No need to panic when OHRP comes a calling
OHRP compliance official explains process
It’s a rare occurrence, but each year some institutions are subjected to a for-cause audit by the Office for Human Research Protections (OHRP).
Such audits often turn up documentation problems and review process problems with the IRB, but occasionally they also highlight very serious problems relating to the clinical trials management, such as failure to provide adequate informed consent or failure to seek an IRB review, according to OHRP officials.1
Complaints come from subjects, internal whistle-blowers, investigators, research coordinators, advocacy groups, media reports, and other sources, says Kristina Borror, PhD, director of the Division of Compliance Oversight.
"Sometimes there’s evidence of problems in the scientific press," Borror says. "We might see a medical journal article about a clinical trial that doesn’t mention informed consent or IRB review, and we may look into something like that."
Once OHRP receives a complaint, staff determine whether OHRP has jurisdiction and then evaluates the complaint by sending an initial inquiry letter to the institution to say what the allegations are and to send the institution a copy of the complaint, she notes.
"We will request them to investigate it and to respond to specific allegations, and we request IRB records, including the protocol, grant application, the IRB minutes of meetings where it was discussed, the continuing review, adverse events reports, and any publications that came out of the research," Borror explains. "We also request information about their system, IRB policies and procedures, forms used and required information about how they educate both IRB members and investigators in human subjects protection."
Systemic problems targeted
Once OHRP receives a response, compliance staff check this for answers to the specific allegations and also for problems with how the system functions.
"The things we consider when deciding whether or not to do a for-cause site visit is whether there is evidence of systemic problems," Borror explains. "The complaint may be about a specific clinical trial, but we may have seen evidence that the system is broken."
Other events that could prompt a full audit are the death of a subject, which may have been caused by problems in the system, she notes.
OHRP compliance officers also may be concerned if they are having difficulty getting to the bottom of what’s going on at a particular institution, so this would prompt an on-site visit, Borror adds.
"If a complaint is about a particular protocol, we request interviews with the investigator or their research coordinator," she says. "We don’t call them inspections — we call them evaluations, and it’s done either all on paper or sometimes we’ll do telephone evaluations."
Typically after receiving correspondence from an institution, investigators, or IRBs, OHRP compliance officials will find a few problems that require corrective action. The institution is then asked to take corrective action, and if it does this to the satisfaction of OHRP, then the issue is concluded. But there are times when the actions haven’t been carried out and these would trigger a site visit, Borror reports.
If OHRP officials decide to conduct an on-site audit, then the staff give the institution four to six weeks notice whenever possible, she notes.
"We don’t go in unannounced," Borror adds. "We give them a chance to get records together."
OHRP compliance staff will ask the IRB to pull records of 50-75 additional protocols, particularly those related to high-risk and vulnerable populations, she says.
Expedited reviews and protocols that resulted in interesting discussions at the IRB meetings also will reviewed, Borror says.
"When we have a for-cause site visit, we will often interview the different researchers separately so we can make sure no one is feeling coerced into answering questions depending on who is present," she explains.
OHRP compliance staff also will interview clinical trials staff and, sometimes, research coordinators to make certain that everyone understands what they are responsible for doing and what the protocol is all about, Borror says.
The goal is to see if the allegations are substantiated or not, she adds.
"We ask them about their responsibilities, what they are responsible for, and what their relationship is with the IRB and PI [principal investigator] and ask about specific instances where maybe there’s a case of a particular subject who complained and the subject is known," Borror says. "We ask about the interaction with that subject, and we ask what they say and how they interact with the subject and investigators."
The main purpose for these types of questions is to figure out how the trial is being run and how the research is being conducted, she explains.
Since OHRP officials already have requested all of the written materials they will need to conduct the audit, the clinical trials manager and investigator do not have to bring anything with them to the in-person interviews, Borror notes.
However, sometimes clinical trials staff will bring additional information to these interviews, she says.
They may include specific details about the protocol, material that helps to clarify certain points, such as a table that shows exactly what subjects are doing and when with regard to dosages, etc.
"Or they may bring the results of an audit that they performed or somebody from the outside performed and they want to see results, or maybe some sort of organizational chart that shows different people in organizational reporting lines of reporting," Borror says.
OHRP officials also will ask clinical trials staff about how informed consent is handled, she notes.
Borror offers this advice to clinical trials managers and investigators who want to be prepared in the event of a for-cause audit: "Just make sure records are in good shape and easily accessed and easy to read."