Latest revision of clinical research emergency response guidelines

The core revision logic of the 2024 version of the "Clinical Research Emergency Response Guidelines" is to change the previous passive processing model of "filling holes afterward" to a proactive response framework of "leaving holes beforehand, having evidence during the incident, and having boundaries afterward". The three core adjustments are to include emergency response to public health incidents into regular prerequisites, clarify the fault tolerance and exemption list of the sponsor, research institution, and ethics committee, and add new emergency response rules for special population research.

How difficult was it for front-line CRC and researchers who encountered extreme situations in the past few years? I was in charge of a phase II diabetes trial in 2022. At that time, an old subject who had been enrolled for half a year lived in a quarantine area and had been off medication for 2 days. I made 17 calls back and forth with the agency office, the sponsor, and the community, stamped 5 official seals, and it took a full 30 hours to deliver the trial medicine to the patient's home. Now, in accordance with the requirements of the new version of the guidelines, I only need to send a registration voice message with location to the ethics committee, take a photo of the sealed medicine, and then ask a trained community doctor to deliver the medicine to my door on the same day. As long as I keep the video and signature records of the whole process, I will not be sentenced to violation at all.

This point really hits the pain point of many front-line researchers. In the previous version of the guide, the handling of extreme scenarios such as public health incidents and natural disasters were all "special additional terms". There were no clear operational guidelines. If something went wrong, everyone would not dare to make a decision for fear of taking responsibility. This revision directly changes the emergency response for this type of scenario from an "optional add-on" to a pre-module that must be reviewed for all project approvals. It requires that alternative transportation plans, backup cold chain points, and cross-agency collaboration contacts be prepared before the start of each trial. This is equivalent to filling in the pit in advance.

In addition to adjustments to extreme scenarios, what shocked the industry the most was the first clear list of fault tolerance exemptions. Of course, this is not a small matter. Conservative ethics experts feel that the opening is too wide - for example, the list clearly states that "emergency response errors that are not subjective and intentional and subject to procedural compliance are exempt from liability." Some people are worried that some sponsors will take advantage of the loopholes and package ordinary serious adverse events (SAE) as emergencies to skip regular reviews? A similar incident has indeed happened before. In order to rush forward with the progress of phase III trials, a pharmaceutical company reported the allergic reactions of ordinary subjects as "mass suspected drug risks" and adjusted the dosage before the ethics meeting was held. In the end, it was found to be a false report. If it is ignored, it will definitely be severely punished. According to the new version of the guidelines, if it can prove that there is no subjective malice, can it be exempted from liability?

In fact, there is really no need to worry too much. When I attended the GCP training meeting last month, Director Wang from the ethics office of a hospital who participated in the revision said very truthfully: "Relaxing the rules does not mean letting go. The premise of all exemptions is that the operation leaves traces." ”If someone really maliciously conceals or falsifies data, the exemption clause will not apply at all, but will increase the punishment. On the contrary, many front-line researchers raised their hands in favor of this adjustment. Last year, an anti-tumor drug trial site was hit by an earthquake, and the drug storage cabinet was smashed. 120 blood samples from subjects were about to be scrapped. According to the old version of the guideline, a report had to be sent to the sponsor's headquarters for approval. After 10 hours of tossing, half of the samples were discarded. If the new version of the guideline were followed, the institution administrator could immediately transfer the samples to the backup cold chain of the hospital next door, and the process could be completed within 24 hours, which would not cause such a huge loss.

I have been working as a CRC for 8 years, and the most thoughtful thing for me is the newly added emergency response rules for special groups. In the past, emergency treatment for children and rare disease subjects followed adult rules, which did not fit the actual situation at all. I once met a 7-year-old child who was enrolled in an asthma trial. He had a sudden convulsion during the visit. According to the old rules, he had to go through the trial-related approval process before he could be transferred to pediatric emergency. It was delayed by almost 20 minutes. Now the new version of the guidelines clearly states that emergency treatment for special subjects such as children and pregnant women should be given priority to the hospital's clinical emergency channel, and trial-related approvals can be delayed for 72 hours. Due to the small number of subjects in rare disease trials, if there is a need to urgently adjust the plan, there is no need to wait for the ethics approval of all sub-centers. The ethics approval of the team leader unit can be implemented first, and then the supplementary review process will be followed.

Of course, this revision is not perfect. Last week, I had dinner with GCP specialists from several grassroots hospitals. Everyone was complaining about the "pre-reserve of emergency supplies" required by the new version, such as backup cold chains at minus 80 degrees Celsius and dedicated emergency communication equipment. Many county-level hospitals simply cannot come up with budget allocations, which means that no matter how well written the terms are, they cannot be implemented. There are also provisions for cross-regional emergency collaboration. Now the management requirements of GCP institutions in different provinces are different. If you really want to transfer samples and subjects across regions, you still have to go back and forth. These issues will have to be adjusted slowly in the future.

Yesterday I was sorting out documents in the agency office, and I happened to see the new CRC girl squatting on a chair in the renovated version of the guide. You see, this is probably the meaning of the revision. In the final analysis, all guidelines are for front-line workers. They can solve practical problems and are better than any false and empty provisions.