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Once drowning in paper, the Baylor College of Medicine informatics group's paperless IRB process is now the envy of medical centers nationwide.

By Deborah Ausman

 Denise Canales, director of research informatics at Baylor College of Medicine, spearheaded the development of BCM's "life changing" IRB software.
April 15, 2003 | Mention clinical trials data management and most often the parties involved (be they sponsor companies or investigators) will grouse about scheduling patient visits, collecting and tracking patient data, analyzing outcomes, or mitigating billing snafus for study participants. No wonder the rules-laden, paper-intensive, day-to-day grind of running clinical studies has become a magnet for software developers seeking to streamline workflow.

But before medical institutions or research organizations earn the right to experience these study-specific data management hassles, they must overcome another rules-laden, paper-intensive process: the initial review and ongoing oversight of research protocols.

Federal regulations mandate that all human and animal studies be reviewed by either an institutional review board (IRB), in the case of humans, or an institutional animal care and use committee (IACUC). These committees serve as gatekeepers, ensuring that any research undertaken at a site minimizes risks and protects the rights of study participants. Like all committees, IRBs and IACUCs generate correspondence, minutes, evaluations, and decisions, which institutions must document and track to comply with regulations.

"It was a nightmare," recalls Denise Canales, director of research informatics at Baylor College of Medicine (BCM), as she describes piling photocopies of 200-page protocols along the hallway to create packets for 30 IRB committee members to review. Today, this task is gone, as are the piles of paper. BCM's IRB and IACUC processes have been entirely paperless for more than a year, thanks to a Web-based system developed by BCM's Office of Research (OOR).

If You Only Had a BRAIN 
The Biomedical Research and Assurance Information Network, or BRAIN, is software designed to handle regulatory compliance mandates. Here are some of its most valuable benefits.

Read More 
Canales and the investigators, committee members, and OOR staff supported by the Biomedical Research Assurance Information Network, or BRAIN, quite literally refer to the system as "life-changing" (see "If You Only Had a BRAIN," right). BCM has seen at least four-fold decreases in turnaround time on key reporting and documentation tasks. BRAIN handles regulatory language and paperwork requirements automatically, reducing clerical errors and enabling board members to focus on the science behind the protocol rather than bureaucratic minutiae.

BRAIN has even resulted in upgraded job descriptions, transforming BCM's OOR analysts from clerical workers to regulatory experts that play a critical role in protocol review.

All of which explains why BRAIN received top honors in November 2002 in the Health Improvement Institute's inaugural competition honoring the best institutional practices for protecting human research subjects. And why BCM's informatics team is partnering with the Academic Performance Institute and e-business software developer TransDigital Solutions to generalize BRAIN into a for-sale product for research institutions across the United States.

'Staff Was Burning Out'
"Files that can't fit in the cabinets." This is a sign commonly found on stacks of boxes shoved behind rows of file cabinets in research offices across the country. Indeed, BCM's OOR file room was once similarly cluttered. At any given time, BCM has more than 2,000 active studies underway among its seven Houston-area hospitals. All these studies are monitored by the OOR, which is responsible for enforcing regulations, coordinating communication between the investigators and the IRBs or IACUCs, and educating college research staff about compliance requirements.

"In the paper days, our job was all about streamlining paper-handling and inventing processes to promote efficiency," says Kathleen Motil, associate professor of pediatrics and first chair of BCM's six internal review boards. Like most IRB members, Motil is also an investigator, giving her a multifaceted perspective on the myriad ways that paper-pushing can impede protocol review and approval: The wrong consent form submitted with a protocol; misfiled adverse event reports; stacks of paper carted from place to place for signatures; months of waiting before investigators receive approval to run a study.

Then came the failure of several high-profile gene studies in the late 1990s and 2000, which called public attention to deficiencies in regulatory oversight and reporting mechanisms. It was the proverbial writing on the wall, according to Motil, who was the OOR's director of assurance and compliance during BRAIN's development. "We were being asked to shuffle more paper, better, in the same amount of time, with the same number of employees," Motil says. "Staff was burning out."

Motil credits what she describes as a "visionary administration" for choosing to pursue a paperless solution. Canales concurs, noting that the project was initially slated to take six months and was budgeted at $100,000. "A gross underestimate," she says. All told, BRAIN was two years in development and cost BCM $1.5 million. Yet no one doubts the value of the investment, Canales says.

"It's completely changed the way people work. At first, we were responding to the same regulatory pressures that everyone faces. But because of BRAIN, we're now working on improving processes, on tracking and analyzing things that were once completely obscured by paper."

Paper-Pushers Transformed 
Regulatory pressures define the clinical trials workflow, from initial approval to study closure. Even the mass of activities and documentation associated with IRBs and IACUCs ultimately follows a clear workflow path that's "amenable to automation," according to Bernard P. Wess Jr., president of Perseid Software.

