Research Ethics Infrastructure Challenges in Establishing an Effective

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

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

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

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

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

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

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 – Do. H very vague on this point – CIOMS and UNAIDS Guidance disagree 7

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

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 9

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

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 11

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 • Creating a centralized registry of clinical trials – International clinical Trials Registry Platform (WHO) http: //www. who. int/ictrp/en 12

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 13 issue

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? 14

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

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

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

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

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?

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

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

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

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

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

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 25 ethics networks in developing countries