Research Trial Staff Forum

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Research Trial Staff Forum

• 5th May 2005
• 9.30-10.30am Seminar Room 6
• Robin Brook Centre St Barts Hospital
• Siobhan Lim/ Johanna Piper
• Research Governance GCP Managers
• BLT/QMUL

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Agenda

• Overview of results from a MHRA inspection in a
  NHS Trust.
• Update from Good Clinical Lab Practice Course.
• Regulations update.
• External courses to attend.
• Open floor discussion.

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Findings from the MHRA inspection at United
Bristol Healthcare Trust
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Why inspect NHS Trusts?

• Assess compliance with Good Clinical Practice.
• Assess compliance with Medicines for Human Use
  (Clinical Trials Regulations), 2004.
• Why inspect UBHT?
• Suspected case of research fraud in Trust.
• Preliminary MHRA visit in Jan 2004.
• Trust volunteered for inspection.
• May 2004 statutory inspection.

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Inspection Plan

• Prior to inspection
• Documents requested-
• Overview of Trust facilities
• List of clinical trials
• Index of SOPs
• Detailed SOPs

• Day 1
• Open meeting
• RD Department
• Medical Records
• Pharmacy

• Day 3
• Labs - Haematology, Clinical Chem,
  Histopathology, Microbiology.
• Radiology.
• Closing meeting.

• Day 2
• Study 1
• Study 2
• Study 3

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Findings from the inspection

• Critical findings evidence exists that the
  safety, well being or confidentiality of trial
  subjects has been (or has potential to) be
  jeopardised.
• and/or
• Where serious doubts exist relating to the
  accuracy or credibility of trial data.
• There were no critical findings.

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Major findings

• Reveals significant and unjustified departure
  from UK regulations. Or
• No. of minor departures from UK GCP regs. Or
• Non- compliance with legislative requirements.
• 5 Major findings revealed in inspection.
• Finding - 1- Clinical Trial Authorisation/Sponsors
  hip
• Trials running without sponsors in place.
• Sponsorship is a legal requirement.
• Pharmacovigilance implications /SUSAR reporting.

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Major finding - 2

• Role responsibilities of PI
• Involvement of PI in study variable.
• PIs involvement in trial activities not
  documented.
• Poor document control.
• Delegation of responsibilities NOT documented.
• Lack of evidence of delegation to suitably
  trained individual/s.
• Lack of awareness regarding SUSAR reporting
  requirements.

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Major finding - 3

• Records management retention
• Study documents not in secure place/access issues
• Retention period of documents not long enough.
• Major finding 4
• Information management technology
• Potential risks to clinical trial data held on
  systems
• Lack of Trust wide evaluation of computer systems
• Lack of security / confidentiality on local
  systems.

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Major finding - 4

• Other findings
• Insurance/liability cover not clear.
• Study protocols not compliant with GCP Regs.
• Original copies of consent not available for all
  pats.
• Some prescriptions not signed by Investigators.
• Discrepancies between dosage in protocol
  prescriptions.
• Some drug accountability forms not checked.
• Annual updates to IB not documented.
• Contractual arrangements between sponsor
  collaborators was not clear.

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• Update from Good Clinical Lab Practice Course
• Run by BARQA
• (British Association of Research Quality
  Assurance)

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Good Clinical Lab Practice

• For clinical labs which undertake the analysis of
  samples from clinical trials
• EU Directive GCP does not define the standards
  labs should follow !
• GCLP to assist labs to understand the standard
  expected

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ICH GCP states

• 2.13 Systems with procedures that assure the
  quality of every aspect of the trial should be
  implemented
• 8.2.12 Essential Documents medical/
  Lab/technical procedures/tests
• certification or accreditation or established
  quality control and/or external quality
  assessment or other validation (where required)
• 8.3.7 Any updates of the above

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Confused ?

• Good Lab Practice is pre-clinical and animal
  testing labs
• Therefore has very HIGH standards and strict
  guidelines to adhere to.
• GCLP is guidelines for satisfying GCP standards
  with the labs

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Clinical Samples

• All phases of clinical trials and also academic
  research
• Safety screening
• Routine pathology tests
• Pharmacokinetics (PK)
• Pharmacodynamics (PD)
• Diagnostic eg. Cancer studies
• Are just a few examples

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Other lab activities

• Equipment provision
• Materials provision
• Documentation
• Training
• Shipping transport
• Storage of samples
• Electronic data transfer

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Audits

• The FDA have never inspected a clinical lab !
• Even though analysis of samples is vital in
  clinical trials !
• Audits will begin to include labs in more detail
  with GCLP guidance.

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Training

• Plan to organise training sessions on GCLP in the
  Autumn
• This may include more detailed content on
  shipping transport
• Will be incorporated into our internal audits

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Regulations Update

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Research Governance Framework

• 2nd edition incorporates Clinical Trials
  Regulations reference to GCP MHRA
  authorisation.
• Emphasis on establishing the same standards of
  governance in research in health and social care.
• Inclusion of Human Tissue Bill (2006) Mental
  Incapacity Bill (2005) in the Framework.
• Just been released so we are yet to read it in
  detail but well keep you informed !

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European Commission Directive 2005/28/EC

• Directive for GCP, released April 2005.
• The European Commission has published Directive
  laying down principles and detailed guidelines
  for good clinical practice as regards
  investigational medicinal products for human use.
• Requirements for authorisation of the
  manufacturing or importation of such products.

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European Commission Directive 2005/28/EC

• Member States shall bring into force the laws,
  regulations and administrative provisions
  necessary to comply with this Directive by 29
  January 2006 at the latest.
• The Directive includes specific provisions for
  non-commercial clinical trials.
• Appears to be very similar to ICH GCP.
• We are still reading it to spot the differences
  !!

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Mental Incapacity Act 2005

• The Mental Capacity Act 2005 has been passed.
• The act sets out clear parameters for research,
  other than research covered by the Clinical
  Trials Regulations 2004, involving adults who may
  not be able to make their own decisions.
• Individuals incapacitated due to an illness such
  as dementia, accident/brain injury, mental
  illness or because of learning difficulties.
• The Act is likely to come into force in 2007.

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Mental Incapacity Act 2005

• Act provides a statutory framework to empower
  protect vulnerable adults who are unable to make
  their own decisions.
• 5 key principles-
• Presumption of capacity,every adult has right to
  make their own decision/ must assume capacity.
• 2) Right of individuals to be supported in
  decision making given help before decide
  incapable.

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Mental Incapacity Act 2005

• 3) Individuals retain right to make what might
• seem eccentric or unwise decisions.
• 4) Best interests - anything done on behalf of
• people without capacity - in their best
  interests.
• 5) Least restrictive intervention - anything done
  
• on behalf of people without capacity should be
  least
• restrictive of their basic rights freedom.
• Research involving these group requires ethical
• approval, benefits must outweigh risks
  justification
• for inclusion.

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Courses

• Research Governance
• Good Clinical Practice
• Ethics 24th May 2005
• Contact ann.smith_at_bartsandthelondon.nhs.uk
• For dates and bookings

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Courses contd.

• RD Forum Annual Conference 2005
• 10th May 05,www.rdforum.nhs.uk
• UK Clinical research 1 year after the
  directive, 14th June 05, ABPI
• Institute of Clinical research (check
• www.instituteofclinicalresearch.org

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RD Internet site

• Due to open end of May 2005 !!!

Queen Mary University of London
Barts The London
RD joint INTERNET (includes public access)