Ethical Codes & Research Standards
Reason for the Coming up of the Code
Came into being as a result of the heinous human experimentation performed by the Nazi doctors in the concentration camps throughout the German Regime
Twin Experiment- Josef Mengele, German physician and captain of Auschwitz Carried out human experiments on camp inmates, especially twins . Nazi human experiments were aimed at protecting military personnel under various conditions; others were aimed at breeding a superior race. Twins were often subjected to horrendous Nazi experiments to try to understand their unique genetic similarities.
Extensive Nazi experimentation on subnormal body temperature, or hypothermia Long-term exposure to extremes in cold temperatures, air pressure, toxic gases (phosgene gas) and other conditions, taking blood and urine samples
Limits of human endurance and existence at extremely high altitudes experiments The victims were placed in the low-pressure chamber and thereafter the simulated altitude therein was raised. Many victims died; others suffered grave injury, torture, and ill-treatment.
Tuberculosis medical experiment
Radiation Exposure Experimentation- Sterilization experiments were conducted at Auschwitz, and other camps from March 1941 to January 1945 by Dr. Carl Clauberg. The aim is to develop a method of sterilization that would be capable of sterilizing millions of people with a minimum of time and effort
Lessons from Nazi human medical experiments in concentration camps
A need to conform to well-defined ethical standards
Justification that such experiments may yield results for the “greater good of society”
“The voluntary consent of the human subject is absolutely essential”
Followed by an explicit clarification of all the associated requirements
The Tuskegee Study of Untreated Syphilis in the African American Male
Began in 1932, at at a time when there was no known treatment for syphilis, a contagious venereal disease This was considered the longest non-therapeutic experiment on human beings in medical history. Designed to determine the natural course of untreated latent syphilis in some 400 African American men in Tuskegee, Macon County, Alabama The research subjects, had syphilis when they were enrolled in the study Were matched against 200 uninfected subjects who served as a control group
Tuskegee Study Bioethics Violations
Respect for autonomy
(participants were not fully informed in order to make autonomous decisions)
Non-maleficence
(participants were harmed, because treatment was withheld after it became the treatment of choice)
Justice
(only African Americans were included in the study; issue on unfair subject selection
informed consent (Major ethical issue)
refers to telling potential research participants about all aspects of the research that might reasonably influence their decision to participate
Subjects were recruited with misleading promises of “special free treatment,” which were actually spinal taps done without anesthesia to study the neurological effects of syphilis, and they were enrolled without their informed consent
Subjects received heavy metals therapy, standard treatment in 1932, but were denied antibiotic therapy when it became clear in the 1940s that penicillin was a safe and effective treatment for the disease
When penicillin became widely available by the early 1950s as the preferred treatment for syphilis, this therapy was again withheld
The investigators took advantage of a deprived socioeconomic situation in which the participants had experienced low levels of care
The contacts were with doctors and nurses who were seen as authority figures
Practiced deception in recruiting subjects for the study; it was never explained to the subjects that the survey was designed to detect syphilis
Subjects were never told they had syphilis, the course of the disease, or treatment
Withholding of treatment
Patient welfare was consistently overlooked, although there have been multiple attempts to justify why penicillin treatment was withheld. Physicians felt that repair of existing damage would be minimal Others felt that the damage that could result from reactions to the penicillin therapy, including fever, angina, and ruptured blood vessels, would outweigh its benefits
No data was available on the efficiency of penicillin treatment in late syphilis Short- and long-term toxic effects of drugs had not been well documented (when the study was evaluated periodically, researchers judged that the benefits of nontreatment outweighed the benefits of treatment)
The subjects were never given a choice about continuing in the study once penicillin had become available; in fact, they were prevented from getting treatment. Treatment was not offered, and even when the experiment ended in 1972, the remaining funds could not be used for treatment
Proper Data Management
