According to ICH-GCP, section 5.19.1:
“The purpose of an audit, which is independent of and separate from routine monitoring and quality control functions, should be to evaluate trial conduct and compliance with the protocol, Standard Operating Procedures (SOP), Good Clinical Practice (GCP) and the applicable regulatory requirements.”
Therefore, a clinical site audit evaluates different quality aspects of a clinical trial but it can also help in identifying training needs and correcting procedures.
Without doubt, site audits put pressure on clinical trial management staff but they are very useful to improve how the research is being performed.
Getting Ready for a Clinical Site Audit
Consider the following initial recommendations to get ready for an audit:
- Educate staff on how to communicate with the auditor
- Ensure personnel understand the protocol and the scientific details of the trial
- Identify which team members are responsible for specific aspects of the study
- Ensure that all trial documents are well organized and updated
These initial guidelines may assist in having a successful audit.
Then, what else do you need to get ready for an audit?
Key elements for a successful clinical site audit preparation include:
1.- Notify trial personnel about the date and time of the audit (Principal Investigator, Study Coordinator, Project Manager, Clinical Research Associate).
2.- Ensure all required personnel will be available on the day of the audit. It is very important that the Principal Investigator is present during the audit.
3.- Book a room for the auditor. The auditor will need to have office space to work.
4.- Assign a person to assist in preparation for the audit and for the actual audit itself.
5.- Perform a comprehensive revision of the:
- Study procedures,
- Protocol,
- Patient information sheet and informed consent forms,
- Case report forms and queries,
- Source data including medical records,
- Protocol deviations and corrective and preventive actions (CAPAs),
- Serious adverse events (SAEs),
- Site files (patient’s notes, pharmacy and drug records, signed financial documents/receipts, pharmacy agreements, documentation relating to doses/dispensing, etc.).
6.- Review qualifications and training of the trial team members.
7.- Meet with the support team to monitor audit preparation, identify issues to address, and take corrective actions as required.
Common Findings in Clinical Trial Audits
In addition, here you have a list of some common findings identified during trial audits:
Legal and administrative documents:
- Change of investigator not reported to the regulatory authority and ethics committee
- Annual safety report, end of study letter and/or protocol amendments not submitted to the regulatory authority and ethics committee
Essential documents:
- Structure and content of the investigator file difficult to assess
- Archiving facilities not appropriate
- Document retention period not defined
Case Report Form (CRF):
- Inaccurate completion
- Excessive corrections done
- Not completed in a timely manner
Informed consent form (ICF) procedures:
- The ICF has been obtained after the start of the trial
- The wrong version of the ICF has been signed
- Trial staff have dated the ICF on behalf of the patient
- A copy of the ICF has not been given to the patient
Source data:
- Location of source data document missing
- No record that the patient is participating in a clinical trial
- Confirmation of patient eligibility by investigator missing
Conduct of the trial:
- Patients not meeting the eligibility criteria have been included in the trial
- Patient visits are outside the window defined in the protocol
- Protocol amendments have been implemented too early or too late
Organization and personnel:
- Not all staff involved have been mentioned in the Delegation log
- The tasks assigned are not in accordance with the actual conduct of the trial
- Previous experience in clinical trials is not mentioned in the Curriculum Vitae (CV)
- Evidence of GCP is missing in the CV
- The CV has not been recently updated and signed
- No records of GCP training for the trial staff are available
- No study specific training records are available
Investigational Medicinal Product (IMP) handling:
- Accountability is incomplete or inaccurate
- Inventory is missing
- The storage area is not secure
- The temperature log is missing
Adverse events:
- The timelines for reporting have not been met
- The reports are incomplete (e.g. date missing)
- The follow-up reports are missing
Laboratory:
- Inappropriate equipment used
- Calibration of equipment incomplete or not done
- SOPs on receipt of samples or specimens, calibration, documentation of samples, etc. not followed
Monitoring:
- The monitoring plan is not being followed
- Issues identified are not being followed up
- Basic mistakes have not been identified
- The monitoring reports are inadequate (poorly completed)
Additional Clinical Trial Advice by FDA Auditor
Finally, we recommend watching the following video, in which Patrick Stone provides highly valuable advice about clinical trial audits:
Why wait for an audit to find compliance issues or deficiencies in your clinical practices?
Do you need help with a clinical trial audit?
You can contact Sofpromed to ensure that you have properly implemented the Good Clinical Practice procedures that auditors will be expecting to see.
