Research center's compliance program makes use of prospective monitoring

Center receives full accreditation with distinction

A prospective monitoring program is not for the faint-hearted, but it can result in better education for clinical research staff and prevent many research problems from occurring, according to experts who've created such a program.

The key is to initiate a prospective monitoring program out of the research compliance office and use this for educational purposes, as well as for achieving compliance goals.

Such a program also can save research resources overall.

"We wanted a group that could do friendly monitoring," says Philip Cola, MA, vice president of research and technology management at the Center for Clinical Research of University Hospitals Case Medical Center in Cleveland, OH.

"How can we help investigators take a fresh look at how they conduct research," Cola says. "We don't want to call it auditing."

The center's prospective monitoring program appears to be a success, and it takes pressure off the institution's IRB, which previously was the office where investigators and clinical research staff sought answers to their regulatory questions.

In a recent IRB office audit from the FDA, the institution did very well, Cola recalls.

"It's the best FDA audit I've ever seen in the years I've been here," he says.

Cola attributes the successful audit to a dedicated staff and to the IRB's re-focus on its chief role of reviewing protocols.

"By having this specialized additional resource of a monitoring team, the IRB is doing what it's supposed to be doing," he adds.

Also, the office recently received full accreditation with distinction in June 2007 from the Association for the Accreditation of Human Research Protection Programs (AAHRPP) of Washington, DC.

"I don't think, honestly, we would have been ready to be fully accredited without the full compliance of this monitoring program," Cola says. "That piece is central and critical to what we do."

To many research professionals, the image of an auditor is someone who shows up and reviews documentation for a couple of days and then disappears, Cola notes.

"I wanted this process to be friendly with a 'We're on your team type of approach,'" Cola says. "Secondly, I wanted it to be in the arena of self-evaluation."

Since the compliance department is in the same institution and essentially on the same team as the investigators, it seems like a better approach to have someone come in from their team to prospectively check their studies for potential red flags, he says.

"In my mind this is a self-evaluation because we're all part of the same institution," Cola says.

The prospective monitoring program is intended to be investigator-friendly, and it includes education support, says Carol A. Fedor, ND, RN, CCRC, a clinical research manager of the office of research compliance at the Center for Clinical Research of the University Hospitals Case Medical Center.

"It's a good clinical practice approach that is based on supporting investigators and being proactive," Fedor says.

The center occasionally receives feedback from clinical research sites, and much of it is positive, says Cristina Ferrazzano Yaussy, MPH, research compliance specialist in the office of research compliance.

"Most recently, an investigator we monitored commented to another [clinical trial] group that his site had been a part of the monitoring, and it was great because it really taught them what they needed to do," Yaussy recalls.

Based on data recently published, the research institution has saved resources by using the prospective monitoring program, Cola says.

"We actually ended up saving resources that we would have utilized to fix something that went wrong," Cola explains. "Prevention is a better use for resources than riding in [on a white horse] when there's a problem."

The way the compliance office has developed its prospective monitoring program includes the random selection of studies to be part of the review process, Fedor explains.

"It's random, but there is a hierarchy in the way they're chosen," Fedor adds. "There are high-risk studies where there's an increase of risk to participants, and those are generally part of the group that is chosen more frequently for monitoring."

Also, studies that involve vulnerable populations, including children and people who are decisionally impaired, and investigator-initiated studies would be more likely to be monitored, Fedor says.

Typically, the compliance office will pick sites for monitoring visits in groups of 10, Yaussy says.

"Once the protocols are chosen we send a letter to the investigator, letting them know they are selected as part of the review process," Yaussy explains. "Then I follow up and contact them to schedule a monitoring visit."

When the IRB makes a request that the office monitor a particular study, this visit will be added to the workload, she notes.

"We select areas to focus on based on what we understand to be common areas of noncompliance," Fedor says. "We want to be proactive and prospective in monitoring, so we look at what the federal government finds in their own quality assurance programs, and we look at the literature to see what the trends are."

The FDA's findings tend to be consistent over time, Fedor notes.

For instance, informed consent tends to be a major problem area for clinical trial sites, she says.

"It's the nature of the beast," Fedor says. "The screening and consent process have many details and variability, and errors can occur particularly during those times of the research study."

The compliance office is most concerned about areas that most greatly impact human subjects and their safety, Fedor adds.

For example, to have a person enrolled in a study when the person isn't eligible would be a potentially serious deviation, so the compliance office will review that carefully and consider eligibility criteria a priority area, Fedor says.

"Our aspiration is to use a preventive approach, rather than have the monitoring focus on those required directive requests from the IRB, Fedor says.

Also, prospective monitoring tends to be more cost-effective than directive monitoring, Fedor notes.

The monitors have a great deal of preparation work to do before a visit, Yaussy notes.

"The upfront work includes reviewing the IRB file, the protocol, consent form, and understanding the people who are identified to the IRB as research staff members," Yaussy says. "This is so that we can have an understanding of who is involved in the research, as well as what resources are used."

When discrepancies are discovered during the monitoring visit, the monitors make sure these are addressed at the site with the principal investigator, Fedor says.

"If the investigator chooses to have his staff present, we'd be happy to talk with him as well," Fedor adds. "And we'd certainly plan to schedule further educational sessions to make sure this service is seen as a support to them and not necessarily a punitive approach."

The education component is important because it helps research staff understand what the requirements are immediately and doesn't mean they have to wait for a month to receive a letter that outlines the problems discovered, Fedor says.