- Distinguishing Statements of Ethical Principles and Regulatory Guidelines
- Comparative Analysis of International Documents Addressing Protection of Research Participants
- Statements of Ethical Principles
- International and U.S. Regulatory Guidelines
- Other Ethics of Research with Human Subjects Documents
- Reports on the Ethics of Research in Developing Countries
- Ethics Guidance for HIV/AIDS Research
Distinguishing Statements of Ethical Principles and Regulatory Guidelines
The U.S. Office for Human Research Protections (OHRP) distinguishes ethical principles and regulatory guidelines. The former are a statement and sometimes a discussion of fundamental ethical values and principles important to protecting human subjects in scientific and medical research. A statement of fundamental values and principles is important since, as explained in the Belmont Report, codes of rules "are often inadequate to cover complex situations; at times they come into conflict, and they are frequently difficult to interpret or apply. Broader ethical principles will provide a basis on which specific rules may be formulated, criticized and interpreted." Regulatory guidelines are not a discussion of ethical values, but usually are a list of do's and don'ts or procedural standards. In the U.S., U.S. regulatory guidelines have the force of law.
International institutions who apply for a U.S. Federalwide Assurance (FWA) are asked in their application to select:
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(i) a statement of ethical principles (one from the list below) which they promise will guide all research at their institution, and
(ii) a set of regulatory guidelines or procedural standards (one from the list below) which they promise will guide all federally-conducted or -supported research at their institution.
By clicking on the links below you can access U.S. and international documents regarding the ethics of research with human subjects. Note: document descriptions are excerpted from the corresponding websites.
Comparative Analysis of International Documents Addressing Protection of Research Participants
(This document can be found in volume two of the NBAC report on Ethical and Policy Issues in International Research.) "This chart compares the texts of 25 documents that address the protection of research participants. [It includes] seven documents … developed by various international organizations [that] provide general guidance, … The remaining 18 documents come from countries around the world and provide regulations or guidance specific to that country." The documents are compared with regard to: (i) informed consent and disclosure, (ii) assessing risks and benefits, (iii) selection of participants and distribution of risks and potential benefits, (iv) study design considerations, (v) obligations to research participants, (vi) legal considerations. (a pdf file - select vol. II)
Statements of Ethical Principles
The Belmont Report (English) - This document provides an ethical foundation for the U.S. Federal Regulations for the protection of human subjects (45 CFR 46). Written by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and published in 1979, the Report discusses three key ethical principles and their application to the conduct of research (informed consent, assessment of risks and benefits, and selection of research subjects).
The Belmont Report (French) - This is a pdf file.
Declaration of Helsinki, 2000 - "The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data."
International and U.S. Regulatory Guidelines
U.S.A. Code of Federal Regulations, Title 45 Public Welfare and Human Services, part 46 (45 CFR 46) - These regulations are derived from the ethical principles discussed in the Belmont Report. Here you will find definitions of research and human subject, and regulations regarding (i) IRB membership, functions, review of research, and (ii) requirements for informed consent.
U.S.A. Code of Federal Regulations, Title 21 Food and Drugs, part 50: Protection of Human Subjects (21 CFR 50) - These regulations apply to clinical investigations regulated by the U.S. Food and Drug Administration and regard informed consent.
U.S.A. Code of Federal Regulations, Title 21 Food and Drugs, part 56 (21 CFR 56) - These regulations apply to clinical investigations regulated by the U.S. Food and Drug Administration and regard Institutional Review Boards.
U.S.A. Code of Federal Regulations, Title 21 Food and Drugs, part 312 (21 CFR312) - These regulations apply to clinical investigations regulated by the U.S. Food and Drug Administration and regard Investigational new drugs and the investigational use of FDA approved drugs.
Canadian Tri-Council Policy - This Tri-Council Policy statement describes standards and procedures for governing research involving human subjects." This document includes an ethics framework, discussion of IRB review of research, informed consent, privacy and confidentiality, conflict of interest, research involving aboriginal peoples, clinical trials, human genetic research, research involving human gametes, embryos or fetuses, and human tissue. (You can choose to read this site and the guidelines there in English or French.)
2002 Council for International Organizations of Medical Sciences (CIOMS) Guidelines for Biomedical Research Involving Human Subjects - "CIOMS is an international, nongovernmental, non-profit-making organization established jointly by WHO and UNESCO in 1949. A main objective of CIOMS is to facilitate and promote international activities in the field of biomedical sciences."
International Conference on Harmonization (ICH) General Considerations for Clinical Trials - A product of the regulatory authorities of Europe, Japan, and the United States, this document is intended among other things to: "describe internationally accepted principles and practices in the conduct of both individual clinical trials and overall development strategy for new medicinal products." Topics discussed include the protection of clinical trial subjects and scientific approach in design and analysis.
