Magazine Article | April 5, 2010

Á La Carte Or Prix Fixe – Is There A Right Menu For Clinical Trials Technology?

Source: Life Science Leader

By Anne Zielinski

Sponsors choosing eClinical technologies face alternatives similar to diners’ menu options. Those with specific preferences may be better served by making their own choices for each course of their meal, while those who trust the chef’s palate and execution may be tempted to surrender control.

Similarly, choosing favored eClinical technologies from various providers could mean they may not work together easily, while the fixed menu may result in some technologies that fall short of expectations. The benefits also apply to the set of tools available: A diner’s eating pleasure would be seriously affected if, in selecting a prix fixe dinner (i.e. a collection of predetermined items presented as a multicourse meal at a set price), he finds that the side dishes and desserts he wants not only do not come with the meal but cannot even be ordered at the restaurant.

The appeal of choosing preferred systems á la carte must be weighed with the possible challenges of integrating them for rapid data sharing. Today, through strides in interoperability approaches, cherry-picking best-of-breed tools — an organization’s preferred IVR (interactive voice response)/IWR (interactive Web response), eDiary, EDC (electronic data capture), and other systems — becomes a much more appealing option for an integrated eClinical environment. It can also lay a foundation of interoperability for integration with other systems within the company.

Integrating Data And Making Systems Interoperable
Traditionally, integrating one clinical system to another has involved batch loading of data, triggered either at a scheduled time or ad hoc, in which data from multiple visits, subjects, and sites is transmitted from one system to another. Setup of these integrations has required custom programming for both applications. Thankfully, CDISC (Clinical Data Interchange Standards Consortium) data models offer a common language among systems to help reduce integration efforts. Moreover, the availability of CDASH (Clinical Data Acquisition Standards Harmonization) forms, which identify basic recommended data collection fields, further streamline integration.

Enter Web services, a software system designed to support interoperable machine-to-machine interaction over a network (as described by Wikipedia). Web services provide a means for eClinical systems to share data in real time so that, to the user, two systems interoperate to appear as one. Think of a universal remote control device that controls a television, Blu-ray player, and amplifier, each produced by a separate manufacturer. Like that remote control, Web services require no programming to enable interoperability, just the initial configuration.

While using standards and Web services makes interoperability of multiple systems easier and faster to set up, it also improves data quality. Standard definitions can be used to set up multiple systems, and systems receiving data can send automated messages confirming success or pinpointing reasons for failure in receipt of transmitted data.

The Case For Interoperable Systems
To illustrate the benefits of standards-based integration, let’s examine the activities of some key players in clinical trials. Since most data originates at the investigator site, it’s a good place to start. The systems involved are likely to include an IVR system for randomization and supply tracking, an EDC system for investigator-generated data, a laboratory system, and perhaps an eDiary for patient-reported outcomes. Some data — for instance, patient number — needs to be in each system. Any site coordinator who has had to enter the same data into multiple systems knows the pain of such double work, and managers know the reconciliation headaches. Since data is only entered once when systems are interoperable, site staff enjoy streamlined data entry, while data managers benefit from better data consistency and reduced need for data reconciliation.

For good subject management, especially when there are adverse events, investigators want to see a complete view of subject data from across systems. Without interoperable systems, an investigator must log in to several systems or wait weeks or months until data is combined for analysis. Interoperable systems offer a convenient, one-stop view of subject data.

Delays in sponsors’ payments have frustrated investigators for years. In an eClinical environment, payment systems that accept information from EDC systems at trial milestones theoretically can pay sites via wire transfer within hours of completion of a clinical trial task.

Monitors reviewing sites as well as subjects benefit from having one user interface that includes data gathered in multiple systems. Safety staff whose reports are time-critical appreciate having data from the EDC system transmitted to their safety reporting system as soon as it is entered. Without the need to reconcile mismatched data, data managers can focus on reviewing and preparing clinical trial data for analysis.

Up-to-date information on trial progress and overall program status is critical for executives managing resources across a portfolio of compounds. The more quickly trial data from various systems is consolidated, the more quickly executives have insight to help make critical business decisions, including which programs to continue to fund and which to terminate.

Other Considerations
Several considerations are necessary when systems are interoperable. A crucial one is data security. For systems to be interoperable in clinical trials, they need to inherit role-based security. For instance, an investigator who is blinded to subjects’ treatments cannot have access to that information, even though that data which exists in the IVR/IWR system is also available in the EDC system (both in eCRFs [electronic case report forms] and in reports). It is crucial that the same restrictions on data access are enforced.

When systems are sharing data, it is important to identify which system is the “owner” of each data point. If a subject is created in an IVR system and the subject number is then transmitted to an EDC system and an eDiary system, the “owner” of that data point must remain the IVR system. The EDC and eDiary systems must not allow that data point to be changed. This will support proper source verification, data monitoring, and data cleaning.

Interoperability need not be one-way; trial setup should derive as much benefit as possible from an eClinical environment. Laboratory test values that determine into which study arm a subject will enroll can flow from a lab into EDC and then to the IVR/IWR system that communicates to the site which kit to provide the subject. Dispensing information can then be entered in the IVR/IWR and transmitted back to the EDC system.

System interoperability facilitates unified reporting, based on the security models inherited between systems. Logging into one system, users can access reports that include data from many systems. Designers of standard reports will want to take full advantage of all available data to optimally streamline business processes for those conducting and managing trials.

Á La Carte Or Prix Fixe
When selecting the right systems for an eClinical environment, it becomes important to understand how they fit together. eClinical suites that have been designed and built to work together are a strong choice to the extent that the functionality of their individual tools meets an organization’s needs. Ideally, the components can work together or alone so that sponsors can swap out components that, for whatever reason, they don’t want to use. Think of the diner with an allergy to a component of one menu item, and the restaurant that allows a substitution to the prix fixe menu. Other considerations are that some packaged eClinical offerings may still only connect via batch transfer that requires labor-intensive custom code to tie them together, and some may have poor interoperability with other systems at the sponsor.

Meanwhile, some stand-alone technologies offer state-of-the-art Web services APIs (application programming interfaces), CDISC- and CDASH-based configurable interfaces that can be reused from trial to trial, allowing applications to be easily and reliably plugged together for real-time interoperability. Configuration of these interfaces can be simply a matter of hours.

In reality, both the prix fixe and á la carte approaches can work well for sponsors, but to make the correct choice it is important to understand the flexibility and adaptability of the specific system or group of systems while matching functionality requirements with the capabilities of the eClinical technology menus.


About the Author
Anne Zielinski is VP of alliances at Medidata Solutions. She has 10 years of experience in the EDC industry. She previously served as VP of strategic alliances at CB Technologies, where she directed CB’s activities in EDC, including managing large, multiyear projects for major pharmaceutical companies.