Accurate records were not kept
The number of subjects who died from syphilis was never known
The number of survivors was estimated to be between 76 and 111, and the number of dying was estimated between 28 and 101
The US STD Experiments in Guatemala: Do No Harm
Beginning in 1946, the US government engaged in research experiments in which more than 5000 uninformed and unconsenting Guatemalan people were intentionally infected with bacteria that cause sexually transmitted diseases. The study involved at least 5128 vulnerable people, including children, orphans, child and adult prostitutes, Guatemalan Indians, leprosy patients, mental patients, prisoners, and soldiers. Between 1946 and 1948, health officials intentionally infected at least 1308 of these people with syphilis, gonorrhea, and chancroid and conducted serology tests on others
Though it began in the US, but was moved to Guatemala when researchers were unable to consistently produce gonorrhea infections in prisoners at a Terre Haute, Indiana, prison The public had no knowledge of the experiments for more than half a century, and even today little is known about these violations of medical ethics and human rights
Moral, ethical, and legal implications of the Guatemala STD experiments
Experiments were not conducted in a sterile clinical setting in which bacteria that cause STDs were administered in the form of a pin prick vaccination or a pill taken orally
Researchers systematically and repeatedly violated profoundly vulnerable individuals, some in the saddest and most despairing states, and grievously aggravated their suffering
Issues: inequalities in 1946, Public Health Service investigators in a study funded by the NIH, with the cooperation of Guatemalan authorities, engaged in a series of immoral and unethical human medical experiments conducted without the participants’ informed consent
Nuremberg Code (1946) The Nuremberg Code aimed to protect human subjects from enduring the kind of cruelty and exploitation the prisoners endured at concentration camps. The Nuremberg Code has served as a foundation for ethical clinical research since its publication 60 years ago. This landmark document, developed in response to the horrors of human experimentation done by Nazi physicians and investigators, focused crucial attention on the fundamental rights of research participants and on the responsibilities of investigators. It was prepared at a very momentous occasion, following the formal surrender of Germany at the end of the Second World War.
Nuremberg Trials, these were a series of military tribunals, held by the victorious Allied forces, wherein prominent members of the political, military, and economic leadership of the defeated Nazi Germany were prosecuted.
Trial of the Major War Criminals – held before the International Military Tribunal, which tried 22 of the most important captured leaders of Nazi Germany, though several key architects of the war (such as Adolf Hitler, Heinrich Himmler and Josef Goebbels) had committed suicide before the trials began. The initial trials were held between November 20, 1945 and October 1, 1946.
Doctor’s Trial In Nuremberg - trials of lesser war criminals was conducted under Control Council Law No. 10 at the US Nuremberg Military Tribunals; the case was about the medical set up in Germany and the affiliation of defendants to the different arms and services.
each of the defendants was indicted and finally spoke of violation of Medical ethics where 20 physician defendants had violated the Hippocratic Oath including its fundamental principle “Primum non nocere” (non-maleficence
they had violated the Hippocratic Oath and behaved in a manner incompatible with their education and profession. The defendants were charged with war crimes and crimes against humanity.
The accused were indicted on four counts viz.
Count I--The Common Design or Conspiracy
Count II--War Crimes
Count III--Crimes against Humanity
Count IV--Membership in a Criminal Organization
The 10 elements of the code are:
Voluntary consent is essential
The results of any experiment must be for the greater good of society
Human experiments should be based on previous animal experimentation
Experiments should be conducted by avoiding physical/mental suffering and injury
No experiments should be conducted if it is believed to cause death/disability
The risks should never exceed the benefits
Adequate facilities should be used to protect subjects
Experiments should be conducted only by qualified scientists
Subjects should be able to end their participation at any time
The scientist in charge must be prepared to terminate the experiment when injury, disability, or death is likely to occur
The Significance Of The Nuremberg Code
The Nuremberg Code is one of several foundational documents that influenced the principles of Good Clinical Practice (GCP).
