A large sample of clinical trials will come! 8 cases will be judged problematic
Medical Network June 5th Following the sampling of the production, distribution, and use links, the era of clinical sampling of medical devices is also coming.
On June 1st, the Office of the State Drug Administration Bureau publicly solicited opinions on the “Regulations and Principles for the Examination of Medical Device Clinical Trials” document, which is a enterprise , Inspectors and data clinics need to understand the documents.
This document, which lists in detail the principles of medical device clinical testing and the principles for the determination of liability, has thisstandard ', is not far away from the regular sampling across the country.
3 years ago on July 22, drug The clinical data verification storm has come, has far-reaching impact, or will be credited to China medicine R&D history. Now, coming soon medical instruments What is the impact of clinical sampling on the industry?
According to the problems found in the inspection, one of the following conditions is found in the inspection results, and it is determined that there is a problem of authenticity:
1. Compilation of subject information, main test process records, research data, test data and other clinical trial data, affecting the safety of medical devices, effectiveness evaluation results;
2. Clinical trial data, such as exclusion criteria, major efficacy indicators, and important safety indicators cannot be traced;
3. The use of medical or in vitro diagnostic reagents for testing is unrealistic, such as replacement of experimental medical devices with controlled medical devices, replacement of control medical devices with experimental medical devices, and use of false test medical devices in other ways;
4. Defective medical devices that report serious adverse events and may cause serious adverse events, combined medications or medical devices that are prohibited from the program;
5. The safety and efficacy data in the clinical trial report of the registration application is inconsistent with the data in the clinical trial report kept by the clinical trial institution;
6. The clinical trial statistical analysis report of the registration application is inconsistent with the data in the safety and efficacy data and the data in the database or subcenter summary;
7. The clinical trial protocol does not clearly specify that clinical trial samples can be reused, and clinical trial samples are reused during clinical trials;
8. Other cases of intentional destruction of the authenticity of medical device clinical trial data.
Attachment: Main Points and Judgment Principles for Medical Device Clinical Trials (Draft for Soliciting Opinions)
According to "medical device supervision and management regulations" "medical device registration management methods" "in vitro diagnostic reagents registration management methods" "medical device clinical trial quality management specification" "in vitro diagnostic reagents clinical trials technical guidelines" and other related requirements.
No.
Check points
Inspection Method
1
Prepare for clinical trials
1.1
Clinical trial institutions should have the qualification to conduct clinical trials of related medical device products
Log on to the website of the State Drug Administration and check the clinical trial organization's confirmation notice. The clinical trial institution is an accredited drug clinical trial institution (test project conducted before 2019) or a medical device clinical trial institution filing management information system. The filing date is earlier than the start date of the clinical trial
1.2
Third type of medical device requiring clinical trial approval should be approved
Medical device clinical test approval document
1.3
Clinical trial items are filed according to relevant regulations
With the “Registration Form for Clinical Trials of Medical Devices” issued by the provincial bureau, the date of filing is earlier than the start date of clinical trials
1.4
Clinical trials should be approved by the ethical committee of the clinical trial institution
With an ethical review approval document, the approval date is earlier than the start date of the clinical trial, and the record date is earlier than the start date of the clinical trial
1.5
The development of medical devices for testing complies with the applicable requirements of the medical device quality management system
A statement that the development of a medical device for testing meets the relevant requirements of the applicable medical device quality management system
1.6
The test medical device has a self-inspection report and a product registration inspection report issued by a qualified inspection agency within one year. The in vitro diagnostic reagent has a product registration inspection report.
Have corresponding inspection report
1.7
Clinical laboratory facilities and conditions are compatible with clinical trial projects
Have the main equipment and facilities conditions involved in the test plan
1.8
Certificate of quality control (if any) with clinical or laboratory operation in a clinical trial institution
Clinical laboratory to carry out clinical inspection of indoor quality control, with a clinical laboratory quality evaluation certificate
1.9
Test related instruments and equipment should be regularly maintained and calibrated
Test related instruments and equipment have maintenance, calibration records
1.10
Researchers should have professional qualifications, clinical expertise, qualifications and capabilities
Check the investigator's qualifications, professional titles, resumes, etc. The investigator responsible for clinical trials should have associate chief physician, associate professor, associate researcher, and other relevant professional technical titles and qualifications in the clinical trial institution.
