Ethics Committees

1
Ethics Committees

• Joan Perou - GCP Consultant
• November 2005

2
Ethics Committees

• The Directive allows each Member State to adopt
  their own process of ethics review, conditional
  upon
• Each Member State implementing the core
  requirements for ethics committees as identified
  in Articles 6 of the Directive
• Member States must incorporate into Law these
  core requirements and add processes to make a
  complete legal framework under which ethics
  committees will operate
• The U.K. ethics review system is called GAfREC
  (Governance Arrangements for Research Ethics
  Committees)

3
Differences between European Member States on
ethics committees

• The Directive does not define
• who can be an ethics committee member .
• how many members an ethics committee should have
• who can make application to an ethics committee.
• whether there should be just national committees
  or national and local committees
• Each Member State will have to make decisions on
  the above and incorporate them into their own
  national laws.

4
EU Directive on GCP in Clinical Trials
(2001/20/EC)

• Article 6
• For the purposes of implementation of the
  clinical trials, Member States shall take the
  measures necessary for the establishment and
  operation of Ethics Committees
• Article 7
• For multi-centre trials Member States shall
  establish a procedure providing for the adoption
  of a single ethics committee opinion for that
  Member State

5
EU Directive on GCP in Clinical Trials
(2001/20/EC)

• Definition of a multi-centre trial (Article 2)
• a clinical trial conducted according to a
  single protocol but at more than one site,
• and therefore by more than one investigator

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Directive 2001/20/ECEthics Committees must
consider

• procedure for obtaining consent
• arrangements for recruitment of subjects
• indemnity/compensation for subject or patient
• insurance or indemnity to cover the liability of
  sponsor and investigator
• payments and financial agreements

• relevance of trial and design
• risks/benefits, conclusion justified
• the protocol
• suitability of investigator and supporting staff
• Investigator Brochure
• quality of the facilities
• consent Form/Patient information sheet

7
EU Directive on GCP in Clinical Trials
(2001/20/EC)

• The ethics committee shall have a maximum of 60
  days from the date of receipt of the valid
  application to give its reasoned opinion
• A single request may be sent for supplementary
  information
• No extension to 60 day period except for trials
  involving gene therapy, somatic cell therapy,
  xenogenic cell therapy

8
Governance Arrangements for Research
Ethics Committees (GAfREC)(U.K. ethics review
system)
9
Research Ethics Committees(in the U.K.)

• The language
• MREC Multi-centre Research Ethics Committee
• LREC Local Research Ethics Committee
• COREC Central Office for Research Ethics
  Committees
• OREC Office of Research Ethics Committee
• GAfREC Governance Arrangements for Research
  Ethics Committees
• UKECA United Kingdom Ethics Committee
  Authority
• NPSA National Patient Safety Agency

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Central Office for Research Ethics Committees

• Administrative body generating policy for all
  Research Ethics Committees
• Based in London
• Became part of the National Patient Safety Agency
  from 1st April 2005
• The Head of the NPSA is Prof. Sir John LIlleyman
  who has ultimate responsibility for COREC
• Janet Wisley is Director of COREC

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Composition of an REC
• 12-18 members
• Balanced age and gender distribution
• Sub-committee encouraged
• Lead Reviewers suggested
• Quorum of 7 members stipulated and defined
• Co-opted members allowed as defined to ensure
  balance of committee is maintained

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Recognised Research Ethics Committees are defined
  as
• RECs that are recognised by the United Kingdom
  Ethics Committee Authority (UKECA) for the
  purpose of reviewing CTIMPs (Clinical Trials
  involving medicinal products)
• Authorised Research Ethics Committees are defined
  as
• RECs established under GAfREC but not recognised
  by UKECA. An authorised REC may review all
  applications except those relating to CTIMPs
  (clinical trials using medicinal products) and
  multi-centre research in two or more domains.

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Under the Clinical Trials Regulations a trial
  site means a hospital, health centre, surgery or
  other establishment or facility at or from which
  a CTIMP or any part of a CTIMP is conducted. For
  research taking place within the NHS this will
  normally be
• An acute NHS Trust
• A NHS Health Board (in Scotland)
• A Health and Personal Social Services Trust (in
  Northern Ireland)
• A GP Practice

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Research sites outside the NHS could include
• an academic institution
• a research centre funded by the voluntary sector
• a Government Department or other public body
• a prison establishment or secure unit
• a private company or corporation
• a private hospital or clinical practice

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• A Chief Investigator is the person with overall
  responsibility for multi-centre studies
• Principal Investigator is the person at each
  research site who has responsibility for the
  study at that site.

