Latest revision time of clinical research emergency response guidelines

At present, the latest revision of the "Technical Guidelines for Emergency Management of Drug Clinical Trials (Trial)" of the domestic drug regulatory system for drug clinical trials is December 28, 2023, and is officially announced by the Center for Drug Evaluation (CDE) of the State Food and Drug Administration.； The latest revision of the "Clinical Research Safety Emergency Management Standards" led by the National Health Commission and covering all types of clinical research (including medical devices and public health observational studies) is September 2022. ； The emergency treatment-related provisions in the ICH GCP E6 (R2) appendix that need to be aligned for international multi-center trials were last revised in November 2021.

At the end of December last year, I happened to be working on the supervision of new anti-tumor drugs at the Phase I clinical center of a tertiary hospital in Guangzhou. I caught up with the center to organize a training for all employees on the 23-year-old new guideline. During the break, several familiar CRCs complained that they had just memorized the 2020 version of the emergency procedure, and they had to update the knowledge base. Even the quality control forms issued by the institution had to be revised accordingly, which made my head ache.

Many newcomers who have just entered the industry are often confused. Why are there several different revision times for the same topic guide? In fact, to put it bluntly, the applicable scenarios are different: if you are doing clinical trials of drugs and medical devices that need to be reported to the NMPA for listing, then you must give priority to following the latest version of CDE in 2023. After all, this is the basis for declaration clearly required by the drug regulatory department. ； If it is a clinical study led by universities and hospitals that does not involve product registration, such as a long-term follow-up cohort for a chronic disease, then it is enough to follow the 22-year norms of the National Health Commission. ； If it is an international multi-center trial with dual reporting from China and the United States, in addition to domestic requirements, it must also comply with the relevant provisions of ICH revised in 2021, otherwise it will not pass the FDA inspection.

Now there are different voices in the industry regarding this set of rules that are “applicable by scenario”. Many quality directors of sponsors feel that there is no need to be so detailed. No matter what type of research is done, it should be prepared according to the strictest 23-year CDE version of the guidelines, so as not to have to make up materials one day when the regulatory requirements change. Anyway, you will not make mistakes if you do more. However, many ethics committees of grassroots hospitals that I have contacted do not approve of this "one size fits all" approach. I once went to a hospital in a prefecture-level city in Yunnan to hold an ethics meeting. An ethics committee member with a background in the emergency department said that many of the studies their hospital received were public health survey studies that did not involve intervention. If the requirements of CDE are applied rigidly, emergency personnel on duty 24 hours a day and a full set of rescue drugs must be provided. The hospital's emergency manpower is not enough, which is a waste of medical resources. According to the 2022 version of the National Health Commission, only emergency contact mechanisms and referral channels are sufficient.

I came across a living example last month. There was a sponsor who was conducting a Phase II trial of a topical acne cream. The emergency plan that had been prepared according to the old 2020 guideline was directly rejected when it was submitted to the ethics committee and asked to complete the emergency treatment process in the decentralized trial (DCT) scenario. This is also one of the biggest revision points of the 23rd CDE version of the guideline. The previous The old version of the guideline defaulted to subjects going to the research center for on-site medication. The 23rd version explicitly required for the first time that if subjects were allowed to take medication at home, the entire process requirements from adverse reaction reporting, researcher response, nearby referral to follow-up traceability must be clarified. The sponsor had not considered this at all before, and it took almost two weeks to change the plan alone, which delayed a lot of start-up time.

There is another pitfall that is easy to step on. I would like to remind everyone that when looking for guidelines, you must go to official channels. Don’t just search for unknown websites on Baidu. Either go to the “Guiding Principles” column on the CDE official website, or go to the science and technology education section of the National Health Commission’s official website to find the officially released version. Not long ago, a CRA who just joined the industry took an old guide compiled by the company in 2019 to give training to the research center. After only 10 minutes of lecture, the director of the agency office kicked him out and asked the sponsor to replace him on the spot. It was extremely embarrassing.

In fact, there is really no need to worry about which version is the "absolutely latest". You should first figure out what category your project belongs to and which department it is under, and then find the latest version released by the competent department. If you are really unsure, send a consultation email to the institutional office or ethics committee of the research institution in advance and spend 10 minutes to ask. It is much easier than changing the plan and making up the process later.