1.11
Researchers trained in the use and maintenance of clinical trial protocols and experimental medical devices/in vitro diagnostic reagents
Researchers have training records for the use and maintenance of clinical trial protocols and test medical devices/in vitro diagnostic reagents. The training date is earlier than the start date of clinical trials.
1.12
In vitro diagnostic reagents should be pre-tested for clinical trials
With the agreement/contract signed by the sponsor and the clinical trial institution, their responsibilities are stipulated
1.14
Agreement/contract contents in line with test medical device/in vitro diagnostic reagent information
Check agreement/contract and clinical trial program, consistent information
2
Subject rights protection
2.1
Ethical review
2.1.1
Ethics Committee members trained
With ethics committee members training record or training certificate
2.1.2
Ethical review content meets relevant specifications, guidelines, and SOP requirements
The contents of the ethical review should meet the requirements of Articles 17, 33 and related guidelines for the quality control of medical device clinical trials (GCP), and the requirements of the SOP.
2.1.3
Ethical review record complete
The data kept by the ethics committee shall be complete, including the documents stipulated in the SOP, such as review materials, examination forms, check-in forms, voting papers, meeting records, examination approval documents, etc.
2.1.4
The Ethics Committee voted in accordance with relevant regulations, guidelines, and SOP requirements
Ethical review opinions, membership of the ethics committee, voting records should comply with GCP 30, 32, 35 and SOP requirements
2.1.5
Revision of clinical trial protocols/informed consent documents, requests for deviations, resumption of clinical trials suspended, should be approved in writing by the ethics committee
Relevant information has ethical committee written approval documents
2.1.6
Ethics Committee follows up on approved clinical trials
For clinical trials lasting more than one year, there is a record of periodic review by the ethics committee. The periodic review time limit is no more than one year.
2.2
Informed consent (Objectively impossible to obtain subject informed consent, subject to informed consent of the subject after review and approval by the Ethics Committee)
2.2.1
Informed consent content complies with relevant regulations, guidelines, and SOP requirements
The content of the examination of the informed consent shall comply with Article 22 of the GCP and relevant guidelines, and the requirements of the SOP
2.2.2
Subjects or their guardians and investigators signed the name and date on the informed consent form prior to the clinical trial, in accordance with the relevant specifications, guidelines, and SOP requirements (except for consent-free consent)
Check the subject's screening form and the signed informed consent form. The number should be the same, signed by the subject himself or his guardian and the researcher before participating in the clinical trial. Exemption from informed consent and exemption from informed consent Ethical review opinions or approval documents
2.2.3
The signed version of the informed consent agrees with the version passed by the ethical review
Check the version and content of the informed consent form, and the signed informed consent form should be consistent with the version and content adopted by the ethical review.
2.2.4
Informed Consent is updated, and the affected subject or his guardian’s informed consent should be obtained again in the clinical trial
After the informed consent form is updated, the affected subjects or their guardians in the trial shall re-sign the updated informed consent form.
3
Clinical trial program
3.1
Clinical trial program confirmed by all central researchers and sponsors
The clinical trial program should have all central researcher and sponsor signatures and clinical trial agency official seals
3.2
The content of the clinical trial program executed is consistent with the contents of the clinical trial program for ethical review
Check clinical trial protocols and clinical trial protocols maintained by the ethics committee. The version and content should be consistent.
3.3
The test plan executed by the centers of multi-center clinical trials is the same version
Check the version of the clinical trial protocol maintained by each clinical trial center, which should be the same version
3.4
The contents of the clinical trial program submitted by the registration application shall be consistent with the contents of the clinical trial program maintained by the clinical trial institution
Check the clinical trial plan submitted by the registration application and the clinical trial plan kept by the clinical trial institution. The version and content should be consistent.
4
Clinical trial process
4.1
Persons involved in clinical trials should be authorized by major researchers and related training
Check the division of labor grant form and the researcher training record, signature proofs, authorization date after training
4.2
Clinical trial-related medical decisions should be the responsibility of the investigator
Check the staff resume and the staff division table. The personnel authorization in the division table should be reasonable. The medical decision in the original document should be signed by the researcher.
4.3
With case screening selection records
The reasons for the failure of the patient screening in the screening list should be consistent with the records in the original medical record, and the researcher can provide the subject identification file.
