Kimberly Irvine, CIP, CIM

A recent paper published in PLOS ONE(1) addresses research institutions’ willingness —or lack thereof—to defer to central institutional review boards for multicenter clinical trials. Among other concerns, the respondents to the authors’ survey reported the loss of revenue to the institution when IRB review was centralized. The respondents also expressed general “discomfort” with the perceived loss of control they saw in outsourcing IRB. Additionally, after a review of local IRB responsibilities, it seemed their activities had extended beyond the original purpose of the IRB.

BRANY has been working since 1998 with academic institutions that pioneered the use of the BRANY central IRB. This white paper addresses some of the key benefits for institutions that use central IRBs, as well as tips on how to ensure a smooth transition to the use of central IRBs.

Running a local IRB can be a complex and expensive endeavor for any research institution. Between research office staff salary and benefits, as well as the infrastructure — office space, furniture, supplies, etc. — annual operations can cost up to hundreds of thousands of dollars. Even with sponsors paying for studies, many IRBs may be operating at a loss.

Some IRBs may feel that by outsourcing to a central IRB they lose control of the institution’s human subject protection requirements and relevance within the organization. IRB staff members may also think that this is an all or nothing proposition—either all activities are managed internally or all of them are contracted to a central IRB.

Even with a central IRB in place, there are other key responsibilities and activities that could fall to the IRB research office staff. In fact, the use of a central IRB can increase productivity in areas of critical importance to institutions because resources can be redeployed to focus on establishing institutional clinical research priorities and operationalizing systems to improve clinical trial performance.

 A 2009 report by AAHRP demonstrated that nearly 90 percent of organizations reported increased workloads, with the average IRB reviewing 400 protocols. As both study sites and sponsors are seeking ways to improve efficiencies and reduce redundancies, the role of a central IRB requires another look. There are various ways to ensure a streamlined approach so that local and central IRBs can co-exist, each with a clear understanding of the others’ responsibilities.

Some institutions have expressed concerns regarding the reimbursement from sponsors for IRB activities. These fees may contribute to the research budget and outsourcing the IRB may have a negative impact on the bottom line.

There are other activities that can yield as much, if not more, funding than an IRB review fee. By utilizing a CIRB for selected protocols, an institution can re-deploy staff to other related clinical research departments. This requires a new way of looking at the role of the research staff and a process by which to operationalize the functions of the team.  A research nurse, for example, can spend more time screening for subjects and enrolling rather than data entry. Other staff can focus on research compliance. Generally speaking, the reimbursement per patient enrolled in a study will be higher than the reimbursement to the IRB for protocol review.

 The first step for an institution considering the use of a central IRB is to be familiar with the CIRB organization/review board conducting the protocol review. AAHHRP accreditation can provide and extra level of comfort for institutions. Additionally, by increasing access of a representative from the local IRB, a central IRB may seem less mysterious. Here are some tips to increase familiarity:

Institutions can request to include a representative from their organization as a member or alternate member on the central IRB to ensure visibility and also to become more comfortable with the process.

Institutions should be allowed to conduct an occasional audit of the central IRB’s activities and documentation.

 Changing regulatory guidelines, along with highly publicized litigation about patient safety and non-compliance, have made many institutions anxious about their liability. Over time some IRBs have evolved to include a variety of responsibilities that are best suited for other committees. This “mission creep” can lead to inefficiencies and a lack of focus.

Rather than spending precious time collecting documentation for industry sponsored multi-center trials, internal resources can be used to focus on real, on-the-ground patient and employee safety issues.

 The frustration of investigators with the IRB process is well-documented. Too often this creates a tension between the researcher and the IRB and the risk of misconduct can increase (2).

Unfortunately, too often the delays in IRB review are administrative and not substantive or relevant to patient protection. The February 2010 issue of 

 (3) reported that 67 percent of changes to a clinical trial participant consent form, submitted by local IRBs at research sites, was primarily reflecting institutional language and did not offer any substantive changes to the protocol. The price tag for these changes was $100,000.

