Researchers at Northwestern University’s Feinberg School of Medicine noticed more IRBs were offering detailed advice on study design that went beyond just ensuring the safety of participants. Some IRBs were offering methodological advice related to the technical aspects and scientific merit of proposed studies.
“We were also finding that some investigators were encountering more problems and delays with IRB approvals than others. We wanted to better understand if there were systemic reasons for this,” says Murad Alam, MD, vice chair of dermatology and professor of medical social sciences at Northwestern.
Alam and colleagues studied the most common reasons for protocol deferral by IRBs. They surveyed IRB chairs at 21 NIH-funded institutions. Those chairs reported the main focus of most IRBs was ethical considerations and participant safety.1
The most common ethics-related reasons for protocol deferral were inadequate informed consent, insufficient protection of participants’ safety, inadequate detail of risk assessment, and inadequate minimization of risks. Still, some study protocols were not approved due to issues of scientific merit, such as adequate adverse event reporting or the importance of the knowledge to be gained. Considering these findings, Alam offers recommendations for study investigators to avoid delays:
• Fill out IRB forms correctly, following all instructions. While IRB protocols are designed to ensure participant safety, they also are stylized documents evaluated by an IRB bureaucracy. “As such, they need to be completed with all the care, precision, accuracy, and transparency of a tax return,” Alam says.
• Less experienced researchers should consider working with more experienced ones to submit IRB protocols. The study support staff of more experienced research units often are adept at preparing high-quality IRB submissions. “These sail through regulatory approval, thereby allowing researchers to commence data collection right away,” Alam explains.
• Pay special attention to providing adequate detail to enable reviewers to make determinations regarding study safety. For instance, if a questionnaire is going to be used to elicit data, the IRB also may want to know which questionnaire and who will be administering it.
• Ensure there is consistency between the IRB protocol and the associated consent form. It is not just study investigators who should be considering these issues. “IRBs should consider what they can do to expedite good science,” Alam asserts.
IRBs should consider these questions: How can the IRB provide affordable, accessible resources to enable less experienced investigators to produce high-quality protocols on the first pass? Is less scrutiny warranted for unfunded, investigator-initiated protocols with low to moderate risk? How can the IRB avoid creating a barrier that excellent researchers with fewer resources cannot surmount (and in the process, impeding good, low-cost science)?
“In particular, by generating many minor queries about issues that do not directly impact patient safety, the IRB may needlessly slow down and frustrate those who have submitted a protocol but are less experienced in how to respond — and may not be able to do so in a timely manner,” Alam explains.
Why should the IRB choose (or not) to expand its purview into the more controversial realm of rigorously assessing the scientific merit of submitted proposals? Notably, many surveyed IRB chairs reported there were few externally imposed limits on their IRB’s purview. “Really, no authority is going to call out IRBs for being too careful and deliberate, even if this is unwarranted,” Alam observes.
Thus, some IRBs expand their purview, as members deem appropriate, to include questions of scientific merit. “We did not investigate the implications of this finding, or whether this is in fact beneficial,” Alam reports.
It is unclear to what extent IRBs are qualified to assess science. Also, it is unclear what IRBs do if there are no content experts on the IRB panel for specific studies. For example, studies requiring a therapeutic or diagnostic intervention may require a content expert to gauge the actual degree of associated risk.
Alam and colleagues found less-experienced investigators submitting unfunded proposals encounter more scrutiny from IRBs. Those less-experienced researchers may encounter more delays. On one hand, this is understandable, since researchers with fewer regulatory resources may be more prone to make technical errors and omissions. “On the other hand, it is concerning that protocols without external funding are often viewed by IRBs with more skepticism than those with industry funding,” Alam says.
It is possible some of the industry-sponsored proposals were vetted by for-profit, private IRBs. However, these often are less rigorous, non-institutional IRBs. “Moreover, there is a clear conflict of interest inherent in studies being performed by a company in furtherance of FDA approval or expansion of indications for a drug or device,” Alam notes.
Alam says this is an important question to tackle in a future study: “To what extent are sponsored proposals expedited because there is money at stake for the academic medical center, and not because such protocols are inherently better written, safer for participants, or scientifically superior to investigator-initiated studies without external funding?”
For investigators, the single best way to ensure quick IRB approval is to be sure the application is complete, according to Maggie DeBon, PhD, executive director of the Baptist Clinical Research Institute.
Common omissions in study protocols include a lack of documentation of the Data Safety Monitoring Board, training of all study personnel, and appropriate requests when the investigator wants a waiver or alteration of consent.
DeBon says the second most common reason for delays are tardy responses to IRB queries. Each application is reviewed for completeness. If there are any questions for the investigator or the regulatory staff, the IRB office will inquire. “These queries need to be addressed before the application can proceed for board review,” DeBon says.
REFERENCE
1. Reynolds KA, Harikumar VB, Poon E, et al. While ethical considerations predominate, scientific merit can impact Institutional Review Board (IRB) determinations: A cross-sectional study. J Clin Epidemiol 2022;150:12-17.
The most common ethics-related reasons for protocol deferral were inadequate informed consent, insufficient protection of participants’ safety, inadequate detail of risk assessment, and inadequate minimization of risks. Some study protocols were not approved due to issues of scientific merit, such as adequate adverse event reporting or the importance of the knowledge to be gained. Read on to learn how to prevent these problems and avoid delays.
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