4.4
Subject identification documents or screening entries, physical records, etc. The original records cover subject identification information
Subject identification documents or screening entries, physical examinations and other original records covering subject ID, name and other identification information
4.5
Researchers should follow the randomization procedure for clinical trials (if applicable)
Subject selection number, the distribution of random numbers should be in accordance with the test plan
4.6
The auxiliary examination items such as the subject's physical examination and laboratory should be consistent with the test plan
The auxiliary inspection items such as medical examinations and laboratories in the original medical record shall be consistent with the requirements of the plan, and the inspections of deviation plans shall be recorded.
4.7
Are laboratory and other auxiliary inspections within the time frame set by the plan?
The auxiliary laboratory inspection time shall be within the time range specified in the plan, and the deviation from the time range shall be recorded.
4.8
Subject enrollment meets the criteria for inclusion and exclusion of the trial protocol
Check the medical history, medication history, laboratory tests, and diagnosis in the original medical record. The subject should meet all the criteria for inclusion and exclusion in the trial protocol.
4.9
Test medical equipment / in vitro diagnostic reagents use original records
Check the original medical record, device usage record, subject's diary card, and record the use of the medical device/in vitro diagnostic reagent for testing, consistent with the data in the CRF.
4.10
Medical device product name, specifications, and methods of use (eg date, time, status, etc.) consistent with the protocol and the investigator's manual
Check the original medical record, device usage record, the medical device product name, model number, and usage method (eg date, time, status, etc.) recorded in the subject's diary card, which should be consistent with the trial plan and the researcher's manual.
4.11
Observe that the follow-up point is consistent with the protocol. Record the follow-up that has not been done, the test that has not been conducted, the test that has not been done.
Check the follow-up records in the original medical records, consistent with the data in the CRF, and the deviations from the protocol should be recorded
4.12
Deviation from the plan in case of emergency should be reported in writing
Any deviation from the plan in an emergency shall be recorded and reported to the sponsor and the ethics committee in a timely manner.
4.13
Subjects with any reason to withdraw and lose follow-up should record and specify
Check the selection list, the original medical record, the CRF or the sub-center summary form to complete the test. The withdrawal and loss should be recorded and detailed
4.14
Safety, effectiveness evaluation should comply with test plan requirements
Check the safety in the original medical record, and the effectiveness evaluation method should be implemented according to the requirements of the plan. The original data is consistent with the CRF.
4.15
Investigators should verify data that significantly deviates from or exceeds clinically acceptable clinical trial schedules
Inspection inspection report, the investigator should determine the abnormal value
4.16
For the combined use of drugs, the condition of the medical device should be recorded according to the test plan, and there should not be any drugs for combination use that violate the requirements of the test plan. Medical devices (if applicable)
Check the original medical record, the hospital HIS system, the investigator should record the combined use of drugs, medical equipment, and be consistent with the data in the CRF, database
4.17
Adverse events, complications and device defects should be documented
Check the original medical records. The investigator should record adverse events, complications, and device deficiencies that are consistent with the data in the CRF and the database.
4.18
Timely treatment and management of serious adverse events/adverse events (SAE/AE) followed up
Check the original medical records, serious adverse events/adverse events and treatment treatment should be timely, and follow-up follow-up
4.19
Severe adverse events (SAEs) and device defects that may cause serious adverse events are reported to regulatory agencies within the specified time
Check the report form of serious adverse events, the records shall be complete and relevant information shall be reported within 24 hours. Written report shall be made to the relevant ethical committees and clinical trial institutions in provinces, autonomous regions, and municipalities directly under the jurisdiction of the drug regulatory authorities and health and family planning authorities. Institutional Medical Device Clinical Trial Management Department Reports Ethics Committee Review
4.20
When suspending or terminating clinical trials, subjects should receive appropriate treatment and follow-up
Examine original medical records, subjects have appropriate treatment and follow-up
4.21
Blind test according to the requirements of the test program (if any)
Checking blind records, verifying that blindness meets program requirements
4.22
Sponsors conduct audits of clinical trials
Check the auditor's audit records. The investigator should promptly take corrective measures against the problems found during the audit.
