February 5, 2018
At some point, we have all had to make hard decisions to remedy an issue impacting an important process. Whatever the circumstance surrounding the decision, personal or professional, borne of opportunity or duress, the decision will create some degree of hope or discomfort for those involved.
The field of clinical research is no exception. Every study leader, clinical research associate (CRA), investigator or study coordinator who cared about making the right decision, has made that hard decision; whether to protect a study patient, to address conflict at study sites or within study teams, or when dealing with questionable data the decisions with consequence.
When I was a relatively new CRA, I was faced with a very difficult decision. It was the right decision, but there were consequences. Over 10 years ago I was assigned to help monitor a global dermatology study that had experienced high CRA turnover. The investigational sites had continued to enroll patients without regular monitoring visits, and a large amount of screening/enrollment/visit data lay unreviewed. The imminent priority was to quickly retrieve the latent data and get the sites back on a regular monitoring schedule.
I completed a series of focused, one-off monitoring visits at sites that had not had a monitoring visit in months, and felt understandably neglected by the study team. Though they were bursting at the seams with accumulated data and study drug, they were not always motivated to fit me in for a last-minute monitoring visit.
I was instructed by the project manager to conduct a high-priority monitoring visit at a dermatology practice in the southeast. They had enrolled five new study patients and had replaced their study coordinator in the time-period since their last monitoring visit. It was, therefore, critical to visit the site to review data and verify their continued capability for study conduct.
I contacted the study coordinator, introduced myself and apologized for the lack of appropriate monitoring. I explained the importance of visiting the site as soon as possible to retrieve the study data and assist the site with any issues or questions they had. The study coordinator was surprisingly sympathetic and accommodated a two-day monitoring visit for the following week.
When I arrived at the site, the study coordinator escorted me to a monitoring room overwhelmed with study records and disorganized regulatory binders. I began review to the informed consents and screening data for the newly enrolled patients. The central IRB approved consent form required investigator signature, in addition to signature of the “individual obtaining consent.” To my dismay I discovered that the investigator had neglected to sign any of the informed consents; this important action was overlooked for all new patients.
After reviewing patient data, and discovering many protocol deviations, I began the cumbersome task of drug accountability. The site had enrolled a total of 15 patients, and drug accountability had not been completed in months. Study drug and matching placebo were packaged in blister packs, and used/returned drug had been piled into a corner of the room. It was a daunting task to try and reconcile drug accountability log entries with returned study drug when the accountability logs were missing entries or had indecipherable data; some entries had been crossed out, or changed, but were missing the required initials and date of the individual making the change, and thus could not be authenticated.
The final straw was a missing shipment of study drug from a locked drug storage room. The study coordinator assured me that all used study drug was in the monitoring room and unused study drug was safely locked in the drug storage room. The site had received 10 kits of study drug that I could not locate. I checked every inch of the IP storage room and the box of returned blister packs with no success. I could not even find the drug requisition form to confirm the site had received the drug. Puzzled, I decided to ask the study coordinator for help, but when I called her she did not answer her phone. When I walked to the lobby to ask the receptionist to page her, I could not believe my eyes. The missing blister packs had been placed alongside the regular commercial drug samples, on open shelves in the practice lobby. There was no separation from investigational product and commercial drug and it was the antithesis of secure, limited access.
I left a note on the study coordinator’s desk, requesting her to find me upon her return, and returned to the monitoring room with a sinking feeling. This was the worst situation I had ever encountered as a monitor. It would take much more than a two-day monitoring visit to get this site back in shape. Though it was a difficult decision, I knew I had to speak to the investigator about the findings and escalate immediately to the project manager. I was not looking forward to the difficult conversations the severity warranted.
When the study coordinator returned, I informed her of the informed consent, and data and drug accountability findings. I showed her the location of the study drug shipment and advised her to move it to the storage room as soon as possible. Her defensive response lacked concern and initiative. She blamed her predecessor for the problems and even took a personal phone call in the middle of our conversation. So much for the anticipated teaching moment.
My discussion with the investigator was equally fruitless. He only had 10 minutes to spare between his afternoon clinic patients and maintained an unreadable expression while I recounted the findings. Before my recommendation for corrective action, his cell phone buzzed and he rushed out of the room with a patient emergency. He requested I email him the remaining items for discussion. While I had avoided an unpleasant conversation, his lack of response belied a level of apathy that was much more concerning than any confrontation would have been.
That was the moment I knew I needed to contact the project manager as soon as possible to escalate my findings. It would take two to three monitors and at least a week on site to get through the rest of the patient charts, drug accountability and issue resolution, and that was only if the site were not enrolling patients. The investigator was clearly an absent leader who left study conduct to an overwhelmed, inexperienced study coordinator. The sponsor could decide to halt enrollment at the site through the cleanup period, or close them altogether. I could survive the knot in my stomach, with potential site reaction. But making the easy choice to avoid the difficult conversations, and letting the project manager talk to the investigator, was no choice when it involved patient safety and data quality.
Elizabeth Blair Weeks-Rowe, LVN, CCRA, has spent nearly 14 years in a variety of clinical research roles including CRA, CRA trainer, CRA manager and clinical research writer. She also is author of the novella Clinical Research Trials and Triumphs. Currently she works in relationship development/study startup in the CRO industry. Email firstname.lastname@example.org or tweet @ebwcra.