Compliance Corner

Checklists, tools, help site manage QA/QI reviews

Forms help with trial oversight

Increasing numbers of research institutions have opened offices to provide oversight of investigator-initiated clinical trials, but they often lack the basic tools needed for this process.

"You need a checklist of what to look for when reviewing consent form documents," says Cindy Kern, RN, CCRC, CIP, education and compliance coordinator and assistant director for the office of investigator-sponsored IND/IDE support at the University of Pittsburgh in Pittsburgh, PA.

The University of Pittsburgh has developed a series of checklists and tools, including a signature, training, and delegated responsibility log, to assist with trial oversight.

"Our office reviews any research that is not funded by industry because no one else would be monitoring that research," Kern says. "It's unlikely they'd have CRO monitoring, and it wouldn't be an efficient use of our time to look at studies already monitored by industry."

The reviews are called RISE for Research Investigator Start-up Education, and they've helped prevent problems, especially for less experienced investigators because they're typically held very early in a study.

Since the review process was enhanced and improved with checklist tools, the office has not found as many significant issues in ongoing research, Kern notes.

"That's ended up increasing the morale in our office because we're not dealing with as many negative issues," she says.

Also, RISE reviews are shorter since they take place before a study has enrolled subjects. This change resulted in the institution increasing its investigations from meetings with 43 investigators in the first 10 months of 2005 to meeting with 48 investigators in the same period in 2006 and 72 investigators in the first 10 months of 2007, Kern says.

"That's a 33% increase," she adds.

This increase in reviews occurred despite a period when the support office worked with fewer staff due to budget cuts.

"So even though we had less staff, we could still make an impact on conduct of research at the university," Kern says.

Here's how the tools are used:

Use simple MS Word worksheets: "Our worksheets are merely tables in a Word document," Kern says. "We address all eligibility criteria, and then we go through the study procedures."

This process can take eight to 15 hours, depending on the complexity of the protocol, she says.

"For each meeting with the study team we have two members of our office who attend," she explains. "One of us takes primary responsibility for that meeting, and that's the person who develops the worksheets."

The worksheets are developed from the protocols and consent documents.

"We use that information to pull out all points that need to be addressed during documentation," Kern explains. "It's really what they write in their protocol, and we reinforce with them that they indicated it in the protocol."

The support office also recommends that investigators keep a running tab on all adverse events in a study, Kern says.

"We provide them with some documents to keep track of adverse events, and we do an assessment of that," she says.

Use checklists during reviews: The checklists for good clinical practice (GCP) include protocol adherence, safety monitoring, institutional review board processes, regulatory documents, subjects records, drug or device accountability and handling, and investigator involvement.

Compliance coordinators use checklists when meeting with investigators.

"What we like to do is ask them how they plan to implement their study," Kern says. "So I say to them, 'Tell me what you're going to do with the certificates from the time subjects come in to the time they're finished with study participation.'"

Compliance coordinators review the protocol and consent document for study procedures and eligibility criteria, and then they make a checklist based on these.

"Once we have those worksheets in place then we take them with us and hand them to the study team and discuss how they'll document all of those things," Kern explains. "We have templates that we make specific to each study."

The office also sends an electronic version of the templates to the investigator so they can alter and use them as needed. (See sample informed consent template.)

"Most of the time they find those very helpful in documenting everything they need to have documented," Kern says.

Each checklist has space for simple answers of "yes," "no," and "N/A."

"Each page has space for notes about findings or other things that need to be addressed," Kern says. "There might be comments that necessitate an investigator responding to a report."

Stress importance of documentation: "One of the things we try to reinforce with investigators is that if it wasn't documented then it wasn't done," Kern says. "'Let's look at your records and see how complete a story you can tell with your documentation,' so things have improved a lot."

For example, the GCP checklist for regulatory documents lists these areas of focus:

- FDA 1572 current, signed, dated, complete, correct;

- Required CVs on file;

- Financial disclosure forms completed by all listed investigators and sub-investigators;

- Protocol and accompanying instruction manual;

- Current clinical laboratory certification and normal ranges;

- Current investigator brochure;

- Documentation of all regulatory submissions (IRB, scientific review, FDA, CTRC, Radiation Safety);

- IND annual reports.

And the drug or device accountability and handling checklist includes these items:

- Records of receipt;

- Records of subject dispensing and returns;

- Records of disposition;

- Documentation of transfers;

- Storage conditions/monitoring methods per protocol;

- Drug supply agreement in place;

- Secured storage area.

"We emphasize to study teams that everything has to be documented," Kern says. "Once they grasp that process their documentation is much better."