When BRAIN development began in 1999, Canales and her team could find no Web-based systems addressing IRB processes. Even today, competitive systems are "IT-focused," says Anne Hirshfield, assistant dean for research at the University of Maryland, which is evaluating BRAIN. "They are general solutions, which don't offer the fine points that we need to stay compliant."

In terms of infrastructure, BRAIN is quite simple: an Oracle 8i backend connected via Visual Basic middleware to an ASP-based, browser client. But the guts reflect the input of OOR staff, investigators, board members, veterinarians, department chairs. BRAIN supports the entire lifecycle of a protocol, from all the tasks and communiqués associated with a protocol's initial creation and review through the acknowledgment of adverse event reports to the submission and review of amendments, renewals, and closure requests.

In particular, BRAIN automates the most mundane and paper-intensive points in the protocol lifecycle, ultimately aiming to eliminate the need for paper entirely. Take the previously described act of creating packets for IRB review. With BRAIN, principal investigators complete protocols entirely online and obtain signatures electronically. When the last signature is obtained, BRAIN whisks the protocol automatically to the OOR and assigns it to a committee. Review can commence immediately — again, online — without OOR staff having to make a single photocopy or route a single packet.

BRAIN's workflow orientation also builds key 21 CFR Part 11-compliant security features into the system, in addition to those obtained by coupling BRAIN directly to BCM's main IT infrastructure. Only investigators, for instance, are provided with the access to approve and send protocols to the OOR. Similarly, the OOR's need to track protocols from review to closure gives BRAIN extensive auditing capabilities that staff members are now finding useful not just for Part 11 security compliance, but for monitoring and validating system usage and improving process control.

"Given the nature of the data and our desire to use the Internet, we took Part 11 regulations regarding authentication, security, and auditing very seriously," says Charles Molsberry, the consultant who served as project manager for BRAIN before joining BCM as director of application development. "But we found that being data-driven made much of Part 11 compliance automatic — it was just part of what we wanted the system to do."

Addison Taylor, associate dean for clinical research at BCM, considers the new analyst role at BCM one of the biggest changes effected by BRAIN, and one of its most critical benefits.

"We had lots of people who knew the regulations better than anyone, but they were so swamped with things like copying investigator's brochures that they couldn't use their knowledge," Taylor says. "Now we're spending more time on prereview and paying more attention to the science, all without extending the turnaround."

Clearing out the paper has also enabled BCM to adjust and refine its processes. Taylor sees more effective electronic data sharing between institutions and drug-company sponsors as necessary, not just to speed clinical trials, but ultimately to help patients. "We're at the point where we can assess adverse events across studies in real time," he says. But to report these findings to sponsors, institutions like BCM must still resort to paper. "We've seen instances where, had there been more effective or efficient mechanisms for tracking and reporting events, we might have been able to avoid having any of those events occur here," Taylor says.

Hirshfield at the University of Maryland envisions IRB software as a key component of clinical trials data management. Study schedules that show for every planned encounter which procedures are clinical and which are for research could be received electronically from sponsors, reviewed by IRBs, then ported to a clinical data management system for scheduling, "and the system would flag which results need to go to the investigator," she says. "You could even tie the data into billing and insurance."

Today, BCM. Tomorrow...? 
The University of Maryland is just one of the major medical centers eyeing BRAIN, which will be marketed as BRAAN commercially. In fact, BCM's IT team has found the interest from outside institutions somewhat distracting. Canales considers BCM's agreements with the Academic Performance Institute and TransDigital critical, not just to BRAAN's eventual success in the open market but also to its ongoing development at BCM.

Strategic Insights 
· Regulatory Compliance
· Easing the Pain of Part 11
· Part 11: The FDA's New View
· Rising to the Regulatory Challenge
· E-Sourcing: Covering the Regulatory Bases
And while systems like BRAIN are somewhat rare, competitors do exist. In particular, the extranet vendor Webridge is aggressively promoting its compliance package and announced in January a license arrangement with the University of Washington. Undoubtedly, more systems like BRAIN will be surfacing at medical institutions. They have to, according to Wess. "21 CFR Part 11 has forced everyone kicking and screaming into a world that manufacturing and finance have been in for nearly a decade."

Recognition, like that conferred on BRAIN by the Health Improvement Institute in its 2002 best practices awards, will help.

Peter Goldschmidt, president of the institute, said the annual awards were established "to provide a positive incentive to institutions, rather than always challenging them with regulations."

"There are good things being done" in the application of IT to human research protection, Goldschmidt says. "By disseminating these practices broadly, it's our hope that everyone will benefit."

Deborah Ausman is a science writer based in Houston. She may be reached at 


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