[06.11] Research Ethics (TG09-CG13) (V1).pdf

Research Ethics Module 06: Research and Epidemiology Henrietta de la Cruz, MD |Asynchronous TABLE OF CONTENTS I. INTRODUCTION................................................................................ 1 II. FRAMEWORKS FOR RESEARCH ETHICS.............................................1 A. PRINCIP...

Research Ethics Module 06: Research and Epidemiology Henrietta de la Cruz, MD |Asynchronous TABLE OF CONTENTS I. INTRODUCTION................................................................................ 1 II. FRAMEWORKS FOR RESEARCH ETHICS.............................................1 A. PRINCIPLES OF ETHICS................................................................. 1 B. CONSEQUENCE VS DUTY BASED.................................................. 1 C. VIRTUE ETHICS............................................................................. 1 D. ETHICS OF CARE........................................................................... 1 III. LANDMARKS IN THE EVOLUTION OF RESEARCH ETHICS GUIDELINES. 1 A. NUREMBERG CODE......................................................................2 B. UN DECLARATION OF HUMAN RIGHTS........................................ 2 C. DECLARATION OF HELSINKI, WORLD MEDICAL ASSOCIATION..... 2 D. TUSKEGEE STUDY......................................................................... 2 E. CIOMS (2002, 2007)..................................................................... 2 IV. ISSUES IN RESEARCH ETHICS IN DEVELOPING COUNTRIES............... 3 A. SCIENTIFIC VALIDITY.................................................................... 3 B. APPROPRIATE RISK-BENEFIT RATIO.............................................. 3 C. FAIR SUBJECT SELECTION AND RECRUITMENT............................ 3 D. HEALTH DISPARITIES.....................................................................3 E. SOCIAL VALUE AND CULTURAL CONTEXT.....................................4 F. COLLABORATIVE PARTNERSHIP.....................................................4 G. DATA PRIVACY ACT 2012.............................................................. 4 V. HOW TO IMPROVE PROCESS OF ETHICAL REVIEW............................4 A. COMMITTEE MEMBERSHIP..........................................................4 B. COMMITTEE PROCEDURES.......................................................... 4 QUESTIONS......................................................................................... 5 ANSWER KEY.......................................................................................5 RATIONALE..........................................................................................5 ○ Important framework controversies and ethical research ○ Four principles: ▸ Autonomy: respect for persons ▸ Beneficence: benefits commensurate to risk ▸ Nonmaleficence: prevent unreasonable harm or injury ▸ Justice: fairness, equity, and impartiality in decision making B. CONSEQUENCE VS DUTY BASED ● Utilitarian/consequence-type based theories: important in analyzing the total happiness and utility for the most number of people ● Deontology/duty-based theories: Kantian way of stressing the role of duty and respect for persons as the primary determinant of ethical decision Table 1. Ethical theories Types of theory Advantages Disadvantages Consequencebased (Utilitarian) Stresses promotion of happiness and utility Ignores concerns of justice for the minority population Duty-based (Deontology) Stresses the role of duty and respect for persons Underestimates the importance of happiness and social utility C. VIRTUE ETHICS ● Asks what a virtuous person would do ● In a controversy, what is truly right is how individuals ought to act on the basis of universal virtues (e.g., compassion) LEARNING OBJECTIVES D. ETHICS OF CARE 1. Apply ethical principles and foundations in the evaluation of health research 2. Use international tools to guide ethical review of issues related to health research ethics ● Grounded on feminist ethics ● Emphasizes individual as relational beings ● Emphasizes the special obligation of a person to care for participants I. INTRODUCTION III. LANDMARKS IN THE EVOLUTION OF RESEARCH ETHICS GUIDELINES ● What is research ethics? ○ Research ethics encompasses general guidelines for the responsible conduct of all phases of research ○ Which choices throughout the research lifecycle would be the most just, fair, or responsible? ● 2 major resources ○ International Ethical Guidelines for Health-related Research Involving Humans of the Council for International Organizations of Medical Sciences (CIOMS) ▸ Also known as the CIOMS guidelines ○ Marshall: ethical challenges in study design and informed consent for health research in resource-poor settings II. FRAMEWORKS FOR RESEARCH ETHICS A. PRINCIPLES OF ETHICS ● Ethical deliberation for research ethics is no different from other ethical deliberations ● Angeles framework: 1. Verify facts 2. Identify stakeholders 3. Define the ethical issues and dilemmas 4. Examine values and apply ethical frameworks 5. Examine alternative options and weigh consequences 6. Give a final decision ● Principlism YL6:06.11 ● More specific guidelines have evolved in research ethics ● A person educated in Research Ethics should be familiar with the international codes that have been developed as early as 1947 ● 1947: The Nuremberg Code ○ Arose