Good Clinical Practice is an attitude of excellence in research that provides a standard for study design, implementation, conduct and analysis. More than a single document, it is a compilation of many thoughts, ideas and lessons learned throughout the history of clinical research worldwide
Declaration of Helsinki, 1964 - Ethical Principles For Medical Research Involving Human Subjects
The Declaration of Helsinki is a set of ethical principles regarding human experimentation developed for the medical community by the World Medical Association (WMA) It is widely regarded as the cornerstone document on human research ethics
The fundamental principle
respect for the individual (Article 8),
his right to self-determination and the right to make informed decisions (Articles 20, 21 and 22) regarding participation in research, both initially and during the course of the research.
The investigator's duty is solely to the patient (Articles 2, 3 and 10) or volunteer (Articles 16, 18), and while there is always a need for research (Article 6),
the subject's welfare must always take precedence over the interests of science and society (Article 5),
and ethical considerations must always take precedence over laws and regulations (Article 9).
The recognition of the increased vulnerability of individuals and groups calls for special vigilance (Article 8).
It is recognized that when the research participant is incompetent, physically or mentally incapable of giving consent, or is a minor (Articles 23, 24),
then allowance should be considered for surrogate consent by an individual acting in the subject's best interest, although his consent should still be obtained if at all possible (Article 25).
Morally binding obligation for physicians – overrides national laws/legislations, thus a higher standard
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Research
Is one of the leading works concerning ethics and health care research. The Nuremberg Code set the example for subsequent codes that established rules to help protect human subjects involved in research. But these rules were found to be inadequate to cover complex situations, at times in conflict, and frequently difficult to interpret or apply. Thus the primary purpose is to protect subjects and participants in clinical trials or research studies A statement of basic ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of research with human subject. This served as an ethical framework for protecting human subjects and its recommendations incorporated into other guidelines.
The Three Basic Ethical Principles and Their Applicability to Clinical Trials
Respect for persons, is made up of two important, but distinct, requirements.
people are autonomous and entitled to their own opinions and choices, unless detrimental to others.
recognition that due to various reasons, not all people are capable of self determination and instead require protection. The amount of protection provided to an individual should depend on the risk of harm and the likelihood of benefit offered by the research.
The Report promotes the idea that in most cases, respect for persons demands that people enter into research voluntarily and with adequate information.
Beneficence, is the recognition that people are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts, or, more specifically, making it an obligation, to secure their well-being. The Belmont Report identifies two general and complementary rules regarding beneficence:
do not harm,
maximize possible benefits and minimize possible harms.
The Report notes that it is the obligation of scientific investigators and members of their institutions to think about both maximizing benefits and reducing risks in their research
Justice, raises questions about who ought to receive the benefits of research and who ought to bear its burdens. Following a provocative discussion of equality and differential treatment.
The Belmont Report considers the need to scrutinize whether some classes of people - economically disadvantaged, racial and ethnic minorities, or persons confined to institutions - are systematically selected as research subjects due to their position or vulnerability rather than their connection to the problem being researched. Today, the principle of justice may demand scrutiny of whether classes of people considered compromised or vulnerable are excluded from participation in clinical trials due to financial and other barriers even though they have a connection to the problem being considered. The Report states that justice demands therapeutic devices and procedures developed from public funds must not provide advantages only to those who can afford them
National Bioethics Advisory Commission (NBAC)
PROTECTION OF HUMAN RESEARCH SUBJECTS AND CREATION OF NATIONAL BIOETHICS ADVISORY COMMISSION (USA- Executive Order 12975 of October 3, 1995),
NBAC identified and laid down broad principles to govern the ethical conduct of research.
This is a policy making body that is task to rectify the scandal done scandals concerning social science research and medical research conducted with the sick and the illiterate during the past. Research involving human participants has become a vast academic and commercial activity, but this country’s system for the protection of human participants has not kept pace with that growth. Since the 1974 formation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the activities in the early 1980s of the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research
Outline of the Report
Protecting the rights and welfare of those who volunteer to participate in research is a fundamental tenet of ethical research.
