Tool helps demystify central IRB process
Considerations Document defines roles
The Office of Human Research Protections (OHRP) and the Food and Drug Administration (FDA) encourage the use of the central IRB model to increase the efficiency and quality of multisite trials. However, many research institution IRBs are reluctant to use a single IRB of record. The Clinical Trials Transformation Initiative (CTTI) conducted a study to identify barriers to central IRB use and developed a guide IRBs can follow to adopt the model. CTTI is a public-private partnership established by Duke University and the FDA that comprises more than 60 member organizations to improve the quality and efficiency of clinical research.
"One of the goals [of CTTI] is to improve the efficiency of the clinical trials process in the US and identify areas where there are opportunities to improve," says Cynthia Hahn, vice president, Clinical Research and Regulatory Affairs, The Feinstein Institute for Medical Research at North Shore-LIJ Health System in Manhasset, NY. "We started looking more at the central IRB question and what the barriers are to the adoption of central IRB review," she says.
Finding barriers
To identify barriers to central IRB use, CTTI researchers conducted a literature review and interviewed IRB representatives from institutional IRBs, federal IRBs, commercial IRBs, and industry and regulatory agencies. The project ran from December 2010-January 2013. A follow-on project is currently underway.
"One of the immediate challenges we found was that no one had the same definition of what it means to be a central IRB," says Hahn, who is a team lead for the CTTI Use of Central IRBs follow-on project. "They would think, 'I'll contract with a commercial IRB and they'll do all our IRB review.' That's not a central IRB — that's outsourcing."
During the interviews, CTTI researchers provided interviewees these definitions of a central IRB: "a single IRB of record for a multicenter clinical trial," and a longer definition, "a properly constituted IRB to which sites cede all regulatory responsibility for scientific oversight and integrity of the protocol from initial review to termination of the research, including review of informed consent."1
Another concern, Hahn says, was that interviewees confused institutional responsibilities with ethical review responsibilities. For example, some participants did not realize that reporting of serious or continuing noncompliance is an institutional responsibility, and not one that is just left to the outside IRB to handle. "You have an obligation to report noncompliance, regardless of the IRB that is utilized," she says. "That concept was a little confusing to people."
What also became clear is that many groups simply don't have a strong track record of using an outside IRB, Hahn says. "What came out of the conversations is that it's very unknown — 'Can I trust the review? Is it as good as what we would do?'"
Interviewees identified other barriers to central IRB review, including the following:
- the feasibility of working with multiple outside IRBs, each having its own protocol submission process;
- loss of revenue generated from fees for review of commercial-sponsored studies;
- concern for noncompliance and regulatory liability;
- concern for legal liability in the event of litigation secondary to errors, omissions, or negligence of an IRB not directly affiliated with the IRB conducting research;
- quality of review;
- potential loss of local context (for example, unique patient populations, local knowledge of investigators, or a center's resources for conducting the research).1
Defining responsibilities
CTTI held an expert meeting following these interviews, and developed its Considerations Document for central IRB model implementation. The document helps demystify the process of creating centralized review, and lays out the responsibilities of the institution's human research protections program and the IRB of record, and shared responsibilities. For example, one shared responsibility between the institution and a central IRB is to execute an IRB authorization agreement.
The document names responsibilities of the central IRB, including the following:
- Maintain program for education and training in human subjects research for IRB personnel.
- Register with the Food and Drug Administration and the Office of Human Research Protections.
- Ensure clinical trial meets generally accepted ethical standards of human subjects protections and complies with applicable regulations.
- Collect, review, and take into account site-specific information provided by the individual sites.
- Review and approve the informed consent form and any other research-related documents or media.
Some of the institutional responsibilities include the following:
- Maintain policies and procedures for the conduct of human subjects research as appropriate for the particular institution.
- Designate the IRB of record for the protocol.
- Ensure that the investigator/researcher is conducting research and recruiting potential research participants in accordance with IRB-approved protocol, procedures, and documents.
- Notify the IRB promptly in writing of serious or continuing non-compliance or unanticipated problems involving risks to subjects or others.
The full Considerations Document can be found on the CTTI website at http://www.ctti-clinicaltrials.org/files/documents/CentralIRBConsiderationsDocument.pdf.
Since publication of the study results and the Considerations Document in January 2013, Hahn has seen much more interest in the central IRB model. "We [NS-LIJHS] used to get only one request a month about using a central IRB — now we're fielding multiple requests every week, asking if they [institutions] can rely on us," she says. "Institutions have told us that they're developing standard operating procedures around the model."
Addressing concerns
A major concern of IRBs around central IRB use is whether it will affect jobs in the individual institutions. "One of the biggest questions we get is, 'If we consolidate, will I still have a job?' I believe very strongly that IRB professionals will still have a job — the job changes, and we're protecting subjects better," Hahn says.
Instead of having employees dedicated to review and processing of the protocol submission to a committee, the resources can be directed to other areas, such as informed consent monitoring or meeting with investigators for help in protocol design, understanding regulations, etc. "They can be more active in the implementation of the study. They can take those resources and get out there where the rubber hits the road and be side by side with investigators. It's a better use of resources than sitting in an office and processing applications," Hahn says.
Hahn and researchers also address the issue of recouping IRB fees. "People were concerned that by removing local IRB review, you'd be removing that revenue source for the IRB office," she says. "As the grant budget gets tighter, it has a dramatic impact."
To offset this, Hahn suggests institutions could develop a fee for the human research protections program. "Just because you are not doing IRB review doesn't mean you're not doing human subjects protections," she says. "Authorization agreements, reporting, monitoring, making sure investigators are qualified — none of those things go away."
The fees are comparable to IRB fees, and can still allow for IRBs to send staff to conferences and other educational and outreach opportunities. "A couple of institutions I worked with have tried this," Hahn says. "I haven't seen one company say no to a fee. I think a lot of people don't realize they can do this; it's the one thing everyone scribbles down [at seminars]."
CTTI is currently following up with the Central IRB Advancement Project, which will take the findings a step further by giving institutions more tools for adopting the central IRB model. The team is also working to develop a standard reliance agreement template. "There is an enormous amount of variability in adopting a central IRB," Hahn says. "Some authorization agreements are two pages, and some are 20 pages. This [template] will give people a foundation in which to start."
Reference
- Flynn KE, Hahn CL, Kramer JM, Check DK, Dombeck CB, et al. (2013) Using Central IRBs for Multicenter Clinical Trials in the United States. PLoS ONE 8(1): e54999. doi:10.1371/journal.pone.0054999.
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