Feb. 12, 2007 | Electronic Data Capture (EDC) has been the focus of industry attention for more than a decade. But EDC is only one piece of a much bigger puzzle. Many unsolved problems in conducting clinical trials cause delays, wasted resources, team frustration, and even safety issues. Thus, the industry is turning more of its attention to Clinical Trial Management Systems (CTMS).
CTMS is a diverse and important area that addresses inefficiencies inherent in the operational side of research, including site performance tracking and management, patient recruitment, team collaboration, resource management, supply chain management, and regulatory document management. One could argue that non-clinical workflow inefficiencies have as much impact on the cost of clinical research as working with paper case report forms (CRFs). Despite this, CTMS has only recently been gaining interest, overshadowed by the resources necessary for often painful and complex EDC implementations.
Biopharma sponsors are now starting to recognize the potential opportunities that exist with EDC-CTMS integration. Sarb Shergill, Genzyme’s senior director of clinical research, says: “By creating simpler, more value added trip reports (CTMS) and having access to real-time data (EDC), CRAs are able to focus more attention on site relationship management activities.”
As companies consider development or purchase of CTMS systems, inevitably questions of if and how to integrate CTMS systems with EDC systems arise. Interviews with a number of industry experts reveal a few common themes:
• Emphasis is shifting from integrating systems to interfacing systems
• Data warehousing has a significant impact on EDC-CTMS integration
• The industry needs to do a better job exchanging data electronically with sites and adding value to their business processes
• Regardless of chosen software applications, be prepared for significant investment in business process changes that accompany the deployment of new technologies
CTMS provides tools for visualizing and solving operational problems on a real-time basis. Most of the premiere EDC vendors, including Oracle Clinical, eTrials, and ClinPhone now offer CTMS solutions that integrate with their EDC solutions. Some are robust stand-alone systems while others are “bolted on” to EDC solutions and do little more than pull operational-type data out of the clinical system.
Nicholas Richards, COO of DataLabs (a ClinPhone company), notes that, “There is a lot of focus in our industry on creating an integration strategy built around a data management system. But data management isn’t the center of the eClinical ecosystem.” He adds that, “trying to force other sources such as lab, ePRO, clinical data, and business metrics into a data management system doesn’t make sense. Take other industries such as the auto industry, finance, or reservations industries. Their integration strategy isn’t built around a specific system.”
While some CTMS systems have been around for years, defining exactly what it is and what it should do will take time. Unlike EDC, however, CTMS may never really reach a specific point of definition, as research administration and operations are not regulated by the FDA in the same way as clinical protocols and data. There is little governmental intervention with respect to how the business side of clinical research is conducted. As long as an FDA-approved protocol is strictly followed from a clinical perspective, the data is valid and clean, and state and federal business laws aren’t broken, every sponsor or CRO is free to run their business any way they choose.
Because every sponsor and CRO have a different business model mode of operation, no single out-of-the-box CTMS product is likely to satisfy the majority of business management needs of any organization. The diversity of business models and needs among sponsors and CROs have created a crop of diverse CTMS tools — much more so than EDC tools. Some packages have regulatory management or resource planning features, others include team collaboration or site payments. Not surprisingly, evaluating CTMS can be confusing and time-consuming.
While selecting a CTMS, it’s important to address how and why a CTMS should be integrated with an EDC system. Integrating or interfacing CTMS and EDC is at or near the top of everyone’s wish list. But multi-vendor integration projects can be painful.
Integration vs. Interface
Full-blown integration (in the form of a true “blending”) between EDC and CTMS is a complex undertaking that ultimately locks firms into one or two vendor’s products because the two systems have to be interwoven so tightly. In other words, integration implies that two systems mix together in some way (often involving the user interfaces) to smooth out the workflow from one system to the other, but this requires big dollars and customizations.
“Perhaps a better way to categorize the discussion is to use ‘centralized’ vs. ‘federated’ models,” notes Richards of DataLabs. “In a centralized model, all data is housed in one system. In a federated model, users want access to the systems but don’t necessarily want to have data in one system. It’s costly and obviously there are a lot of risks with all data in one system.”
James Rogers, president and CEO of Nextrials, agrees that it may not be feasible or realistic to achieve full system integration. Says Rogers: “As more and more eclinical tools are being adopted by various outside vendors, sponsors have even more needs to expand access to and interface with these systems. Is it practical to have one core software package for the long term that truly integrates all functionality? Or, is it more important to build seamless capability for software packages to efficiently talk to each other?”
A simpler approach is to leave EDC and CTMS separate but interface them by defining metadata and communication standards that allows them to share data. “Interfacing” is not an attempt to blend products together, but rather to form a common language that both products can speak in order to share data. “Consistent metadata definitions help to automate the handshake between EDC and CTMS systems,” says Keith Howells, VP of development at Medidata. This provides more flexibility at much less cost, but the workflow isn’t necessarily as smooth.
