Introduction to Bioethics

Introduction to Bioethics Dr Adedeji O. Adekanye MBBS, FWACS(Urol), Dip.(Health Res. Ethics) Director, CHAR & Program Coordinator, Residency Training Urology Unit, Department of Surgery, Federal Medical Centre, Bida. Nigeria. E-mail: tokiade@yahoo.com

Bioethics – what is it? • Morality is the general term for an individual individual’s or society’s standard of conduct, both actual and ideal, and of the character traits that determine whether people are considered good or bad • The scientific study of morality is called descriptive ethics – in this case, a scientist describes the moral judgments, beliefs or actions of individuals or societies in empirical terms and the reasons given for actions and beliefs

Bioethics – what is it? • There are two philosophical approaches to studying ethics • Meta-ethics – analysis (meaning) of the methods, concepts and terms of reasoning • Normative Ethics – analysis of what the standards of moral judgment ought to be. A reflection on the kinds of actions and principles that will promote moral behavior

Bioethics – what is it? Ethics is different from morals. • Ethics tries to probe the reasoning behind our moral life, by examining and analyzing the thinking used to justify our moral choices and actions in particular situations • Bioethics is a specific discipline that probes the reasoning behind our moral life within the context of the life sciences; how we decide what is morally right or wrong bioscience

Bioethics – what is it? • Bioethics is normative ethics applied to the practice of science and medicine. It falls under the general group of applied and professional ethics • It is predicated on an assumption that some solutions to the ethical problems that arise in science and medicine are more moral than others and that these solutions can be arrived at by moral reasoning and reflections

Bioethics – what is it? • It is a branch of knowledge like mathematics, and thinking in this field is not wholly different from thinking in those other fields, however it cannot be reduced to them. • Bioethical conclusions cannot be unambiguously proved like mathematical theorems

Let us remember that a slower progress in the conquest of disease would not threaten society, grievous as it is to those who deplore that particular disease be not conquered, but that society would indeed be threatened by the erosion of those moral values whose loss, possibly caused by too ruthless a pursuit of scientific progress, would make its most dazzling triumphs not worth having - Jonas

History of research ethics • Perhaps the earliest clinical trial was that of Lind – conducted over a 6 year period in the 18th century Sailors were allocated to receive or not receive fruits and vegetables during an investigation of the etiology of scurvy

History of research ethics • About 25 years after that, Edward Jenner conducted his famous chickenpox vaccination studies for prevention of smallpox, using children in his neighbourhood including his own children • In 1897, Sanarelli discovered the cause of yellow fever and to prove his claim inoculated 5 people with his isolate with disastrous consequences for the participants

History of research ethics • 3 years later, the U.S. commissioned yellow fever study under Walter Reed • There was public concern in the United States about this research • Walter Reed Reed’s s “Yellow Fever Board Board” sketched some guidelines for research ethics including • Self experimentation • Enrollment of only adults • Signed contract with sliding scale compensation

History of research ethics • In 1931 Germany enacted arguably the first research ethics regulations in response to the increasing use of human participants in research being driven by the strength of the German health research and chemical industry • The very strict “Richtlinien” outlined how to conduct human experimentation and the use of innovative therapies in medicine

History of research ethics • Two of the 14 provisions of these guidelines concerned consent requirements • Questions about nature of appropriate information, bona fide consent, careful research design, special protections for vulnerable subjects were all carefully outlined • Experimentation on dying patients was completely forbidden

History of research ethics • No other nation had such legally and morally advanced regulations at this time • These regulations were in force and binding throughout Germany before and through the duration of the Second World War

History of research ethics • Yet, the Nazi experiments comprehensively ignored and violated every one of the regulations • The Nuremberg trial that followed the second world war experiments focused attention on the need for a code of research ethics • Prosecutors argued that the experiments violated fundamental ethical standards of civilized society

Nuremberg code 1948 • While there was concern about ethical research before it, it was the Nuremberg trial that focussed attention on the need for a code of research ethics • This was the trial of Nazi doctors who conducted experiments on prisoners. Prosecutors argued that the experiments violated fundamental ethical standards of civilized society, however at that time, there were no codes of ethics for conducting research on human beings

Nuremberg code 1948 • The main components of the code are • Requirement for voluntary participation • Informed consent • Favorable risk/benefit analysis • Right to withdraw without penalty • Criticized for being legalistic • Largely ignored by medicine • No mention of independent review or fair selection of participants

