Latest revision time of clinical research emergency response guidelines

In the pharmaceutical field, in November 2022, the Center for Drug Evaluation of the State Food and Drug Administration will issue the "Guiding Principles for Emergency Management of Drug Clinical Trials (Trial)"； In the field of medical devices (including in vitro diagnostic reagents), in August 2023, the Device Review Center of the State Food and Drug Administration will complete the revision and issue the "Guidelines for Handling Emergency Events in Clinical Trials of Medical Devices". In addition, WHO's emergency response guidelines for global multi-center clinical research were last revised in February 2024. If the project involves overseas centers, it is also necessary to refer to the regulatory documents of the corresponding region simultaneously.

To be honest, the most common pitfall for those who are new to the industry is to search for guidelines without looking at the categories. The emergency requirements for drugs and devices are not even the slightest bit different. When I was stationed at a phase III clinical site for a targeted lung cancer drug at the end of 2022, the new version of the guidelines from the Center for Drug Evaluation had just been released, and the sponsor's CRA changed three versions of the SOP overnight - before 2018 The old version of the guideline only mentioned the reporting process for serious adverse events (SAE), and did not cover external emergencies such as epidemic lockdowns and public incidents. If two centers happened to be under lockdown, the subjects would not be able to return to the hospital for follow-up. If the remote safety assessment was done according to the requirements of the new version of the guideline, it would be compliant. There was no basis for it in the old version, and I almost reported a plan violation.

There are actually some differences in the frequency of revision of guidelines in the industry. Most of them are institutions and ethics practitioners. They feel that the current pace of revision every 2-3 years is just right. After all, the core compliance logic of clinical research has not changed much. If revisions are too frequent, SOPs and personnel training will need to be revised repeatedly, and the cost of implementation will be too high.； The other group is mostly sponsors of cutting-edge projects such as cell therapy and AI-assisted diagnosis. They feel that new therapies and new scenarios have emerged too quickly in the past two years. Last year, there were three clusters of related cytokine storm events in a CAR-T clinic. The emergency classification and subject compensation items for cutting-edge therapies in the existing guidelines are still too general. It is best to issue a supplementary patch every year without making major changes, and just add some requirements for responding to new scenarios.

Don’t underestimate this revision time difference. Last month, we were conducting a multi-center clinical trial of an AI-assisted fundus diagnostic reagent. The center in Guangzhou encountered extreme rainstorms, and the sample storage cabinet on the first floor was flooded. We soaked 217 serum samples from subjects. If we follow the 2017 version of the old equipment guide, this kind of There is no clear reporting time limit for non-medical emergencies. According to the new 2023 guidelines, reporting to the institution, ethics, and sponsor within 4 hours, and simultaneously informing all involved subjects of the potential risk of sample damage, we completed all the procedures on the same day, and nothing happened. Oh, by the way, there is another special situation. The special emergency guidelines for clinical research for public health emergencies were released in March 2020 and have not been revised since. If you do similar clinical research related to public health emergencies, you still have to refer to the special requirements of this version.

I usually note two times when saving the guidelines, one is the official revision and release time, and the other is the time when our center completes the SOP adaptation. After all, after the official release, it will take at least 1-2 months to complete the training and implementation at the institution. If you happen to start a project when the old and new guidelines alternate, don't just impose new requirements. Say hello to the ethics secretary in advance, which can save a lot of trouble on both sides. If you are doing a multinational multi-center project, you need to pay more attention. For example, the EU's latest clinical research emergency guidelines were revised in March 2023, and similar guidelines from the US FDA were updated in September 2022. Don't use domestic guidelines to apply to overseas centers. It will be too late to cry if you hit the regulatory red line.

To put it bluntly, those who are engaged in clinical research should save the official website of the State Food and Drug Administration in their favorites and browse it easily. Don’t wait until an emergency occurs and realize that they are looking at old guidelines from three or four years ago. This will dig a big hole.