On-demand, web-based solutions offer another option and may reinforce the growing trend toward system integration as highlighted by the recent partnership between Clinical Force (CTMS system) and TrialStat (EDC system). Jonathan Barker, president and CEO of TrialStat, notes that “our customers are telling us they want CTMS and EDC in a single integrated solution.”
Oracle has a web-based integration option as well. While the company is still supporting its SiteMinder product, a site-based investigational tool, Dennis Constantinou, Oracle's senior director of life sciences, strategy, and marketing, says Oracle now believes that SiteMinder is better suited for an academic research environment. In March 2006 Oracle released a wholly web-based umbrella product called Life Sciences Data Hub for the pharmaceutical industry.
The web-based product links the Siebel CTMS, which Oracle acquired in January 2006, with Oracle Clinical and Oracle Remote Data Capture. "Managers can look at a clinical trials very holistically and monitor the progression of those trials," says Constantinou, adding that Data Hub strives to be a single product that "does all the aggregation and integration of clinical and non-clinical information in a regulatory-compliant environment."
The key consideration is whether the business operation requires actual integration or just interfacing. The flexibility of interfacing comes from the ability to plug in (or quickly unplug) different solutions that provide different functionality. You’re not as vested in specific solutions if you interface rather than integrate.
“People in the industry see EDC and CTMS as competing systems,” says Keith O’Leary, senior product marketing manager for Phase Forward. “Part of the confusion stems from the fact that some EDC vendors have built in some rudimentary CTMS-like capabilities. From our perspective, sponsors don’t want these few extra “bells and whistles” tacked onto their EDC systems. They are looking for robust, standalone CTMS systems that provide their value, but that can communicate when appropriate, to EDC systems for additional value.”
Naturally, Clinical Data Interchange Standards Consortium (CDISC) provides a basic platform that can be used to interface CTMS with EDC. “The use of industry standards is allowing the interchange of data from ‘various best of breed’ tools, thereby enabling sponsors to select the components that best fit their business needs,” says Shaghig Palanjian, VP, worldwide technology implementation for PAREXEL International. Nonetheless, there’s no such thing as plug-and-play, even with CDISC. You have to synchronize both data and semantics between systems. For example, if the status of a screened subject in a CTMS system is changed to “On Study,” does it mean that the subject has been randomized and is ready for the first treatment, or that the subject is only qualified to be randomized to a study arm? Such details are clearly an obstacle, but you can’t interface systems without defining them first. CDISC offers an excellent structure for organizing data. That’s more than half the battle, but it doesn’t define the actual semantics of the metadata.
Data warehousing is having an impact on EDC-CTMS integration. A data warehouse provides a repository where information can be stored and easily mined for business intelligence. The format of the data differs from a standard relational-style, single-application database. It is specifically designed for grouping and aggregations across broad categories with built-in dimensions for time, money, counts, and so on. Data warehouses can be “fed” by almost any system in a vendor-neutral way, although some warehouses are vendor-specific. Allowing CTMS, EDC, and/or clinical data management systems (CDMS) to deposit key information in a single data warehouse reduces the need to create so many connections between multiple systems.
Data warehouses are offered or supported by most leading vendors, and many sponsors build their own and require that vendors feed information from EDC and CTMS directly into them. The first warehouses were built mostly for clinical data mining, but newer warehouse designs factor in data from CTMS, which adds operational intelligence to clinical intelligence.
A warehouse-centric model is one of the approaches being taken by Perceptive Informatics. According to Kate Trainor, VP integration services group, “We’ve moved from the concept of a data management system as being the sole place for data to reside to more of a data warehousing view. As long as data can be mined for analysis and reporting, it doesn’t really matter what type of system one has; and standards are driving this change.” This strategy will ultimately be preferred by sponsors who want flexibility without being locked down by one or two vendor’s product architectures.
This is where the concept of data ownership comes in. “A key decision point in pursuing integration or interface of systems is to determine which application owns the data,” says Trainor. Howells concurs: “Who owns the master billing record, the patient data record? ...How will it be broadcast to the other side? Understanding the implications of cascading changes and deletions is also key.”
But in the new eClinical world, is the traditional view of data ownership appropriate? For example, the investigative site is first registered in CTMS. Traditionally and classically patient enrollment was owned by CTMS. Now it fits more logically in EDC. “Determining the most immediate and complete “data ownership” master is where the emphasis is shifting,” says Howells.
Beyond EDC-CTMS system integration is the problem of integrating systems with investigative site business practices. Experts agree that the industry must do a better job exchanging data electronically with sites, thereby reducing the site’s time and cost of doing the trial.
“It’s essential that sponsors keep the investigator in mind so that they are happy with the tools and services being provided...this goes above and beyond merely having user friendly systems. The application must provide real value to the sites,” says Trainor.
