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Experience of a MHRA Inspection Aled Rees Senior Lecturer Centre for Endocrine and Diabetes Sciences PowerPoint PPT Presentation


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Experience of a MHRA Inspection Aled Rees Senior Lecturer Centre for Endocrine and Diabetes Sciences. Timelines. Trust informed June 2007 Pre-inspection dossier submitted July 2007 Informed early October that my trial had been chosen

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

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Experience of a MHRA Inspection Aled ReesSenior LecturerCentre for Endocrine and Diabetes Sciences


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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 2005-000115-10

  • SAE list for all trials sent late October

  • Inspection visit 3rd – 7th December 2007


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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!


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The weeks leading up to the inspection

OR

?

  • Neither

  • Plan:

  • Familiarise myself with all regulations pertaining to clinical trials

  • Ensure the trial master file was as good as it could be


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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 (www.nres.npsa.nhs.uk)

  • MHRA clinical trials (www.mhra.gov.uk)

  • 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 (www.ct-toolkit.ac.uk)

  • Others


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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)


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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)


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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


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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


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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


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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


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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


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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


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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


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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


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Thank you


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