Better understanding of UPs leads to fewer unnecessary IRB reports
Better understanding of UPs leads to fewer unnecessary IRB reports
UCLA’s P&Ps provide best practice model
Human research protection offices have found that adopting policies and procedures regarding the reporting of unanticipated problems (UPs) has helped to reduce IRB busywork and improve the research community’s understanding of when to report problems, experts say.
The key is to follow best practices through keeping policies up to date with regulatory changes, institutional requirements, and technological evolution. The University of California, Los Angeles (UCLA) recently updated its guidance and procedure for reporting UPs, which is a model for educating researchers and IRB staff about how to decide what is a UP and when to file an immediate and separate report.
UCLA’s research protection office fine-tuned its UP reporting policy as the institution was seeking accreditation from the Association for the Accreditation of Human Research Protection Programs (AAHRPP) starting in 2008, says Sharon Friend, MS, CIP, director of the UCLA office of the human research protection program (OHRPP).
“First we let people know the changes were coming and gave them guidance,” she says. “Then we changed everything we did, provided training, and alerted people to the drop-dead due date to follow the new procedures.”
AAHRPP and later the Office of Human Research Protection (OHRP) provided guidance and definitions for unanticipated problems versus adverse events (AEs) and serious adverse events (SAEs). These materials are incorporated in UCLA’s UP reporting policies and explained both in words and visually with diagrams. For instance, one bubble chart shows three separate bubbles for AEs, protocol violations, deviations and incidents, and updated study safety information. These three bubbles touch, but do not overlap, while a bigger bubble, labeled “unanticipated problems,” overlaps a portion of each of the three smaller bubbles.
Rewriting and revamping
UCLA’s change in UP and AE reporting parallels changes made at some other large research protection offices, where IRBs have seen a large decline in weekly reports, Friend and other experts say.
IRBs were inundated with serious adverse event reporting and with not-so-serious AE reporting prior to the mid-2000’s. Investigators, at the urging of their sponsors, would report every adverse event as it occurred.
“We used to get literally boxes full of reports,” says Kathy McClelland, CIP, research compliance director of Stanford University in Stanford, CA.
“Drug companies wanted their sites to report every little issue to the IRB immediately, and there are a lot of adverse events,” McClelland adds.
“Now they understand that what’s important to report are the unanticipated problems,” she explains. “You still have to report adverse events and serious adverse events, and one of these could become an unanticipated problem, but it’s a different mechanism for how these are reported.”
The University of Utah in Salt Lake City adopted UP guidelines about six years ago, and the IRB office has continually refined and improved them, says John Stillman, CIP, IRB director.
An AAHRPP accreditation process was what led to the institution’s extensive UP reporting changes, Stillman says.
“It has greatly improved our system; we focused our attention on unanticipated problems and our reporting caseload went down,” Stillman says.
“We spend a lot of time looking at our report forms, standard operating procedures, and guidance,” Stillman adds. “This is always something that can be challenging for IRBs and investigators.”
Even research institutions that rarely have AE reports can benefit from new UP policies and procedures. It’s not difficult to pull together information from OHRP, the FDA, and other websites, says Susan A. Walsh, PhD, RN, CCRN, IRB chair at Clayton State University in Morrow GA.
Although Clayton State University mostly has bio-behavioral and history research, the institution is starting to see an overall increase in research with some more diverse studies coming to the IRB. These have led the institution to revise and modify its Web page, bylaws, and policies and procedures, Walsh says.
“We’re doing a lot of rewriting and revamping to meet the change,” she adds.
AAHRPP and OHRP began to promote the term “unanticipated problems” in the mid-2000s, encouraging research sites to reduce their workload through more judicial reporting of AEs and other events. First, AAHRPP began to promote UP reporting as research organizations sought accreditation. Then OHRP published its Jan. 15, 2007, guidance on reviewing and reporting unanticipated problems, and this gave IRBs a framework for policies and procedures for reporting UPs, Friend and McClelland say.
OHRP has not tracked the trend of AE reporting but notes anecdotal evidence of an improvement.
“I have heard fewer complaints from IRBs about being inundated with adverse events reporting since OHRP issued its guidance,” says Kristina Borror, PhD, director, division of compliance oversight, OHRP.
“However, we have not conducted a scientific sampling,” she adds. “OHRP saw a steady increase in reporting in the years immediately following the 2007 guidance, but those reports also involved other things, including noncompliance, suspensions, and termination issues in addition to unanticipated problems.”
“Unanticipated problem”
OHRP’s guidance and use of the term “unanticipated problem” made it clear that not all adverse events needed to be reported immediately to the IRB, and it spelled out criteria for when an incident qualified as an unanticipated problem and needed to be reported. This change six years ago has helped reduce IRB workloads and has resulted in more efficient reporting and monitoring of adverse events, IRB experts say.
“Back in the days when we had paper files, some of our IRB chairs had files to review as high as they were, and all of these were adverse event reports,” Friend says.
“If there was one occurrence of an adverse event for an investigational drug, then it would be reported for all of these different studies, and it was very frustrating for the IRB chairs,” Friend recalls.
Still, there was some resistance to the program’s change when policies about UPs first were introduced, she notes. The UCLA research community was not fond of the term “unanticipated problem” when UCLA first began to use it in guidance, Friend says.
These initial reservations disappeared after investigators began following the new UCLA guidance, policies and procedures for UPs and SAEs. The UCLA research community also became more invested in making changes when the human research protection program sought AAHRPP accreditation. AAHRPP had been encouraging IRBs to develop UP policies and procedures, Friend recalls.
“We did major educational outreach so people would understand a UP is more than an adverse event, and an adverse event might not be a UP,” Friend says. “What we focus on here is post-approval reporting.”
The result of the change has been a significant reduction in unnecessary AE reports, she adds.
“We made the change in 2008 and saw the reports drop right away, and there has been a continuing drop,” Friend says. “People were thrilled.”
The guidance’s latest stage of evolution has been its integration in the IRB’s online system. All paper references are gone, Friend notes.
Another change has been having researchers summarize all of the anticipated AEs and problems in one report at the time of continuing review, which gives the IRB context and the opportunity to note any trends, Friend says.
“What we needed was a summary of violations/deviations,” she explains. “If something affects safety or the participant’s welfare, we need to know right away, but if someone came in on the wrong day or missed an appointment, these are smaller things.”
Before the UP change, there often was no distinction between small study deviations and major protocol violations or problems, she notes.
At Stanford University, all adverse events that do not qualify as unanticipated problems are reported at the study’s continuing review, McClelland says.
When institutions have investigators report the expected AEs in one report, the IRB can see the big picture more clearly, noting any trends or greater-than-expected rate of any particular AE.
Although investigators still tend to report a little conservatively, the guidance has brought about the changes the IRB had intended, Friend says.
“People are very happy with this because they don’t want to report every little thing to us,” she says. “And the IRB is happy because they can focus on what’s important.”
Human research protection offices have found that adopting policies and procedures regarding the reporting of unanticipated problems (UPs) has helped to reduce IRB busywork and improve the research communitys understanding of when to report problems, experts say.Subscribe Now for Access
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