In order to better carry out the scientific supervision of risk-based clinical trials, according to the arrangements of the state bureau, our center CDE organized the drafting of the “technical guidelines for program change during drug clinical trials” and the drafting instructions.


CDE has issued a draft technical guideline about protocol amendment during clinical trials for industry review and comments due by end of March. The guideline aims to harmonize the current protocol amendment registration pathway with US, EU and Japan standards to ensure patient safety during clinical trials.

According to the impact of the protocol changes on the safety risks of subjects, the standardization and data integrity of the clinical trial, the protocol changes during the clinical trial are categorized into substantial changes and non-substantial changes.

Substantial changes

1.  Changes of primary objective.
2. Changes in primary or secondary endpoints that have an important impact on the safety and science of the study.
3. Changes in the determination methods of primary and important secondary endpoints.
4. Changes in the material of the investigational drug that may result from major or medium CMC process changes;
5. Changes in dose and administration.
6. Changes of dosing regimen, such as dosing time, interval, dosing cycle.
7. Change, add or delete control/comparator arm (including placebo).
8. Changes in inclusion or exclusion criteria that may have an important impact on the efficacy and safety of the study, such as significant changes in the characteristics of the subject population.
9. Reduce the number of safety indicators, visits or shorten the follow-up time.
10. Changes in diagnosis, treatment methods or procedures that may have an important impact on the safety and efficacy of the trial.
11. Changes to the basic treatment that may have an important impact on the safety and efficacy of the trial;
12. Change in combination drug.
13. Change the definition/criteria of the end of the study, such as criteria for trial suspension, discontinuation or discontinuation.
14. Changes in statistical analysis methods for primary or important secondary variables.
15. Withdrawal of the Data Safety Monitoring Committee;
16. Others.

Non-substantial changes

Non-substantial changes refer to changes that have no significant impact on the safety of clinical trial subjects, the efficacy, integrity and standardization of the study, and the reliability of the study data.

Examples of non-substantial changes

1.  Incorrect printing of the text.
2. Changes of sponsor contact person, contact information, etc.
3. Changes in clinical research institutions, investigators, contact information.
4. Changes of contract research organization, contact person, contact information.
5. Changes to relevant parties, contacts, contact information, for sample testing, statistical analysis, data management.
6. Change the batch number of the investigational product or control drug.
7. The overall number of subjects remained unchanged and the number of subjects between participating institutions was adjusted appropriately.
8. Appropriate adjustments in the format or content of documents to record trial data.
9. Increase the number of safety measurements or visits for preventive purposes rather than emergency risk control.
10. Addition of test participating institutions.
11. Others


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