Data review committees offer additional protection
Data review committees offer additional protection
DRC stays on top of adverse event issues
Data review committees (DRCs) could provide an additional layer of protection for human subjects at clinical trial sites where research often involves high-risk populations or high-risk studies.
The Texas Children’s Cancer Center and the Center for Cell and Gene Therapy at Baylor College of Medicine in Houston have used DRCs to review protocols for adverse events for five years, and the system has worked very well, says Bambi Jo Grilley, RPh, CCRP, CCRC, CIP, director of the clinical protocol research and regulatory affairs for the two centers.
"I think the DRCs are really helpful," she says. "I don’t think IRBs are capable of providing the proper oversight at the level that a data safety monitoring group does because the expertise in an IRB is quite diffuse."
The members of the centers’ DRCs are oncology specialists, including oncologists, oncology nurses, and research staff, Grilley explains.
"They all have experience with oncology or oncology patients," she says. "How could a cardiologist or dermatologist assess whether we’re seeing a high level of a subset of malignancies among patients."
Also, the DRCs, which meet twice a month, have a caseload of about 270 phase I and phase II studies, whereas the IRB will review more than 2,000 studies, Grilley adds.
The DRCs fit into the research institution as one part of a multifaceted process with the purpose of ensuring high-quality research and high-quality subject protection.
The Texas Children’s Cancer Center and the Center for Cell and Gene Therapy also have protocol review boards that assess each study for scientific soundness before the protocols are approved and sent to the IRB.
The protocol review board also decides whether a study will require data safety monitoring and, if so, how frequently it will be reviewed by the DRC, Grilley explains.
"If there’s an external review process, we don’t require it to go through ours," she notes. "If the study involves treatment, it definitely goes to the DRC, and the third criteria is any study that has risk for patients."
For instance, a cancer/genetics study that does not involve treatment may have important implications for the patients whose tissue samples are used, so this kind of study also would be reviewed by the DRC, Grilley continues.
While the DRC serves the same purpose as a data safety monitoring board (DSMB), which mainly monitors phase III studies, the chief difference is that all 25 members of the DRC are affiliated with Baylor College of Medicine, she adds.
Federal guidance defines DSMBs as boards that have outside representation to ensure objectivity in the review of studies.
"There is only one study that requires a full DSMB, and this is where we’ll have conference call meetings and include researchers from different time zones," Grilley explains.
Although the DRC members are not outsiders, they include members from all of Baylor’s different branches, so physicians are not looking at their own data, and the membership includes a statistician, she says.
The centers also have quality assurance and quality control staff who monitor internally sponsored studies, performing the same type of checks and balances as does a sponsor’s clinical trial monitor, Grilley says.
DRCs provide annual review
The DRC’s role typically begins either at one year from when the protocol was approved by the IRB — or with studies involving higher risk, at an earlier date if a designated number of patients have been enrolled, she says.
Grilley and her staff spend a total of about 10 hours per week on DRC business, including the time spent mailing DRC meeting reminders to principal investigators whose studies are up for review and sending out review packets to DRC members.
The rest of their time is spent on quality assurance and quality control and protocol review, she says.
"For all of the DRC meetings, we have 21 binders at half-way through the year," Grilley explains. "It takes a lot of maintenance, and having a DSMB is an unfunded mandate."
Before each weekday meeting, which lasts about one hour, DRC members receive a packet of one to five studies they will need to review. Investigators may be called in to discuss the study and to answer questions.
The investigators then leave, and the DRC deliberates and discusses the study in private. There is no required quorum, although the DRC always must have at least one physician and statistician in the room, Grilley says.
"We do sometimes have members who send their comments when they can’t attend, and we’ll discuss those comments, as well," she says.
Finally, the board makes a decision about whether the study should continue and mails the principal investigator a letter that states that decision. The PI must send a copy of that letter to the IRB, which asks for proof that a study is safe to proceed, she explains.
"Ninety-nine percent of the studies are found safe to proceed," Grilley notes.
Here’s one example of how the board works: "We had an emergent adverse event that was long term, so it was discovered when patients were off the therapy," she says. "The PI came to the DRC to describe what had happened and to have a discussion about whether we should tell all the patients, and if so, would it be by letter or by bringing them in for a visit. In this case, we decided to send letters to the patients’ parents, because the patients were children; and we contacted local physicians because many patients go back home."
The advantage to having a DRC is that PIs sometimes overlook trends due to their professional bias of finding what they expect to find, Grilley notes.
In another case, there was a study that was designed with the objective of achieving a 70% success rate, she says. Investigators recruited many patients, and when the DRC reviewed the research, members found that the study treatment had not achieved anywhere near the 70% success rate, although the patient recruitment was 50% complete, she says.
"The PI said, If every patient I enroll now does well, I’ll have my 70%,’ so the DRC asked, What is the likelihood of that happening?’" Grilley recalls.
The result was the DRC decided to close the study since the treatment obviously was not working, she says.
"Prior to having the DRC, the study would have played out, whereas with the DRC we were able to stop it early," Grilley adds. "Ultimately, the PI was in agreement with us, but it helps to have people outside the immediate circle of the study say, Have you thought about this?’ and Logically, does this make sense to you?’"
Data review committees (DRCs) could provide an additional layer of protection for human subjects at clinical trial sites where research often involves high-risk populations or high-risk studies.Subscribe Now for Access
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