Latest revision of clinical research emergency response guidelines

The first is to abandon the previous disposal template that was common to all research types and match differentiated response processes according to the classification of clinical phases I to IV, medical devices/biological products/chemical drugs.； Second, it includes for the first time special handling rules for two special scenarios: remote intelligent clinical research (DCT) and rare disease clinical research. ； The third is to shorten the maximum ethics approval period for serious adverse events (SAE) from 72 hours to 24 hours, and simultaneously clarify 12 exemption situations for "dispose first and supplement materials later".

To be honest, I just helped the oncology department of a tertiary hospital last week to revise the emergency plan for a phase III drug study targeting rare targets. I took the old version of the guideline and put it into the new standard and it got stuck. The previous general template did not require high-risk rare disease research to have a 24-hour dedicated medical liaison. The new version directly listed this as a mandatory requirement. The revised plan passed the ethics test on the same day. Last year, it was said that it would take at least 3 days. To put it bluntly, the old version of the guide is just a uniform size uniform. Whether you are doing a high-risk phase I climbing test or a phase IV post-market safety observation, it all fits into the same mold. In many scenarios, it will not fit at all. This revision is equivalent to customizing exclusive work clothes for research with different needs, and the practicality is indeed much stronger.

However, the most controversial aspect of this revision is the rule of “dispose of materials first and then replenish materials.” When we held an industry closed-door meeting last week, the two groups had a heated argument: Senior experts from the perspective of the hospital ethics committee felt that the loosening of restrictions was too much. Last year, there was a case where a small molecule drug research team failed to report a subject's past penicillin allergy history in order to save time for disposal, and subsequently used emergency drugs to induce more serious adverse reactions. They insisted on adding a precondition of "double review risk" to this rule, otherwise the ethical risks would be too great. ； On the other hand, the clinical operations staff of innovative pharmaceutical companies all agreed with their hands, saying that the golden treatment window for many acute and severe SAEs is only one hour. By the time you complete the review process, people will feel cold. Originally, the purpose of shortening the approval time is to ensure the safety of subjects, but adding preconditions is equivalent to blocking the opening of the reform. At present, CDE has not given an official response to this dispute. Many institutions are now running two sets of plans in parallel. In the event of an emergency, rescue people first, and then attach a description of the situation when supplementing materials.

Speaking of adjustments that are easily overlooked, in fact, this revision has filled a lot of gaps in the increasingly popular remote clinical research. Last year we encountered a DCT project for type 2 diabetes. The dynamic blood glucose monitoring bracelet worn by the subject reported a hypoglycemia threshold alarm three times in a row. The research nurse thought it was an error caused by the device being loose and did not take it seriously. As a result, the subject fainted at home due to hypoglycemia in the afternoon and had to pay a small compensation of 200,000 yuan to solve the problem. The old version of the guide did not mention whether remote device early warning is considered a suspected SAE. This time it is written down directly: if the wearable device exceeds the safety threshold three times in a row + the subject has corresponding subjective symptoms, a first-level response will be directly triggered. ； If it is just a single jump, contact the subject first to verify the situation, and there is no need to go through the reporting process. Now we are making an emergency plan for the DCT project and directly put this red label on the wall of the operations office to avoid stepping into the same pitfalls again.

Having been in clinical operations for 8 years, I think the most down-to-earth aspect of this revision is that many of the "hidden rules" that were previously defaulted by the industry have been given to Minghua. In the past, when a subject had an SAE outside the hospital, the rules of each institution were different whether to contact the family first or to ask the PI to sign the case first. When meeting a serious ethics teacher, you would contact the PI first and say that you did not respect the subject's right to know, and you would contact the family first and say that you were delaying the disposal opportunity, which is a disservice to both parties. The new version clearly spells out the order: if the subject is conscious, his or her consent must be obtained before starting the reporting process. ； If you are unconscious, call 120 as soon as possible and contact the PI and family members simultaneously. There is no need to wait for any approval. Just this one thing has reduced the hassles in our projects by more than half this year.

Of course, there are still many details to be implemented. For example, clinical research on rare diseases requires a "similar adverse event comparison database." There are currently no more than 10 institutions in the country that can produce mature databases. Most small institutions cannot build it at all, and there is a high probability that additional details will be issued later. But at least now when we encounter an emergency, we finally don’t have to read ambiguous old guidelines while being afraid of stepping on ethical red lines - for us practical people, this is enough.