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Compliance Best Practices Research institute establishes best practices in preventing trial mistakes
Use comprehensive corrective action plan
Research institutions need a best practice plan for preventing and handling regulatory issues whether they have 50 or 500 new studies a year.
"As with most institutions that have a lot of investigators, we have seasoned investigators and newer investigators," says Marion Olson, CIP, CCRP, supervisor of human research regulations at the University of Texas M.D. Anderson Cancer Center's Office of Protocol Research (OPR) in Houston, TX.
There were issues, so the institution's IRB office developed a corrective action plan (CAP) template that outlines compliance issues and lists steps taken to address those issues. (See table on reasons for implementing a CAP, below.)
Multiple reasons why sites should use a CAP
Non-adherence is # 1
There are many reasons why clinical research sites should use a corrective action plan (CAP) and keep a CAP process and template on hand.
Experts at the University of Texas M.D. Anderson Cancer Center in Houston, TX, offer this list of reasons for implementing a CAP:1
Non-adherence to the study design1
Lack of timely reporting1
Incomplete consenting processes1
Documented and inadequate management of conflicts of interests1
"Departments were struggling with what they should include in a CAP, and they were having difficulty with identifying a focus, so we saw a need," Olson says.
For instance, clinical research sites and investigators were writing corrective action plans that were not as comprehensive as the IRB required, says Wanda Quezada, CIP, CCRP, manager of human research regulations.
Compliance issues both minor and major needed to be addressed more consistently.
Minor problems could be an investigator having repeated patient visits outside the window detailed on the protocol. Or there could be major issues involving safety procedures, says Evanna Thompson, MPH, CIP, supervisor of human research regulations.
A CAP template provides a structure for dealing with any kind of research compliance issue. So the Cancer Center's human research regulations staff created a CAP template that could be used by investigators when compliance issues arise and also as a way to prevent problems.
"We wanted to be proactive and provide an educational tool for investigators and research staff, as well," Thompson says. "It's not mandatory, but we strongly guide or encourage our investigators because everyone wants to be compliant."
Investigators that choose to use the CAP also might find that they become more efficient with their time and resources, Thompson says.
The OPR staff discussed the CAP template at departmental grand rounds, which were attended by mostly departmental research staff, Olson notes.
"The departments would see there was a need, and they'd invite us to go to these grand rounds to present it and assist their department with implementing it," she adds.
Also, they presented the CAP template at OPR brown bag sessions, which typically have 160-200 attendees. They're held each Monday from 12 noon to 1 p.m.
"We announce new and updated policies and procedures at the brown bag sessions," says Marci Montemayor, CIM, supervisor of human research regulations.
"We also provide departmental training, new research staff training, and education for IRB-noncompliant investigators and research staff," she adds.
When departments first use the CAP process, human research regulations staff will ask to be included in their first working group meetings so they can answer any questions investigators might have about the development process, Quezada says.
"The investigators also work closely with our auditing groups," she adds. "We are all very accessible; the auditing group administers a research support clinic that is open once or twice a week, and principal investigators can go in and sit with staff one-on-one."
There is also a 24-hour helpline that goes directly to Quezada's pager after hours.
Since implementing the new CAP process, the IRB has had only minor suggestions that need to be implemented on studies with compliance issues that were handled through a corrective action plan, Olson notes.
"In the past PIs would submit a CAP that was not approved by the IRB, so the CAP template has been pretty helpful," she adds.
The new process also has built-in monitoring.
"We ask the departments to give progress reports on the CAPs," Thompson says. "They should be monitoring things to make sure the goals outlined are being met and achieved, and, if not, then the CAP may need to be revised."
Here is how the CAP process works:
Access:Compliance problems typically are identified during an audit or monitoring visit. When this happens, the research site begins a comprehensive correction action plan, beginning with an investigation of the problem.
For example, the compliance issue could be that the site is missing blood draws on day 2 of the cycle. The investigation would determine how many subject visits were impacted, Olson says.
If an audit found that five out of 20 patients had missed blood draws, then this becomes a trend and a potential significant issue, she adds.
Evaluate: The goal here is to conduct a not-for-cause analysis by identifying criteria, condition, and cause.1
For instance, it could be that patients do not arrive at the clinic on time and miss their blood draw appointments. Or maybe some of the patients live out of town and have difficulty coming into the clinic, Olson says.
The cause could relate to the lab never receiving the blood draw order, she adds.
Part of the evaluate phase of CAP is to analyze the compliance problem's impact on the research.1
"Maybe it's not a safety concern," Olson says.
Assign: "Establish who is accountable for that problem," Olson says. "Assign and identify the person who could affect the change."
This would be anyone who is familiar with the research, including be the principal investigator, who could say whether the blood draw really is necessary and eliminate it if it's not needed, Olson says.
Or there might be other collaborators with the study who need to discuss ways to prevent this problem from happening again, she adds.
Devise: "When devising measurable outcomes you look at what's happening and try to get a plan in place," Thompson says. "Look at the different roles and responsibilities of each person on the protocol."
As part of this phase, a research site would use internal controls, such as policies, training, and segregation of duties.1
"Look at the different roles and responsibilities of each person on the protocol and decide what's going on," Thompson says. "You can put more checks and balances in there, such as having another research nurse come in and make sure orders are in."
Or the PI could look at the scheduling to make sure patients are scheduled every hour instead of every 30 minutes, or they could contact the lab where the blood is drawn.
CR sites also could use a delegation log to define staff roles and responsibilities.1
Design: In the design phase, a CR site would create a list of required tasks, set reasonable expectations and time frames, and seek IRB approval prior to implementation.1
"You would meet with department heads and figure out how to place those resources so the problem won't happen again," Thompson says. "Then submit the plan for IRB approval."
It's important to create a plan that is practical and will use only the amount of resources a CR site has readily available.
"We tell PIs, 'Don't put something down that looks good on paper that you can't carry out,'" Thompson explains. "So if you can't allocate space for extra nurses, don't write down that you can hire extra staff."
Monitor: The purpose of the monitor phase is to verify and assess the CAP's effectiveness, revising if necessary.1
Also, CR sites should schedule periodic meetings to discuss progress and deliver reports to accountable owners and the IRB.1
Once the CAP design is sufficient and implemented, it should be monitored by an IRB, compliance officer, or QA department.
"You can monitor this every 12 weeks or six months, depending on findings and whether more frequent monitoring is needed," Thompson says.
Measure: The last phase involves measuring outcomes to see whether the objectives were met.
In this final stage, a CR site will also verify that the recommended changes have been completed, that training was implemented, and whether there have been any adverse events.1
"This is the chance for the department or PI to say, 'Have we met the goals of the CAP, or are problems still occurring?'" Quezada says.
If problems continue, then go back to step one, she adds.
"When the procedures put in place don't work, we ask the PIs or departments to report this to the IRB," Quezada says. "Also, the departments have to conduct internal audits and should assign a quality assurance person to go through and say which is working and which is not working in a protocol."
M.D. Anderson has a quality assurance person who monitors the IRB and PI regulatory files to ensure compliance with federal regulations, Quezada notes.
"Even while we preach the CAP process to investigators and departments, it's important for the IRB to have its own internal monitoring process to make sure we're practicing what we preach," she adds.