out of the controversies raised by the experiments under the Nazi regime ● 1948: UN Universal Declaration of Human Rights ○ Made Nuremberg Code provisions more universal ● 1964: World Medical Association: Declaration of Helsinki ○ Acted on UN Universal Declaration of Human Rights ○ Outlines the duty of physicians in conducting ethical research ● 1979: The Belmont Report ○ Made by the US ● 1993: CIOMS International Ethical Guidelines for Biomedical Research (updated 2002) ○ Provides an international perspective that summarizes many of the previous guidelines ● 1997: International Conference of Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use 十 ○ Guided the research process related to the development of pharmaceutical products TG09: Barin, Choudhry, Cu, Jamisola, Sanota, Simbulan, So, Tagulob, Umil, Urrutia, Velasco, Yu CG13: Abad Santos, Ahalajal, Alba, Bernardo, Binobo, Cai, Dy, Gamboa, Pacis, Rejuso, Tan 1 A. NUREMBERG CODE ● Arose from the many trials of many Nazi scientists and physicians who used inmates to check for: ○ Freezing points ○ Mustard gas effects ○ Effects of contagious diseases ▸ Malaria ▸ Typhus ▸ Yellow fever ▸ Infectious hepatitis ○ Other controversial experiments ● Outlined the major provisions that are now used as the basis for many other additional codes preventing unethical research ● The code states that: 1. Voluntary consent is absolutely essential 2. Research should be for the good of society 3. Design and solid basis from the results of animal studies or the natural history of disease 4. Avoid all unnecessary physical suffering and injury 5. No reason for disabling injury 6. Risk should not exceed the importance of research 7. Preparations should be in place for the remote possibility of injury, disability or harm 8. A scientifically qualified person should conduct the research 9. Voluntary withdrawal 10.Termination of experiment for injury, disability or death B. UN DECLARATION OF HUMAN RIGHTS ● Following the Nuremberg code, the United Nations prepared a more sweeping declaration of human rights that outlined: ○ Human dignity, human rights and fundamental freedoms are to be fully respected ▸ Should be accorded not only in research but in general governance ● Tenets: ○ Respect for autonomy ○ Risk-benefit ○ Consent ○ Respect and protection for vulnerability ○ Protection of privacy and confidentiality ○ Equality, justice and equity; non-discrimination ○ Respect for cultural diversity, and pluralism ○ Solidarity, cooperation and sharing of benefits ○ Protection of the environment, biodiversity ● Important principles that are adopted in many of the subsequent guidelines C. DECLARATION OF HELSINKI, WORLD MEDICAL ASSOCIATION ● While the UN Declaration bound many nations to adhere to the fundamental freedoms, ○ The World Medical Association, represented by many medical societies worldwide, began to craft the Declaration of Helsinki in 1964 ▸ Revisions: 1975, 1983, 1989, 2008 ● States that it is the duty of physicians who participate in medical research to protect the: ○ Life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects ● Other duties: ○ Protection against environmental harm ○ Requiring research protocols for approval by an ERB1 with declaration of funding and registration in a database ○ Confidentiality ○ Informed consent; assent for minors ○ Protection of the vulnerable populations ○ Benefits to participants ○ Precaution for use of placebos 1 D. TUSKEGEE STUDY ● Despite the comprehensive guidelines protecting the rights of the vulnerable in 1964, it was exposed that the National Institute of Health (NIH) had an ongoing study ● From a 6 year study, the study lengthened to 40 years 1932 ● 399 African-Americans diagnosed with Syphilis were enrolled for monitoring the course of Syphilis until death ● At that time of enrollment, it was known that there was no cure for the illness ● Men were offered free medical exams, free meals, and free “treatment” 1945 ● Penicillin was published by the NIH to be an effective treatment for Syphilis ○ Men enrolled in the study were not treated ● Even after the declaration of a cure, the African Americans continued to be observed without benefit of treatment ● It was the exposure of a journalist that brought the study to light 1972 ● Press leaked the story of the untreated subjects 1974 ● The US paid $10 million out of court settlement was offered ● Gave public apologies to the Tuskegee participants and their families BELMONT REPORT (1979) ● The following principles were emphasized: ○ Respect for persons ○ Beneficence ○ Justice ● Giving guidelines accrued to: ○ Fair subject selection ○ Risk-benefit assessment ○ Informed consent ● Became a backbone for many of the research ethics guidelines in the US E. CIOMS (2002, 2007) ● The existing standards for ethical guidelines were limited to the World Medical Associations ● Thus, in 2002, a Council of International Organizations of Medical Sciences (CIOMS) was formed under the auspices of WHO and various medical institutes ● These guidelines are more comprehensive and are constantly being updated ETHICAL GUIDELINES ● Outlined the recommendations for ethical review committees ● Ethical review of externally sponsored research ● Obtaining informed consent ○ Making tenets that are more specific for informed consent ○ Essential information for prospective research subjects ● Obligations/responsibilities of sponsors and investigators to participate ● Vulnerable populations including communities with limited resources, women, children, and persons with mental incapacity ● Equitable distribution of burdens and benefits in the selection of groups of subjects in research ● Safeguarding confidentiality was reiterated ● Right of subjects to treatment and compensation were specified ● Strengthening the capacity for ethical and scientific review and biomedical research ● Ethical obligation of external sponsors to provide healthcare services to participants and the communities that it served Ethical Review Board YL6:06.11 Research Ethics 2 Active Recall Box 1. Which framework asks what a virtuous person would do? A. Consequence based B. Duty based C. Virtue ethics D. Ethics of care 2. Which guideline arose from the many experiments done by Nazi scientists and physicians? A. Nuremberg Code B. UN Declaration of Human Rights C. Declaration of Helsinki D. Belmont Report Answers: 1C, 2A IV. ISSUES IN RESEARCH ETHICS IN DEVELOPING COUNTRIES ● Despite the international guidelines for many research institutes, various issues in research ethics still emerged ○ Particularly in developing countries ● Research in developing countries creates a greater risk of exploitation: ○ Individuals or communities in developing countries assume the risks of research, but most of the benefits may accrue to people in developed countries ● Poverty, limited health-care services, illiteracy, cultural and linguistic differences, and limited understanding of the nature of scientific research neither cause nor are necessary for exploitation ○ However, they still increase the possibility of such exploitation ○ This is why research in developing countries should give special attention to these ○ Anything that hampers the full participation and consent of people in developing countries should be considered ● Research must minimize exploitation Take Note! ● The Developing World of Bioethics is the resource Doc Henri asked us to go through for this part of the lecture A. SCIENTIFIC VALIDITY ● Even before discussing ethical issues, scientific validity should always be foremost in the review of protocols [Case] The Willowbrook Study, New York, 1958 ● In 1958, despite the guidelines, a physician conducted an experiment in a home for mentally disabled and orphaned children ○ He injected them with Hepatitis B virus to determine response to gamma globulin ○ A consent form was given (see Figure 1) Figure 1. Consent form used in Willowbrook study ● He failed to mention that the virus would be injected into the children ● His justification was that injecting gamma globulin immediately after infection would have a better outcome than if the children had contracted the disease otherwise YL6:06.11 Research Ethics ○ This was not considered scientifically valid as a justification for infecting the children ● Created controversy when the study was exposed by a journalist years later B. APPROPRIATE RISK-BENEFIT RATIO ● Another source of exploitation is the Risk-Benefit Ratio ● When participants confront a higher risk of disease, the ERB should examine if greater potential benefits may justify greater risks in research design ○ First, the risk-benefit ratio for individuals must be favorable in the context in which they live ○ Second, is the risk-benefit ratio for the community also favorable? ● In the Willowbrook Study, the physician justified the injection of Hepatitis by stating that: ○ Other children in the orphanage had an 80-90% chance of contracting Hepatitis, which is initially undetected and runs a more severe course ▸ Did not address the situation of why a very high percentage of transmission was happening ● Important for ethics review committees to understand that the appropriate risk-benefit ratio should be more clearly understood in the context of fairness and equitable practice C. FAIR SUBJECT SELECTION AND RECRUITMENT ● In many studies in developing countries, fairness in subject selection and recruitment can become situations of exploitation when: ○ "Historically, [the] poor, uneducated, or powerless are unable to defend their own interests/rights, and are targeted for high-risk research” ● Important to ask: ○ “Does high prevalence, incidence, or transmission rates of an infection, special drug-resistance patterns, or particular combinations of diseases justify the choice of individuals?” ● While in one hand, benefits may be given to the vulnerable populations, it must be considered whether: ○ “Issues of vulnerability considered eg. familial coercion, social marginalization, political powerlessness, and economic deprivation will lead to situations of coercion?” ● Minimizing risk is essential D. HEALTH DISPARITIES ● Situations of disparities in health access may apply not only to those marginalized but also other vulnerable populations including: ○ Mentally-challenged ○ Children ○ Pregnant women ○ Participants in a hierarchical relationship (e.g. doctor-patient) ○ Patients who will not eventually afford medications ● They must be protected by ethics review committees so that interventions should be socially, culturally, and economically appropriate ● Most research in developing countries are now being examined whether medications can eventually be afforded by the population from which they are tested ○ For example, will guarantees for accessibility to the medications be given by the government? ○ And, whether the access to healthcare can be institutionalized or continued as a result of the partnership between the research institute and the local government or health unit ● Important questions to ask: ○ Will the researcher’s interventions be socially, culturally, and economically appropriate changes in the health-care system? ○ Will results be useful in the context of the health problem in the developing country? ○ Are the research objectives considerate of the health-care services that participants are entitled to? ▸ Does the research require services that are not feasible to deliver in the context of the country's health-care system? 