ethical issues in medical research eligius lyamuya md, mmed, phd department of microbiology and...
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ETHICAL ISSUES IN MEDICAL RESEARCH
Eligius Lyamuya MD, MMed, PhD
Department of Microbiology and Immunology, Muhimbili University College of Health sciences
Learning objectives
Know the Basic Research ethics documentsUnderstand the Principles of Research
EthicsUnderstand Informed ConsentKnow the Local regulations
Disposition
PreambleBackgroundBasic Research ethics documentsPrinciples of Research EthicsInformed ConsentLocal Regulations
Preamble: Definitions - 1
Research is a systematic investigation designed to develop or to contribute to generalizable knowledge.
Health research makes discoveries about how to improve health
Health research involves many disciplines, including biomedical and social sciences
Definitions - 2
A human subject is a living individual from or about whom an investigator conducting research obtains data through intervention, interaction or identifiable private information
Intervention includes both physical procedures for data gathering and manipulations of the subject or the subject’s environment that are performed for research purposes
Definitions - 3
Interaction includes communication or interpersonal contact between investigator and subjectDirect interactions, such as obtaining data
by taking medical history, interview, drawing blood samples etc.
Indirect interactions, such as analysis of specimens or data already obtained from people
Definitions - 4
Private information includes information about behaviour that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place; also includes information that has been provided for specific purposes by an individual and which will not be made public.
Background
Three parties have legitimate interests in any research involving human subjects:Investigator, who initiates itSociety, that provides conditions for itSubjects, who participate in it
It is essential to prevent conflict of interest between these parties
Basic Research Ethics documents
1964: Nuremberg code1974: The Declaration of Helsinki 1978: Belmont Report1993: Council for International
Organizations of Medical Sciences (CIOMS) Guidelines
1946: Nuremberg code: History
Development of ethical guidelines for the conduct of research involving humans began in late 1940s.
1946, 23 Nazi defendants (20 of them physicians) tried for war crimes and crimes against humanity
16 guilty: 7 hanged, 9 sentenced to prison terms, 10 years-life
Nuremberg code
Out of the Nazi experience grew a set of principles known as the Nuremberg Code
Intended to apply primarily for medical research, but are also useful for other types of research (behavioural and social science)
Principles from the Nuremberg code-1
1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved, as to enable him to make an understanding and enlightened decision. This latter element requires that, before the acceptance of an affirmative decision by the experimental subject, there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person, which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.
Principles from the Nuremberg code-2
2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the experiment.
4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
Principles from the Nuremberg code-3
5. No experiment should be conducted, where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even
remote possibilities of injury, disability, or death.
Principles from the Nuremberg code-4
8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
9. During the course of the experiment, the human subject should be at liberty to bring the experiment to an end, if he has reached the physical or mental state, where continuation of the experiment seemed to him to be impossible.
10. During the course of the experiment, the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgement required of him, that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.
1964; revised 2001: The Declaration of Helsinki
The well-being of the human subject should take precedence over the interests of science and society
Consent should be in writingUse caution if participant is in dependent
relationship with researcherLimit use of placeboParticipants benefit from research
1974: From the Belmont Report to the Code of Federal Regulations
Evolution of research ethics in the United States of America
The Tuskegee study: Ethical problems with research are identified
The Belmont Report: Fundamental principles for the ethical conduct of research are advocated
The Code of Federal Regulations: Specific regulations are adopted
Tuskegee syphilis study-1
Research began in 1932 in the USA; involving 600 men, all poor and all black, funded by Public Health Service
Study purportedly designed to monitor and record their health, some told they had “bad blood” but none were told they had syphilis
Given free medical attention, hot meal and promise of government support to cover their burial expenses
Tuskegee syphilis study-2
2/3 had evidence of tertiary syphilis at recruitment; many control subjects acquired disease during course of study
However, even after penicillin was discovered to be a cure for syphilis in 1943, it was not offered to the subjects as treatment
Tuskegee syphilis study-3
Project ended in 1972 after press reports of details of the study
Senator Edward Kennedy held hearings on the study, government sued, case settled for $10 million in 1974, to be shared among surviving subjects and the heirs of the deceased
1997 President Clinton formally apologized on behalf of the government to the survivors
Belmont Report: Ethical principles
Following Kennedy hearings in 1974, National Research Act passed, National Commission for Protection of Human Subjects of Biomedical and Behavioural Research created.
