Epilepsy Phenome/Genome Project (EPGP)

National Epilepsy Research Initiative Built in 12 Months with Web-Based Technology

Epilepsy is among the most common neurological disorders in the world. In an effort to harness progress made in mapping the human genome, a team of scientists in epilepsy centers across the United States received a grant to study the complex genetic factors underlying some common forms of epilepsy. To meet their mission, the team needed a technology framework that would allow them to manipulate a huge number of variables in a cost-effective manner while complying with strict regulations and privacy policies. To meet this challenge, the EPGP turned to Microsoft and Chennai, India–based TAKE Solutions to develop a robust but flexible Web-based infrastructure. The team has helped to advance medical science in the area of epilepsy research by using advanced technologies to streamline clinical operations and remove IT from the critical path of discovering new therapies and cures.

Situation

According to the Epilepsy Foundation, over 3 million Americans of all ages are afflicted with a disease that not only brings distress, fear, and pain to patients and their families, but also generates an estimated $12.5 billion in direct and indirect healthcare costs. One in 10 Americans will experience an epileptic seizure in their lifetime. But because of the nature of this disease —the fact that it is often a genetic disorder— both the causes and potential cures have been difficult to assess.

For instance, while it is known that heredity plays a major role in many common forms of epilepsy, there is a consensus among the scientific community that a combination of mutations in multiple genes may determine an individual’s susceptibility to seizures, as well as the responsiveness to anti-epileptic medications. Recent breakthroughs in mapping the human genetic structure have created new opportunities to understand the disease and to develop effective treatments and pursue cures.
 

What we just did in this project is take something that usually requires between three and five years to complete and we have compressed it into 12 months. Michael Williams CIO, Epilepsy Phenome/Genome Project

That is the ultimate mission of the Epilepsy Phenome/Genome Project (EPGP). Funded by a $15 million grant from the National Institute of Neurological Disorders and Stroke (NINDS), the project will bring together over 50 researchers and clinicians from 13 medical centers around the country. EPGP researchers plan to enroll approximately 3,750 patients and 3,000 controls over the course of the study to correlate genetic factors with physical symptoms. Details about seizure types, EEGs, imaging studies, and effects of treatment will be collected and archived in a central data repository, and all participants will be asked to submit a sample of blood as a source of their DNA. (All clinical information and DNA samples will be de-identified so that it cannot be traced back to a specific individual.) Once this first phase of the study is completed, principal investigator Dr. Neil Risch, Professor of Human Genetics, a the University of California, San Francisco, and his colleagues will carry out “whole genome scans” and look for potential connections between patterns of DNA sequences and specific characteristics of epilepsy in the study population.

From an information technology perspective, the challenges associated with the EPGP project are daunting—especially considering that the IT infrastructure was built from scratch because it was a brand new initiative. But it was precisely the scope and the breadth of the requirements that attracted CIO Michael Williams to the project. This research trial builds upon the work of the Human Genome Project, and it provided Williams with an opportunity to bring over 25 years of IT experience to create a new standard for using the latest technologies to cost-effectively, rapidly, and securely manage a new generation of clinical research initiatives.

“I am very excited about the fact that we will contribute to understanding and treating epilepsy,” says Williams. “But because I have been able to start this project in a ‘greenfield environment,’ this project allows us to conceive and build an enterprise system for this type of research from the ground up without having to worry about legacy systems and processes.”
 
The challenge Williams faced was to put together an enterprise network that would have the computing capacity to:

• Capture, share, and track data from over a dozen research sites.
• Store millions of data points in an encrypted manner that complies with HIPAA, FISMA and other privacy regulations.
• Enable scientists to easily access and analyze multiple data points at the various stages of the research process.

Solution

Human genome mapping is a relatively young science. As a result, the information systems to support these types of research trials are relatively immature. However, having received a major grant, it was important to rapidly deploy the underlying technologies that would allow the project to move forward smoothly to ensure the early and ongoing success of this project.

From that perspective, the natural place to start looking for the right technology was from solutions already offered by providers in the life-sciences sector. An early review of technologies in the field, however, did not prove to be promising.

This project allows us to conceive and build an enterprise system for this type of research from the ground up without having to worry about legacy systems and processes. Michael Williams CIO, Epilepsy Phenome/Genome Project

“We were not able to find packaged solutions that we felt suitably mapped to our requirements. Most solutions on the market are oriented toward regulatory-compliance and are designed for the pharmaceutical industry’s needs. They are not able to handle the very heavy and rigorous demands that we have in terms of things like collecting information for data-intensive surveys,” says Williams.

With existing packaged applications deemed untenable, Williams determined that the project needed solid generic workflow and document management technologies on top of which new applications could be rapidly and cost-effectively developed. He was specifically interested in technologies that could be managed in a Web-based environment. After an exhaustive review of technologies, vendors, and industry best practices, Williams and his team decided to standardize on Microsoft® technology to provide the basic functionality.

• Microsoft Office SharePoint® Server was selected for its comprehensive document management and data aggregation capabilities.
• Microsoft ASP.NET was chosen for its flexibility in delivering customized Web-based functionality.
• Windows Server® 2003 was chosen as the operating system of choice.
• Microsoft Internet Security and Acceleration (ISA) server was selected to provision firewall security.
• Microsoft SQL Server® 2005 data management software was chosen as the database application for the data repository.

With the enterprise infrastructure elements in place, Chennai, India—based TAKE Solutions, a Microsoft® Gold Certified Partner, was tapped to develop the specific applications that would drive the various mission-critical processes of the project.

“We discovered TAKE Solutions at a BIO IT conference put on by the Drug Information Association. As we talked to them about our requirements, we included them in our short list of consultancies to consider. Ultimately, we found that TAKE Solutions had the most competitive and compelling approach to addressing our requirements,” says Williams.