3 E. SOCIAL VALUE AND CULTURAL CONTEXT ● For developing countries, the concept of social value is important ● In effect, what we want to avoid are mosquito researchers ○ Researchers coming in and sucking all the benefits and leaving without benefits to the community ● In some situations, introducing healthcare practices can undermine the existing healthcare services when: ○ Create situations wherein eventual access to health by other communities is channeled to a study site ● Important questions to ask: ○ First, what is the potential value of the research for each of the prospective beneficiaries? ○ What mechanisms are in place to enhance the social value of the research? ○ Does it undermine the community's existing health-care practices and available health services? F. COLLABORATIVE PARTNERSHIP ● The context where the trial is taking place matters ● Guidelines for research in developing countries emphasizes the need for collaborative partnership ● The presence of community representatives is recommended to begin even in the planning phase ○ So that elements of cultural significance and context where the trial is taking place can be considered in planning interventions ● ERBs should consider if it is enough for participants in clinical trials to benefit from their participation by obtaining much needed medical care ● Ethical Imperialism should be avoided ○ Imposing Western ethical guidelines on a local community or subjects of diverse backgrounds where tenets may be misunderstood or unable to address the cultural situation G. DATA PRIVACY ACT 2012 ● Unsanctioned release of sensitive information including identifiable information affecting the individual is punishable by law ○ Includes information on the disease status of patients, which may be a subject of the research ● Collection of personal data "must be a declared, specified, and legitimate purpose" and further provides that consent is required prior to the collection of all personal data. ● Penalties of imprisonment ranging from one (1) year to three (3) years and a fine of not less than Five hundred thousand pesos (Php500,000) but not more than Two million pesos (Php2,000,000) ○ This shall be imposed on persons who process personal information without the consent of the data subject, or without being authorized under the Act or any existing law V. HOW TO IMPROVE PROCESS OF ETHICAL REVIEW Figure 2. How to improve the process of ethical review ○ Requires one to challenge expertise in research methods and to look at evidence ● Emphasis on issues of expediency ○ As emphasized in the emerging issues of research in developing countries ○ Whether it is possible and realistic to conduct the research given the health setting of the community ● The previous experience of the institute is important ○ Setting a record of decisions of similar cases in the institute ● It takes a comprehensive view of all of these issues to arrive at a decision A. COMMITTEE MEMBERSHIP ● The World Health Organization provides guidance on committee membership for ethics review committees to include: 1. Scientific expertise ▸ A scientific expert knowledgeable about the methods and theories behind the research 2. Social/behavioral science expert 3. Expert in legal matters or ethics 4. Layman/community participants 5. Non-institutional member ▸ To balance the views of an ethics review committee ● Quorum: should include at least one layman or non-institutional member ● Majority vote or consensual decision-making ● Prior to the review, it should be important for the committee head to decide whether a quorum is achieved or it should be enough if at least one layman or non-institutional member should be present ○ And whether the vote for a decision should be a majority vote for the greatest number, or ○ Consensual which means everybody should agree on an issue and a single descending view will negate the decision making B. COMMITTEE PROCEDURES 1. Researchers or scientific experts may be invited, though they do not have voting privilege ○ Can be done if the topic is beyond the expertise of the scientists within the community ○ They can explain better whether the scientific validity is sound 2. Appeal procedures should be made available for committee decisions 3. Decisions should be time bound as suited to the REC but not prejudicial to the researchers 4. Confidentiality on all matters should be maintained 5. Pointers to be reviewed: ○ Scientific design and conduct ○ Risks and potential benefits ○ Study selection and recruitment ○ Informed consent ○ Issues of confidentiality and privacy ○ Community considerations 6. Monitoring of progress should always be included as