Indian Council of Medical Research Ethical Guidelines for Biomedical Research on Human Subjects - Written in 2000 the Central Ethics Committee on Human Research of the Indian Council of Medical Research, this document presents (a) a statement of ethical principles and (b) guidelines for the following: (i) Clinical evaluation of drugs/devices/diagnostics/vaccines/herbal remedies, (ii) epidemiological research, (iii) human genetics research, (iv) transplantation research, including fetal tissue transplantation, (v) assisted reproductive technologies.
Other Ethics of Research with Human Subjects Documents
The Nuremberg Code - Written in 1947 as part of the judgment issued at the conclusion of the Nazi doctors trial at the end of World War II, this ten-point code is one of the earliest formalized research ethics codes and is an attempt to formulate universal standards for research with human subjects.
HIV Prevention Trials Network (HPTN) Ethical Guidance for Research - A draft of this document is now available for review and comment; at this time the document is intended for discussion purposes only. "The document is presented in 5 parts. The first part provides a brief overview of the HPTN and the ethical framework for the document; the second part provides a summary of each of the guidance points in a tabular format for easy reference; the third part outlines the mechanism of translating each guidance point into action; and the fourth part provides specifications and justifications for the guidance points. The fifth part provides background information on the ethical challenges that led to the development of this guidance and the ethical debates surrounding these challenges." "The document is built on HPTN aspirations and synthesizes best practices and accepted standards for the conduct of ethical research."
UNAIDS guidance document Ethical considerations in HIV preventive vaccine research - This document, containing 18 guidance points, "highlights, from UNAIDS' perspective, some of the critical elements that must be considered in HIV vaccine development activities… It is hope that this document will be of use to potential research participants, investigators, community members, government representatives, pharmaceutical companies, and ethical and scientific review committees involved in HIV preventive vaccine development. It suggests standards, as well as processes for arriving at standards…"
Reports on the Ethics of Research in Developing Countries
Nuffield Council on Bioethics, The Ethics of research related to healthcare in developing countries, Nuffield Council on Bioethics - This report includes ten chapters addressing these topics: healthcare: the economic context, social and cultural issues, the ethical framework, the framework of guidance, consent, standards of care, ethical review of research, what happens once research is over, conclusions and recommendations. 5 appendices also included.
UNAIDS Meeting on care within the context of HIV/AIDS-related research in developing countries, May 1999, Summary of issues and conclusions - "The objective of the meeting was to develop a framework of care that guarantees that the health needs of participants in HIV-related research in developing countries are given precedence, and that their personal and social integrity are fully protected." Topics addressed include: the framework of care, rights of participants, expectations of research participants, the standard of care, the role of sponsors in the provision of care during research, the proposed comprehensive care package for HIV-related interventional research, care in epidemiological and non-interventional research, et al.
U.S. National Bioethics Advisory Commission (NBAC) Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries
volume I: Report and recommendations of the National Bioethics Advisory Commission, April 2001; topics addressed include: ethical considerations in the design and conduct of international clinical trials, voluntary informed consent, when research is concluded-access to the benefits of research by participants, communities, and countries, ensuring the protection of research participants in international clinical trials, plus 6 appendices.
volume II: Commissioned papers and staff analysis, May 2001. Includes 5 texts: The Challenge of equivalent protection, Attitudes and experiences of U.S. and developing country investigators regarding U.S. human subjects regulations, The relevance of culture for informed consent in U.S.-funded international health research, Comparative analysis of international documents addressing the protection of research participants, international perspectives on protecting human research subjects.
(Click on National Bioethics Advisory Board, listed under OTHER INTERNET RESOURCES. Then click on Reports.)
Ethics Guidance for HIV/AIDS Research
HIV Prevention Trials Network (HPTN) Ethical Guidance for Research - A draft of this document is now available for review and comment; at this time the document is intended for discussion purposes only. "The document is presented in 5 parts. The first part provides a brief overview of the HPTN and the ethical framework for the document; the second part provides a summary of each of the guidance points in a tabular format for easy reference; the third part outlines the mechanism of translating each guidance point into action; and the fourth part provides specifications and justifications for the guidance points. The fifth part provides background information on the ethical challenges that led to the development of this guidance and the ethical debates surrounding these challenges." "The document is built on HPTN aspirations and synthesizes best practices and accepted standards for the conduct of ethical research."
UNAIDS Guidance Document Ethical considerations in HIV preventive vaccine research - This document, containing 18 guidance points, "highlights, from UNAIDS' perspective, some of the critical elements that must be considered in HIV vaccine development activities… It is hope that this document will be of use to potential research participants, investigators, community members, government representatives, pharmaceutical companies, and ethical and scientific review committees involved in HIV preventive vaccine development. It suggests standards, as well as processes for arriving at standards…"
HIV/AIDS and Human Rights, Guideline 6, UNAIDS