Stuart Halasz, Merck & Co., Inc., focuses on the importance of personal and group dynamics in preparing for an FDA site inspection
For clinical trial sites, perhaps one of the most stressful events is preparing for an FDA inspection. Usually the sponsor’s Clinical Research Associate (CRA) is contacted by the Study Coordinator in a panic, notifying them that the FDA has called and they are scheduling their visit (usually on short notice as described in the FDA Bioresearch Monitoring Compliance Program Guidance Manual). The first questions for the site staff are whether it is indeed an FDA inspection, or perhaps an internal IRB audit or an audit by some Sponsor company? Is it OUR study that is being inspected, or perhaps a competitor’s? If we have multiple studies placed at this site, which study is being inspected? Did the FDA mention that the inspection is routine, or for cause?
Once this has been established, preparations can begin. Who participates in the preparation, of course, depends on the interval between contact with the site and when the inspection will begin. Sometimes the sponsor may send individuals from headquarters in addition to the CRA who monitored at the site to help organize and prepare the site for the inspection. Aside from the obvious review of regulatory binders and patient charts, the site staff should also notify the IRB, the pharmacy, and other ancillary departments, and even the IT department since there may be technical questions about the Electronic Medical Records system (beyond simply granting access to the inspector).
One area that perhaps does not receive the attention it deserves is the preparation of the study staff themselves. This can be achieved by conducting interviews and role play, but it is important to probe into the personalities of the study staff. Let’s look at a few fictitious characters from the author’s experience conducting onsite inspection preparation visits.
First is Dr. Absentia, the principal investigator (PI) who was largely absent from the day-to-day study activities. This is not just another routine monitoring visit. Does he or she not realize the importance of preparing for the inspection? In some cases they are legitimately too busy to devote time for the inspection, but it is still important to create a sense of urgency by reminding them of their obligations. Some PIs only make themselves available for 10 minutes to discuss the upcoming inspection with the sponsor personnel; while others (who are much more hands-on) have “dropped everything” and required all study staff to meet as a team for several hours to go through each element of preparation.
Dr. Omniscient, on the other hand, cannot be bothered preparing for the inspection, and may have talked to an old medical school friend who gives their assurance that the inspection is “no big deal” and there is no reason to be alarmed. Another PI (sometimes due to cultural background) may be “too eager to please” and must be admonished not to answer questions about activities they did not perform during the study. For example, a PI might try to give answers about data entry or drug supply reconciliation when they did neither during the study. They must be reminded to resist this, even though their intent may be only to help the inspection proceed more smoothly and demonstrate their oversight.
The Study Coordinator(s) of course are also the key to a successful inspection. “Chatty Cathy” is the study coordinator who seems unable to keep quiet. This may be as a nervous response to the stress of being inspected, or just the result of an outgoing personality, but she needs to be coached to pause, breathe, and count to five before answering or speaking. For example, she tells the inspector, “I am so glad you didn’t show up until today because some of the binders were completely missing and the charts were a disaster. I didn’t find the one until this morning! We were here all weekend trying to organize them because they were such a mess!” In fact, she is a very conscientious and meticulous study coordinator, but her exaggerated story comes across as though the site is not as organized as it actually is. Cathy needs to be told to slow down, recognize this habit, and be reminded several times during the preparation visit about her exuberance.
“Silent Sue” is the other study coordinator who may be excellent, but is overly intimated by the inspection or is defensive when her work is questioned. She can be triggered simply by asking a question about an error she made, or perhaps reminded of the all too common interpretation of the protocol where “we were told to do it this way, and then they told us not to do that anymore. Why can’t those people at the sponsor make up their minds!” Sue is usually right to be upset, but needs to be reminded that her hostile response doesn’t help the inspection result in a positive outcome. It can also be useful to “push her buttons” a little during the inspection preparation to generate her typical reaction, while explaining to her that it is just to help her practice staying calm and objective, and not questioning her work.
Another problem area with study coordinators is “teamwork.” How? Some study coordinators have “their” patients and “their charts” and don’t like how “she does hers.” These study coordinators may work at different office locations, work on different days of the week, or just not like one another. They need to be firmly reminded that the inspector doesn’t really care who usually sees which patient or how they like the chart arranged, that everyone needs to work together and provide what is asked for. She cannot delay the inspection by refusing to make a copy from the other study coordinator’s chart. Sometimes the PI or office manager may need to be involved in setting the right expectations. Does this seem trivial or childish? Yes, but it happens.
Finally, how about the “rogue” study coordinator who no longer works at the site? While it is very convenient (albeit often factual) to blame everything on her, one needs to remind the current study staff that even though the previous study coordinator is long gone, the PI still has ultimate responsibility for the conduct of the trial. Additionally, the current study coordinator may preface her responses to the inspector that “the previous study coordinator was responsible during that time, but let me answer as best as I can.” This allows the study coordinator to not feel defensive (remember Sue earlier?) yet also does not impede the inspection. The author usually suggests that the exact dates of employment be determined and noted, so that the timeframe can be provided upon request. After all, if there are numerous references to the shortcomings of the predecessor, wouldn’t the dates of her employment be well known?
Spending some time learning the personalities of the study staff and suggesting some minor behavioral changes may seem like a lower priority than most of the other preparation activities in the admittedly hectic period preceding an inspection. However, one might argue that this is exactly the area where some small changes may have a big impact on the outcome of the inspection. After all, we already know that an FDA inspector is expected to review 100 percent of the consent forms if there are fewer than 25 patients. Is having the study staff review all the consents again going to yield a different outcome? If there are errors (e.g. the patient forgot to date the consent, or signed the wrong line) they need to have been corrected during the consent discussion, not now. If a blood draw was not done within the time frame required by the protocol, the lab requisition form and the final lab report are a permanent record of the error. What can be done now? However, interacting with the PI and study coordinators to reveal any extremes in their attitudes or working relationships allows time to suggest subtle behavioral cues which can improve how they interact with the inspector. A professional, courteous, and confident study staff that responds to questions and requests in an even-keeled manner can contribute to a more efficient and positive inspection.
*Stuart Halasz is the Associate Director, Clinical Quality Management at Merck & Co., Inc.