The trusted source for
healthcare information and
Neurology research network starts IRB review
Sites can choose to participate or not
As IRBs continue to contemplate various models of centralized review for multisite studies, projects have begun to pop up, trying out these models.
One recent example, NeuroNEXT, is coordinating IRB reviews for dozens of institutions across the country in order to conduct trials of neurological therapies. The network was created by the National Institute of Neurological Disorders and Strokes (NINDS) to increase the efficiency of these types of clinical trials.
Massachusetts General Hospital and Partners Healthcare System in Boston won an NINDS grant to serve as the clinical coordinating center and central IRB for the network.
Pearl O'Rourke, MD, director of human research affairs for Partners, has had the task of coordinating the infrastructure to support the central IRB (CIRB) model NINDS has asked for.
She says that process has proved much larger than she originally had anticipated. Although there are 25 primary sites within the network, many have several sub-sites where research may be carried out. For example, she says, the State University of New York is a single primary site but has multiple campuses that may serve as research sites. The network made a decision early on that every site that had a Federalwide Assurance (FWA) required its own separate reliance agreement with the CIRB.
"So we are actually now in excess of 60 sites that we have reliance agreements with," O'Rourke says. "Setting this up has been rather interesting and an unbelievable amount of work."
In order to participate in NeuroNEXT trials, the sites must use the central IRB — NINDS has not provided an option for separate reviews, says Elizabeth Hohmann, MD, chair and director of the Partners Human Research Committee. She leads the Massachusetts General IRB panel that will serve as the network's CIRB.
However, she says a site can look at the central IRB's review and decide that it doesn't want to participate in a particular study.
Hohmann says that once the network's protocol steering committee develops a protocol, it will submit it to the CIRB, which will do an initial assessment, making recommended changes to the protocol group.
"Once we say it's IRB-ready, we will send it to the multiple sites who've expressed an interest in the project," she says. "We'll give them two weeks to review it at their local sites, however they wish to — by an IRB chair, an IRB administrator or by the investigators. We hope to get some input from all these folks and to see what issues they may have."
To assist in this pre-review, O'Rourke has spent the last year communicating with all of the sites in order to tease out institutional issues and local requirements that may come into play during a protocol.
She says the CIRB needs to know about relevant state laws, such as those regarding pediatric research or research with decisionally impaired adults, as well as how the site handles issues such as surrogate consent, HIPAA and conflict of interest.
O'Rourke says that while there are a lot of similarities across the network, there are small but important differences that must be dealt with.
For example, she says, institutions handle research-related injuries in different ways, and use different language to describe it in informed consent documents.
"It's been fascinating to see how different people do it, as well as the language they use in the consent forms," she says.
She says the CIRB will draw sites' attention to particular issues in pre-review based on this information.
"We'll say, 'This is a pediatric protocol, please look at this in terms of your pediatric state and local laws and regulations,'" O'Rourke says. "We're going to give them leading questions so we can get the information that we need regarding local context."
Once the sites have weighed in with their responses, Hohmann's CIRB will conduct the official review. Sites have the option of accepting this review or declining to participate in the study.
She says the sites will all use a NeuroNEXT template consent form, which will contain certain areas in which they can insert customized language such as contact information, HIPAA language or subject injury information.
"There will be fields where you can insert your own customized language but that will have to come back to us for final review," Hohmann says.
The NeuroNEXT model — where various sites have input into the central IRB's decision but the central IRB carries out all the regulatory requirements — is one of several different approaches currently being used or considered across the country for centralized review.
O'Rourke says one of the strengths of the NeuroNEXT approach has been the strong support of NINDS for her group's decisions.
"The program staff at NINDS has been spectacular in terms of saying, 'We respect the decisions you've made, and we will support this to all of the sites.' If we didn't have that, I think this wouldn't be doable," she says.
She's interested in seeing what issues arise when the network takes on an actual protocol in the next few months. "Have we identified the problematic areas appropriately or not?"
O'Rourke says the group has funding to hold a conference of network members after about a year of operation, to see how the review process is working.
Eventually, she hopes that the experience of setting up the IRB component of this network can add to the national conversation about the best ways of carrying out centralized review.
"I personally see this as experiment — we're an experiment within an experiment," she says. "What I'm hoping is that this experience will allow us to maybe put more information on the table to say, going forward, if this is going to be a model, this is what you're going to need for infrastructure."
The proposed revision of the Common Rule (advance notice of proposed rule-making or ANPRM) released last year by the Department of Health and Human Services asks whether central IRB review should be mandated for multi-site studies.
George Gasparis, CIP, is executive director for the Human Subjects Protection Program/IRB at Columbia University in New York City, one of the NeuroNEXT sites. He says regardless of the decision HHS eventually makes, the field is moving in the direction of central IRBs.
"Regardless of whether the ANPRM develops into a new regulation, there's going to be a push for more central IRBs," says Gasparis. "I think you're going to see more and more NIH institutes push for central IRB models that work well."