EMPHNET

Ethical issues in Public Health research

Ghaiath M. A. HusseinMBBS, MHSc. (Bioethics), PhD Researcher

Email :.ghaiathme@gmail com

Regency Hotel, Amman, Jordan15-19 June, 2014

Module’s Objectives

• Recognize the significance of ethical review of research and ‘research-like’ activities

• Differentiate between public health research and similar activities

• Describe the ethical issues encountered during and after the conduct of public health research

• Apply an ethical framework for moral reasoning and analysis of the ethical issues related to the conduct of public health research

What is Research? “Research” is defined as an undertaking intended to extend

knowledge through a disciplined inquiry or systematic investigation.

A determination that research is the intended purpose of the undertaking, is key for differentiating activities that require ethics review by an ethics review and those that do not.

Systematic methodological scientific approach for basic facts around a certain problem in order to find solutions based on these facts.

السكان من مليون لكل المنشورة العلمية المقاالت عدد يوضح وجدول المنشورة، العلمية المقاالت عدد حيث من العالم دول حجم توضح خريطةwww.worldmapper.org: المصدرم. 2001لعام

Research in Context...the KMC

Generation

Dissemination

SynthesisUtilization

Assessment

Policy makers

Research

Statistics

Clinicians

Knowledge Management Cycle

Public

ations

Confere

nces

Cochraine

EMBase

“Good” research: Good Science & Good Ethics

“Good” Evidence: near-top to hierarchy of Evidence

Evidence-Based Healthcare: Better practice that is based on best evidence

Better health status

Here Comes RECs

!

Better Ethics is Better Health

What Makes a Good Research?

Good science

Good Ethics

•Problem selection•SMART objectives•Proper methodology•Proper analysis

•Fair subject selection•Favorable Risk-Benefit Ratio•Independent Review•Informed Consent

Ethics: when in research?

Before

•Justice: Fair selection of participants•COI: research design

•Benefit/Harm balance: Ethical review

During

•Autonomy: obtaining informed consents•Privacy & confidentiality

•Integrity: adequate use of the appropriate methods

After

•Transparency: in reporting the •Integrity

•Publication ethics

Ethical review of research

• A process by which research is submitted to be reviewed by an ethics review committee against a set of ethical standards that are stated in ethical guidelines

• What’s an IRB/REB/REC? What role it plays?

Research or not research?

• What among the public health activities is research?– Census?– Household Surveys?– Surveillance?– Outbreak Investigation?– Audits?– Quality Assurance?

• How to differentiate? Is it important?

What’s Research Ethics? It is the field of ethics that systematically analyze the

ethical and legal questions raised by research involving human subjects.

Its main focus is to ensure that the study participants are protected and, ultimately,

that clinical research is conducted in a way that serves the needs of such participants and of society as a whole.

It works when and only when it is applied before the research is conducted

HISTORICAL BACKGROUND

BORN IN SCANDAL… THE EVOLUTION OF RESEARCH ETHICS

18th and 19th Centuries

• James Lind “scurvy study in sailors - Salisbury• Edward Jenner cowpox vaccine test• 1897 Giuseppe Sanarelli yellow fever test

1900 Walter Reed established several [first ever]“safeguards”• Self-experimentation• Only adults would be enrolled in research• Written informed consent• Reimbursement (inducement)

History of Research Ethics

Pre-World War II• Research standards left up to the discretion of the individual

researcher

World War II• Experiments conducted on inmates of Nazi concentration camps• 1945-1949 - Trials in Nuremberg, Germany– physicians convicted

of crimes against humanity

Nazi Doctors’ Experimentation

Development of the main International Research Guidelines

Nuremberg Code (1947)

­ As a result of WWII Nazi experiments­ First international code in research ethics

• Voluntary consent absolutely essential (restricting research with infants, children, developmentally

challenged, etc.)

