Clinical Research Emergency Response Guide

Always put the safety of subjects first, flexibly adjust disposal actions within the compliance framework, take into account the integrity of research data, and ultimately minimize risks. Any approach that disregards the safety of subjects and talks about compliance, or completely ignores the rules will cause big problems in the end.

Last year, when I was working at a phase II oncology trial site in a tertiary hospital in Jiangsu and Zhejiang, I encountered a textbook emergency: at around nine o'clock on Friday night, less than ten minutes after receiving the trial drug on the third day of enrollment, a subject suddenly broke out in red rash all over his body and his blood pressure dropped to 80/50. He couldn't stand on the spot and fell into the arms of his family members. At that time, the site CRC returned to his hometown after get off work, and the PI was unable to make it back from the annual meeting in Guangzhou. There was only a research nurse on duty who had just been transferred for half a year, and there was no one on site who could make decisions.

In the industry, there are always two groups of completely different handling logics at this time: one group is the old-school researchers who "compliance first", requiring that no matter what the situation is, they must first report to ethics and get approval before starting treatment, for fear of being labeled as "plan deviation"； The other group, mostly young PIs with clinical backgrounds, advocates rescuing people first and refining all processes afterwards. At worst, they end up recording process deviations from the plan. The nurse didn't worry so much that day. She pushed promethazine first, called 120, and simultaneously made a voice call to the PI and left a recording. While explaining to the family, she recorded the time points and dosage of the entire process in her workbook. After the subject was sent to the emergency room and the condition was stable, she sorted out the materials overnight and reported them to the ethics and sponsor. In the end, nothing happened. No one was delayed, and no compliance red line was touched.

To be honest, not all emergencies require ethical reporting. I have encountered a novice CRC before. The subject had a slight rash after joining the group. It was an expected mild AE listed in the protocol. Applying some ointment on her own was enough to cure it. However, she was so nervous that she wrote a report and asked the PI to sign it. She also made three phone calls to the subject to repeatedly confirm the symptoms. In the end, the subject was frightened into thinking that she had suffered serious side effects and had to withdraw from the group, thus losing an effective case. To put it bluntly, the first prerequisite for emergency response is that you must first understand the level of the incident: if it involves life safety, you must respond in seconds. It is just a small issue of data recording and material management. Just follow the process. There is no need to scare yourself.

In addition to SAEs related to the subject's health, many seemingly "non-fatal" emergencies are actually bigger pitfalls. Last month, the experimental refrigerator of a center in Northeast China tripped in the middle of the night. The administrator was off duty over the weekend and did not receive the alarm. Only when he came to work on Monday did he discover that the 42 batches of experimental drugs stored in it had been left at room temperature for 36 hours. At that time, the sponsor's CRA's first reaction was to directly scrap the batch of drugs. All 12 subjects enrolled in the study were considered to have dropped out, and the data was scrapped. ； However, the PI of the site disagreed, saying that the accelerated stability test of this batch of drugs showed that it could be stored at 25°C for 48 hours. It was completely possible to send samples for testing first, and continue to use them if there were no problems. The final test results came out and indeed met the standards. It did not delay the subjects' medication, and also preserved nearly one million research data. At this time, the professional accumulation of all parties is tested, and sticking to the provisions of the plan can sometimes cause unnecessary losses.

Many centers don't take emergency preparedness seriously at all. When I went to check, I saw that the emergency kits at many sites were just decorations. The epinephrine in them had expired for almost a year. The key to the rescue vehicle was placed in the head nurse's drawer, and no one could open it when the head nurse was on vacation. Last year, our center held an emergency drill and simulated a subject suffering from anaphylactic shock. Halfway through the drill, they found that they could not find the key to the rescue vehicle. Everyone was sweating with anxiety. After that, we directly pasted the key on the wall next to the rescue vehicle with hot melt glue and put a seal on the outside. In emergencies, we could just tear the seal to get the key. This problem has never happened again. There is also a list of emergency contacts. Don't just print it out and post it on the wall. It is best to have a copy in everyone's mobile phone, including the PI's, the ethics secretary's, 120's, and the sponsor's medical inspector. If something goes wrong, it will be more life-threatening than not being able to find someone.

The industry has been quarreling for several years about recording afterward: some people asked that everything be recorded in detail, including who made the call to 120 and how long the call lasted, otherwise the record would be considered incomplete.； Some people think that there is no time to remember so much when rescuing people. As long as the core time points, handling actions, and medication dosage are correct, it will be fine. Other minor information can be made up later. My personal experience is to remember the key information first. If you really don’t have time, you can record the voice first, and then compile it into a written record when things are stable. But you must not make it up afterwards. Just write what you did when you did it. Even if there are really irregularities in the process, it is better to write it truthfully than to falsify it, which is a direct red line.

In fact, after all, this guide and that guide are not as useful as the experience accumulated by practicing twice more and stepping on a few more small pits. Clinical research itself is full of uncertainties. It is impossible for all situations to go according to the plan. If the core bottom line is maintained, the rest is to be flexible. Don’t stick to the rules and don’t mess around. Basically, there will be no major problems.