Recently, the VP of Research of a leading university called Quorum asking for help. A leading investigator of his university had demanded that the university’s IRB serve as the single IRB (sIRB) of record for multi-site NIH studies won by that researcher. Even though the university’s IRB could manage multi-site studies, the VP was worried that the investigator would not have the resources necessary to manage multi-site communications and asked if Quorum could summarize for him the resources that a research team would need. The results surprised even us!
Under new federal policies, it is the responsibility of NIH grant awardee investigators—and soon all federal grant awardees—to arrange for a single IRB to review all of the sites in a multi-site study.1 Many investigators balk at the cost of outsourcing to a commercial IRB, and assume their local institutional IRBs can simply retool in order to accommodate the review of multiple performance sites. However, the NIH policy also expects awardees to develop a plan for managing communications between sites and the sIRB. In outlining the roles of the parties, the NIH guidance dictates that:
“Awardees are responsible for ensuring that authorization agreements are in place; copies of authorization agreements and other necessary documentation should be maintained in order to document compliance with this policy, as needed. As appropriate, awardees are responsible for ensuring that a mechanism for communication between the sIRB and participating sites is established. Awardees may delegate the tasks associated with these responsibilities.”2
The guidance further explains that the sIRB is responsible for collaborating with the awardee to establish “a mechanism for communication between the sIRB and the participating sites,” and the funding institute/center [I/C] is responsible for the “management and oversight” of the award.3
Commercial IRBs Know Site and sIRB Communications
In our experience at Quorum, a leading commercial IRB, managing communications between the sIRB and participating sites can best be described as herding cats. If you can imagine busy study staff at sites across the country; professionals trained in the sciences and not in data entry; and the many sets of documentation required for IRB review, then you can imagine the challenge of managing communications between the sIRB and participating sites.
A perennial challenge, for example, is ensuring that the sites’ submission forms are fully completed. In our experience, only 30-40 percent of initial site submissions are complete when submitted, and it can take as much as a month of solicitations by IRB staff to obtain a complete set of submission materials. Managing communications about the finalization of consent forms also is time-consuming, as each institution maintains its own unique consent form language for terms relating to HIPAA, compensation for injury, and other issues. Many back-and-forth communications are often required between the funding I/C’s sIRB and the site to reconcile those terms with the model consent form in the multi-site study.
Adequate resources are also needed to ensure that performance sites submit their continuing review reports in a timely manner. Most institutional sIRBs probably require all participating sites to undergo continuing review on the same date, and so staff time will have to be dedicated to collecting the reports and then ensuring they are complete. Institutions also should assume that despite staff efforts, at least five percent of performance sites will miss the deadline. Those sites will need additional resources to communicate the lapse in IRB oversight and to collect documentation for re-establishing oversight.
Don’t Underestimate Resources Needed for Communications
Site communications take time—and they also need to be documented. Communications comprise “correspondence between the IRB and the investigators,” and both the Common Rule and FDA regulations require that records of the correspondence between the sIRB and the investigator be documented and retained for at least three years after completion of the research.4
The NIH Policy allows institutions and their awardee investigators to decide among themselves who is responsible for managing communications with participating sites. Institutions might determine that the IRB office should manage all communications, or the awardee’s study staff, or some combination thereof. Whoever is responsible will require additional headcount, as well as recordkeeping systems and processes to manage and document the communications.
Below is a rough estimate of the time required to manage and document communications between the sIRB and participating sites. These estimates include communications only, and do not include the time required to build IRB agendas, manage IRB meetings, or generate approval documents. These calculations are for a typical 10-site clinical study.
|Task||Time required to manage and document communications||Overall staff time required for 10 sites|
|Initial site submissions at the time of study start-up||1-3 hours/site to ensure the submission is complete||10-30 hours during study start-up|
|Negotiating consent form finalization at the time of study start-up (note that most clinical studies have 3 or more consent forms)||1-3 hours/site to explain and reconcile IRB concerns and revisions, funding agency concerns and site concerns||10-30 hours during study start-up (assuming one consent form)|
|Managing study amendments that require consent form revisions (in clinical studies, typically occur twice a year)||0.5-1 hour/site to explain and reconcile IRB concerns and revisions, funding agency concerns and site concerns||5-10 hours, typically twice a year (but timing is unpredictable)|
|Managing submissions of safety reports and submissions of recruitment, retention and educational materials (assume one per month, although clinical studies can have hundreds)||0.5-1 hour/site to explain and reconcile IRB concerns and revisions, funding agency concerns and site concern||12 hours sporadically throughout the life of the study|
|For an unanticipated problem that must be reported to federal agencies, coordinate corrective actions with the performance site and send findings letters to OHRP/FDA (assume one per year)||1-5 hours per reportable incident||2-10 hours throughout the life of the study|
|Annual or semi-annual continuing review||0.5 hours/site to notify sites about the due date|
0.5-1 hour/site to ensure the submission is complete
For 5% of sites: 8 hours/site to communicate about the missed deadline, lapse of IRB oversight, and manage the steps needed to re-open IRB review
|10-30 hours in the weeks preceding the annual or semi-annual continuing review date|
|Closing a study||0.5 hours/site to collect final documentation||5 hours at the close of the study|
Finding and retaining employees to support these functions can be difficult, especially given the sporadic nature of the work. Managing communications for a multi-site study requires employees who are familiar with the IRB’s forms and processes and who are attentive to detail. Managing good documentation of communications also requires careful oversight and occasional auditing to ensure the accuracy of the records.
Commercial IRBs Can Address This Challenge
After considering these issues, many investigators and IRB administrators may ask, “Can’t I outsource this specialized and sporadic workload that is subject to regulatory enforcement actions?” In the United States, commercial IRBs are available to undertake those tasks.
Commercial IRBs have been managing the communications of multi-site IRBs for as long as the Common Rule has been in effect. Commercial IRBs routinely review and oversee multi-site trials with hundreds of sites. Commercial IRBs have invested millions of dollars to build the computer systems needed to track complex multi-site studies, and they have developed the teams and processes needed to manage these communications.
Moreover, these systems are tested: the largest IRBs are audited by pharmaceutical companies and other sponsors about 12 to 24 times a year; audited by the FDA about every three years; and undergo AAHRPP accreditation visits every three to five years.
Nevertheless, we realize that some institutions will desire to build their own sIRB capabilities. Quorum and Kinetiq are happy to share our expertise and provide consulting to help institutions towards that goal.
1 NOTOD16094: Final NIH Policy on the Use of a Single Institutional Review Board for MultiSite Research (July 6, 2016); NOTOD17076: Revision: Notice of Extension of Effective Date for Final NIH Policy on the Use of Single Institution Review Board for Multi-Site Research
2 Id. at p.9
4 21 CFR 56.115; 45 CFR 46.115