Going beyond reporting adverse events to IRBs
ORIO system is explained
Investigators often find it difficult determining what types of information should be reported to an IRB, and they may report too many incidents or omit important information.
At the University of Michigan in Ann Arbor, MI, IRB officials have developed a new methodology that assists investigators in screening for the correct reportable events, whether they are adverse events or other occurrences.
"We wanted to develop a methodology for other things IRBs are responsible for keeping track of," says JuneAnne Insco, CIP, IRBMED coordinator at the Medical School Institutional Review Board at the University of Michigan. The new system is called Other Reportable Information or Occurrences (ORIO).
"We didn’t want to change what the regulators wanted us to monitor, but there are other types of things that need to be reported," Insco says.
The system captures information about unanticipated problems, protocol deviations, and serious noncompliance issues, even when these do not harm subjects, Insco says.
For example, a drug included in the study might have been mislabeled or not handled appropriately, Insco says. "Even if the drug is not administered to subjects in the study and the subjects don’t have an adverse reaction and are not hospitalized, this still could pose a risk on another day, so it’s a situation that needs to be addressed," Insco explains.
The acronym ORIO was designed to be familiar and easy to understand, and its name is general enough to include every reportable incident of interest to the IRB, she says.
For instance, an ORIO might include a situation in which one subject involved in a study is arrested and incarcerated, she says. When this happens the investigator will need to complete additional paperwork in order to keep the subject in the study, and the IRB would need to be notified, Insco says.
It may be in the best interest of the person to stay on the study drug, but the prison is not able to administer it, and so other arrangements would have to be made, Insco says. "There are other research-impacting events that don’t involve adverse events per se, and these are always the ones that you want to hear about," Insco says.
Sometimes it’s unclear whether the incident is related to the study, but investigators should report the possibility. "Perhaps someone has an auto accident and no one is hurt in it, but you had taken blood from that person for eight hours all day, and it was a fasting study," Insco says. "And so there’s a reasonable idea that the person might have passed out behind the wheel from fasting, and that could have caused the accident."
Since the subject wasn’t hurt in the auto accident, there wouldn’t be an adverse event report, but it would require an ORIO report, Insco says. "Given the nature of the research and the fact that the person had just left the clinic, it could be considered a causal relationship," Insco says.
Here’s how the electronic AE/ORIO reporting system, called eResearch, works:
• Investigators/clinical trials staff select the study name. The person filing the report first clicks on the link for "approved studies," then click on the name of their own study, entering the study work-space to view more details.
• They follow instructions for new adverse event/ORIO reporting. From a line below the AE/ORIO prompt, the person filing the report selects whether the reportable event is an AE or an ORIO, and then he or she completes the title information with a reference identifier, such as Subject #2, SAE 3-25-06.
For AE submissions, the questions asked include the date of the event, the responsible site for the event, the grade of event according to the FDA’s definition of serious, whether the event is related to the intervention, and whether the event was expected, Insco says.
The interactive electronic form then asks that, if applicable, the person completing the report notify the principal investigator that the report is ready to be reviewed and submitted, by posting correspondence and checking the "PI box" in the study team member list. This will trigger an e-mail.
• IRB staff review AE/ORIO reports. The AE/ ORIO reports are automatically routed to the IRB office for immediate review by IRB staff, Insco says. When IRB staff receives a new AE they will automatically see all of the AEs that the study team previously has submitted for the study.
"In the old system we would require investigators to submit AEs in summary format with their continuation of review, but this way the system is doing the decision-making triage for them," Insco says. "And when we do the scheduled continuing review, our reviewer will automatically see all the AEs the study team has submitted for the year."
Since switching to the new reporting system, the IRB has received more reports of protocol deviations than it had in the past, Insco notes.
The system also has reduced some unnecessary reporting and provided a better awareness of tracking protocol deviations, Insco says.
"Our AE reporting is a little more stringent than what is required by the FDA," Insco says. "What we also built into the system is the ability for the study team to develop its own AE reporting plan and to submit that to the IRB for approval."
The IRB might suggest a clinical trial team develop an AE reporting plan when IRB staff has noticed that the site has reported a lot of AEs that are unrelated to the research intervention. "We suggest they develop a plan that’s appropriate to their study so they’re not overburdened with reporting, and we’re not overburdened with their reporting," Insco says. "And the IRB will determine if the AE reporting plan is adequate to protect subjects and then approve it if it is."
Before developing the ORIO reporting system, the IRB had asked investigators to report the additional incidents to the IRB on their progress reports. But investigators found it to be counterintuitive to report problems on a progress report, she notes.
"We tell investigators that the ORIO reporting doesn’t represent a new regulatory burden, the reporting requirement was always there," Insco says. "What we did was systemize it, develop methodology and procedures to make it more self-evident."