This aspect of clinical research is almost completely broken, and is something CTMS systems should focus on. “It’s very difficult if not impossible for sites to use various sponsor systems when there is no standardization in the industry” notes Michael Vernia, an independent technology consultant.
Whether it is tracking subject enrollment statistics, protocol amendments, site payments, clinical inventory, or dozens of other items, a CTMS should reduce the amount of tedious human intervention required. Rogers of Nextrials notes that the site payment process is a good example of where sponsors should take advantage of the capabilities of the technology to facilitate improved sponsor-site business processes. “The information generated from the “integrated” EDC-CTMS system provides confirmation of what the site has actually done and sites gain value by prompt payment so it’s a win-win solution for everyone.”
An information systems manager from a major biopharma, on condition of anonymity, indicated that one of the key drivers influencing the move to integrate EDC and CTMS systems is the opportunity to streamline the site payment process. EDC systems enables users to track the activities that drive the site payments with appropriate triggers to the CTMS system to request payments from finance.
Many sites use their own independent CTMS to track all of these things, so the sites can manage their operations and
finances. Sites would much rather use the data they’ve already entered into their own CTMS to report patient visit logs or submit payment/reimbursement requests. Unfortunately, many sponsors don’t even know (or care) that sites have their own CTMS systems, and require sites to re-enter the same information in the sponsor’s CTMS.
For example, site payments are triggered when certain CRFs are received through the EDC system, but this doesn’t allow for capturing other costs not associated with a specific patient visit or CRF, such as additional advertising expenses approved by the sponsor in the middle of the study. Without an efficient way of mutually tracking these items on both the sponsor and site sides, the billing, payment, and reconciliation process is a nightmare. As a result, clinical research finances involve a huge amount of guesswork, and that ultimately costs both the sites and sponsors money.
Vernia reinforces this message: “Sponsors should be worried about inefficiencies in the current site payment process — keeping good performing sites happy is key. CTMS systems appear to take second priority over EDC systems and most CTMS systems don’t have a robust site payment process built in.”
There are only a few site-based CTMS systems in widespread use, so an effort like this could have a fairly broad impact. Advanced Clinical Software’s StudyManager is installed at nearly 2,000 sites — more than any of its competitors, largely due to ACS’ 13-years in the business. According to ACS president Bruce Schatzman: “If we want to see the cost of
research come down, we’re going to have to start electronically bridging the gaps
between sites and sponsors. The cost of all that phone-and-paper-based interaction, along with the cost of entering data multiple times at the site is a huge barrier that isn’t being prioritized by enough people. The sites supply the patients and the clinical data, and if their costs are high, so are yours. ACS is now in the process of leveraging the CDISC standards to make it easier to interface almost any system with StudyManager at the site level.”
Sponsors that implement ways to make their interaction with sites simpler, easier, and less costly for the sites will out-compete other sponsors for the best available sites to participate in their trials. Yet sponsors continue to add data entry fields to their own CTMS and EDC systems to capture new information that is already available in site-based CTMS. This may give sponsors some additional business intelligence, but increases the work for sites and drives costs up.
Business Process Impact
For sponsors, CROs, and sites, regardless of which technology solution they elect and whether they favor an integration or interface approach, the business process changes associated with new technology deployment consume much time and
effort. Notes Shergill, “Process change management is more important than technology integration per se.”
Charles Buchanan, grants & contracts administration, Swedish Research Center in Seattle agrees, having tackled a large CTMS integration project. “The adoption of technology and new tools drive work process changes; these are the most intensive aspects of the implementation of new software solutions and are often underestimated,” Buchanan says.
Many roles may change as a result of implementation of EDC/CTMS systems and sponsors need to manage the cultural resistance to change. It’s also inevitable that technology may dictate certain ways of doing the business. You may need to re-adjust the business process or develop new processes based on the constraints of the software system.
There are many aspects to consider when evaluating the EDC-CTMS systems integration process (see Table). But as Phase Forward’s O’Leary says, “Most sponsors quickly realize the benefits far outweigh the process changes required and that the process changes themselves yield additional benefits.”
The EDC landscape continues to change. In the past, there were calls for monolithic systems that did everything — EDC, CDMS, CTMS, and perhaps even BioStats all in one package. This would be the equivalent of something like a “Microsoft Office” for clinical research. Nowadays, sponsors and vendors have decided that the “Swiss-army knife” approach is counter-productive because there are far too many functional requirements across the entire data supply chain, and many of them don’t really require serious integration.
The new mantra encourages innovation and new functionality by requiring vendors to interface to each other using CDISC and other standards, and to be able to feed data into warehouses when required to analyze information collected across multiple systems. This creates a true “free market” for clinical research software. Although it’s a little more chaotic than creating monolithically integrated systems, it brings out the best in everyone and allows sponsors, CROs, sites, and software vendors to cooperate in a way that will drive down the cost of clinical research.
Beth Harper is President of Clinical Performance Partners. Email: firstname.lastname@example.org
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