Draft guidance outlines IRB responsibilities
Guidance defines role in vetting investigators
To better clarify the IRB’s position in investigating clinical investigators and sites for clinical trials, the Food and Drug Administration (FDA) has released draft guidance for reviewing those qualifications.
While the points made in the guidance are nothing new, the FDA has made clear the role of IRBs in reviewing qualifications for IRBs that may be confused or unclear about the responsibilities.
“FDA has received questions from time to time about an IRB’s responsibility for reviewing the qualifications of investigators and study sites,” the FDA’s Center for Drug Evaluation and Research (CDER) wrote in a statement to IRB Advisor. “FDA became aware, however, that some IRBs may be confused about their responsibility to review the qualifications of investigators and sites after recent findings that some IRBs approved studies without checking the qualifications of investigators and/or adequacy of sites identified in the study materials. FDA thought it was important to issue a reminder to all IRBs about these responsibilities.”
Though the information isn’t new, some IRBs welcome more clear guidelines from the FDA.“I think that a lot of the regulations refer to the sponsor’s requirements and some IRBs may think the onus is on the pharmaceutical sponsor,” says Raffaela Hart, BS, CIP, CIM, senior director of IRB and IBC services at the Biomedical Research Alliance of New York (BRANY). “This does say in a clear way that the IRB has a part of the responsibility. It’s a great way to understand the FDA’s interpretation of the regulations, and shows more consistency across the IRBs. We hear all the time about how there’s no good way to know if IRBs have a consistent way of doing things, and these guidelines really help in that regard. If we know what their [the FDA’s] expectations are, we can consistently apply them.”
“What’s new to me is that the FDA is formalizing what’s been expected all along,” she continues.
While the FDA places much responsibility on the trial sponsor to select qualified investigators, the draft guidance describes the IRB’s role in the selection.
If the IRB has no previous relationship with the investigator, the IRB should obtain statements of qualification from other institutions. Additional steps, such as reviewing medical licensure, may also need to be taken.
“Another consideration is that a sponsor may not be aware that an investigator is conducting other studies in addition to the sponsor’s,” according to CDER. “The IRB, on the other hand, would be more aware of the other studies a particular investigator is conducting, the size of the investigator’s staff, other commitments the investigator may have that could impact his/her ability to conduct the study, etc.”
The document uses this example: “If the reviewing IRB has no knowledge of either the clinical investigator or the institution (e.g., the IRB is not affiliated with the institution where the research will be conducted; the IRB has no previous experience with the investigator), the IRB would likely need to take additional steps to evaluate the investigator’s qualifications (e.g., reviewing the curriculum vitae of the investigator, subinvestigators, and other necessary study staff; verifying professional associations and medical licensure; reviewing relevant publications).”
Pay particular attention to an investigator’s experience and training related to the specific study, particularly if the study is high risk.
“The regulations state that in order to approve FDA-regulated research, each IRB must determine that all of the criteria for approval have been met, including that ‘risks to subjects are minimized’ and that ‘risks are reasonable in relation to anticipated benefits, if any, to subjects...’ (See 21 CFR 56.111(a)(1) and (2).) An integral part of these determinations includes evaluation of the investigator’s qualifications and the adequacy of the research site. If an IRB fails to evaluate either of these, subjects could be placed at unreasonable and unnecessary risk,” according to CDER.
The IRB’s responsibilities for determining the eligibility of a study site is also described.
For example, “If a proposed clinical investigation involves administration of medical procedures by qualified healthcare providers using medical equipment, the IRB should be prepared to assess the adequacy of the facility’s staff and equipment, including the availability of emergency or specialized care if the need should arise. If the proposed research site is part of a major medical institution, the IRB would likely be able to simply note that fact. If, however, the IRB is unfamiliar with the proposed investigational site, the IRB would likely need to confirm whether the site is appropriately staffed and equipped to conduct the proposed research. The IRB should be able to obtain a statement from an appropriate person or persons at the research site or institution stating that the facilities are adequate.”
BRANY requires that potential investigators submit curriculum vitae and provide training-related documents. The IRB also checks with the FDA to make sure the investigator has never been disqualified from research. “There are a number of ways to look for red flags in terms of documentation,” Hart says. “We look at the CV to ensure they have adequate training for what they want to do and have experience in that area. There have been instances where our IRB has questioned whether someone was qualified, and we had to request a change of investigator.”
“We ask for a lot of information — we’re an independent IRB and many facilities may use us,” Hart continues. “There are questions on the applications about the facilities, their procedures for emergency responses.”
When it comes to delving deeper into an investigator’s qualifications, “definitely don’t be afraid to ask questions,” Hart says. “Some investigators may have experience but may not adequately document in their CV. Don’t be afraid to ask for information on their qualifications. We found a lot of useful information in databases on licensure information, such as whether a license has ever been suspended or put on probation.”
The FDA’s Guidance for IRBs, Clinical Investigators, and Sponsors can be found at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM328855.pdf.
To better clarify the IRBs position in investigating clinical investigators and sites for clinical trials, the Food and Drug Administration (FDA) has released draft guidance for reviewing those qualifications.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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