agree that the proposed clinical research interoperability standard (HITSP IS158) can make the process even more complicated and that it may be missing the big picture. We also agree that Clinical Ink’s approach is quite interesting, such so that Tommy Littlejohn showed it to us a few years back. If the Clinical Ink tablet was used for all clinical trial sites for a given study and Clinical Ink worked closely with the sponsor to assure proper mapping to the Pharma database it could solve some but not all issues. However, as there are some risks, the following should be taken under consideration: 1) the device needs to be distributed to all sites so this creates some logistical issues; 2) what happens if the tablet malfunctions or is stolen or misplaced before data are transferred? 3) how are queries managed? 4) since it is a thick client, how complicated is it be to make changes to the tablet application e.g. an edit check needs changing? and 5) there may be some issues concerning the control of original data since at the end of the study, SureSource™ documents are transferred to long-term storage servers and the research site receives a CD containing copies of each subject's source chart.

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    Space limits prevented me from specifiying what IMHO is the biggest hurdle to EHR/EDC seamless integration. The article totally ignores the real world situation where, according to there are over 250 EHR providers. Many of them much larger than any EDC company except Oracle. Since 21CF11 requires all systems used to electronically collect data in support of the clinical trials meet the requirements stated therein, I assume this means the EHR systems would need to meet these standards. They would need compliant audit trails, access controls, and all other functionality called out in Part 11. Plus, if they are using electronic signatures they would need to meet the administrative prerequisites. Evidence of user acceptance testing by the site would be required and training documented for all persons involved in the design, programming, installation, etc. of the systeme would need to be available.
    Now, assuming not all of the sites in a clinical trial are using the exact same EHR system the validation excercise needed to bring these systems into compliance could be overwhelming and totally mitigate any cost savings. Plus, it could be implied in the predicate rule that, assuming an EHR system is in use, the vendor, version and how and when the data are integrated would need to be specified in the protocol. Pity the medical writers on that.
    Then, the software nuts and bolts issues with how to maintain "round trip" synchronicity of data. How would the EDC system know if the EHR system changed the subjects date of birth? Or weight or medications. And, assuming the change was entered in the EHR system would the reason for change be recorded as required in guidance docs and predicate rules? Probably not. Each of these use cases would require a work-around. Work-arounds cost money and decrease quality.
    More discussion is needed and, as a community we need to be much more creative and open.

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    First - author "Full Disclosure" should preface any article, even opinion based articles laced with "facts" and "statistics". Second - In the paragraph on potential cost savings the 12% for data management activities, 43% for monitoring visits and 26% for project management accounts for 81% of the study budget? How is that possible? Surely investigator payments, pharm tech, medical writing, statistical analysis, submission preparation and other miscellaneous functions performed in clinical trials account for far more than 19% of the overall clinical trial costs.
    Third - eliminating SDV is not possible or advisible. Without on site SDV how do you know with reasonable assurance that all the data collected are entered until the CRA compares the sponsor's version of the data to the patient medical records - EHR or paper? And certainly no one is proposing that electronic copies of patient medical records be made available to the sponsor. To do so would require redacting all patient identifiers to insure patient privacy and HIPAA compliance. The CRA site visit and comparison of the sponsor's data to the existing patient/subject data is the only way to safely verify that there are no errors or omissions (to the degree possible in manual inspections).
    Fourth, in the section promoting the Clinical Ink product Ed states that using [his product] successfully could reduce overall study costs by 25%. I would like to see the breakdown of cost savings that would result in such a significant savings.
    Finally - the third paragraph that actually talks about EHR/EDC integration is very interesting. However, it misses the biggest hurdle to integration.

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    remainder of previous post:

    Luckily, the upcoming DIA conference will be hosting its first Interoperability Showcase sponsored by CDISC and IHE. Multiple EHR vendors and EDC vendors including Nextrials will be there. More telling is that Pfizer and the FDA are participants in the showcase and will be available to discuss their thoughts of this new paradigm. I guarantee they will not label it as “largely a pipe dream.”

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    It is unfair to criticize a program still in development as being incomplete. CDISC and IHE have created a roadmap for robust data exchange including tools to facilitate clinical trials like the ability to enroll a patient into a clinical trial directly from the site’s EHR. A community of EDC and EHR vendors is building these tools – some are already in place, some are still in development. (I have never regarded the UK government as the standard of innovation, so I am not discouraged that they have not been able to achieve this goal.)

    More important than the technical Connectathons are the multiple HIMSS Interoperability Showcases that have been held where the technology has been demonstrated using commercial software from EHR vendors, including GE, Allscripts, Epic, Tiani-Spirit, e-MDs, Greenway and Cerner and commercial EDC systems from Nextrials and Outcomes. This is not smoke and mirrors. For obvious reasons, real patient data is not used, but the software is live production software.

    In addition, the technology exists beyond Connectathons and Interoperability Showcases. Pilot studies have been conducted including the NextGreen project (see the April 2010 issue of Applied Clinical Trials) that involved a collaboration between Nextrials and Greenway. Over 75% of the data was auto-populated from Greenway’s EHR. (For an interesting application of EHR use for pharmacovigilance, I suggest readers check out Pfizer’s ASTER project at

    Edward is correct to point out that rarely will 100% of the data needed for a prospective clinical trial be recorded in the EHR. That is why the standard was written to surface CRFs within the EHR to capture this data. But let’s not underestimate the value of auto-populating medical history, physical exams, laboratory data and concomitant medications – some of the most dense and error-prone data collected in clinical trials.

    I realize few people in our industry attend the HIMSS conference. Luckily, the upcoming

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