Commission produced the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research, published in 1978 which developed ethical principles of research:
Respect for persons Beneficence Justice
1993; revised 2002: Council for International Organizations of Medical Sciences (CIOMS)
Guidelines
Prepared by CIOMS in collaboration with WHO 21 specific guidelines, each followed by
interpretative commentaries Indicate how the Declaration of Helsinki could
be effectively applied, particularly in developing countries, given the socioeconomic circumstances, laws and regulations, and executive and administrative arrangements
Summary: Research Ethics documents
From Nuremberg to CIOMSThree Universal principlesProtection of the participant
Fundamental Principles of Research Ethics-1
The Belmont report enumerates three basic principles for investigators conducting research with human subjects:
Respect for persons Beneficence Justice
These remain to be the universal fundamental principles of Research Ethics
Fundamental Principles of Research Ethics-2
These are considered to be universal; they have no national, cultural, legal or economic boundaries
Every researcher should understand and follow them
Availability of resources needed to maintain these principles is not universal of evenly distributed
Respect for persons
Each individual: Is autonomous, unique and free Has the right and capacity to decide Has value and dignity Has the right to informed consent
Vulnerable persons are entitled to special protections Minors, pregnant women, prisoners, mentally disabled,
illiterates (or limited formal education), persons with limited access to health services, women in some settings
Beneficence
Latin = to do good Researchers must:
Do no harm (non-maleficience) by protecting physical, mental and social well-being of study participants
Maximize possible benefits and minimize possible harms
Justice
Researchers must: Conduct equitable recruitment of research
participants Ensure fair distribution of risks and benefits of
participation Provide special protection for vulnerable groups
Summary: Principles of Research Ethics
Health research is conducted according to 3 universal principles: Respect for persons Beneficence Justice
Researchers must work for the well-being of populations that participate in their studies.
These principles were developed to provide guidance and ensure that the well-being of each participant is always considered.
Informed consent-1
Consent given by a competent individual who:Has received the necessary informationHas adequately understood the information
(comprehension)After considering the information, has arrived
at a decision without having been subjected to coercion, undue influence or inducement, or intimidation (voluntary decision)
Informed consent-2
4-step process:Step 1: Information is provided Step 2: Information is understood
(Comprehension)Step 3: A Voluntary decision is made Step 4: Comprehension is monitored and
maintained
Informed consent-3
Essential elements:1. Research description2. Risks3. Benefits4. Alternatives5. Confidentiality6. Compensation7. Contacts8. Voluntary participation and withdrawal9. Documentation
Description of the Research
Research studyObjectives of the studyExpected responsibilitiesProcedures involvedStudy durationExplanation of randomization or placebo
Description of Risks
Anticipated or foreseeablePhysical, social, psychologicalLikelihood, severity, duration
Description of Benefits
Reasonably expectedNot overstated or exaggeratedDuration
Available Alternatives
Alternative procedures or treatmentAdvantages and disadvantagesAvailability
Confidentiality
Degree of confidentialityIndicate persons or organizations who may
have access to the informationAnticipated future use of data or biological
samples
Compensation
Fully explained and not coerciveFair payment for time, travel and
inconveniencePossibility of treatment and compensation
in case of research-related injury or complications
Degree of health care to be made available
Contact Persons
Research teamEthics committeeSpecial groups
Voluntary Participation
Free of coercion and undue influenceRight to discontinue at any timeNo penalty for refusal or withdrawal
Documentation
Is only part of the informed consent processSignatures may not always be possibleWaiving of documentation requires ethics
committee review and approval
Summary: Informed Consent
Ethical, not just legal requirementFree of coercionDocumentation neededComprehensibility essentialSupport materials helpfulPilot-testing encouraged
Local Regulations and Guidelines
Rapid growth of international researchMany countries, including Tanzania, now
have national guidelinesGreatest need in developing countries
From Fundamental Ethical Principles to Local Guidelines
National regulations and international recommendations
Local/Institution operational guidelines
3 principles•Respect for persons•Beneficence•Justice
Conclusion
Research ethics is a growing field of study generating a great deal of attention.
International research ethics should guide research conducted at any level to ensure that international expectations and standards are followed.