1. Applicability of CIOMS 2002 Guidelines to developing countries (CIOMS 2002 International Ethical Guidelines for Biomedical Research Involving Human Subjects) Prof. Juhana E. Idänpään-Heikkilä, MD, PhD Secretary-General Council for International Organizations of Medical Sciences (CIOMS) c/o WHO, Geneva, CH
Juhana E.Idänpään-Heikkilä, October 2003

2. biomedical science organizations/bodies
What is CIOMS?
International, non-governmental, non-profit organization
Established 1949 by WHO and UNESCO
A forum to consider and prepare advice on
contentious issues in health and research ethics (for WHO,UNESCO and others)
Members: Over 70 international/national
biomedical science organizations/bodies
Juhana E.Idänpään-Heikkilä, October 2003

3. Purpose of CIOMS guidelines
Indicate/advise how fundamental ethical principles
can be applied effectively in medical research
worldwide in different:
cultures, religions, traditions;
socioeconomic circumstances;
national legal and administrative contexts;
and situations in developing countries
implementation in practice of the Declaration of Helsinki

4. CIOMS 1993 Guidelines Revision Process
Steering Committee, May 1999
Consultation, March 2000, a report published
Drafting Group, January 2001
Draft on CIOMS website, July-Oct. 2001
Comments requested from some 400 institutions/persons and more than 70 replied
Electronic editorial group, Oct
CIOMS Conference, Fabruary 2002
Final version on CIOMS website, Sept. 2002
Revised Guidelines published in mid-October 2002

5. Titles and Categories of Guidelines (1)
GL.1: Ethical justification and scientific validity of biomedical research involving human subjects
ETHICAL REVIEW
GL. 2: Ethical review committees
GL. 3: Ethical review of externally sponsored research

6. Titles and Categories of Guidelines (2)
INFORMED CONSENT
GL. 4: Individual informed consent
GL. 5: Obtaining informed consent: Essential information for prospective research subjects
GL. 6: Obtaining informed consent: Obligations of sponsors and investigators
GL. 7: Inducement to participate
GL. 8: Benefits and risks of study participation
GL. 9: Special limitations on risk when research involves individuals who are not capable of giving informed consent

7. Women as research participants
GL. 16: Women as research participants
GL. 17: Pregnant women as research
participants

8. Titles and Categories of Guidelines (3)
Special situations:
GL. 10: Research in populations and communities with limited resources
GL. 11: Choice of control in clinical trials

9. Titles and Categories of Guidelines (4)
Vulnerable groups
GL. 12: Equitable distribution of burdens and benefits in the selection of groups of subjects in research
GL. 13: Research involving vulnerable persons
GL. 14: Research involving children
GL. 15: Research involving individuals who by reason of mental or behavioural disorders are not capable of giving adequately informed consent

10. Titles and Categories of Guidelines (5)
Women as research participants:
GL. 16: Women as research participants
GL. 17: Pregnant women as research
participants

11. Titles and Categories of Guidelines (6)
GL. 18: Safeguarding confidentiality
GL. 19: Right of injured subjects to treatment and compensation
GL. 20: Strengthening capacity for ethical and scientific review and biomedical research
GL. 21: Ethical obligation of external sponsors to provide health-care services
Appendix I: Items to be included in a protocol

12. GL. 1: Ethical justification and scientific validity of biomedical research involving human subjects
Justification: If the prospect is to discover new ways of benefiting people’s health
Ethical justification:
-Respect and protect and be fair to participating subjects
-Conform to scientific principles
-Design scientifically sound, competent investigator/staff
-Research protocol to be submitted for review/clearance/ approval to scientific and ethical review committees ( Items to be included in the protocol, see Appendix 1)

13. GL. 2: Ethical review committees
Review of protocol for scientific merit and ethical acceptability (one or more committees, science!)
Independent of research team, financial or material benefits
Clearance or approval, further reviews, monitoring progress
Scientific review: criteria
Ethical review:criteria
Ethical review of emergency use of investigational therapy
National (centralised) or local review
Committee membership
Multi-centre research
Sanctions

14. GL. 3: Ethical review of externally sponsored research
Definition: what is “externally sponsored research”
Ethical and scientific review
Committees in both country of sponsor and host
Committee of sponsoring country: are scientific methods sound, suitable to the aims of research, are products safe, justification for not conducting study in sponsoring country
Committee of host country: Responsiveness to health needs and priorities of country, understanding of customs and traditions, means of obtaining informed consent, competence of research team

