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 e-mail: idanpaanj@who.int www.cioms.ch Juhana E.Idänpään-Heikkilä, October 2003

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

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

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. 2001- CIOMS Conference, Fabruary 2002 Final version on CIOMS website, Sept. 2002 Revised Guidelines published in mid-October 2002

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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!!)

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

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”

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.

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)