Respecting Research Participants - The report’s recommendations provided a coherent rationale for the federal policies and rules that created the current U.S. system of decentralized, independent research review coupled with some degree of federal oversight. In reference to the decisions in Nuremberg trials and the Belmont Report
Ensuring Independent Review of Risks and Potential Benefits - A central protection for research participants is the guarantee that someone other than the investigator will assess the risks of the proposed research. No one should participate in research unless independent review concludes that the risks are reasonable in relation to the potential benefits.
Formation of an Institutional Review Board (IRB), who’s responsible for conducting such reviews. improves the likelihood that decisions are made free from inappropriate influences that could distort the central task of evaluating risks and potential benefits. participants. A critical purpose of independent review is to ensure that risks are reasonable in relation to potential personal and societal benefits.
Obtaining Voluntary Informed Consent -Even when risks are reasonable, however, no one should participate in research without giving voluntary informed consent (except in the case of an appropriate authorized representative or a waiver). Investigators must make appropriate disclosures and ensure that participants have a good understanding of the information and their choices, not only at the time of enrollment, but throughout the research. The decision to participate in research must not only be informed, it must be voluntary.
Making Research Inclusive While Protecting Individuals Categorized as Vulnerable - Vulnerable individuals need additional protection in research. People whose circumstances render them vulnerable should not be arbitrarily excluded from research for this reason alone. Such as those:
More open to harm - children
more subject to coercion - Institutionalized persons ( those in prison or mental facilities
more “complicated” condition - women, who are considered more biologically complicated than men
more inconvenient - women with small children, who are viewed as less reliable research participants due to conflicting demands on time
Research participants must be treated equally and with respect. Whenever possible, research should be designed to encourage the participation of all groups while protecting their rights and welfare
Compensating for Harms - Participants who are harmed as a direct result of research should be cared for and compensated. This is simple justice. Regardless of individual motives, research participants are providing a service for society, and justice requires that they be treated with great respect and receive appropriate care for any related injuries. It should always be remembered that it is a privilege for any researcher to involve human participants in his or her research
Establishing a Comprehensive, Effective, and Streamlined System
A comprehensive and effective oversight system is essential to uniformly protect the rights and welfare of participants while permitting ethically and scientifically responsible research to proceed without undue delay
Participants should be protected from avoidable harm, whether the research is publicly or privately financed.
a new independent oversight office that would have clear authority over all other segments of the federal government and extend protections to the entire private sector for both domestic and international research.
a new independent oversight office that would have clear authority over all other segments of the federal government and extend protections to the entire private sector for both domestic and international research.
Education as the Key to Promoting Local Responsibility
the ethical obligation to protect participants lies first with researchers, their sponsors, and the IRBs that review their research. To help researchers and IRBs fulfil their responsibilities, the federal government should promote the development of education, certification, and accreditation systems that apply to all researchers, all IRB members and staff, and all institutions
investigators and IRB members and staff successfully complete educational programs on research ethics and become certified before they perform or review research that research ethics be taught to the next generation of scientists, and that research ethics be included in continuing education programs.
Clarifying the Scope of Oversight - Federal policies should clearly identify the kinds of research that are subject to review and the types of research participants to whom protections should apply.
Ensuring That the Level of Review Corresponds to the Level of Risk -Research review and monitoring should be intensified as the risk and complexity of the research increase and at all times should emphasize protecting participants rather than following rigid rules. In addition, the review process should facilitate rather than hinder collaborative research among institutions and across national boundaries, provided that participants are protected.
Providing Resources for the Oversight System -The oversight system should be adequately funded at all levels to ensure that research continues in a manner that demonstrates respect and concern for the interests of research participants.