• Risk/Benefit Analysis essential to ethics review

• Scientific Soundness is important to ethics review

The Nuremberg Code (1947) The first provision of the code requires that “the voluntary informed consent of the human subject is absolutely essential.” The code provides other details implied by such a requirement:

• Capacity to consent• Freedom from coercion• Comprehension of the risks and benefits involved• Experiment to be conducted by highest qualified persons

The code on the web: http://ohsr.od.nih.gov/nuremberg.php3

The Declaration of Helsinki (DOH) The World Medical Association created the Declaration of Helsinki in 1964 and amended in: Tokyo (1975), Venice (1983), Hong Kong (1989), South Africa (1996), Edinburgh (2000), Washington (2002), and Tokyo (2004)

“The well-being of the subject should take precedence over the interests of science and society” Consent should be in writing

Use caution if participant is in dependent relationship with researcher

Limited use of placebo

Greater access to benefit

World Medical Association WMA (1964)

Respect for Persons – people are not a means to an end; researchers have duty to protect life, health, privacy and dignity of research participants

Standard of care must be best available, even for control group

Proxy consent and assent for vulnerable populations

More than 400 African- American men with latent syphilis were followed for the

natural course of the disease rather than receiving treatment.

Continued after penicillin available

40 wives infected, 19 children born with congenital syphilis

TUSKEGEE SYPHILIS STUDY,ALABAMA ( 1932 – 1972 )

Willowbrook Study, New York1956-1972, NYU

800 Children Willowbrook State School for the Mentally Retarded

Researchers injected students with mild form of hepatitis

The Belmont Report (1979) In 1972, the public became aware of the Tuskegee study, which

took place in the southern United States from 1932 to 1972.

In 1974 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was established.

In 1978, the commission submitted its report titled, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research.

Those principles respect for persons, beneficence and justiceare accepted as the 3 fundamental principles for the ethical conduct of research involving human participants.

Council for International Organizations of Medical Science (CIOMS) Guidelines (1993)

• Informed consent• Research in developing countries• Protection of vulnerable populations• Distribution of the burdens and benefits• Role of ethics committees

Year Benchmark

Pre-1900 Edward Jenner smallpox vaccines

1900 Walter Reed’s ‘consent’ for yellow fever experiments

1947 The Nuremberg Code

1964 World Medical Association (WMA) published the Declaration of Helsinki (DOH)

1966 Dr. Beecher’s Article “Ethics and Clinical Research”

1975 WMA updates DOH (Tokyo)

1979 The Belmont Report

1981 US Common rule updated

1983 WMA updates DOH (Venice)

1989 WMA updates DOH (Hong Kong)

1991 US CFR title 45, Part 46 issued CIOMS Guidelines for Epidemiological studies

1993 CIOMS guidelines for biomedical research involving human subjects

1996 WMA updates DOH (South Africa)

1998 Tri-Council Policy Statement (TCPS)published in Canada

2000 WMA updates DOH (Edinburgh)

2002 WMA updates DOH (Washington) CIOMS Guidelines updated

2004 WMA updates DOH (Tokyo)

2008 WMA updates DOH (Seoul)

2010 TCPS updated

2013 WMA updates DOH (Brazil)

Milestones in the history of

research ethics

Is it over?... Torvan trial in Kano, Nigeria

Kano Trovan clinical trials in 1996, on pediatric age group, during the worst ever meningococcal meningitis.

Lack of proper Governmental authorization and informed consent during the studies publicized in 2000, by Washington Post.

Court trial and release of investigation panel reports stalled in Nigeria.

Suit for 5.8 billion USD moved to the USA and report leaked there too.

Settlement out of court being discussed.

Ethical Principles of Research

What makes research ethical?

What Makes the Research Ethical?

1- Social or Scientific Value:• Improve health and wellbeing• Increase the knowledge

2- Scientific Validity• Acceptable methods including analysis techniques to

produce valid data (Test the objectives)

3- Justice and Inclusiveness: • Stigmatized and vulnerable are not targeted• Rich not favored for the benefit of research• Clear inclusion and exclusion criteria according to the

objectives.• Clear Strategies for recruitment

What Makes the Research Ethical? Cont.

4- Favorable Risk-Benefit Ratio: • Identification and Minimization the risk • Enhancement of the potential benefit• Risk to the subject are appropriate to the benefits to the subject and society.

5- Independent Review:

• Review of the Design, the proposed subject selection and risk-benefit ratio.

6- Free and Informed Consent: • Provision of Information• Voluntarily and Consists with the values

7- Respect for the potential and enrolled subjects and Respect for Vulnerable Persons :

• Right to withdrawal• Privacy and confidentiality• Informing about the new discovered risks or benefits• Maintaining the welfare of the subjects.

WHAT ARE THE ETHICAL ISSUES IN RESEARCH?