To those unfamiliar with the IRB administrative process, it can sometimes seem that a local IRB’s main activities are in the collection of documents and checking requirements off a list.  By shifting these administrative responsibilities to a central IRB, the local IRB and research staff can identify meaningful ways to ensure patient safety and increase research opportunities, as well as facilitating investigator-initiated research.

 Often local IRB review is most important for investigator-initiated studies. When a local IRB can focus its time and attention in facilitating review of studies generated within the institution, the institution benefits in multiple ways.

Research office staff can help investigators apply for grants and other funds.

Develop tools to mentor young investigators to develop protocols.

By allowing a central IRB to take care of the human subject protection and administrative compliance tasks for multi-center protocol review, a local IRB and the institution’s research office open opportunities to encourage innovative research and ensure patient safety. An institution can use its resources to create an environment of collaboration and encouragement for researchers to explore ideas and develop research projects that are innovative and help the organization achieve its other mission—improving patient care.

(1) 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  

 (2) Keith-Spiegel, P., Koocher, G. (2005) The IRB Paradox: Could the Protectors Also Encourage Deceit? Ethics & Behavior. 15(4), 339-349.

(3) Ravina, B., Deuel, L., Siderowf, A. and Dorsey, E. R. (2010), Local institutional review board (IRB) review of a multicenter trial: Local costs without local context. Ann Neurol., 67: 258–260. doi: 10.1002/ana.21831

Articles

A recent paper published in PLOS ONE addresses research institutions? willingness ?or lack thereof?to defer to central institutional review boards for multicenter clinical trials.

Playing in the Sandbox--How Local Institutional Review Boards Can Happily Co-Exist with Central IRBs

As industry-sponsored clinical trials become more complex and span larger patient populations in multiple sites across states, the demands on institutional review boards grow. 

Despite the suggestions by Health and Human Services and the FDA to centralize IRB review of multi-site studies, many institutions still have not used a central IRB (CIRB).(1) While over half have used outside IRBs for support, only ten percent of the workload has been transferred to the central IRB. (2)

The reasons for this are varied, but one major concern continues to be liability, although federal agencies have also provided guidance on how to manage risk. Others are concerned that central IRBs’ decisions may be inconsistent with their own institutional policies and procedures. Finally, opponents to central IRBs suggest that only local reviewers can reflect the standards and values of their communities.

In one study (3) that looked at IRB reviews, however, the changes to the protocol are largely 8in alignment with standardized institutional language and offered no meaningful changes to the protocol that would impact local values. Meanwhile, according to the study, the costs of individual reviews by multiple local IRBs was upwards of $100,000.

A 2009 report by AAHRP demonstrated that nearly 90 percent of organizations reported increased workloads, with the average IRB reviewing 400 protocols. As both study sites and sponsors are seeking ways to improve efficiencies and reduce redundancies, the role of a central IRB requires another look. There are various ways to ensure a streamlined approach so that local and central IRBs can collaborate, each with a clear understanding of the others’ responsibilities. 

Institutional research offices and local IRBs continue to have a critical role in maintaining and enforcing policies regarding human subject research, in educating investigators on protocol development, in reviewing investigator-initiated protocols, and in protecting accreditations. 

Investigator-initiated trials have their own issues that require close IRB scrutiny. Without the oversight and structure of commercial sponsors, institutions must fill the gap to ensure regulatory compliance. By shifting IRB responsibility for industry-sponsored trials to a central IRB, more time and attention can be focused on these local trials.

A 2008 study (4) showed that CIRB use could result in shorter review periods and up to six hours of research staff effort. On average, over $700 were saved per initial review. With IRBs reviewing hundreds of protocols, these savings quickly add up. These potential cost savings could allow research offices to reallocate resources to other areas, and improve efficiencies throughout the process.

