Dr. Derrick Aarons

APPENDIX B Draft Position Paper On Human Subjects Research In The Caribbean Dr. Derrick Aarons

Preamble:

This paper draws attention to the need by CARICOM Ministers of Health to regulate the conduct of research with human participants to provide best practices, ensure consistency and harmonization, and protect the countries in the region from harmful exploitative research activities through legislation as a matter of urgency.

STATEMENT OF THE ISSUES:

The international standards to be met:

Research: Research is a step into the unknown, but it is essential to gain new knowledge that benefits individuals and society. Because research seeks to understand something not yet known or revealed, it often entails risks to research participants and to others. History offers unfortunate examples where research participants have been needlessly, and sometimes profoundly harmed by research, sometimes even dying as a result. Consequently, research with human participants should be carried out only by, or strictly supervised by, suitably qualified and experienced investigators and in accordance with a proper research protocol that has been scientifically and ethically appraised by one or more suitably constituted review bodies, independent of the investigators. As required by the Declaration of Helsinki, the Council for International Organizations of Medical Sciences (CIOMS), and other International Health Research Regulatory bodies, all proposals to conduct research involving human participants must be submitted for a priori review of their scientific merit and ethical acceptability to an ethical review committee. The investigator must obtain their approval or clearance before undertaking the research.

Sanctions: Ethical review committees (research ethics committees) generally have no authority to impose sanctions on researchers who violate ethical standards in the conduct of research involving humans. These committees should be required to monitor the implementation of an approved protocol as well as its progression, and to report to governmental authorities or project sponsors any serious or continuing non-compliance with ethical standards in the protocol that were approved by the research ethics committee. Failure to submit a protocol to the committee or to adhere to the approved protocol should be considered a clear and serious violation of ethical standards, and subject to an appropriate sanction.

The ethical review of research: Contemporary research often involves collaborative partnerships among researchers from multiple countries or sites. Researchers and sponsors from outside the Caribbean region should submit their research protocols for ethical and scientific review in their own country as well as in the Caribbean country in which research is proposed, and the ethical standards applied should be no less stringent than they would be for research carried out in developed countries. The health authorities of the researched country, as well as any national or local

Appendix B…….….cont’d

research ethics committee, should ensure that the proposed research is responsive to the health needs and priorities of the researched country and meets the requisite ethical standards. Vulnerability to exploitation: Before undertaking research in a population or community with limited resources, the sponsor and the investigator must make every effort to ensure that: the research is responsive to the health needs and the priorities of the population or community in which it is to be carried out; and

any intervention or product developed, or knowledge generated, will be made reasonably available for the benefit of that population or community.

This is a CIOMS guideline that is concerned with countries or communities in which resources are limited and the extent to which they are, or may be, vulnerable to exploitation by sponsors and investigators from the relatively wealthy countries and communities. It is not sufficient simply to determine that a disease is prevalent in the population and that new or further research is needed; the ethical requirement of "responsiveness" can be fulfilled only if successful interventions or other kinds of health benefit are made available to the population. This is applicable especially to research conducted in countries where governments lack the resources to make such products or benefits widely available. Even when a product to be tested in a particular country is much cheaper than the standard treatment in some other countries, the government or individuals in that country may still be unable to afford it. If the knowledge gained from research in a less developed country is used primarily for the benefit of populations that can afford the tested product (i.e. developed countries), the research may rightly be characterized as exploitative and, therefore, unethical. Various types of harm to research participants are also always possible. If an investigational drug has been shown to be beneficial, the sponsor should continue to provide it to the subjects after the conclusion of the study, pending its approval by a drug regulatory authority. If there is good reason to believe that a product developed or knowledge generated by research is unlikely to be reasonably available to, or applied to the benefit of the population of a proposed host country or community after the conclusion of the research, it is unethical to conduct the research in that country or community. Right of injured subjects to treatment and compensation: Investigators should ensure that research subjects who suffer injury as a result of their participation in research are entitled to free medical treatment for such injury and to such financial or other assistance as would compensate them equitably for any resultant impairment, disability or handicap. Further, that in the case of death as a result of their participation, their dependents are entitled to compensation. Research participants must not be asked to waive the right to compensation. Strengthening capacity for ethical and scientific review of biomedical research: In externally sponsored collaborative research, sponsors and investigators have an ethical obligation to ensure that biomedical research projects for which they are responsible in less developed countries contribute effectively to national or local capacity to design and conduct biomedical research, and