•Benefit/harm analysis•Vulnerability (Risk-Vulnerability Matrix)•Informed Consent•Fairness and equity in research participation•Privacy and confidentiality•Conflict of Interests (COI)

Benefits

• Benefits to research subjects

• Benefits to society• Specific new, effective intervention • Knowledge which some time in the future may

lead to effective interventions

Benefits to Research Subjects

Direct Benefit– Arising from the intervention being studied– Information that can influence care, e.g., diagnostic

Collateral “indirect” Benefit– Arising from being a subject, even if one does not receive the

experimental intervention– Extra supervision from being in the research study (?)– Access to medical care not available for economic reasons– Unplanned or unanticipated benefits

Benefits to Research Subjects

Inspirational

Aspirational• Benefit to society (arises from the results of the study)

Payments or incentives – benefits?

Any level of research risk could be offset by such gains ifthey were significant enough

Benefits to Research Subjects

No benefits from the research– Phase I trials testing maximum tolerated dose– Non-therapeutic research procedures

• Mechanism of disease

Risk/Harm• Risk:

– Means any harm or injury that affect the subject or the participant under study.

• Risk:– “ A state of uncertainty where some of the possibilities

involve a loss, catastrophe, or other undesirable outcome. ”

Types of risks

Physical risks:1. Cold: Nazi Experiments with ice tanks2. Pressure: Nazi experiments in high altitude3. Heat: Heat stroke; Burn; Exhaustion4. Noise: High noise may lead to impairment or loss of hearing 5. Light: Dim light may affect the vision

Nazi Experiments

High Altitude Experiments

Types of Risk…Cont.Medical Risks:1. Therapeutics: (Tuskegee expirement)2. Preventive: (Trials of polio vaccine)3. Diagnostic:

• Irradiation: - Teratogenic effect to the fetus. - Carcinogenic effect.

• Samplings: - Biopsies: tissues that contain genetic information about

the participant. - Surgical hazards. - Too risky procedures (under anesthesia)

The Forgotten Risks Social Risks: Stigma (e.g. research on HIV-AIDS, STDs).

Emotional Risks: On families when their children were chosen for trial of

new vaccine; research in war.

Psychological Risks: Questionnaires with sensitive questions to participants in sensitive positions, as to ask poor people about there nutrition and houses.

Risk to the Society Manipulating environmental factors (Pathogenic organisms and

toxic chemicals).

Economic risk

Legal risks: Vulnerable groups, e.g., prisoners, children, pregnant women.

Categorization of RiskRisk is categorized by severity into:

1. Minimal Risk: As routine blood sample , throat swabs, vaginal swabs, sputum exams

2. Above Minimal Risk: That can be minimized, and within the toleration of the participant.

3. Too Risky: The most dangerous type, and the Researcher should not be allowed to conduct a research that endangers the life of the participants e.g. live cancer cells , live virus

Minimal Risk

The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during routine performance of physical or psychological examination or tests

Clinical Equipoise• Clinical equipoise means a genuine uncertainty on the

part of the expert medical community about the comparative therapeutic merits of each arm of a clinical trial.

• The tenet of clinical equipoise provides a clear moral foundation to the requirement that the health care of subjects not be disadvantaged by research participants.

Minimization of Risk

Adequate facilities ,procedures and personnel for dealing with emergencies .

Arrangement made for monitoring and detecting adverse out comes .

All trials should be reviewed by a Data Safety Monitoring Board (DSMB).

All potential toxins, mutagens or teratogens used should be justified.

The National Committee for Atomic Energy should complete risk assessment for the use of the radiation and radioactive substances .

Minimization of Risk

For Drugs:- Registration, its trade name, chemical name and

pharmacological class .

- Recommended dose, form of administration in the study.

- Known or possible interaction with other drugs, side effects and adverse reactions.

- Placebo should be justified.

Minimization of Risk

Social Risks:- The research should have potential to enhance the future

health of the society .

For vulnerable groups :- Additional safeguards needed to protect there rights and

welfare .

For recruitment materials:- (posters, newspapers, T.V, videos ……). Should be acceptable if submitted.

Minimization of Risk

For Psychological Risks :• Sensitive questions for sensitive group like those with AID, STDs,

T.B, can be questioned through 3rd person or ask the help of psychologists .

Economic Risks :• Traveling cost can be solved out.• Absentees issues should also be solved out.

