Delayed study startup times obstruct the enrollment process for prospective participants in clinical trials with a therapeutic intent. That is an ethical concern. “There are patients waiting to start on these studies. Delays in IRB approval will delay the patient obtaining access to research procedures that are integrated with their clinical care,” says Nathalia Henry Whitely, MS, CHRC, CIP, executive director of the IRB office at Northwestern University.
Delays in IRB approval hinder enrollment, data collection and analysis, and submissions to regulatory oversight agencies. It takes longer to learn if new therapies are effective and safe. Updated product labeling and product approvals are held up. “In the long term, it means delays in those discoveries being available to patients at the bedside,” Whitely says.
Some multicenter, industry-sponsored studies include specific enrollment time frames. Delayed IRB approval might mean the enrollment window closes. “The institution misses the opportunity to conduct the study. Patients affiliated with that institution miss the opportunity to participate in the research,” Whitely says.
There are a few reasons for delays in the IRB approval process:
• IRBs and research teams might be challenged by the sheer volume of studies that need preparation, submission, and review. “Due to human research portfolio growth and expansion, institutions face increases in the influx of studies coming down the pike. That is a good problem to have,” Whitely says.
However, many institutions are finding their human research portfolios are growing at a much faster pace than their human research protection program (HRPP) infrastructure. To keep up, HRPPs, IRBs, faculty, and support teams must be adequately staffed. It is a challenge. “Research teams are constantly laboring to find and retain qualified research personnel with the appropriate level of expertise,” Whitely says.
• Certain studies require review by an ancillary committee before the IRB can give final approval. The scientific review committee might need to review oncology studies, or an investigation might need conflict of interest review. “To prevent delays, it is important for the principal investigator [PI] and the research teams to know which ancillary reviews must occur prior to or in parallel with IRB review,” Whitely says.
• Regulatory bodies, such as the FDA, might need to provide additional oversight. For studies in this category, the PI and/or the industry sponsor might need to obtain a determination from the regulatory body (e.g., obtaining an investigational new drug or an investigational device exemption from the FDA) before the study can begin.
• Poorly written protocols raise additional questions. “IRBs work with PIs to iron out protocol discrepancies and bolster protocol content that adds the clarity needed for the IRB to perform a thorough review and appropriate risk determination. That takes time,” Whitely notes.
If any component of a protocol is unclear, such as research procedures, risk mitigation plans, participant eligibility criteria, recruitment plans, or participant compensation, PIs will field multiple clarification requests from the IRB to adjust the protocol. “If an IRB notes an issue with a protocol, the IRB will send the protocol back to the PI for clarification and resolution of the issues,” Whitely says.
For industry-sponsored studies, the sponsor must approve any protocol changes that result from an IRB’s questions. “Therefore, during the IRB process, there are blocks of time where the study may be sitting with other parties outside of the IRB who need to take an action, such as the PI or industry sponsor,” Whitely observes.
It is critical for PIs to maintain close oversight of their teams. “PIs must ensure research staff have the appropriate expertise and receive adequate training to adhere to detailed instructions provided by the IRB and regulatory bodies,” Whitely says.
At the University of Texas at El Paso, many IRB review delays happen because of a lack of clarity about risks and benefits. “These include lack of congruency and researchers not responding to requested modifications in a timely manner,” says M. Lorraine Torres, EdD, MT(ASCP), clinical laboratory sciences program director.
Some protocols describe procedures in which participants would be partaking, but it is not consistent with what the consent form says. Many researchers ask participants for sensitive information, such as criminal activity, drug use, or sexual behaviors. “This could compromise participant privacy and confidentiality, thus affecting their employability, insurability, and overall reputation if a breach were to occur,” Torres cautions.
For social-behavioral projects deemed as “clinical trials,” the IRB advocates for preparation meetings with the researcher before submission. This promotes open discussion so issues can be ironed out proactively. Recently, the IRB raised the question of whether identifiers were absolutely necessary in a study. The IRB recommended excluding identifiers to minimize potential risk to the participant. Whatever the issue, “the office can assist the researcher in finding solutions that are allowable within the regulations and acceptable to the IRB committee,” Torres says.
Ryan Spellecy, PhD, views lengthy delays of IRB review as interfering with the ethical principle of beneficence. “We ultimately delay the opportunity for individuals and society at large to benefit from research,” explains Spellecy, chair in bioethics at the Medical College of Wisconsin.
Life-saving or life-improving treatments could be delayed. “Even the clinical trials that fail are important as we [can] learn from them,” Spellecy notes.
One might assume long turnaround time happens because of understaffed, overworked IRBs. This can be the case, but delays also can happen when investigators take too long to respond to IRB requests. Clearly written protocols can prevent too much back-and-forth between the IRB and the PI.
“IRBs and study teams need to work together to identify the causes of delays at their institutions and collaboratively design solutions,” Spellecy says.