Quality assurance in trials protects human subjects

Ensures they receive treatment specified in protocol

Quality assurance programs for clinical trials do more than improve the data coming out of studies and the validity of the results.

They also can improve the protection of human subjects by ensuring that the intervention an IRB approves is the one that subjects actually receive, says Thomas J. FitzGerald, M.D., a radiation oncologist and director of the Quality Assurance Review Center (QARC) in Providence, R.I.

QARC is a research program of the University of Massachusetts Medical School that provides services for National Cancer Institute-supported clinical trials involving radiation therapy. QARC coordinates everything from credentialing sites to ensure they are equipped to carry out trials, to managing data and providing feedback to physicians during the course of trials so that study interventions are carried out as planned.

The center helps NCI clinical trials cooperative groups put together multisite protocols that meet the needs of NCI and the FDA, as well as dealing with IRBs' varied requirements, Fitzgerald says.

"One of the things an IRB looks for is consistency and uniformity in a clinical trial and that the trial is written in a standard template that will permit trial execution and trial closure," Fitzgerald says.

Navigating IRB process

Fitzgerald says that while he occasionally talks directly with IRBs that have questions about a protocol, he usually works with investigators to help negotiate the IRB process at their own institutions.

When an IRB raises an issue with a protocol, QARC can help the investigator figure out a way to address it while maintaining uniformity with the trial as a whole.

"We can say, 'That's a good point, but here's how others have addressed that point,'" Fitzgerald says. "So sometimes we can bring that language back to them and they can think about that and say, 'Well, yeah, you've addressed that point. I see what you're saying.'

"I think so much of it is the ability to keep an open mind and understanding there are many ways of achieving the correct objective."

As the trial moves forward, QARC maintains a database that is connected to institutions around the world conducting the study.

"Let's say you're in Australia and a patient is entered on a particular cooperative group trial," Fitzgerald says. "QARC is notified at the same time. And we will update the Children's Oncology Group; we'll send a note to the investigator in Australia that day that this is the data that's expected for this particular trial at this particular time. If it doesn't arrive, our (clinical research associates) are working with the Crass on site to get the information and data to QARC."

Fitzgerald says 50% of the time data is sent to QARC, it's incomplete. The center continues to go back to researchers and collect the necessary data to ensure it meets the guidelines outlined in the protocol.

Review protects subjects

The center also conducts real-time review of the data, comparing it to trial guidelines and suggesting changes when necessary. Fitzgerald says that review can keep a well-designed trial from running off the tracks. For example, he says QARC worked on an international trial for head and neck cancer that included radiation therapy. "On that trial, which was approximately 900 patients, we were responsible for doing a review of the images and radiation therapy treatment objects within the first three days of patient treatment," Fitzgerald says. "I asked for changes in the treatment plan on 211 patients, because I felt the tumor wasn't being fully covered with the intended radiation field."

In every case where the investigator made changes at QARC's recommendation, the patient had a long-term survival equal to the nearly 700 patients whose radiation was compliant the first time.

"Of those patients where the adjustments were not made, there was a 20% decrease in patient survival," Fitzgerald says. "Quality assurance on clinical trials is important and it does affect the potential outcome of a trial, as well as outcome for individual patients.

"The oversight function actually improved protection of human subjects as well as creating uniformity for the patient which could then further validate the results of the trial."