Clinical Research Emergency Response Guidepdf

[Opening core conclusion] The core value of this version of the guideline is to cover the four most common emergency scenarios throughout the clinical research cycle (serious adverse events/major protocol deviations/data security incidents/public health emergencies). The core principles for handling are "subject safety first, compliance bottom lines not loose, and hierarchical responses not overstepped." There is no unified template for the entire industry. Different institutions can adjust the implementation details based on their own research types and center scales under the GCP framework. Currently, there are many practical ideas for handling different scenarios in the industry, all of which have compliance basis.

Many people look for this PDF and want to find a SOP that can be applied directly. To be honest, I have been working in clinical research operations for 7 years, and no two emergency incidents I have seen are exactly the same. I really can’t stick to the template. For example, last year I followed up on the Phase III clinical trial of the COVID-19 oral drug in the respiratory department of a tertiary hospital. On the third day after taking the medicine, a subject suddenly had a high fever and his blood oxygen dropped to 92%. The first reaction of the CRC who was new to the industry was to look through the guidelines to find the reporting process. The PI held him down and called 120 to send him to the emergency room. He waited for the patient's condition to stabilize and then went through the reporting process. In the end, he was not criticized by the supervisor. In essence, the first rule of all guidelines is that patient safety always trumps all process requirements. No one has any objection to this.

Oh, by the way, when it comes to the reporting process, there are indeed two different execution schools in the industry: the academic institutions insist that all emergencies must be ethical at the first time. Even if it is a small deviation such as a subject missing a dose of trial medicine, a written explanation must be submitted within 2 hours; but once Most field researchers believe that for ordinary adverse events that are not SAEs and minor deviations from the protocol that do not affect the safety of subjects, remedial measures can be taken first and reported within 24 hours. Otherwise, they will be busy and have to find time to gather the reporting materials, which will delay the business. There are currently compliance cases for both approaches. The core is that you have to find out the ethical requirements of your center in advance, and it is not wrong to go high or low.

Don’t think that only when subjects have problems is it called an emergency. Last year, a CRO’s CRC threw a USB flash drive containing more than 200 subjects’ encrypted medical records on the subway. At that time, the entire project team stayed up for three days, contacting the subway’s lost and found department, calling subjects one by one to inform them of the risks, and synchronizing drug supervision and ethics submissions. In the end, although there was no information leakage, they were suspended from the group for one month as an ethics penalty. There are currently two ways of dealing with this kind of data emergency in the industry: one group advocates that even if there is no actual loss, all relevant parties must be fully transparently informed to avoid unclear disputes in the future; the other group believes that if it is encrypted and stored, and it is clear that there is no risk of leakage, it can be rectified internally and leave traces, without expanding the impact and causing unnecessary panic to the subjects. At present, there are no clear compliance restrictions for both approaches. The core depends on the risk level of the event.

There are also seemingly inconspicuous small problems, such as forgetting to check the subjects' hepatitis B status when enrolling, and only discovering after enrollment that they do not meet the exclusion criteria of the plan. This is a major deviation from the plan. Some PIs advocate directly eliminating subjects to ensure data standardization, and some feel that As long as it does not affect the safety evaluation, the subject data can be retained, and sensitivity analysis and annotation can be done at the end. Both of these methods are supported by literature from top journals. There is no absolute right or wrong. As long as the ethics and sponsors are communicated in advance and all written records are kept, there will be no problem.

Many people have saved dozens of versions of the guide, but they still panic when something goes wrong. In fact, the most valuable thing in this PDF is not the principle of lengthy articles at all. There are only three tables worth saving on your desktop and printing them out: The first one is the emergency contact list. The phone numbers of the PI, ethics liaison person, drug regulatory liaison, and subject's family members are arranged according to priority to avoid anything happening to you. I spent half a day flipping through my address book; the second one is the incident classification and determination form. I can quickly distinguish whether it is a general incident or a major incident. Don't blame the PI for any big thing, and don't treat the SAE as a small deviation and not report it; the third one is the reporting material template. The core information is listed, and it can be sent after filling it out, saving you from writing the wrong content in an emergency.

Oh, by the way, don’t just save the old version of the guide and forget about it. The emergency guide that a center took out when it was inspected last time was still the 2018 version. It didn’t even update the new requirements of the 2020 version of GCP, so it was directly opened by the inspection team. The content of the guide should be updated at least once a year. When new regulations are introduced, center personnel change, or even when you handle an emergency incident yourself, you can add a note on the side. After all, no matter how good the standardized guide is, it is not as useful as the practical experience gained through going through the pits yourself.