The latest emergency response guidelines for clinical research

The latest version of the core guidelines for clinical research emergency response is an integrated version of the "Technical Guiding Principles for Emergency Management of Drug Clinical Trials" issued by the Center for Drug Evaluation of the State Food and Drug Administration in March 2024 and the practical consensus of the domestic GCP alliance. The core logic overturned the previous rigid requirements of "one-size-fits-all suspension of testing and full-process reporting" and clarified the three priorities of "priority of subject rights, adaptation of hierarchical response, and data traceability". At the same time, public opinion response and cross-agency collaboration were included in the legal emergency process for the first time.

Last month I was doing an inspection at the Phase I clinical center of a tertiary hospital, and happened to encounter a superimposed emergency incident: a patient with advanced lung cancer suffered a high fever of 40.2 degrees 2 hours after infusion of the experimental drug. At the same time, the cold chain cabinet of the pharmacy's experimental drug suddenly lost power due to a circuit failure. The cabinet contained monoclonal antibodies from the same batch worth more than 3 million yuan. Switching to the old guidelines before 2022, the first reaction when encountering this situation would definitely be to suspend all enrollment, then report it step by step, and wait for ethics approval before handling the follow-up. However, the CRC at the center did not panic that day. According to the grading rules of the latest guidelines, it was divided into two things: the patient first went through the SAE emergency process. , he was first pushed to the ICU for observation, and at the same time, the medicines in the cold chain cabinet were transferred to the spare cold chain box prepared in advance. The two things were done in parallel, and it took less than 40 minutes. Later, it was determined that the patient's high fever was his own cancerous fever and had nothing to do with the experimental drugs. The enrollment was not stopped during the whole process, and no drug loss was caused. It was unthinkable before.

In fact, this adjustment of the guidelines was finalized after the industry argued for three or four years. In the past, most of the institutions affiliated with universities were conservative and thought that they would stop everything if they encountered SAE. After all, compliance risks are a top priority. However, biotech companies doing innovative drugs have particularly strong opinions: if a phase I trial is suspended for three months, the subject subsidy and center operation and maintenance costs alone will cost millions. If a small company has difficulty in financing, it will be directly delayed. The latest version of the guidelines is equivalent to a concession from both sides: emergency incidents are divided into three levels. Only when there are 3 or more cases related to SAE, experimental drugs have major safety risks, or when there is force majeure such as earthquake epidemics, all reports need to be stopped; single cases are not Second-level emergencies such as SAE-related and single-point equipment failures only require partial processing and reporting to the organization for filing; if it is just a third-level minor issue such as EDC system downtime and missing items in ICF signatures, there is no need to report it, and it will be rectified within 24 hours to leave traces.

To be honest, I have seen too many teams in a mess during emergencies. Either they can’t find the ethics contact’s phone number, or they can’t find the ice cubes when the cold chain is out of power. I would say that before starting each project, it is best to prepare a palm-sized emergency kit in advance. It does not need to be complicated: put in the SAE blank reporting template with the institutional seal, 24-hour ethics and sponsor contact cards, 4 pre-frozen ice cubes, and several green channel cards for subjects. When something happens, it is more useful than flipping through 100 pages of SOPs.

Of course, the current guidelines are not perfect, and there are still many debates in the industry. For example, regarding the time limit for supplementary recording of EDC data in emergency situations, most institutions in the north require that the data must be completed within 24 hours, otherwise the data will be considered falsified. However, many institutions in the south feel that as long as there are paper traceability records, it is no problem to complete the supplement within 72 hours. This time the guideline is not stuck. It only says that "with traceability as the core, each center is allowed to adjust according to the actual situation," which is equivalent to giving room for practical operation and leaving room for controversy. There is also the response to public opinion from the families of the subjects. Some institutions think that as long as they are well-informed, there is no need for special contact. However, for the rash incident I encountered last time, the family members originally wanted to take a video and post it online. This is because we set up a dedicated family contact person in advance. We were on site within 10 minutes and showed the recovery records of similar subjects. We also arranged a free dermatology consultation, which was solved on the spot. If we had followed the previous rules and waited for the process, we may have caused trouble.

In fact, in the final analysis, emergency handling in clinical research is never a paper rule written to cope with inspections. It is the experience accumulated through many years of trial and error. To put it bluntly, the latest version of the guidelines turns the previously only perceived practical experience into explicit rules, which can not only maintain the bottom line of subject safety, but also save unnecessary costs for sponsors and institutions. After all, the core of what we do in this industry are two things: either we can make truly useful new drugs, or we don’t let the people who participate in the trials be wronged, right?