5
Records and reports
5.1
Clinical trial record
5.1.1
Accurate, complete, clear and timely completion of clinical trial records
Check original medical records, CRF, records should be accurate, complete, clear, timely
5.1.2
Correct mistakes, omissions
Check the records in the original medical records, the data query table and the response records, and correct the errors and omissions
5.1.3
The modification of the clinical trial record should explain the reason, modify the signature and date, keep the original record clearly identifiable
Check the record of the revision of the original medical record, and the modification shall meet the requirements, and record the reason for the modification
5.1.4
Laboratory inspection, imaging department, electrocardiogram room, endoscopy room, etc.
Check the hospital LIS, PACS and other systems, related auxiliary inspection data should be traceable in the system
5.1.5
The data in the CRF is consistent with the original medical records
Check the CRF and original medical records, the data should be consistent
5.1.6
Electronic clinical databases or remote electronic clinical data systems should ensure that clinical data are controlled, true, and complete verification documents (if applicable)
Check electronic clinical database or remote electronic clinical data system. There should be training records, independent account number, use permission, data review, verification file, audit tracking function
5.2
Clinical trial report
5.2.1
After the completion of multi-center clinical trials, clinical trial summary/clinical trial reports are available at each of the centers.
Each branch center should keep clinical trial summary / clinical trial report
5.2.2
Clinical trial summary / clinical trial report signed by the investigator, dated, with clinical trial agency review comments, dated and stamped with clinical laboratory seal
The clinical trial summary/clinical test report should be signed by the investigator, dated, reviewed by the clinical trial organization, dated and stamped with the clinical laboratory seal
5.2.3
Database data used for statistics or sub-center summary data is consistent with CRF
Randomly check the data in the CRF and the database. The data should be consistent
5.2.4
Clinical trial report, statistical analysis report is consistent with database data used for statistics or sub-center summary data
Check the clinical trial report, statistical analysis report and database or sub-center summary, the data should be consistent
5.2.5
The content of the clinical trial report submitted by the registration application is consistent with the content of the clinical trial report kept by the clinical trial institution
Check the clinical trial report submitted by the registration application and the clinical trial report kept by the clinical trial institution. The version and content should be the same.
6
Test medical device/in vitro diagnostic reagent management
6.1
The information of the test medical device/in vitro diagnostic reagent includes name, model, specification, date of receipt, date of manufacture, product lot or serial number, quantity, etc.
Inspection test medical device/in vitro diagnostic reagent transfer order, should have name, model, specification, date of receipt, date of manufacture, product lot number or serial number, quantity, etc.
6.2
Test medical device/in vitro diagnostic reagent and test report, product name, specifications in the clinical test report
Check the usage records, test reports, specifications of the test medical device/in vitro diagnostic reagent in the clinical test report, the information should be consistent
6.3
Complete records of transport, receipt, storage, distribution, recovery and destruction of test medical devices/in vitro diagnostic reagents
Check records for transportation, receipt, storage, distribution, recycling, and destruction. The contents should be complete. Reasons for records with inconsistent quantities
6.4
Transportation conditions, storage temperature, storage conditions, storage time, safe and valid period, etc. meet the requirements
Inspection of transport, receipt, storage records, transport conditions, storage temperature, storage conditions, storage time, safety and validity period, etc. shall be in accordance with the requirements of the test plan
6.5
The number of used or returned items is the same as the quantity provided by the sponsor.
Check receipt, use, recycling records, quantity should match the data provided by the sponsor
6.6
The preservation and use of special types of medical devices is consistent with the contents of the summary report
Field inspection of large-scale medical devices (such as large-scale radiotherapy equipment) with special site preservation requirements. The preservation conditions and use conditions should be consistent with the contents of the summary report.
7
Management of samples for clinical trials (Applied in vitro diagnostic reagents)
7.1
Clinical trials use sample source, numbering, preservation, use, retention, and destruction of each link should have original records
Check the sample for clinical trial acceptance, preservation, use, retention, destruction records, content should be complete, number, quantity and other information, and related personnel signature and date
7.2
The clinical test is consistent with the provisions of the sample test and the clinical trial program, with complete original records
Check the sample test records and test methods for clinical trials, the conditions should be consistent with the program requirements, complete test records
7.3
If there is repeated use of samples for clinical trials, corresponding instructions should be provided
If a sample is to be reused, it should be specified in the clinical trial protocol. The sample should be kept for repeated use and the repeated use should be described in the summary report.
