Keeping an Arrhythmia Trial in Perfect Rhythm

Monitoring a clinical research study requires more than comparing case report forms against medical records. The fate of an entire clinical trial may rest upon a clinical research associate’s less apparent skills. The diligence, professionalism and exceptional communication skills of an experienced clinical research associate may be needed to salvage a critical situation. This was one such situation where the clinical trial sponsor wisely insisted on an Emissary clinical research associate to monitor an important clinical trial.

In developing a new arrhythmia drug, a pharmaceutical company awarded its Phase III program to one of the international publicly traded contract research organizations (CROs). Shortly after the project got underway, the client requested that a number of the most impor­tant clinical research sites be re-assigned to Emissary, even though the 1,000-em­ployee CRO has a dedicated cardiovascular department. The sponsor argued that the project warranted certain skills and a level of ex­perience that is not typically found in the monitoring staff of a large contract research organization. This decision proved to be a good one.

As one of the last pivotal trials was winding down, David, an Emissary Clinical Research Associate (CRA), was given the task of closing out one of the largest and most critical sites in the trial. When he called the investigator to schedule the monitoring visit, David was told that the site was abruptly closing their doors and the investigator and his study coordinator wife were moving out of the country. The dubious situation called for swift action.

Although this particular protocol was being closed early, the subjects were to be rolled-over to a new protocol. An interim analysis had demonstrated an unexpected need to evaluate a higher dosage level. The sponsor now needed to get the higher dose study completed quickly; losing the thirty-five subjects at this site would mean a major delay in this pharmaceutical company's overall clinical development plan.

The logical answer was to transfer these subjects to another site. Unfortunately, the closest site was several hours away. Even worse, that site was already short-handed and did not want the burden of additional subjects.

Luckily, David was the monitor there as well and he had established a good working relationship with the site. By carefully explaining the extreme importance of keeping these subjects in the trial, David was able to make a convincing argument to this other investigator. David also arranged for the sponsor to sweeten the deal by funding an additional coordinator. To reduce the inconvenience to the study participants, David even helped arrange for chartered bus transportation.

Next, David needed to conduct the closeout visit. Unfortunately, communication with the site became difficult as the clinic staff were in turmoil over the investigator's recent unexplained actions. David made many attempts to contact the site, but received no reply. Finally, he received a phone message from the investigator agreeing to a visit, but delaying it until only a few days prior to the investigator’s departure from the country. Additionally, the investigator stated he could only allow a brief meeting. Under normal circumstances, the workload would have required a week to complete.

Anticipating complications, David arranged to have an ad­ditional member of the monitoring team attend the visit. He also made it clear to the investigator and coordinator that this would be an extremely important visit and would require their full attention and cooperation. He laid out the multiple tasks that must be accomplished to closeout the study and transfer the subjects and their medical records to the new site. He then sent a confirmation letter.

Arriving on-site at the agreed time, David was greeted with a distressing message: the investigator and coordinator were too busy to meet with him. Clinical research associate praiseQuickly extending his trip, David tried repeatedly over the next several days to get an audience with the investigator and his coordinator. He knew that the pair had a flight departing soon, and if he failed, the data from this site would be unevaluable: the 35 subjects would be lost and the overall development timeline for this new drug would be delayed.

Finally, after much persistence including a phone con­versation with the Investigator at midnight, the coordinator (his wife) agreed to set aside a few short hours of her time to address the many issues. Amazingly, David and his assistant were able to resolve the many queries on the case report forms, close out the study, deter­mine disposition of all materials and study medication and ship all of these items to their designated locations, all within the coordinator’s unreasonable time limit.

Through professionalism, persistence, and some ingenuity, this Emissary Clinical Research Associate was able to resolve an extreme situation. As a result, the site was properly closed, the subjects were successfully transferred, and the sponsor was ultimately able to meet their critical deadline.