Appendix B………....cont’d

to provide scientific and ethical review and monitoring of such research. Capacity-building may include, but is not limited to, the following activities: establishing and strengthening independent and competent ethical review processes/ committees

strengthening research capacity

developing technologies appropriate to health-care and biomedical research

training of research and health-care staff

educating the community from which research subjects will be drawn

External sponsors and investigators have an ethical obligation to contribute to a host country's sustainable capacity for independent scientific and ethical review and biomedical research. Before undertaking research in a host country with little or no such capacity, external sponsors and investigators should include in the research protocol a plan that specifies the contribution they will make. The amount of capacity building reasonably expected should be proportional to the magnitude of the research project.

What is happening in some Caribbean countries:

Many Caribbean countries lack the capacity to assess or ensure the scientific quality or ethical acceptability of biomedical research proposed or carried out in their jurisdictions. Some CARICOM countries have established research ethics committees (RECs), some have committees in name only, while some do not have any type of ethics committee. For those who have RECs, whilst a few members of these committees may have received some training in research and research ethics, the majority of members are in need of specific training in the international ethical standards to be met for research in developing countries. A recent survey by the Caribbean Public Health Agency (CARPHA) of research ethics committees currently working in the Caribbean revealed that they varied widely in their ability to properly evaluate research proposals, that their members were all volunteers who sometimes could not meet to carry out the work of the committee effectively, that some have resource shortages, and that all would welcome training for their members.

In many developed countries, research with human participants is governed by regulation or legislation that specify the terms and conditions to be met in carrying out research within their various jurisdictions. For example, in the USA (from whence the majority of sponsors and researchers come for research in our Caribbean countries), the HHS Regulations, 45 CFR part 46, govern all aspects of research with human participants. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) brought together the regulatory authorities of Europe, Japan, and the United States to produce the Guidelines for Good Clinical Practice that was adopted by several countries, including Canada, for clinical trials research.

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The UK Clinical Trials Regulations 2004 stipulate that the regulations are intended to protect the rights, safety and well-being of research participants, and to simplify and harmonize regulatory processes. The European Union Clinical Trials Directive and the Oviedo Convention have been ratified by several European countries, and reflect ethical principles regarding research with human participants upon which a broad consensus across Europe has been reached. These and other legal instruments are referred to and referenced where appropriate, and it is required that researchers and research ethics committees comply with all the relevant laws in those countries. In the Caribbean, only Guyana has any regulation that addresses medical research involving human participants. However, that regulation now needs updating to address matters such as the fair selection of research participants, specific safeguards for confidentiality, the right of research-injured participants to appropriate treatment and compensation, and enforcement and penalties. Some Caribbean countries are presently being approached for conducting drug studies and similar research because they are viewed as not having the very stringent ethical requirements for research that exists in the more developed countries, and where the costs of conducting research is far less. Where local expertise does not exist to properly evaluate these research proposals to the international ethical standards, and law does not exist to specifically protect the participants in research, then local participants may be exploited and harmed. Ethically, harms may not only be physical, but also psychological/emotional, social, financial/ economic, and legal. A regional Research Ethics Committee now exists at CARPHA, and is fully constituted with experts to give support in all matters of research and research ethics. If invited to do so, CARPHA can also provide training in this area.

PROPOSALS FOR ADDRESSING THESE CONCERNS:

CARPHA’s Research Ethics Secretariat hereby recommends the following to CARICOM Ministers of Health:

1. The establishment of a Regulatory Framework for the conduct of research with human participants based on the principles and standards outlined above and including the following requirements:-

i) All researchers must apply for approval from an appropriately designated national or regional research ethics committee before embarking on research ii) An appropriately constituted research ethics committee with the required legal authority shall review all research proposals that involve human participants iii) All approved research should be monitored for the well-being of research participants by the research ethics committee

2. The preparation of a model legislation for CARICOM countries to regulate research with human participants. The legislation should contain the provision of appropriate sanctions for non-compliance.

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3. That CARICOM Ministers of Health approve the Proposals for implementation of a regulatory framework in principle, and agree to their adoption as Policy. 4.This Policy will have immediate effect, pending the implementation of the process for enactment of legislation.

Submitted by:

Derrick Aarons MD, PhD

Ethicist – The Caribbean Public Health Agency (CARPHA)