Minimization of Risk

Legal :- The risk should be reasonable in relation to the anticipated benefits to the subjects or society.

- Privacy of subject should be adequately protected.

- For tissue samples containing genetics information the subject should have option to withdraw at any time.

Vulnerability (Risk-Vulnerability Matrix)

Definition Vulnerable: “Vulnerable persons are those who are relatively (or

absolutely) incapable of protecting their own interests. More

formally, they may have I insufficient power, intelligence, education, resources strength, or other needed attributes to protect their own interests.” (CIOMS, 2002)

Saudi Commision for Health Specialties

Who is Vulnerable?

Making use of this definition… let’s brainstorm!

www.amanet-trust.org

Who is Vulnerable?

1. WOMEN Women in the reproductory age group are usually excluded in drug/vaccine studies where the possible effects on fetus are not known.

As justice to women, their health conditions should be addressed through involving them in research.

Types of research that benefit women directly include, obstetrics and gynecology, sexually transmitted infections, vitamin studies etc.

Who is Vulnerable?

2. PREGNANT WOMEN Should be awarded special protection because of additional health concerns during pregnancy and the risk of damage to the fetus.

Pregnant women must be excluded from research unless the purpose is to meet the health needs of the mother, and

The fetus will be placed at risk only to the minimum extent necessary to meet such needs or

The risk to the fetus is minimal

Who is Vulnerable?

3. CHILDREN Particularly vulnerable group. The major ethical issue for involving children is that parents are the primary decisions makers for their minor children.

There must be no undue inducement to participate for parent, guardian or child, although reimbursement of expenses is allowed.

A “small gift” to the child after completion of the research is however acceptable.

Requirements for involving in Research

The purpose of the research is to obtain knowledge relevant to the health needs of children

A parent or legal representative of each child should give permission;

The agreement (assent) of each child has been obtained to the extent of the child`s capabilities; and

A child`s refusal to participate or continue in the research should be respected.

Assessment of Risk in children Minimal Risk- risk in relation to normal experience of average,

healthy normal children – daily life/routine physical psychological exams

Minimal Risk varies with age but not social status, illness or circumstances

Consultation with experts – pediatricians , social workers etc

Who is Vulnerable?

4. MENTALLY ILL / MENTALLY HANDICAPPED PERSONS Is he/she capable of self-determination?

Respect for the immature and the incapacitated may require protecting them as they mature or while they are incapacitated (Belmont Report)

It is usually that informed consent will be provided by a surrogate/ legal representative of that person.

The golden rule for involving mentally ill or handicapped people is that ; The objections of these subjects to involvement should be honored, unless the research entails pro-providing them a therapy unavailable elsewhere.

Who is Vulnerable?

5. THE ELDERLY Old age alone does not render a person incapable of consenting to health research.

In the absence of any indication to the contrary, elderly patients are generally assumed to be competent to consent to research.

However, consideration should be given to the possibility of mental deterioration, the ability to comprehend, and the dependence and vulnerability of the elderly

Who is Vulnerable?

6. PRISONERS Prisons are organizational structures exacerbate vulnerability of the incarcerated individuals.

They have limited economic power, inadequate protection of human rights, limited availability of health care and treatment options.

The prison structure makes the incarcerated prisoners confined, stressed, crowded, psychologically devastated with symptoms such as psychosis, severe depression, and complete social withdrawal.

Who is Vulnerable?

7. CAPTIVE/DISPLACED/RETURNING POPULATIONS Have constrained movements and choices

Refugees, those in police custody, and displaced population,

Hospitalized patients, students, institutionalized persons and military personnel.

Readily available for research activities for extended periods, enhancing their attractiveness to research enterprise.

Researchers should always have to be sure if participant’s decision making capacity is not compromised.

How to Decide? Nature and degree of risk

The condition of the particular population involved and,

The nature and level of the anticipated benefits.

Relevant risks and benefits must be thoroughly arrayed in documents and procedures used in the informed consent process

Assessment of Risk-Vulnerability

Research Risk depends on both Level of Invasiveness

(physical, psychological or emotional) and Vulnerability of

participants.

Vulnerability is generally a pre-existing condition, in that it

exists regardless of whether the research is conducted or not.

It can be inherent or situational.

Assessment of Risk-Vulnerability (2)

Invasiveness: consider the physical, psychological,emotional and legal harms that could be caused byor exacerbated by the research.

