Clinical Research Emergency Response Guide

First, let’s give a solid background to all CRC, CRA or institutional quality control positions who have just taken on projects: there has never been a standardized universal SOP for emergency response in clinical research, and the core principles are only three sentences.—— First ensure the safety of subjects, then ensure research compliance, and finally control project losses. , all the fancy processes have to revolve around these three points, and it is all in vain if they are separated from them. If you have been in this business for a long time, you will know that emergency response is like encountering a falling rock on a mountain road. It is useless even if you memorize all the traffic regulations. The first reaction is always to avoid risks first, and then go back and make up the process.

Last year, I encountered an extreme situation in a phase II new drug trial in a tertiary respiratory department: on the third day of enrollment, a subject had a fever of 39.8°C at home at night. The family directly called the PI at 1 a.m. At that time, there was no time to go through the AE reporting process and ethics filing. The PI first judged on the phone that there was a high probability of an adverse event related to the experimental drug. Regarding the incident, the first sentence was to ask the family members to go to the nearest emergency room first, with all expenses paid first, and the experimental team fully paid for it. At the same time, the CRC on duty was asked to record the treatment points by recording the phone calls simultaneously. All reporting materials were completed before 8 o'clock in the morning that day. In the end, the subject's fever subsided without any sequelae. During the drug regulatory inspection, no objection was raised when the record was found.

In fact, the controversy over the priority of disposal in the industry has never stopped: the quality control posts of many institutions have to leave traces first and then dispose of them. They are afraid that the timeline will not be correct during follow-up inspections. If they really want to be held accountable, it will all be the fault of the front line.； But most of the researchers and CRCs who spend time in the department tend to save people first. After all, if the subjects are really harmed, no matter how perfect the traces left are, they cannot withstand ethical accountability, and they may even face administrative penalties. In more than a dozen projects that I have worked on, there are both options. After going through the pitfalls, I have also figured out a balanced method: most of the time, disposal and traces can be done simultaneously. The whole process of telephone reporting is recorded. Materials that need to be signed must be video-recorded first, and all written procedures must be completed within the next 24 hours. Both parties can basically cover it.

Don’t think that emergencies are all bad things related to subjects. I know at least three people in CRC who have come across experimental materials. Last year, a girl from the oncology project put experimental drugs in the department's public refrigerator. The cleaning lady thought they were expired waste drugs and threw them directly to the medical waste station. She was so frightened that she almost cried. Her first reaction was not to write a review, but to contact the medical waste treatment center to find the drugs. After confirming that they could not be recovered, they first checked whether the existing stock was enough for the 12 subsequent subjects. If not, she applied to the sponsor overnight for a transfer, and reported the situation to the institution and ethics explanation the next day. Regarding the reporting threshold for abnormal test materials, there are now different opinions: the foreign sponsor's SOP is so stuck that even if a placebo is missing, it must be reported at the national level. ； Most domestic domestic companies are flexible. As long as they confirm that they have not been misused or leaked from the hospital, and internal rectification has left traces, it is enough. My personal suggestion is to follow the most stringent approach. Over-reporting is better than under-reporting. If an under-reporting is really detected, the fine will be much higher than the cost of going through the process.

Oh, by the way, there was also an emergency last summer. The hospital was suddenly notified of an eight-hour power outage. The backup generator was only enough to supply the ICU and wards. The constant-temperature refrigerator storing the experimental drugs was about to overheat. Several members of our project team carried transfer boxes at minus 20 degrees Celsius and ran to three adjacent areas. The hospital looked for a usable scientific research refrigerator, and finally transferred more than 200 test samples and drugs 10 minutes before the temperature exceeded the standard. At that time, there was no time to go through the cross-hospital material transfer approval, so we had to save the things first, and the teachers at the institution fully understood the need to apply for reimbursement afterwards.

I always keep an emergency kit in my office drawer, which contains the printed phone numbers of the PI, ethics, institution, and sponsor contacts of all projects, as well as a blank AE record sheet, a quick-drying pen, and even two antipyretic patches and mints. If you have to deal with emergencies in the middle of the night, you will know how devastated it is when your phone is out of battery and you can’t find a contact or even a pen. When communicating with anxious family members, passing a bottle of water can calm your mood half way.

Finally, I have to say something heartfelt. If you have been in this business for a long time, you will know that all the guidelines and SOPs are prepared for routine situations. You never know whether the next emergency situation will be that the subject secretly feeds the experimental drug to the dog at home, or the express delivery is stuck on the road during a typhoon and the supply of the experimental drug is cut off. Grasping the three core principles, don’t panic and don’t hide anything when something happens, is much more effective than memorizing a 100-page process manual. Oh, by the way, remember to order yourself a cup of iced milk tea after taking care of everything. Staying up late to deal with emergencies is really exhausting.