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.