Nuremberg code 1948 • It also seem to prohibit many aspects of medical research because of its unqualified demand for voluntary informed consent • The Nazi doctors themselves were not judged on the basis of the code as this would have been an instance of ex post facto justice • There is also controversy about the origins and inspirations for the Nuremberg code

1950s Wichita Jury Study • Social science researchers from the University of Chicago conducted a study involving secret audio taping of jury deliberations in order to better understand decision making process of jurors in criminal trials • Their hypothesis was that showmanship on the part of trial attorneys was affecting the outcome of trials • When the results were presented in respectable academic forums, public reaction was markedly negative

1950s Wichita Jury Study • People objected to deception for research purposes in a setting where privacy and confidentiality were critically important • This prompted the U.S. Congress to pass a law prohibiting recording of jury deliberations, marking the first time that actions of well meaning researchers will result in action to protect people from exploitation • Case highlighted the fact that some research questions cannot be answered without compromising the integrity of significant and cherished social institutions

1950 Willowbrook Hepatitis Study Researchers deliberately exposed children and adolescents with disabilities to hepatitis virus in order to discover a way of preventing the disease Critics claimed the study was coercive because • New admission into the institution was closed • Parents of children on the waiting list were written to inform t them that their children could be placed on a research ward after which they could be transferred to the facility

1950 Willowbrook Hepatitis Study • The researchers argued that almost all the children admitted into the facility develop hepatitis anyway and this mitigated the deliberate exposure for the benefit of science • However at the time the study was initiated, the rates of hepatitis had declined considerably • Researchers argued that they had obtained consent from the parents

1950 Willowbrook Hepatitis Study • That all various university, state and U.S. Armed Forces Epidemiological Board (which funded the study) committees had reviewed and approved the study • Critics argued that because the participants were severely mentally retarded children whose parents wanted placed in one of few public institutions available rendered the consent invalid • Researchers argued that the mental retardation was besides the point while critics retorted that that was precisely the point

1960s Thalidomide Study • Thalidomide was introduced for the treatment of hyperemesis gravidarum in Europe and while still undergoing review in the U.S., an influential group of East Coast practitioners started using it before it became clear that it was causing a large number of birth defects • Public outrage led to legislation that required investigators to obtain informed consent before administering investigational medications

Jewish Chronic Diseases HospitalStudies • In July 1963, 2 physicians at the Brooklyn Jewish Chronic Disease Hospital injected ill elderly patients with live hepatic cancer cells without their informed consent • The aim of the study was to study “rejection of human cancer cells cells” • Background studies suggest that such cells would be rejected by immune reaction leading to their rejection from the body • It was then argued that the experiments present no risk to the participants

Jewish Chronic Diseases HospitalStudies •The researchers argued that informing participants about details of the research would have caused them needless psychological distress •Failure to inform was thus based on the need to minimize distress

Jewish Chronic Diseases HospitalStudies •The Board of Regents (Governing Council) of the University of the State of New York argued that while “therapeutic privilege” may justify non-disclosure in a physician-patient relation, same is not true of researcher-participant relationship • This case, among other things, highlighted the problem of conflicting loyalties for physician-researchers

Tuskegee • Study was initiated in Macon County, Alabama in 1932 • Designed to take advantage of an epidemic of syphilis among the black population to take study the natural history of syphilis • Over 400 sharecroppers were recruited • Neither they nor their partners were informed about the nature of the research or about their condition

Tuskegee • When penicillin became available, they were not given an opportunity to use it • They were in fact prevented from accessing it or obtaining information about it • Papers from the study were regularly published in medical journals and it did not evoke any ethical response • In 1972, press reports finally prompted an investigation and stoppage of the study

Tuskegee • 74 of the original participants remained alive • Some saw no reason for the outrage after all, the study was not secret and was well known • Others contented that the issues at stake were more about racism • In the 70s participants were compensated and in 1997, U.S. government apologized for the study

1964 World Medical Association Declaration of Helsinki • This basically builds on the Nuremberg code • Started in 1953/1954, revised in 1975 and subsequent revisions were in 1983, 1989, 1996 and 2000. • It adds two additional points • That the interests of the subject should always be given a higher priority than those of society • That every subject in clinical research should get the best known treatment • They have been incorporated in many national and international guidelines

Other seminal events • Henry K.Beecher’s article in NEJM in 1966 • 1973 Congressional hearings on quality of health care and human experimentation • Main catalyst for this was the Tuskegee Study (1932 – 1972), but there were others, like • 1950 Willowbrook Hepatitis Study • 1960 Jewish Chronic Diseases Hospital Studies • 1960 Milgram study of obedience to authority • 1970 San Antonio study of contraceptive pills • 1970 Tearoom Trade Study