Group Invasiveness Vulnerability Low Medium HighLow Exp. Exp. FullMedium Exp. Full FullHigh Full Full Full

Risk/Vulnerability Matrix

Conclusion (to vulnerability) Vulnerability is considered to offer better protection, not to stop research on the vulnerable

Vulnerable groups should not be denied their right to participate in relevant research

The risk assessment varies with the degree of vulnerability

Informed Consent

Definition “Autonomous authorization of a medical intervention…by

individual patients/participants“ (Beauchamp and Faden, 2004)

It's the practical expression of patient's autonomy, and the respect for him/her personality

Components of FIC:

1. "Disclosure" refers to the provision of relevant information by the clinician and its comprehension by the patient.

2. "Capacity" refers to the patient's ability to understand the relevant information and to appreciate those consequences of his or her decision that might reasonably be foreseen.

3. "Voluntariness" refers to the patient's right to come to a decision freely, without force, coercion or manipulation.

Disclosure

VoluntarinessCapacity

1. Disclosure

This refers to the process during which physicians provide information about the proposed research to the participant.

Eight Required Elements[45 CFR 46.116(a) & 21 CFR 50.25]

1. Statement that study in research and information on purposes / duration / procedures / experimental procedures

2. Reasonably foreseeable risks or discomforts

3. Reasonably expected benefits

4. Alternative procedures

Eight Required Elements Cont.[45 CFR 46.116(a) & 21 CFR 50.25]

5. How confidentiality will be maintained

6. Information on compensation for injuries (unless minimal risk)

7. Contact persons for information on research, injury, subject’s rights

8. Voluntary participation, no penalty or loss of benefits for refusal or withdrawal

Six Additional Elements

1. Statement that there may be risks which are unforeseeable2. Under what circumstances investigator could terminate

subject’s participation3. Additional costs to subjects4. Consequences of subject’s withdrawal from research5. Statement that will be told of new findings6. Approximate number of subjects in study

Forms of Consent

Normally, should be provided by participants themselves. • Deferred consent: is where the subject is entered into a research

study and consent is gained from surrogates after a specified period of time for continuation of the subject’s inclusion in the trial.

• Prospective informed consent : represents an attempt to canvass support in advance from a population considered at risk of developing a serious illness.

• Surrogate consent (SDM): ideally a substituted judgment made by a person responsible for health care decision-making for a particular patient under the relevant legislation

Waiver of Informed Consent

REC must find and document that the following criteriahave been satisfied:

Poses no more than Minimal risk research Waiver or alteration will not adversely affect the rights and welfare of the subjects Research could not practicably be carried out without the waiver or alteration Does not involve a therapeutic intervention Subjects will be provided with additional pertinent information

All of the above must apply

Documentation of Informed Consent

Written consent document Language understandable to the subject or the subject’s Legally

Authorized Representative (LAR) Signed by subject or subject’s LAR Copy SHALL be given to subject Opportunity to read before signing

Principles for Providing Information the Participant:

Make it clear; avoid jargon

Use language appropriate to the patient's level of understanding in a language of their fluency

Pause and observe patients for their reactions

Invite questions from the patient and check for understanding

Principles for Providing Information the Participant: Cont.

Invite the patient to share fears, concerns, hopes and expectations

Watch for patients' emotional response: verbal and non-verbal

Show empathy and compassion

Summarize the imparted information

Provide contact information (and other resources)

2. Capacity:

Refers to the presence of a group/set of functional abilities a personneeds to possess in order to make a specific decisions

(Griso and Applebaum, 1998).

These include: To UNDERSTAND the relevant information To APPRECIATE the relatively foreseeable consequences of the

various available options available.

3. Voluntariness:• Refers to a participant’s right to make participation decisions

free of any undue influence.

Influences include:• Physical restraint or sedation• Coercion involves the use of explicit or implicit threat to

ensure that the treatment is accepted• Manipulation involves the deliberate distortion or omission of

information in an attempt to induce the subject’s participation

Voluntariness

• Free of undue influence• Persuasion: appeals to reason• Manipulation• Coercision: explicit or implicit threats• Force: restraint or sedation

MANIPULATION

• Distortion of facts or omission• Non-coercive alternation of choices• Undue financial payment• Undue influence, government funding only at

grade eight for hpv

Practical Challenges to a "Fully Informed Consent"

• Diagnostic uncertainty• Complexity of medical information• Linguistic and cultural differences• Overworked health personnel• Paternalistic approach in doctor-patient

relationship in developing countries, including Sudan.

