Application of International Guidelines to National Regulations on Research: Building research ethic

1
Application of International Guidelines to
National Regulations on Research Building
research ethics infrastructure in Lithuania

• E. Gefenas
• Vilnius University, Lithuanian Bioethics Committee

2
Diversity of RECs systems in the Baltic states

• Lithuania 2-tier system of ethical review of
  multicenter protocols 1 National Committee plus
  two regional RECs
• Latvia - 7 RECs and the National one only takes
  specific projects (genome project)
• Estonia 2 RECs based at the universities
• Some other examples
• Czech Rep. 9 Regional RECs, 100 local RECs

3
Steps of developming RECs system in Lithuania
(population 3,5 mln)

• Late eighties/early nineties Pre-legal state -
  Started from two IRBs at two largest medical
  schools
• 1997 a special Decree of the MoH on the ethical
  expertise of biomedical research - LBEC is the
  only institution authorized to issue approvals
  upon the recommendation of the SDCA )
• 2001 The Law on Ethics of Biomedical Research -
  two tier system (nationalregional RECs)
• 2004 Amendments of the Law EBR (changes of the
  procedure - approval by SDCA, favourable opinion
  of REC)
• 2007 Amendments of the Law on EBR (changes of
  the regulation of regional RECs)

4
Tendencies behind the RE infrastructure Down
top approach

• active researchers/institutions established RECs
  in order to start co-operation with international
  partners
• Positive self-regulation, flexibility
• Negative
• diverse structures
• interests of the research participants play a
  secondary role
• Diving force legitimating of pharmaceutical
  clinical trials

5
Dynamics of commercial/non-commercial research
reviewed by RECs in 1997-2005
6
Tendencies behind the RE infrastructure Top-down
approach

• after joining the Council of Europe and the EU
  implementation of international instruments and
  harmonization of national legislation
• Positive
• structured approach changes in the law
• universal implementation all over the member
  state
• primary purpose protection of human rights
  approach
• Negative
• bureaucratization of the system
• Discrepancies between different regimes of
  ethical review applied to different types of
  human research

7
International background

• European international instruments in the field
  of biomedical research
• Council of Europe The Convention on Human Rights
  and Biomedicine, Oviedo Convention, 1997
• and its Additional Protocol on Biomedical
  Research, 2004 (AP-CHRB-BR) - deals with all the
  biomedical research including pharmaceutical
  trials
• European Union Directive 2001/20/EC on Clinical
  trials on medicinal products for human use

8
Europe
9
The European Union 27 countries

• Initially established to deal with trade and
  economy, now it also deals with human rights
  issues
• Its directives are mandatory to the member
  states
• Old Member States (MS) - 15
• Enlargement - May 1, 2004, when 10 states joined,
  and the most recent on January 1, 2007, when
  Bulgaria and Romania joined.
• Directive on CT deals with clinical trials on
  medicinal products for human

10
European Union before the enlargement in 2004
11
The Council of Europe

• 47 member states
• A state may become a member of the Council of
  Europe if it is deemed able and willing to
  respect human rights and fundamental freedoms
• Its Conventions are legally binding after the
  Member States ratify them (and additional
  protocols)

12
Areas of concern

• RECs
• Institutional vs regional RECs
• Problematic process of ethical review (emphasis
  on IC, monitoring of AE, etc.)
• Researchers
• Conflicts of interest
• Structural
• Non-equivalence of ethical review

13
RECs I Problematic points in the process of
ethical review

• emphasis on procedure rather than ethics
  (N.Goodman, Chair of Southmead LREC, UK, 2004)
• Emphasis on IC, methodology of biomedical
  research/clinical trials is not always critically
  evaluated
• How efficient is monitoring of ongoing research
  safety information collected (e.g., piles of
  adverse events reports)
• Clinical drug trials how to achieve an efficient
  collaboration with the competent authorities?
  (e.g., solved by UK Memorandum of understanding
  between MHRA, COREC, GTAC)

14
RECs II Regional or Institutiona?

• How to establish de facto independent system of
  ethical review?
• Is the regional model feasable in the context of
  weak municipal health services? Are universities
  the only realistic host for the RECs?
• The EFGCP Report on The Procedure for the
  Ethical Review of Protocols for Clinical Research
  Projects in Europe (Update March 2008)
• Question 16. How is the independence of members
  ensured? Answer from one of the member states
• Mainly by an appeal to their conscience.
• http//www.efgcp.be/Downloads/EFGCPReportFiles/Flo
  w20Chart20Czech20Republic20(revised)2008-04-0
  1.pdf

15
Researchers I Conflict of interest

• Physicians acting as researchers in industry
  sponsored research
• Physicians salaries are a few times smaller in
  CEE than in Western/Northern Europe
• E.g., a newly qualified Hungarian doctor earns
  about 500 Euro which is less than a quarter of a
  similar salary in the UK (W. Underhill, 2006,
  MSNBC.com)
• It seems that the payments for researchers would
  significantly exceed the compensation for their
  clinical work (with their own patients!) or
  university initiated research
• Often these are direct payments

16
Researchers II What is acceptable payment?

• Per capita payments should be comparable to the
  physicians or researchers usual professional
  fee
• TCPS, Article 7.3, Canada 1998
• RCP, UK 2007
• difficult to evaluate because it is possible to
  overestimate the time required for each patient
  (J.M.Rao, L.J. Sant Cassia, 2002)

17
Non-equivalence or Asymmetry of ethical review

• Strigency of regulations decreases as we go from
• clinical drug trials (double control, legally
  binding provisions of ethical review)
• to other types of biomedical research
  international instruments (e.g., AP to the Oviedo
  Convention) not yet implemented
• to non-biomedical human research no binding
  instruments

18
Is this a valid perception of RECs/IRB II?!

• RECs recognize that they are generally a group
  made up of conscientious, sincere and
  disinterested amateurs who are reviewing too
  much, too quickly, with too little experience
• (The Lancet Oncology, vol 5, May 2004, p. 235)