1. Experience of a MHRA Inspection Aled Rees Senior Lecturer Centre for Endocrine and Diabetes Sciences

2. Timelines Trust informed June 2007
Pre-inspection dossier submitted July 2007
Informed early October that my trial had been chosen
A Randomised, Double Blind, Placebo-Controlled Study Of The Effects Of Dehydroepiandrosterone Replacement On Vascular Function In Patients With Primary And Secondary Adrenal Insufficiency. Eudract No
SAE list for all trials sent late October
Inspection visit 3rd – 7th December 2007

3. Why me? MHRA chooses 5-6 trials to inspect
Unlikely a random process and will be chosen to best test the range of systems involved e.g. a multi-centre study, investigator-initiated single centre etc
1 University-sponsored trial chosen…mine!

4. The weeks leading up to the inspectionOR ?
Neither
Plan:
Familiarise myself with all regulations pertaining to clinical trials
Ensure the trial master file was as good as it could be

5. Reference resources accessed
GCP training update (Tanya Symons course) July 2007
Useful up-to-date information on ICH-GCP, EU Clinical Trials Directive and subsequent amendments, ethics committees, informed consent, pharmacovigilance & reporting requirements etc
National research ethics service (
MHRA clinical trials (
Draft records management guidance Cardiff University
CU/Trust SOP for trial master file
Cardiff University RACD site SOPs, especially reporting of research related adverse events
Data protection guidance for researchers (Trust guideline)
Clinical trials toolkit website (
Others

6. The interview Day 4 Interview 17 – DHEA 3294E
Interviewed in the Clinical Research Facility
1 and a quarter hours
Present: Me (obviously!), Senior GCP Inspector, Trust R&D Co-ordinator (to take notes)
Co-investigator/nurse not interviewed for my trial but interviewed separately for all others (University sponsored and Trust being inspected)

7. The interview – areas covered
Job history & research experience
GCP training of trial staff and when undertaken (also CVs)
Training in study specific techniques, calibration records discussed
Archiving & retention of data
Where will final data be stored?
Discuss roles and responsibilities of CI and PI (both as a single centre study)

8. The interview – areas covered
Trial set-up – who was involved? (Co-investigators, Clinical Trials Pharmacist, St Mary’s Pharmaceuticals Unit)
Communication with co-investigators
Co-investigator training (certificates in master file)
Trial set-up difficulties – IMP shelf-life/stability issues discussed

9. The interview – areas covered
What is the difference between a substantial and non-substantial amendment?
Any amendments to the study and how dealt with? (change to washout period & approved by sponsor)
I brought up the delay in submission from St Mary’s of a substantial amendment (in relation to batch stability data) – accepted by MHRA but commented upon in inspection report

10. The interview – areas covered
Pharmacovigilance – AE and SAE reporting
What would you do if an SAE occurred? What is an SAE?
Who do you report to?
Timelines of SUSAR reporting etc
What if a co-investigator decided an adverse event had occurred? Could he make a decision? What if CI/PI was on leave?
Could you override co-investigator’s decision?
SOPs for adverse event reporting – Trust v University and Trust incident form also completed

11. The interview – areas covered
Unblinding – emergency and end-of-study
Envelope storage, on-call pharmacist, protocol for emergency unblinding in TMF
Pharmacy issues and St Mary’s – accountability logs, delegation of responsibilities
End of study unblinding ‘SOP’ discussed
Data storage – where held? Identifiable information? Back up.
Source data verification and archiving facilities
End of study statistical plans

12. The interview – areas covered
Trial steering committee?
Risk assessment at study planning
Master file and 5 case notes (list provided by MHRA a week or so before inspection) available for review but I believe may not have been looked at as insufficient time

13. The aftermath
Attended end of inspection report on the Friday afternoon
Trust – 1 critical and 4 major findings later downgraded to 0 critical and 4 major findings

14. The aftermath Inspection report issued to the Trust February 28th
11 page summary!
Findings pertaining to DHEA 3294E (Minor/Other)
3.3.2 Data management and statistics
There was no documented process for database lock and unblinding of blind codes for both …. & DHEA study

15. Conclusions Do not underestimate the importance of the inspection
Be familiar with all the important regulatory documents
Ensure your site file is spot on
Be honest & remember this is an inspection of systems not really of individual trials
The individual trials are picked to test that appropriate systems are in place and that these are running well

16. Thank you