Compliance Corner: Improve quality with a trial monitoring program
Improve quality with a trial monitoring program
Set up a comprehensive program
As federal officials and the media increasingly focus on clinical trials, it’s a good idea to take the proactive step of forming an internal monitoring system for study conduct, according to a clinical research expert.
"I think it’s fairly accurate to say that most academic medical centers don’t have an internal monitoring system for study conduct," says Bambi Jo Grilley, RPh, CCRP, CCRC, CIP, director of clinical protocol research and regulatory affairs for the Texas Children’s Cancer Center and the Center for Cell and Gene Therapy at Baylor College of Medicine in Houston.
The FDA told the institution that ongoing monitoring would be necessary because of its involvement in gene transfer studies, Grilley says.
Since there aren’t many existing models for such programs, Baylor officials decided to use the pharmaceutical industry’s monitoring programs as a guide, Grilley says.
"We call it QA [quality assurance] audits, but it’s really study monitoring," Grilley says.
The most difficult part of establishing the monitoring program was finding funding and deciding how much monitoring could be done by a limited staff, Grilley notes.
"It would be ideal to say every internal study is monitored each month or every three months, but that wasn’t practical," Grilley says. "So what we came up with is something where we hope we’re catching the bigger problems up front, and through random selection, we’re catching other things as they occur."
Last year, the FDA again recommended that the institution make a change. This time the FDA noted that while the QA program with retrospective review was fine, the agency really wanted some prospective monitoring, as well, Grilley says.
"So we came up with the idea of a QC [quality control] program," she says. "The QA focuses on internally-initiated studies with the primary focus on IND studies, where we’re trying to decrease regulatory risk." The QC program is more about reviewing particular employees’ work than studies, Grilley explains.
"We look at how they’re doing studies, whether their research reports are good, what the sponsors find when they come here," Grilley says. "And we’re looking for the opportunity to either improve the system or retrain personnel."
Taken together, the two different types of monitoring programs provide a broad overview of how the research institution is doing, Grilley notes. Each program has one full-time employee, and they may be expanded as the need has grown, she says.
"The QA and QC are complementary programs," Grilley says. "The QC program is interesting because it’s given us an opportunity to look at numerous employees and say, Wow, across the board people don’t understand this.’"
Although the monitoring programs first were initiated in the cancer and gene therapy research areas, they’ve caught on, Grilley says. "We’ve been asked by other sections of the hospital to review their research, as well," she says.
Here’s how the quality improvement programs work:
• Select studies to monitor. Under the QA monitoring program, any time an IND study enrolls its first patient, it is audited, Grilley says.
Also there are for-cause audits and random audits. "All internal studies are up for random auditing, and 10 percent are audited each year," Grilley adds. "The QA program could be a lot larger than it is, but we’ve set up a system that we think allows us to catch the majority of issues we’d be interested in looking at."
The QC program provides ongoing training and orientation training, as well as monitoring of individual investigators, Grilley says.
Under the QA program, each study randomly selected for an audit will be studied over a five to 10 day period, with the monitor checking 10 percent of the patients, Grilley explains.
The institution’s data review committee might request a for-cause audit if they see some questionable data, Grilley says.
The QC monitor contacts an investigator and says she will conduct a QC review on these dates, Grilley says.
"The monitor looks at consent forms, data, all components of the work," Grilley says.
If the person being audited is a research nurse, then the monitor will check all phone logs, as well.
"Then she prepares a report and lists each patients reviewed and what the findings were," Grilley says. "If the monitor discovers that someone’s research charts are a month behind or if someone doesn’t follow standard operating procedures (SOPs), then the monitor will note that in a conclusion to the QC report."
If the monitor finds a more global problem, then she’ll discuss that as well in the report, Grilley adds.
• Determine consequences for problems found. Monitors report any findings regarding patient safety immediately to the clinical research oversight committee (CROC), and the CROC decides whether the study needs to be closed, Grilley says.
"The more likely scenario is that what they bring to us has their findings divided into minor and major problems," Grilley says. "And if they have a lot of majors, they recommend to the committee that the study be stopped, but that hasn’t happened."
There was one situation where a QA monitor conducted an audit and sent the findings to the study’s principal investigator, but the PI failed to respond in a timely manner, Grilley says.
"There was serious discussion of whether the study should be put on hold until the issues were resolved, and we were concerned that the PI wasn’t responsive," Grilley recalls. "But once the PI found out we were thinking of doing this, we got our response."
In another instance, the monitor found that data collected was delinquent, and the CROC told the investigator that if the problem couldn’t be cleaned up within two weeks then the committee would make the study stop enrolling patients, Grilley recalls.
"They cleaned it up," Grilley adds. "We’ve been very fortunate because we have a lot of support from the top, so when we talk about investigator problems, they know we mean it."
One of the most difficult challenges in having an internal monitoring program is providing to investigators that it has teeth, because if they believe the program has no power to levy consequences, then it won’t work, Grilley notes.
However, the monitoring program so far has turned up mostly minor problems, such as the misfiling of documents, Grilley says. "It gives us a good feeling that there’s nothing horrible under the rock that will be discovered by the FDA."
The QC monitor provides clinical research staff with a list of deficiencies or errors that were found, and the person is expected to correct the errors, Grilley says.
"If what the monitor discovers is that there’s something this person is doing that is generally wrong, then we probably will talk more seriously about how we’re going to address that," she adds. "The person is going to need to be retrained, and disciplinary action is needed."
• Develop an efficient system. It took a while for the QA program to get off the ground and to develop the necessary forms and policies, Grilley says. "It’s the set-up part that’s really hard," she explains. "You need someone who can understand the impact of various things."
During the program’s development, the staff worked closely with the CROC, going through ideas for how to run the monitoring program and negotiating policies when necessary, Grilley says.
Likewise, developing the QC program took some planning. Initially, some though the QC monitor should audit each investigator each month, but that proved impractical, so the goal became to audit one person per day, Grilley says.
The monitoring programs each have their own written policies, procedures, standard notification forms, checklists, certificates of completion, and written examples of major deficiencies. (See Sample Checklist.)
When a monitor discovers a problem with a trial that may indicate a more pervasive problem with particular clinical trial staff, then it’s likely there will be a re-audit within three months, Grilley says. "We try to keep these as collegial interactions," Grilley explains. "We say, Here’s what you’re doing wrong, and we’ll help you fix it.’"
As federal officials and the media increasingly focus on clinical trials, its a good idea to take the proactive step of forming an internal monitoring system for study conduct, according to a clinical research expert.Subscribe Now for Access
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