The latest revision of clinical research emergency response guidelines

The first is to refine the protection of subjects' rights and interests from principle requirements to implementable operational indicators. The second is to add new handling specifications for parallel scenarios of public health emergencies and ongoing clinical studies. The third is to clarify the boundaries of powers and responsibilities for cross-regional emergency response in multi-center research. The remaining scattered adjustments are made to complement these three core needs.

A while ago, when I was conducting training on the new version of the guide for CRCs and CRAs in my organization, many people's first reaction after flipping through the guide was "Finally, I no longer have to read the vague terms of the old version." The previous old version was like a general instruction manual with no applicable scenarios. It seemed to mention everything. When it came time to use it, you had to guess by yourself. Last month, a trial of a targeted drug in the oncology department of a tertiary hospital in the south fell into the pitfalls of the old version: the enrolled subjects were infected with the respiratory syncytial virus that was prevalent at the time. The researchers were not sure whether this was a trial-related adverse event. They had a three-day feud with the sponsor, which delayed the subjects' medical insurance reimbursement. In the end, the ethics committee came forward to coordinate and solve the problem. If we look at it now, the new version of the guidelines directly clarifies that "mandatorily reportable infectious diseases during epidemic periods will not be included in the SAE association category unless there is clear evidence of a causal link with the experimental drugs/interventions." There would be no room for such wrangling.

When it comes to the most controversial hierarchical reporting rules in this revision, the attitudes of the two types of practitioners I have come into contact with are completely opposite. Most institutions and ethics teachers agreed with their hands. In the old version, whether the subject had eaten bad and had diarrhea for two days, or had anaphylactic shock and needed to be admitted to the ICU, complete reporting materials were uniformly required to be submitted within 24 hours. Many people got up in the middle of the night to fill out the form, and the prime time for disposal was delayed a lot. However, many quality management personnel of the sponsor are a little panicked. After all, the previous unified time limit was stuck. As long as you click and report, there will be no compliance problems. Now you have to judge the level of the event by yourself. Extremely critical events must be reported within 2 hours. Ordinary events can be relaxed to 72 hours. If you judge the level wrongly, you will still be punished. In fact, the revision team has already considered this concern. The appendix directly includes grading examples of 12 common emergency scenarios, which can basically cover more than 90% of daily situations. If you are really unsure, you can call the ethical 24-hour emergency contact number to determine. It is not as easy to get into trouble as everyone thinks.

There is also the most troublesome issue of "fighting between rights and responsibilities" in emergency response in multi-center studies in the past. The new version also gives a clear explanation: regardless of whether the subject is currently at the enrollment center, first find the nearest medical institution with clinical research emergency response qualifications for treatment. The local clinical research institution is responsible for connecting with local ethics, medical insurance and other processes. The leading center no longer needs to conduct remote command across regions. It only needs to wait for the subject's vital signs to stabilize before completing the materials and following the follow-up process. I encountered a terrible incident last year. A type 2 diabetic patient who was enrolled in the group traveled to Xinjiang and suddenly developed ketoacidosis. According to the old version of the guideline, it was best to return to the Shanghai hospital where the group was enrolled for treatment. The patient’s family almost quarreled with the CRC we coordinated on site, and finally received special approval before being treated in the local hospital. If we put it aside now and just follow the new version of the requirements, there would be no such contradiction at all.

There is another small detail that is easily overlooked. This revision has clearly written the "right to know of the subject's family" into the process. The previous version only said that the subject should be informed. If the subject is comatose or loses consciousness, it is up to the researcher to decide whether and to what extent the family should be informed. Now it is directly clarified that "when the subject loses the ability to make independent judgments, he must inform the legal guardian/close relatives of the treatment plan as soon as possible, and the notification related to the trial shall not be concealed." This is equivalent to reducing the responsibility of the researcher.

To be honest, the core logical change of this revision is actually to reverse the previous priority of "protect compliance first, then protect people". All adjustments are to put the safety and rights of subjects first, and then make up for compliance. Of course, some colleagues complained that some clauses are still too rough. For example, special emergency scenarios for clinical research on rare diseases and clinical research on medical devices have not been listed separately. However, the revision team also made it clear that supplementary versions will be updated every six months. Feedback can be provided at any time on problems encountered in actual operation. It is much more practical than sticking to old rules that have not changed much in more than ten years.