What are the latest revisions to the Clinical Research Emergency Handling Guidelines?

The core adjustment of the latest revised version, which has just been launched in mid-2024, is to compress the response reporting threshold for extremely severe adverse events from the original 24 hours to 2 hours. As long as a subject has a death or life-threatening adverse event, the local research institution does not need to wait for the first draft of the complete incident investigation report, and must immediately report it to the ethics committee and the drug regulatory agency. I just helped a cancer center make compliance rectifications last week. Last month, one of their subjects suffered from anaphylactic shock after taking an experimental drug. According to the old version of the guidelines, they organized a three-hour consultation to identify the triggers before reporting the matter. In the new version, it was already a timeout violation. The rectification report alone took three versions.

In addition, the cross-institutional emergency linkage of multi-center research has been directly written into the mandatory requirements this time. In the past, the risk synchronization between different sub-centers of the same trial relied entirely on the initiative of the leading PI. If center A had a serious unexpected adverse event (also known as SUSAR in the industry), center B might still be enrolled as usual. Now it is clearly required that the leading unit must synchronize the risk to all sub-centers within 12 hours, and the enrollment of the same dose group will be suspended immediately, and it will be decided whether to restart after the risk assessment is completed. There is a lot of controversy in the industry here. Many PIs feel that it is too rigid. If the adverse event is caused by the subjects taking illegal drugs without permission, blind suspension will slow down the progress of the project. However, the attitude of the regulators is also very clear. They would rather sacrifice some efficiency than put the subjects in unknown risks.

The pitfalls that have been trampled by the epidemic in previous years have also been made up this time with clear rules, and emergency handling details in force majeure scenarios have been added. Previously, in situations such as lockdowns and natural disasters, subjects were unable to follow up as planned and were unable to receive experimental drugs. Either they would be directly counted as dropouts and affect the research data, or they would administer drugs privately and risk compliance. Now it is specifically clarified that remote visits, The method of follow-up by designated medical institutions in the same city and drug distribution by local cold chain ensures the subjects' medication and follow-up. Moreover, unplanned visits under special circumstances do not count as subject dropout. Listing statistics of special cases separately does not affect the compliance of the study. When I was doing new version training for several pharmaceutical companies a while ago, this part was the most asked about it. After all, I have suffered too much in the past few years.

There is another inconspicuous change that actually has a big impact. In the past, the emergency response archiving requirement only covered the incident itself and the results of the treatment. Now it is required to leave traces of the entire process of communication with the subjects. Whether it is a phone call to inform about risks, recordings of discussing compensation plans, or communication records on WeChat, they must be archived together with the research data to prevent subsequent disputes without basis. However, some ethics committee teachers have raised concerns that if the requirements are too strict, researchers will have concerns when communicating with subjects and will not dare to speak too truthfully. Now many institutions are also exploring ways to balance the two sides.

Overall, this revision does not have any vague requirements. It is all based on the problems that have been encountered in the industry in the past few years. We now conduct SOP training for newly established projects and have embedded these requirements into the daily process to avoid stepping on red lines when something goes wrong.