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Main REC is an operational term used to describe
  the one (and only) ethics committee undertaking
  the ethical review of a multi-centre study,
  where site specific assessments will be made by
  other RECS.
• A favourable opinion from one Main REC will
  suffice for the whole of the U.K.
• A Main REC can be either an MREC
• or
• A Recognised LREC

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• SSA - Site Specific Assessment
• Principal Investigators must each apply for SSA
• Local Committee must consider the suitability of
  the investigator, facilities and local
  acceptability of the study
• Local ethics committees will receive only part C
  of the ethics application and the CV of the
  Principal Investigator in order to make their SSA
  decision.
• SSA can be conducted outside of the main ethics
  meeting.
• LREC must notify Main REC of SSA decision
  within 25 days

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R D Management approval and funding

• R D Management permission is required at each
  NHS Trust site before research can begin and is
  required for any study involving NHS patients,
  staff and facilities
• R D approval does not come under the 60 day
  time frame stipulated in the Directive for ethics
  review
• Ethics approval is conditional upon the PI
  obtaining
• R D approval.
• For studies in primary care, approval must be
  given by the Primary Care Trust (PCT)

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• For multi-centre studies it is the role of the
  Chief Investigator to apply for ethics review
• All trials for studies involving medicinal
  products must go through the COREC Central
  Allocation System (see COREC website
  www.corec.org.uk)
• The Chief investigator should ensure that all
  principal investigators are informed when the
  application to the Main Ethics Committee has been
  validated.
• Principal investigators can then apply for their
  own local site specific assessment and this can
  run in parallel with the main REC request for
  favourable opinion.

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• General
• The process of favourable opinion and SSA must
  be completed within 60 calendar days (legal
  requirement)
• The REC can only seek clarification on specific
  issues once before a decision is made - written
  request
• The 60 day clock stops while awaiting response
• If the response received is unsatisfactory, REC
  may reject
• The applicant may be given a further chance to
  clarify but the 60 day clock only starts
  once a satisfactory response has been received.
• A Conditions of Approval letter is sent with
  each favourable opinion letter

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Substantial amendments , Investigator Brochures,
  summaries etc should be sent only to the Main REC
  conducting the actual ethics review
• R D departments will also require copies of
  substantial amendments and relevant reports of
  the study
• A change in the management of a site (i.e. new PI
  ) is a substantial amendment and requires a new
  SSA and updated approval from R D.

22
Governance Arrangements for Research Ethics
Committees (GAfREC)

• Safety reports The Main REC who gave the
  favourable opinion should receive the following
• Expedited reports of all suspected unexpected
  serious adverse reactions (SUSARS) occurring in
  the U.K. for the trial on which the favourable
  opinion was given. This includes SUSARS
  associated with active comparator drugs.

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• Safety reports
• There is a standard covering form for sending
  reports to the RECs in the UK.
• Safety reports may be submitted by the sponsor or
  by the sponsors representative or by the Chief
  Investigator.
• There is not a routine requirement to report
  serious adverse events other than SUSARS
• Safety reports only need to be sent to the Main
  REC who gave favourable opinion for the research.
  They do not need to go to local ethics
  committees.

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• UK process
• Competent Authority authorisation
• Ethics favourable opinion (Main REC)
• Site Specific Assessment (SSA)
• R D Trust Management approval
• Sponsors must quote ethics reference number and
  also EUDRACT number

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Governance Arrangements for Research Ethics
Committees (GAfREC)

• SUMMARY
• Ethics committees who review research covered by
  the EU Directive must be Recognised by UKECA
• Committees who are not Recognised will review
  only research that does not involve clinical
  trials with medicinal products
• There is a different ethics process for studies
  not involving medicinal investigational products
  (see COREC website)

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The Warner Report(Review of U.K. Ethics system)

• Recommendations
• Site Specific assessments should transfer to NHS
  hosts
• Integrate the process of research governance
  review with ethics review to allow one form and
  application process
• Reduce the number of RECs and review their
  composition, frequency of meeting etc (possible
  reduction of 50 per cent of RECs)
• Establish national programme of training and
  development for REC members

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Key Messages

• Valid Applications are important - ensure there
  are checklists/ procedures in place.
• Substantial Amendments must be reviewed by
  ethics committees and/or Competent Authorities
  and will have an impact on study timelines.
• Chief Investigators should understand the
  administrative burdens of their role
• Check the Corec website regularly for updates
• www.corec.org.uk