Compliance Corner

IRB effectively handles research concerns

Compliance tools help with success

Human subjects research organizations need a thorough, fair, and effective way of handling complaints and concerns about research trial ethical and regulatory violations.

The key is to investigate potential noncompliance issues with integrity so that the process will be as fair as possible.

"The key philosophy for an effective compliance program is to have the intent to improve the quality and ethical conduct of research," says George Gasparis, executive director of the Columbia Human Research Protection Program at Columbia University in New York, NY.

"You work with those for whom you received allegations of noncompliance to strengthen their research programs," he adds.

Once an investigation is complete, it's important to assist research sites with implementing corrective action plans to prevent future noncompliance.

"It's key that compliance efforts are not seen as punitive or as a policing of researchers," Gasparis says.

The goal for the compliance program is to work with investigators as a team to improve the quality of investigators' research, ethical conduct, and protection of subjects, he adds.

The first step is to recognize noncompliance, and this entails staff education via the organization's website and other mediums. There are several other key steps to achieving this goal. They are as follows:

Separate minor incidents from serious ones: The noncompliance policy makes it clear when an incident is minor and therefore unlikely to impact human subjects. The policy directs the IRB to consider minor noncompliance cases within the review, rather than sending them to the compliance team for action, Gasparis says.

An example of a noncompliance incident would be the investigator whose study has expired prior to his submitting a renewal application to the IRB. If the study had actively enrolled subjects during this lapsed period, then that would be considered serious noncompliance. If data analysis occurred during the lapsed period after all subject activity had stopped, then it would be considered a minor noncompliance, Gasparis explains.

Serious noncompliance issues are reported to the appropriate regulatory agency, including the Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA), he notes.

"We explain to researchers that it's essential that we have an effective compliance program that identifies noncompliance and corrects it," Gasparis says.

Regulators want to know these main points:

  • What did an institution do to prevent it from happening?
  • If the noncompliance impacted subjects, how was the study changed or how did they work with subjects to resolve the concerns that were raised?

Audit studies both proactively and when noncompliance is alleged: Compliance audits serve as educational vehicles and can be used to identify noncompliance risk in cases of study sites that have not had noncompliance complaints.

These audits also can serve as a way to correct problems when noncompliance is identified.

The Columbia IRB uses compliance audit worksheets that help keep auditors focused and thorough.

Research institutions that are just beginning compliance and auditing programs should consult with institutions and individuals that have experience in this area, Gasparis suggests.

Also, national human subjects research conferences are a good resource for training on how to conduct compliance oversight activities, he adds.

The Columbia University IRB's not-for-cause audit and quality assurance visit regulatory worksheet contains nine pages. Among its audit questions are the following:

  • Are all regulatory documents available and in order?
  • For investigator-initiated studies, is there an investigational plan available?
  • Have all unanticipated problems involving risks been reported to the IRB?
  • Have all amendments/protocol modifications been submitted to the IRB and approved prior to implementation?
  • Have all advertisement/announcements been approved by the IRB?
  • Are subjects randomized correctly, according to the randomization plan?
  • Is subject enrollment within the agreed upon numbers?
  • Is the initial protocol approval letter on file?
  • Is the current IRB protocol approval letter on file?
  • Are there any lapses between approval dates?
  • Was any research-related activity conducted during any lapsed period?

Provide follow-up to audit and reported results: "Once our findings are reviewed, we create a summary of how we conducted the investigation, our findings, and our recommendations for corrective actions," Gasparis says.

"We report our findings and develop a report that is reviewed by me and the IRB. Serious noncompliance also is reported to the IRB executive committee, which includes the chair of each of our IRBs, the associate director of the IRB, and the vice president for research operations," Gasparis says.

Corrective actions always include a recommendation for education and training.

If a research site's noncompliance is serious and appears to be part of a trend, then the audit can be repeated or extended to other studies with the potential to have similar problems.

The compliance office can put research sites on a cycle of monthly records review where compliance officers assess whether the site has effectively implemented the corrective action plan, Gasparis says.

"We have had situations where there was noncompliance found in one study, and then we found it in three or four other studies," he explains. "We put the site on a monitoring program, and now they're a model research team."

The site had to hire additional staff because the chief cause of their problems was a lack of resources, he adds.

"If something went wrong, we conduct a root-cause analysis and then apply appropriate corrective actions," Gasparis says.

"There has to be an awareness of what was wrong and how to do it right," he notes. "We need to have confidence that there is a change in the process that likely will prevent the noncompliance from occurring again."