EPGP’s Biomedical Informatics Director, Gerry Nesbitt, led the development projects and engaged with TAKE Solutions in an “extreme programming” initiative that would rapidly develop, test, and field all key EPGP applications. “Delivering informatics solutions on time that met all business requirements was crucial to the success of EPGP. The use of project management and software development best practices ensured that we were able to deliver solutions which exceeded business expectations and adhered to budget and time constraints,” says Nesbitt.

Benefits

The results have been impressive. “We’ve gone through the development of the entire Epilepsy Phenome/Genome Project in 12 months. And we have modeled and tested each key component from cradle to grave,” says Williams.

The use of project management and software development best practices ensured that we were able to deliver solutions which exceeded business expectations and adhered to budget and time constraints. Gerry Nesbitt Biomedical Informatics Director, Epilepsy Phenome/Genome Project

The project is currently underway, with the public EPGP Web site now available to disseminate information to the general public, individuals, and families interested in participating in the clinical study. It is also a focal point for other professionals interested in the EPGP endeavor.

For those directly involved in EPGP initiative, the Web site serves as the starting point for accessing the EPGP intranet site, which contains the document management system, phenotype data collection applications, and specimen management programs. Key processes supported by the Web-based infrastructure include:

Patient Recruitment Management —The Patient Recruitment Management module manages the study preparatory activities that are designed to attract, identify, and manage potential participants (probands, siblings, patients, and healthy controls) to the clinical study. The application also provides functionality to help manage participants’ private health information (PHI) in a secure and confidential manner. Access to the recruitment application is strictly controlled, all PHI data is encrypted and clinical centers are only able to access their participants’ data.

Informed Consent—The Informed Consent module electronically confirms and records that the informed consent process has been completed by a “subject” prior to involvement on the EPGP study. Because the application will be used during the subject visit, it is essential that the application completes the informed consent process expeditiously and allows the subject to continue with the screening visit.

Participant Activity Tracking—The Participant Activity Tracker facilitates the electronic data capture of all participant visits and schedule of events (e.g. questionnaires, specimen collection) across all participant activities. It is the central application for managing patient visits and collecting phenotypic data on patients. The application also captures all clinical study data, participant progress, and clinical center performance for use by the study coordinator at each clinical center and the clinical operations manager across all clinical centers. The Participant Activity Tracker is used primarily by the study coordinator at each clinical center and is used to capture, track, and manage all completed or outstanding tasks in each activity group and for each participant.

Specimen Tracking—The primary user of the Specimen Tracking system is the study coordinator at each clinical center. All subjects at any of the EPGP clinical centers are screened by the center study coordinator to identify potential EPGP enrollees. The study coordinator schedules visits for eligible subjects to describe the study, obtains informed consent, and conducts the interviews. During the screening process, the study coordinator draws two blood specimens from the subject. The study coordinator assigns the collection kit to the subject, collects the specimen, and ships the specimens to the appropriate facilities. The chain of custody is further tracked from when the contracted courier picks up the specimens, electronically documents the source and number of the specimen bags as well as the time and date of pick up, and produces a legible signature. The chain of custody is complete only when the staff at the core laboratory records and confirms that specific specimens have been received and are now technically within their custody.

EEG Review — EEGs for all subjects entered into the study will be reviewed and coded using a standardized data sheet by an on-site neurophysiologist. The life cycle of a subject’s EEG begins when it is loaded into the EPGP system. This triggers an alert to the clinical center’s neurophysiology physician to record their assessment and epilepsy type and eligibility status in the data sheet. Once this process is completed, a second neurophysiologist is randomly picked to review the data sheet and record whether they concur with the physician’s initial classification. If consensus is not reached, the four members of the neurophysiology core review the EEG in real-time to reach a consensus.

MRI Review—The MRI Review is the last step in the sequence to screen for enrollment. Only candidates meeting clinical and EEG inclusion criteria can be considered for MRI screening. Upon receipt of the electronic copy, the physician (or study coordinator) will upload the MRI files to the portal using encrypted File Transfer Protocol (FTP).

In the first review, the Imaging Core Reviewer will check whether the image data is of sufficient quality and meets the specifications of the EPGP study protocol. All study protocol MRI data sets from enrolled patients are randomly assigned to three of the four specialists of the imaging core for phenotype classification. Interpretations and classifications will be performed and recorded online through the interface of the EPGP database-imaging tool. If full agreement on localization and classification of abnormalities is not obtained, the fourth specialist will be notified automatically by the system. An additional review of the MRI scan in question will occur in an effort to find a consensus for final interpretation. The findings of this review will be recorded in the MRI case report forms) and for final classification in the imaging database.

Document Library—The Document Management System is a general purpose application for providing access to the EPGP essential documents, departmental documents, standard operating procedures, agenda and minutes, and other important documentation.

According to Williams, there are two critical lessons to be learned from this process.

• The first is that Web-based technology has the industrial strength and security to support ambitious but sensitive projects like the EPGP initiative.
• The second is that this project is a repeatable solution that can be used by the scientific community as new projects based on the Human Genome breakthroughs get off the ground.

“What we just did in this project is take something that usually requires between three and five years to complete and we have compressed it into 12 months. On the next project, I think we’ll be able to take 12 months and compress it into two months because of virtualization technologies that allow us to essentially take the innovations we have developed and replicate them almost instantly,” says Williams.

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For more information about the .NET Framework 3.0, please go to:
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For More Information

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For more information about TAKE Solutions products and services, call +91-44-6696-4200 or visit the Web site at:
www.takesolutions.com

For more information about Epilepsy Phenome/Genome Project (EPGP) products and services, call (888) 279-3747 or visit the Web site at:
www.epgp.org