Informed Consent from Children

• Written Parental/Guardian consent only required for those below the “legal age”

• Assumption : best interests of the child should be regarded

• Both parents of the child should sign or just one?

• Institutionalised children?• Children without any recognisable legal

guardian?

Assent

After the age of seven and below legal consenting age (which is different for different countries depending on regulations) those who are competent to understand the opinion of the child should be respected

“A child’s affirmative agreement to participate in research. Mere failure to object should not be construed as assent” Silence Assent

Assent

Waiver of parental consent may be granted in adolescent research in certain circumstances i.e. drug abuse, sexual behaviour etc.

Assent documents may include – age appropriate information sheets and forms where applicable

PRIVACY AND CONFIDENTIALITY

Privacy

The right to be left alone and to keep personal information inaccessible to others (the condition of limited access to a person)

Privacy Relates primarily to Process of clinical examination

and collecting dataOften Challenging in Natural EnvironmentCan inconvenience research participantsCan encounter participants in publicProcedures and processes can compromise privacy Some institutions and cultures not accustomed to privacy,

or do not value it

Infringements of privacy

• Infringements is justified under certain circumstances; if:

1. Necessary for research conduct2. Doesn’t create harm to participants3. There is societal benefit

Confidentiality­ The duty to respect the research participant’s confidence

that the researcher/doctor will not disclose the information he/she received as part of research of health care.

­ How someone will deal with the information that was disclosed to him in confidence

­Failure to keep private information is an infringements of confidentiality­ Deliberate­ Accidental

Measures to respect confidentiality

• Avoid identifiable data• Encode the collected data• Limit access to data• Keep in password-protected PC• Destroy the original copies after analysis, or

publication• Training of research team on confidentiality• Release information without identification

To each of the previous conditions, there are ethically-acceptable exceptions

Breaking Confidentiality

• Court order • Communicable diseases• Vulnerable person abuse/neglect• Driving/flying/machine safety• Dangerous patients

Unanticipated Problems: Examples

• STDs research – placement of clinic. Sign on door.• Waiting with others, who knows you?

Important Considerations:

• Retention of data after the study is complete

• Secondary uses and linkage of data (i.e. databases)

• How much personal information is actually necessary for the study?

CONFLICTS OF INTEREST (COI)

What is an interest?

• An interest may be defined as a commitment, goal, or value held by an individual or an institution.

• Examples include a research project to be completed, gaining status through promotion or recognition, and protecting the environment. Interests are pursued in the setting of social interactions.

What is COI?

• COI exists when two or more contradictory interests relate to an activity by an individual or an institution.

• Conflicts of interest are “situations in which financial or other personal considerations may compromise, or have the appearance of compromising, an investigator’s judgment in conducting or reporting research.” AAMC, 1990

What is COI? Cont.

• “A conflict of interest in research exists when the individual has interests in the outcome of the research that may lead to a personal advantage and that might therefore, in actuality or appearance compromise the integrity of the research.”

NAS, Integrity in Scientific Research

Levels of COI

• Researchers• The REB should assess the likelihood that the

researcher’s judgment may be influenced, or appear to be influenced, by private or personal interests, and assess the seriousness of any harm that is likely to result from such influence or from the mere appearance of undue influence (TCPS, 200)

Levels of COI

Conflicts of Interest by REB Members• It is of the highest importance that members of the

REB avoid real or apparent conflicts of interest .

• For example: when their own research projects are under review by their REB or

• when they have been in direct academic conflict or collaboration with the researcher whose proposal is under review.

Levels of COI

Institutional Conflicts of Interest• Situations may arise where the parent organization has a

strong interest in seeing a project approved before all ethical questions are resolved.

• The REB must act independently from the parent organization.

• Institutions must respect the autonomy of the REB and ensure that the REB has the appropriate financial and administrative independence to fulfill its primary duties.

What comprises COI?

• Stock ownership

• Paid employment Board membership

• Patent applications (pending or actual)

• Research grants (from whatever source)

• Travel grants and honoraria for speaking or participation at meetings

What comprises COI? Cont.