15. GL. 4: Individual informed consent
Voluntary informed consent of prospective participant
Not capable of giving consent : legally authorised representative, waiver informed consent uncommon and exceptional, must be approved by ethical committee
Process, language, comprehension, documentation, waiver requirements, renewing consent, cultural considerations, consent for research on biological material, use of medical records and biological specimens, secondary use of research records or biological specimens

16. GL. 5: Obtaining informed consent::Essential information for prospective research subjects
Before consent investigator must provide information in language or other form of communication individual can understand.
26 most important points of information listed

17. GL. 6: Obtaining informed consent: Obligations of sponsor and investigators
Refrain from unjustified deception, undue influence or intimidation
Ascertain adequate understanding, sufficient opportunity to consider
Signed form as evidence -exceptions approved by EC
Renew consent: changes in conditions/procedures or new information becomes available and renew in long-term studies at pre-determined intervals

18. GL. 7: Inducement to participate in research
Acceptable recompense
Unacceptable recompense
Incompetent persons
Withdrawal from a study

19. GL. 10: Research in populations and communities with limited resources
Make every effort that research is responsive to the health needs and priorities of the population/community
intervention developed/knowledge generated be made reasonable available for the population/community
negotiate this in advance with government, local health authorities, representatives of community/advoc.groups:
infrastructure required for safe/ rational use, authorisation to market, payments, royalties, subsides, intellectual property, distribution costs, who is responsible: donor gvnmt, intern. organisation, non-gvnmt organisation, private sector,others

20. GL 11: Choice of control in clinical trials (1)
General rule: control group should receive established effective intervention
Exceptions:
- Established effective intervention is not locally available and study tests an effective locally available alternative treatment
- Alternative responsive to local health needs and will be made reasonably available and local EC satisfied
Comparator can be placebo or no treatment or local remedy

21. GL 11: Choice of control in clinical trials (2)
Some experts strogly oppose to the exceptioonal use of a
comparator other than an established effective intervention
WHY?
-Could result in exploitation of poor and disadvantaged
-If placebo control: exposes to risks and harms
-An economic reason for the unavailability of an establehed effective intervention cannot justify a placebo controlled study in a country of limited resources if the study would be unethical in a country with access to the effective intervetion

22. GL. 20: Strengthening capacity for ethical and scientific review and biomedical research
Capacity-building may include, but is not to:
-establishing/strengthening ethical review committees
-strengthening research capacity
-developing technologies to health-care/research
-training research and health-care staff
-educating community from which subjects be drawn
Negotiate with host-country authorities
Avoid conflict of interest (independent ethics committees!!)

23. GL. 21 : Ethical obligation of external sponsors to provide health-care services
External sponsor ethically obliged to ensure availability:
-health-care services essential to safe conduct of research
-treatment for subjects who suffer injury
-beneficial intervention/product developed to be reasonably available to population/community
Clarify before research is begun- add to protocol, consent
Health care-care during and after trial -how long
Not health-care beyond that which is necessary, but treat diseases contracted during study, found other diseases be referred for medical care

24. CIOMS Guidelines versus Declaration of Helsinki
CIOMS Guidelines depart in Guideline 11 from terminology of the Declaration of Helsinki:
CIOMS GL. 11:
“Established effective intervention”
Declaration of Helsinki paragraph 29:
“The best current…therapeutic method”

25. CIOMS note on GL. 11
“Best current intervention” is the term most commonly used to describe the active comparator that is ethically preferred in controlled clinical trials. For many indications, however, there is more than one established “current” intervention and expert clinicians do not agree on which is superior. In other circumstances in which there are several established “current” interventions, some expert clinicians recognize one as superior to the rest; some commonly prescribe another because the superior intervention may be locally unavailable, for example, or prohibitively expensive or unsuited to the capability of particular patients to adhere to a complex and rigorous regimen.
“Established effective intervention” is the term used in Guideline 11 to refer to all such interventions, including the best and the various alternatives to the best. In some cases an ethical review committee may determine that it is ethically acceptable to use an established effective intervention as a comparator, even in cases where such an intervention is not considered the best current intervention.

26. CONCLUSIONS Purpose of CIOMS GLs: ”situations in developing countries”
Ethical review of externally sponsored research (GLs 2-3)
Obtaining informed consent (GLs 5 and 6)
Research in populations and communities with limited resources (GL 10)
Choice of control in clinical trials (GL 11)
Strengthening capacity for ethical and scientific review and biomedical research (GL 20)
Ethical obligation of external sponsors to provide health-care services (GL 21)