part of recommendations of the ethics review 7. Documentation and archiving of decisions should be addressed 8. Communicating decisions: time bound and offer clear recommendations of how the issues may be addressed ○ Not necessarily the job of the ERC to untangle any scientific issues that may arise or are under question ○ The language of communicating decisions must also be respectful and encouragement ▸ Ethics committees are not there to deride or make fun of the research protocols Figure 2 Nice to Know! ● Reminder that decision making on ethical issues is not limited to a personal view on the issue ● Apply ethical theory, but also empathy for the community, and concern for the participants ● Doc hopes that each graduate of ASMPH will be a steward who safeguards ethics as an important factor not only in research but in all facets of life ● Albert Schweizz (Nobel Peace Prize Winner): “Ethics, too, is nothing but reverence for life” YL6:06.11 Research Ethics 4 A. B. C. D. Active Recall Box 1. Which population group should be protected by ethics review committees regarding disparities in health access? A. Only the economically disadvantaged B. Only mentally-challenged individuals C. Both marginalized and vulnerable populations D. Exclusively pregnant women 2. Which of the following is not a consideration in committee procedures for ethical review? A. Informed consent B. Research funding sources C. Monitoring of progress D. Confidentiality and privacy Answers: 1C, 2B QUICK REVIEW QUESTIONS 1. A researcher forces orphans to participate in their study. Which guideline does this violate? A. Nuremberg Code B. UN Declaration of Human Rights C. Declaration of Helsinki D. Belmont Report 2. A researcher who has no respect for persons hopes to create an atomic bomb which will cause unreasonable harm or injury. Which principle is violated? A. Autonomy B. Benefism C. Nonmaleficence D. A and C 3. Which landmark provides an international perspective that summarizes many of the previous guidelines? A. Declaration of Helsinki B. Belmont Report C. CIOMS International Ethical Guidelines for Biomedical Research D. International Conference of Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 4. T/F: Poverty, limited health-care services, and illiteracy are not necessary for exploitation and thus do not increase the possibility of exploitation. 5. Foremost in the review of protocols A. Scientific validity B. Risk benefit ratio C. Fair subject selection and recruitment D. Health disparities 6. The Willowbrook Study aimed to test the response to which virus through the injection of gamma globulin? A. Hepatitis A B. Hepatitis B C. Influenza D. Measles 7. T/F: Imprisonment is a potential penalty for unsanctioned release of sensitive information under the Data Privacy Act 2012. 8. Which committee member does not usually possess voting privileges in an ethics review committee? A. Scientific expert B. Researcher C. AOTA D. NOTA 9. How should decisions in an ethics review committee be communicated? A. Using disrespectful language for weak protocols B. Communicating clear recommendations in a respectful tone C. Delaying communication to researchers D. Leaving out key points for clarity 10. What is a primary consideration in selecting subjects for research in developing countries? YL6:06.11 Research Ethics High socioeconomic status History of participation in previous studies Vulnerability and fairness in subject selection Political power and influence ANSWER KEY 1A, 2D, 3C, 4F, 5A, 6B, 7T, 8C, 9B, 10C RATIONALE 1. A. Nuremberg Code. The Nuremberg Code states that voluntary consent is absolutely essential 2. D. A and C. Autonomy is respect for persons and nonmaleficence is to prevent unreasonable harm or injury. 3. C. CIOMS International Ethical Guidelines for Biomedical Research. Formed under the auspices of WHO and various institutions. It is more comprehensive and is constantly being updated. 4. False. Although they do not cause nor are necessary for exploitation, they still increase the risk of the possibility of such exploitation. 5. A. Scientific Validity. Even before discussing ethical issues, the scientific validity should be foremost in the review of protocols 6. B. Hepatitis B. The study injected children with Hepatitis B virus to test their response to gamma globulin. 7. True. Penalties of imprisonment ranging from 1 to 3 years and a fine of not less than Php 500,000 but not more than Php 2,000,000 shall be imposed on persons who process personal information without the consent of the data subject or without being authorized under the Act or any existing law. 8. C. AOTA. Scientific experts and researchers involved in the study generally do not vote in the committee. 9. B. Communicating clear recommendations in a respectful tone. Communication should be clear and respectful. 10. C. Vulnerability and fairness in subject selection. Vulnerability should be considered to prevent exploitation. REFERENCES 📄 Dela Cruz, H. (2023, December, 4). Research Ethics. [Lecture slides]. REQUIRED ● Concerns and Feedback form: http://bit.ly/YL6CFF2027 How’s My Transing? form: https://bit.ly/2027YL6HMT Mid-Semester Evaluation form: https://bit.ly/2027YL6MidSem End-of-Semester Evaluation form: https://bit.ly/2027YL6EndofSem Errata Points Trackers: https://bit.ly/YL62027EPT YL6 TransMap: https://bit.ly/2027YL6TransMap FREEDOM SPACE 5