• Gifts Membership of lobbying organizations

• Relationship with the National Research Ethics Review Committee, or with possible reviewers of the paper

• Relationship with organizations and funding bodies Membership of a government advisory board

Is it always bad?

COIs may result in:

1. Loss of objectivity 2. Reordering of priorities towards applied research 3. Degradation of the nature of science as an open and

collegial enterprise 4. Exploitation of trainees 5. Transfer of time and interest to Commercial ventures

• In May 2004, the pharmaceutical giant Pfizer agreed to pay $430 million to settle a lawsuit by a former employee turned whistle-blower, who was joined in the lawsuit by the U.S. federal government and 11 state governments.

• The lawsuit exposes various marketing practices by the company Warner-Lambert – later bought by Pfizer.

• Leading academic researchers were paid to deliver promotional lectures at educational events and to publish favorable reports on the off-label use of its epilepsy drug, Neurontonin.

L. Kowalczyk “Pfizer Drug Strategy Probed: States Question Marketing Tactics for Neurontin,” Boston Globe, October 18, 2002,

Conflicts Can Occur at all Levels of Research

• In reviews/awarding of grant• In ethics review of grant• In recruitment of participants• In analysis of data• In presentation of data

The Case of Nancy Oliveiri

• In 1996, Olivieri found that the drug she was researching (deferiprone, active iron-chelating agent ) at the Hospital for Sick Children in Toronto was showing unexpected potential risks to some patients in the trials.

• The drug company sponsoring her research abruptly terminated the trials and issued warnings of legal action against Olivieri should she inform her patients at the Hospital for Sick Children of the risks, or publish her findings.

The Case of Nancy Oliveiri Cont.

• The manufacturer (Apotex) issued more legal warnings to deter Dr Olivieri from communicating this second unexpected risk of L1 to anyone.

• However, she published her findings in the New England Journal of Medicine and

The Case of Nancy Oliveiri Cont.

• She was subsequently dismissed from her position as Director of the Hospital for Sick Children Program of Hemoglobinopathies.

• Apotex was planning to donate USD 100 Million to the University of Toronto

The Case of Nancy Oliveiri

•After more than seven years of legal battle, an independent committee of inquiry into the matter vindicated Olivieri and concluded that neither the

university nor the hospital offered her appropriate support in her conflict with the drug company .

•Olivieri was reinstated to her position at the Hospital for Sick Children and her actions have also been vindicated by several other independent reports .

The other side of the story

• Deferiprone is the only effective orally active iron-chelating agent licensed for the treatment of patients with thalassaemia major and other disorders of transfusional iron overload.

• It is the only alternative to deferoxamine—a drug that has to be given by daily subcutaneous infusions and fails in many patients worldwide because of the lack of compliance, high cost, toxicity, or hypersensitivity.

The other side of the story

• No other clinicians using the drug had found evidence for long-term liver damage and her interpretation of the data was immediately questioned in letters to the New England Journal of Medicine.

• Four of her patients in whom liver fibrosis had been suggested also had hepatitis C and all five had iron overload—both causes of liver fibrosis.

LET’S DEBATE…!

What do you think?

OR ?

Practical Steps to resolve

• Disclosure / transparency • Stringent analysis of COI, • Review of contracts between funders and

researchers• Close external monitoring• Blinding of study, when possible• Restrict review of colleague’s work• Peer review of manuscripts

ETHICAL REVIEW OF RESEARCH

What is Ethical Review?

• It is a process by which research proposals are reviewed for their compliance and accordance with the national/international ethical principles & guidelines for research involving human subjects.

Research Requiring Ethics Review

All research involving living human subjects by collecting identifiable information or materials including:

Research with human remains, cadavers, tissues, biological fluids, embryos and fetuses.

Interviews, surveys and questionnaires. Secondary data analysis of data from living human

subjects.

Research exempt from Ethics Review:

Research about living individuals in the public arena or artists, based exclusively on publicly available information.

Participant observation of public demonstrations, political rallies and public meetings.

Quality assurance studies, performance reviews or normal educational testing.

Case from your experience…

DISCUSSION…Q & A

References & Readings

• Global approaches to differentiate ‘research’ from ‘non-research’ in public health and their ethical implications

• Ethical review of research: what is it? And why is it important?

• Vulnerability• Informed Consent• Privacy and confidentiality (safety of collected data)• Conflicts of interest• Scientific integrity and publication ethics