1974 U.S. National Research Act • This act established the modern IRB system. The act created U.S. federal regulations that required IRB approval before most kinds of research involving human subjects can be conducted, defined policy and procedures that an IRB must follow when reviewing research, and established the criteria that an IRB must use to approve research conduct • The Institutional Review Board (IRB) – a committee mandated by the federal law to protect the rights and welfare of human subjects participating in research activities

1974 National Research Act • It also established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The function of the Commission is to issue recommendations when what to do is not clear to researchers. • In 1979, the Commission issued the Belmont Report

Ethical principles of the Belmont Report and their implications • Respect for persons • Participants must voluntarily consent • Informed consent must be obtained • Privacy and confidentiality must be guaranteed • Extra protection to those with limited autonomy • Beneficence • The risks of research are justified by their potential benefits • Study is designed to minimize risk • Conflicts of interest are adequately managed

Ethical principles of the Belmont Report and their implications • Justice • Vulnerable subjects are not targeted for convenience • People likely to benefit from research are not systematically excluded i.e. equitable selection of subjects.

CIOMS Guidelines • The Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization (WHO) developed its International Ethical Guidelines for Biomedical Research Involving Human Subjects with special attention to research in developing countries • Particularly in response to growing research in HIV/AIDS • It took the Nuremberg Code and Declaration of Helsinki into account

CIOMS Guidelines • Its principles are designed with the socio-economic and political circumstances of developing countries in mind • Development started in 1982 • Involved consultation with participants from developed and developing countries including health ministry officials, ethicists, philosophers and lawyers • First version was released in 1993 with 15 guidelines, while the second version was released in 2002 with 21 guidelines

CIOMS Guidelines • Starts with an argument on the necessity of research • Proclaimed the need for researchers and sponsors to make every effort to ensure that any intervention or product developed or knowledge generated will be made reasonably available for the benefit of the population or community • The guidelines tackles the issue of placebo trials in guideline 11, articulating conditions when they can be used

ICH ICH-GCP guidelines • International Committee on Harmonization Harmonized Tripartite Guideline – Guideline for Good Clinical Practice was promulgated in 1996 by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use and has been agreed upon by the regulatory agencies in Europe, Japan and the United States

ICH-GCP guidelines • The ICH ICH-GCP guidelines delineates detailed standards for review committees, investigators and sponsors • It is particularly targeted at research on drugs or devices seeking regulatory approval • While it is rooted in the Helsinki Declaration and applicable local codes, it is far more specific than the other codes but not wider in scope • It is criticized for being lax on the use of placebos in clinical trials

Nigeria’s baby steps • National Health Research Ethics Committee has been set up with the following membership • Chairman appointed by Hon. Minister of Health • Membership representing Law, Pharmacy, Medicine, Nursing, Community Health Workers, Christians, Muslim, Researchers and 3 other persons • Ex Ex-officio members from Ministries of Education, Environment, Women Women’s affairs, Agriculture etc. NAFDAC, NUC

Functions of NHREC • Determine guidelines for the functioning of health research ethics committees • Register and audit health research ethics committees • Set norms and standards for conducting research on humans and animals, including norms and standards for conducting clinical trials • Adjudicate in complaints about the functioning of health research ethics committees and hear any complaint by a researcher who believes that he has been discriminated against by a health research ethics committee

Functions of NHREC • Refer to the relevant statutory health professional council matters involving the violation or potential violation of an ethical or professional rule by a health care provider • Institute such disciplinary action as may be prescribed against any person found to be in violation of any norms and standards, or guidelines, set for the conduct of research under this Act • Advise the Federal Ministry of Health and State Ministries on any ethical issues concerning research

Functions of NHREC • Review research proposals and protocols in order to ensure that research conducted by the relevant institution, agency or establishment will promote health, contribute to the prevention of communicable or non-communicable diseases or disability or result in cures for communicable or non-communicable diseases; and • Grant approval for research by the relevant institution, agency or establishment in instances where research proposals and protocol meet the ethical standards of that health research ethics committee

NHREC Current activities Code has been released and can be found at http://nhrec.net where you have the opportunity to either read or download it • Comments can be sent to secretary@nhrec.net, deskofficer@nhrec.net or chairman@nhrec.net • Sub-codes for children, pregnant women, prisoners, people living with AIDS, and others are in development • Standard Operating Procedures (SOPs), prototype MTA, consent forms etc are available on NHREC website

Thank you for your attention

Introduction to Bioethics