  1 Loh ED, Meyer RE: Medical schools’ attitudes and perceptions regarding the use of central institutional review boards. Acad Med 2004, 79:644-651.   2 AAHRP 2009 Report    3 Ann Neurol. Author manuscript; available in PMC 2011 February 1.        

4 Wagner TH: Costs and Benefits of the National Cancer Institute Central Institutional Review Board. American Society of Clinical Oncology. September 2008.

Can a Central IRB Improve Efficiency?

Academic Medical Centers are highly sought-after research study sites, for four primary reasons: the prestige of the institution and its investigators, the sponsors’ desire to cultivate key opinion leaders in a particular medical field, the accessibility of a larger metropolitan area, and the large pool of potential patients available to participate in research. Despite their caché, Academic Medical Centers (AMCs) pose a unique set of challenges for sponsors of clinical trials.

First, as any CRO or sponsor who has worked with an AMC can attest, the layers of review and its attendant impact on pace can delay study start-up by many months. The internal approval process tends to be a labyrinth of sequential, not parallel, department reviews and comments. If one department has a concern or question, the protocol can be held up until the issue is resolved; the other departments along the approval chain do not have the opportunity to review until the previous department has completed its review. Collaboration between departments is often tricky because of the structure of the center with silos between departmental budgets and personnel.

Second, sponsors are sometimes surprised by the slower pace of study enrollment at AMCs. Why is this? The investigator is often a luminary in their field, and is likely engaged in multiple trials, including ones that are investigator-sponsored, which may take a higher priority. AMCs are generally running multiple trials simultaneously, and if a protocol has limiting inclusion criteria (such as “previously untreated patients”), then those patients may be referred to other trials first. Furthermore, if a study does not speak to an AMC’s sweet spot (i.e., not a therapeutic area of focus for the center), then resources may be limited to support the study, thereby impacting enrollment. 

Intellectual property (IP) issues are the third area of complexity when dealing with AMCs. These centers have an affiliation with a university with its own legal counsel, and discussions pertaining to IP can become protracted. Because many biotech and pharma discoveries were first identified in university labs and settings, AMCs are highly sensitized to IP rights and may require detailed and rigorous review of study documentation.

In addition to understanding these unique challenges, here are several tips that may be useful in working successfully with an AMC:

Ensure that the protocol is a good fit for the investigator. Are they interested in the research being conducted? Are the inclusion/exclusion criteria a good match for their patient pool? Are there competing trials that may siphon patients?

Ensure the investigators’ availability to be involved in the trial. Is the investigator on site and seeing patients regularly? Or do they travel constantly and rarely see patients? Is their study coordinator able to run the trial effectively in their absence?

If a CRO is being utilized, be sure that the team has experience with AMCs and can navigate the system effectively. Ask for case studies and request an experienced team.

Establish expectations that are realistic. Determine from the institution/investigator the anticipated timeframe for review. Understand their historical enrollment numbers and discuss barriers to recruitment and retention.

Don’t be afraid to interview the site staff before engaging them formally in the study. Initiate contact with the AMC’s office of clinical research and go from there.  

Consider outsourcing to organizations that are experienced working with AMCs, and can navigate time-consuming yet critical activities, such as: independent institutional review board services, contract and budget negotiations, and internal audits. 

These points of caution are intended to educate—

—sponsors in using AMCs as investigative sites. Entering the process with eyes-wide-open helps inform the study strategy and develop a realistic timeline for enrollment. AMCs are typically aware of the aforementioned issues and want to be good research partners. They continue to be a beacon of research and healthcare in this country, and clinical trials run at these centers are better for it. 

) is the EVP of Operations at BRANY, a national organization providing support services to sponsors and investigators involved in research in all therapeutic areas, 

Kimberly Irvine, CIP, CIM

Articles

Playing in the Sandbox--How Local Institutional Review Boards Can Happily Co-Exist with Central IRBs

Can a Central IRB Improve Efficiency?

Academic Medical Centers as Study Sites: Tips for Success