Latest revision of clinical research emergency response guidelines

The 2024 revised version of the "Clinical Research Emergency Response Guidelines" has been officially released this month by the Drug Evaluation Center of the State Food and Drug Administration in conjunction with the Chinese Pharmaceutical Association. The core change of this revision is to cancel the "unified process priority" rule that has been in use for 8 years and to replace it with a scenario-based handling logic of "treatment priority, hierarchical rights and responsibilities, and multi-center synchronization" Editorial adjustment has added three core modules: Suspicious and Unexpected Serious Adverse Reactions (SUSAR) Rare Subtypes Disposal Pathway, Subject Rights Protection Mechanism, and Grassroots Institutional Adaptation Plan. All institutions conducting drug/medical device clinical trials must complete standard operating procedures (SOP) benchmarking updates before December 31 this year.

Last month, I went to a tertiary cancer hospital in Shanghai to attend an ethics training meeting. I happened to see Director Zhang from the GCP office holding a revised draft filled with red circles and leading the team to revise the emergency SOP. While revising, he complained: "Last year, we had a level 4 immune-related pneumonia. In this case, the sponsor's CRA squatted at the door of the emergency department, insisting on waiting for approval from the headquarters before going through the ethics reporting process, which almost delayed the communication with the family members. Now it's okay. The new guidelines directly put treatment at the front. Anyone who stops the patient first will be counted as a violation. ”

Regarding the article "rescue priority is higher than data integrity", there are actually quite a lot of differences in the industry. Many clinical operations leaders of leading pharmaceutical companies I have contacted have concerns: Especially for registration trials of rare diseases and anti-tumor, there are originally few enrolled cases. If the combination of drugs is adjusted for treatment, node data is missed, and the CDE does not approve the final application, the entire trial may be discounted, and the cost alone will be tens of millions. However, ethics committee experts from various institutions generally hold a supportive attitude: as long as there are complete clinical records of the treatment process and subsequent supplementary reports, CDE will approve it. If something goes wrong with the person, no matter how beautiful the data is, the ethical basis of the entire trial will not be sustainable at all, and the application will not pass.

Last year, a trial of a new second-generation diabetes drug conducted by a county center in Jiangsu Province went through the pitfalls of the old guidelines: a subject developed ketoacidosis after taking the drug. According to the old rules, he had to first report to the sponsor, ethics, and provincial bureau. It took more than 2 hours to complete the process. The patient was finally rescued, but his family felt that the institution only focused on following procedures and did not care about the patient, and they almost got into trouble with the National Health Commission. The new guidelines directly address this situation: as long as it is a life-threatening emergency, clinical treatment can precede all reporting processes, and all procedures can be submitted with a lag of up to 48 hours. It also specifically clarifies that "non-planned operations during the treatment process, as long as they are supported by complete medical records, will not be used as a basis for elimination of trial data."

Oh, by the way, this revision also has a "release" clause that many people have not noticed: in the past, all clinical trial institutions were required to have a full-time emergency response team with more than five people in emergency, ethics, statistics, legal affairs, and operations. Many county hospitals only have two or three staff members who understand GCP, which is simply not enough. They can only pull people from other departments to make up the number. If something goes wrong, no one will be held responsible. The new revised version directly relaxes the situation: grassroots organizations at the county level and below can only have two emergency specialists. When encountering problems, they can directly contact the local GCP emergency cooperation group, and there is no need to shoulder the burden of things that cannot be handled by themselves.

I have been working in clinical operations for almost 10 years, and I have met many small CRAs who are new to the industry. When encountering an emergency, their first reaction is to look through old guidelines to find the process, squat aside and fill in various reports first, and even prevent researchers from prescribing drugs that are not in the plan, for fear of being deducted for non-compliance. Now that the new guidelines have come out, this situation finally has clear criteria for judgment. To be honest, the previous guidelines taught you "how not to make mistakes", but now they teach you "how to do it right first". After all, clinical research still revolves around people.

Of course, there are currently a lot of practical controversies: For example, some people have asked whether there will be loopholes in underreporting if the report is delayed for 48 hours. The judgment standard of rare SUSAR is still vague. It is said that the revision team will update the practical patch every six months to collect feedback from the front line before making adjustments. But no matter what, this revision finally breaks out of the vicious cycle of "compliance for compliance's sake" and is indeed a big step forward for the entire industry.