Compliance Corner: Deal with noncompliance before it reaches the FDA
Deal with noncompliance before it reaches the FDA
Former FDA auditor offers insider tips
The main causes of research noncompliance result from investigators, research staff, and industry sponsor staff misunderstanding or having difficulty interpreting regulations, says a former FDA investigator.
While the average FDA investigator spends a year learning about the regulations and the law, the average clinical trial monitor receives maybe a three-day class, says Tamera Norton Smith, PHD, MT(ASCP), president and senior consultant of Norton Audits Inc. of Lexington, SC. Smith has spent 17 years in medical research compliance and began her career with the FDA as a federal investigator.
"I go inside of sponsor companies and find executive level managers who can’t answer basic law questions," she says.
Clinical trial sites, sponsors, and site monitors could greatly improve their ability to audit a clinical trial site’s compliance and prevent problems that may occur during an FDA audit by following a few important steps, Smith notes.
Here are her suggestions:
1. Develop a corrective and preventive action (CAPA) plan.
CAPAs are necessary for conducting and documenting internal activities for constant compliance assessment of clinical trial research. Norton Audits has a mock CAPA program’s standard operations procedure (SOP) for clinical investigators available for a free download on its web site at www.nortonaudits.com.
Norton Audits also has created a clinical investigator’s corrective action resolution form, a CAPA assessment plan, an issue completion tracking log, and a CAPA assessment tracking log. (See sample compliance tools, above and inserted in this issue.)
"We find during the auditing process that the average monitor is pretty good at identifying errors within a monitoring process, but not very good at making sure their researcher can correct those errors," Smith says. "So when the agency comes in and inspects that position, we often find that those errors have stayed for the duration of the trial, which could impact data or patient safety and reflect poorly on the sponsor."
Sponsors typically use a memo or note to file when errors are found; and while that’s a red flag, it doesn’t correct the problem, Smith notes. There has to be a system to find problems and to teach compliance monitoring to staff, she adds.
2. Write SOPs.
Norton Audits provides training services to the FDA’s Center for Devices and Radiological Health’s Division of Scientific Investigations, as well as to research sponsors and clinical trial sites, and part of its efforts have included developing SOPs to improve compliance quality, Smith says.
The research industry is handling compliance incorrectly, she notes.
"We put a lot of money into education, and we’re not really getting the results," Smith says. "In fact, noncompliance is worse than it has been, which is why we’re trying to get these skills out there and are teaching people how to read the regulations."
For example, the SOPs developed for CAPA includes 15 procedure steps that must be followed, including these examples:
• All clinic research team members can be delegated to in various aspects in concert with their experience, training, and qualifications to achieve ultimate compliance outcomes.
• All monitoring letters received from sponsors or contract research organizations, which identify issue(s) that need to have corrective actions, will need to have a CAPA form completed and issues resolved prior to the next monitoring visit. When issues are ongoing or potentially incorrectly reported in the monitoring letter, the CAPA form should reflect that the issues(s) continues to be open and still is being resolved.
• All CAPA forms are reviewed, signed, and dated by the individual preparing the form and approved by the clinical investigator.
3. Educate and train staff about regulations.
The first step in training staff is to go over the regulations and provide realistic interpretations for what is expected of clinical trial sites with regard to compliance, Smith continues.
"Secondly, we teach skills for setting up a proper infrastructure in a company to be based on quality systems," she explains.
For instance, the infrastructure should include a definition of noncompliance because if it’s not defined in the procedures, how will staff know whether something is in compliance, Smith points out.
"You want them to break apart the procedures and say, In this process where we do informed consent, what are all noncompliance issues that happen in this area?’" she says.
This process may require regulatory changes so the research industry could see regulations that more clearly define and describe noncompliance, Smith notes.
"We’re working with the Center for Devices on this issue," she says.
4. Teach staff how to audit.
"From what we see in the industry, the problem is the average auditor and monitor are doing what I call the practice of inventorying," Smith says. "They look at the case report form and medical chart and compare the two."
That’s not a true audit or an adequate way to monitor compliance, she notes.
"That’s not challenging a record," Smith says.
Sites should train staff to conduct true audits, which include multiple cross-checking of records, she explains.
"They need to know the difference between what is a true source record vs. a transcribed record, which is the anchoring of knowledge," Smith says.
Calling it the Norton method, she says there are a set of skills that need to be developed before a true audit can be performed.
For example, a site has a source medical record that is missing certain entries, Smith adds.
"You have the master drug record, and you can tell it was filled out after the fact; and you have the actual drug product that was returned from the patient," she explains. "And you have to figure out which is the most accurate representation of fact — the medical chart or what came back from the patient?"
The answer likely would be the actual drug that came back from the patient, and that’s what is called anchoring, because it’s the most accurate representation of facts, she says.
5. Work on improving staff’s interviewing skills.
If you have ever wondered how an auditor with the FDA was able to find out so much more than what a research organization volunteers, then the answer is here: It’s because they’re taught interviewing techniques that include paying strong attention to nonverbal cues.
"The average FDA investigator receives training in interviewing, interrogation, and body language," Smith notes. "The paperwork trail tells you one story, and how a person operates tells you another story.
"For example, say I’m doing an interview for a sponsor of a contract research organization involved in the training process, and I ask them how they train monitors, what their important selection criteria are. The training manager tells me how they have a good training process for monitors, but I looked at the records and wasn’t too impressed by the paperwork," she adds.
So the decision boils down to the one-on-one interview.
"This is a good time for the CRO [clinical research organization] to convince me how good their training is, and I want it to be very strong," Smith says.
Instead, the CRO representative sits at the conference table with folded arms. She’s leaning back as far away as she can from the interviewer.
"She’s almost underneath the table, and her crossed arms are telling me she’s not engaged," Smith says. "Her body language tells me a lot: She doesn’t want to be in that room and was trying to get as far away as possible, feeling very closed-in and taking a defensive posture."
Smith sees this body language and concludes the representative is very uncomfortable about sharing information about training because an honest and open person would have the arms open and be frontally aligned with expressive body language as the person discusses how great the program is and how committed the organization is to it. The representative’s body language confirms her suspicions from the paperwork that the training program isn’t adequate, and so the CRO loses that contract.
Research sponsors and even research institutions should train staff engaged in auditing and monitoring how to conduct thorough and useful interviews, Smith suggests.
The main causes of research noncompliance result from investigators, research staff, and industry sponsor staff misunderstanding or having difficulty interpreting regulations, says a former FDA investigator.Subscribe Now for Access
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