The Philippine Health Research Ethics Board (PHREB)
The Philippine Health Research Ethics Board (PHREB) is the national policy making body in health research ethics in the country, created under DOST Special Order No. 091 s. 2006, which ensures adherence to the universal ethical principles for the protection and promotion of the dignity of health research participants.
The PHREB, shall ensure adherence to the universal principles for the protection of human participants in research. In order to promote and establish an effective health research protection system, the PHREB, among other things, shall:
Formulate and update guidelines for the ethical conduct of human health research;
Develop guidelines for the establishment and management of RECs and standardization of research ethics review; and
Monitor and evaluate the performance of RECs in accordance with PHREB approved procedures outlined in a prior agreement including requiring an annual report.”
To fulfil the above functions, PHREB has set requirements to guide in the conduct of quality ethical review of health and health-related research. To this end, PHREB accreditation is a requirement for all RECs.
A Research Ethics Committee (REC) is a body that makes independent decisions regarding the review, approval, and implementation of research protocols/proposals, in order to ensure the protection of the rights, safety, and well-being of human participants and promotes integrity of research data. It shall be constituted by a duly recognized authority and shall adhere to national and international research ethics guidelines.
COVERAGE The requirements for PHREB accreditation shall cover all RECs in the Philippines, which may be any of the following:
Academic Institution RECs
These are RECs of a university, college, medical school, or other professional school or institution. An AI-REC which functions independently of others under the same academic institution must apply for PHREB accreditation separately;
Hospital RECs
These are RECs of a hospital. A H-REC that functions independently of others under a hospital must apply for PHREB accreditation separately; In the case of specialty clinics/departments, additional and specific requirements shall be fulfilled as described in Section VII.
Government RECs
These are RECs of an office, department, bureau, or agency in the government. A G-REC that functions independently of other RECs under a government office, department, bureau, or agency must apply for PHREB accreditation separately. Consortia for regional health and development RECs (CHRD RECs) will be considered as G-RECs for funding purposes but if the different institutions establish their own REC which functions independently of others under the consortium, these institutional RECs must apply for PHREB accreditation;
Cluster RECs
These RECs are formed by groups of institutions that cannot form individual RECs. The management and administration of a C-REC is determined by the memorandum of agreement among these institutions. A C-REC shall register and may apply for PHREB accreditation as one REC;
Research Site RECs
These RECs operate within and for research sites including specialty clinics. An R-REC shall apply for PHREB accreditation as a whole unit regardless of the number of sites or facilities the research will engage
GENERAL POLICIES
Health research encompasses all research that seeks to understand the impact of processes, policies, actions, or events originating in any sector on the well-being of individuals and communities; and to assist in developing interventions that will help prevent or mitigate their negative impact, and in so doing, contribute to the achievement of health equity and better health for all (adapted from the RA 10532 Joint IRR). It implies that improving health outcomes requires the involvement of many sectors and disciplines. On the other hand, a research is considered “health-related” if it is outside of the aforementioned description for health research, but where the research procedures and outcomes can affect the well-being of the participants and the community. Regions with functional Research Ethics Monitoring Boards (REMBs), accreditation of levels 1 and 2 shall be conducted by the respective boards.
The following policies shall be applicable:
All health and health-related research protocols/proposals involving human participants shall be reviewed by a Research Ethics Committee (REC).
Research proposals involving indigenous cultural communities/indigenous peoples (ICCs/IPs) shall secure ethical clearance from a PHREB Level 2 or 3 Accredited REC and approval from the National Commission for Indigenous Peoples (NCIP). In case NCIP is able to establish its own REC, ethical clearance shall be issued by the same depending on feasibility.
Research protocols/proposals involving use of Animals are reviewed by an Institutional Animal Care and Use Committee (IACUC).
Protocols with biosafety issues or pose hazards to the environment including those involving animals and plants need review and approval by the institutional or National Committee on Biosafety of the Philippines (NCBP).