1. 1 Research Ethics Infrastructure Challenges in Establishing an Effective System 1 Ruth Macklin, PhD Florencia Luna, PhD

2. 2 Capacity building Widespread agreement on need for capacity building in research ethics in developing and transition countries –CIOMS international ethical guidelines –Nuffield Council and NBAC Reports –UNAIDS Vaccine Guidance Document –WHO, NIH, and FIC sponsored workshops But how to determine when capacity is successfully built? 2

3. 3 Settled ethical issues An effective research ethics infrastructure must have –Officially recognized regulations or guidelines governing research with human beings –A system of well-functioning research ethics committees (RECs) –Ethics training for researchers and members of RECs –A system for oversight and monitoring 3

4. 4 Challenges Which international guidelines to use? Who should monitor research, and how? How to ensure adequate ethical review of research protocols? What sort of ethics training is appropriate and adequate? Ongoing problems and controversies 4

5. 5 Regulations and guidelines Many developing countries lack laws or regulations governing ethics in research International guidelines are increasing in number and are not harmonized –Declaration of Helsinki –CIOMS International Ethical Guidelines –ICH GCP –UNESCO Universal Declaration on Bioethics and Human Rights 5

6. 6 Regulations and guidelines Regulations and guidelines require interpretation –Cannot deduce a particular application of a guideline –Example from Declaration of Helsinki At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study. –Para. 30 6

7. 7 Regulations and guidelines Guidelines conflict with one another –Multiple and confusing provisions relating to standard of care For participants in control groups in RCTs For participants in prevention trials who acquire the target disease during a clinical trial For participants in any research who develop a treatable disease or condition during the trial –DoH very vague on this point –CIOMS and UNAIDS Guidance disagree 7

8. 8 Ensuring adequate ethical review RECs should have members with expertise in scientific and methodological aspects of research under review –Bad science is bad ethics RECs should clearly indicate which regulations or ethical guidelines they use RECs must have rules of procedure, keep records of proceedings, be accountable 8

9. 9 Ensuring adequate ethical review Desirability of central or regional RECs? Local RECs –Institutional level (hospital based) –Independent but academic based (universities, academic societies) –Independent (for profit) Are for-profit RECs acceptable? –Their client is the sponsor of research but their mandate is to protect human subjects Quality of REC review of research proposals –Avoiding rubberstamping –Avoiding inconsistencies

10. 10 Facilitating ethical review Institutions and governmental agencies should provide financial and administrative support for RECs –Competent secretarial assistance –Photocopying research protocols for distribution to REC members –Communications with investigators –Complete record of REC decisions, progress reports, amendments to protocols 10

11. 11 Ongoing challenges Controversies regarding voluntary vs. professional/paid RECs members Difficulties with voluntary system –Affording protected time –Conflicting demands of job requirements –Recognition of REC service in continuing professional development Preventing REC shopping Confidentiality versus transparency

12. 12 Ongoing challenges Complete follow up of clinical trials and availability of data (publications-bad data) National systems: Sisnep (National system of Information on research ethics involving persons) (Brazil) http://portal.saude.gov.br/sisnep/pesquisador/men uusuario.cfm http://portal.saude.gov.br/sisnep/pesquisador/men uusuario.cfm Creating a centralized registry of clinical trials – International clinical Trials Registry Platform (WHO) http://www.who.int/ictrp/en http://www.who.int/ictrp/en

13. 13 Ethics training Researchers and ERC members should receive ethics training –What sort is adequate or desirable? On-line courses and tests In-person training by experts in research ethics Distribution of the Declaration of Helsinki and other pertinent guidelines or regulations Use of case studies –Total absence of standards or agreement on this issue 13

14. 14 Ongoing challenges Is informal training adequate? Is there a need for official training or standards? Is a system of accreditation of RECs needed? –What would be the standards?

15. 15 Oversight and monitoring Compliance with regulatory authorities for research involving drugs and biotechnology products –European Agency for the Evaluation of Medical Products (EMEA) –U.S. Food and Drug Administration (FDA) –ICH GCP Researchers and RECs must be familiar with these requirements 15

16. 16 Oversight and monitoring Oversight at national or regional level –Some countries have governmental agencies with this responsibility OHRP in U.S. Issues FWAs for other countries –Most developing countries lack any such agency –How to ensure adequacy of REC review and compliance with regulations or guidelines? 16

17. 17 Oversight and monitoring RECs responsible for establishing and maintaining a monitoring system –Adverse event reporting and progress reports –Compliance monitoring necessary to ensure that researchers conduct research properly In compliance with provisions in the protocol In compliance with ethical requirements –Requires a dedicated person knowledgeable about research regulations and ethics –Is time consuming and labor intensive 17

18. 18 Ongoing challenges Informed consent –IC documents provided by industry are overly long, use medical jargon, complex language –Process of obtaining informed consent in conduct of research often flawed, cursory, inadequate understanding by participants –Individual ERCs often not allowed to make changes in consent forms for multicentric trials 18

19. 19 Ongoing challenges Involving communities –Numerous international guidelines refer to community involvement or community participation in the research enterprise Lip service paid to this requirement but little evidence of actual adherence –What forms of community involvement are desirable? Community members on RECs not sufficient –Are there any good models?

20. 20 Ongoing challenges What must RECs review? –Social and behavioral research Not required in some countries or committees Not reviewed even if required –Quality improvement/quality assurance How to distinguish from health systems research? –Public health surveillance or studies in outbreaks How to distinguish from public health research? 20

21. 21 Conflicts of interest What constitutes a genuine conflict of interest in the research setting? –Substantial financial interest on part of researchers or members of RECs –Researchers may not be involved in ethical review of their own protocols Challenges and uncertainties –Members of same academic department, laboratory, or institution as the researcher? 21

22. 22 Controversies regarding money Is it acceptable to pay research subjects for their participation? –Common in some countries, frowned upon in some, prohibited in others –RECs must determine whether and how much Finders fees for recruitment of subjects 22

23. 23 Conclusions Laws, guidelines, and regulations abound –But may conflict with one another –Often do not give clear guidance –May be interpreted differently by RECs RECs are increasingly established in developing countries –Yet reports exist of lack of competency –Hard to obtain information about functioning –General absence of oversight and monitoring 23

24. 24 The way forward Ethical guidelines –No additional ones, please –Can existing ones be harmonized in some way? –Revision and updating needed as things change Declaration of Helsinki and CIOMS, yet controversies remain UNAIDS Guidance for vaccines a new effort 24

25. 25 The way forward Research ethics training and education –More regional workshops needed Train the trainers for in-country capacity building –Educational sessions on research ethics at conferences attended by researchers Industrialized and developing countries Exchange programs and visiting scholars among researchers and REC members –Establishing effective and sustainable research ethics networks in developing countries 25