IRB's deviation reports increase exponentially, leading to process change

QI staff label deviations according to significance

After the FDA in 2000 highlighted the problem of investigators inadequately reporting protocol deviations, sponsors have required all deviations to be reported to the IRB.

This caused the Schulman Associates IRB of Cincinnati, OH, to see an immediate increase in reported protocol deviations from 10-15 per week to 300-450 per week, says Thomas W. Gibson, RN, BS, director of regulatory affairs and quality improvement at Schulman Associates IRB Inc. of Cincinnati, OH.

The dramatic increase in reported deviations has continued each year. In 2006, there were 34,000 deviations reported. This year, the IRB anticipates having close to 40,000 reported deviations, Gibson says.

Another factor contributing to the increase in reported deviations is that the IRB's own business has increased, notes Mary Ellen Kramer, RN, BSEd, CPHQ, senior quality improvement coordinator for Schulman Associates IRB.

"These are challenges that you have to manage all of the time," Kramer says. "You think you've fixed it, and then another issue comes up."

So any QI process created to handle this issue would need to be ongoing, Kramer adds.

"As this number increased we had to do a QI initiative because sponsors were telling all their sites to report everything, whereas the regulations say you only need to report significant deviations in a protocol," Gibson says. "As a result, we had to develop a classification system."

The system divides the reported deviations between those that are significant and must be reported and those that do not need to be reported. The number of reports is too large to take all of them to the IRB, so some kind of triage needs to be performed.

The first step was to look at the study populations involved and to develop a way to classify the reported deviations, Gibson recalls.

For example, if a deviation stated that the study participant was stuck in traffic and, as a result, received the study drug five minutes later than the window allowed, this likely would be an insignificant deviation, he says.

However, if an investigator's computer hard drive, containing confidential study participant information, was stolen, then that needs to be reported and would be classified as a significant deviation, Gibson says.

Also, context matters. If an investigator made an error during the informed consent process, but it was the first time this occurred, and the investigator also filed information about the measures he or she took to correct the problem, then it would be reported to the board, but as an attachment that doesn't require discussion, Gibson explains.

The same incident would become a compliance issue and taken to the full board for discussion if it was the second or third time that the investigator made a mistake in providing informed consent to participants, Gibson adds.

The QI department has whittled down the reported deviations to 3,000-4,000 significant deviations per year that the IRB has to discuss, Gibson says.

The board is notified of many more than that number, but these are not issues of noncompliance and do not need to be discussed, he adds.

Deviations first are entered into the database by three administrator assistants. After that they are handled by a senior compliance coordinator and staff who review them and classify them as insignificant or significant and in need of follow-up, Gibson says.

"About 20% of the deviations require follow-up because they haven't submitted the necessary information to help us understand what's going on," he says. "Or they don't have adequate measures in place to prevent the deviation from happening again."

Deviations labeled as "significant" are put on the IRB's agenda. If the deviation is both significant and a noncompliance issue, then Gibson and the senior compliance coordinator will go to a pre-board meeting on Tuesday morning and meet with several legal representatives, board members, and the IRB chair to discuss these particular deviations and noncompliance issues, he explains.

"At that time they decide whether they want the deviation to go to the board on a Wednesday or Friday meeting, or they say they would like to know more information," Gibson says.

Once this process is done, the senior compliance coordinator will make sure each deviation reviewed is marked as "no action needed," or however it has been handled, and then they're sent back to the investigators for their files.

To make certain QI professionals have accurately identified the significant versus insignificant deviations, there is an ongoing inter-rater reliability check conducted. Several IRB members who are physicians will conduct quality checks on a random number of reported deviations and make their own judgments about whether these are significant and issues that need to be reported to the full board. Their assessments are compared with the staff's assessments, and typically the two are the same, Gibson says.