PRESENTED FOR UNIVERSITY OF KHARTOUM MSC PROGRAMME IN GENETICS/MOLECULAR

BIOLOGY30/04 /2014

Ethical considerations in research involving humans with focus on

biotechnology

Presented by:

Ghaiath Hussein, MBBS, MHSc. (Bioethics)

Doctoral Researcher, Uni. Of Birmingham, UKghaiathme@gmail.com

Outline of today’s session

Introduction: Research and Knowledge Management Cycle (KMC)

Historical background of research ethicsWhat makes research ethical?Examples of ethical issues in biotechnological

and molecular researchHow to proceed with our research ethically?

What is Research?

“Research” is defined as an undertaking intended to extend knowledge through a disciplined inquiry or systematic investigation.

Systematic methodological scientific approach for basic

facts around a certain problem in order to find solutions

based on these facts.

Research on Humans:The systematic undertaking of activities that involve

the collection of human personal data, measurements, and/or biological samples for purposes that are not related to clinical management of a health condition

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

Research in Context...the KMC

Generation

Dissemination

SynthesisUtilization

Assessment

Policy makers

Research

Statistics

Clinicians

Knowledge Management Cycle

Publ

icat

ion

sCon

fere

nce

s

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

Criteria of “Good” Science Research

Systematic: The research developed, implemented and reported in a systematic manner.

Methodolic: Adopt & use skillfully the research methods, materials ,approaches in order to ensure reliability of the results & findings.

Scientific: The research should be scientifically sound through utilizing scientific approaches , tools and techniques.

Criteria for Good Ethics: What Makes Research Ethical?

1. Social or Scientific Value2. Scientific Validity3. Fair Subject Selection4. Favorable Risk-Benefit Ratio5. Independent Review6. Informed Consent7. Respect for the potential and enrolled

subjects

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 theresearch is conducted

Historical Background

Born in Scandal… The Evolution of Research Ethics

History of Research EthicsPre-World War IIResearch standards left up to the discretion of the

individual researcher

World War IIExperiments conducted on inmates of Nazi

concentration camps1945-1949 - Trials in Nuremberg, Germany–

physicians convicted of crimes against humanity

Year Benchmark

2013 WMA updates DOH (Brazil)

2010 TCPS updated

2008 WMA updates DOH (Seoul)

2004 WMA updates DOH (Tokyo)

2002 WMA updates DOH (Washington) CIOMS Guidelines updated

2000 WMA updates DOH (Edinburgh)

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

1996 WMA updates DOH (South Africa)

1993 CIOMS guidelines for biomedical research involving human subjects

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

1989 WMA updates DOH (Hong Kong)

1983 WMA updates DOH (Venice)

1981 US Common rule updated

1979 The Belmont Report

1975 WMA updates DOH (Tokyo)

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

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

1947 The Nuremberg Code

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

Pre-1900 Edward Jenner smallpox vaccines

18th and 19th Centuries

James Lind “scurvy study in sailors - SalisburyEdward Jenner cowpox vaccine test1897 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)

Nazi Doctors’ Experimentation

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 regularly since 1975

The main issues emphasized were: “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 )

The Belmont Report (1979)

1972: the public became aware of the Tuskegee study

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

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 justice are 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

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.

WHAT’S ETHICALLY UNIQUE ABOUT

MOLECULAR BIOLOGY AND BIOTECHNOLOGY?

Ethical Issues in research on humans

Very rapidly progressing…

Very wide possibilities…

Identification of the genes responsible for human diseases,

Identification of the mutations underlying a vast number of phenotypes

health care (medical), crop production and agriculture, non food (industrial) uses of crops and other products

Examples: biodegradable plastics, vegetable oil, biofuels), and

environmental uses. manufacture of organic products (e.g. milk products) Used to recycle, treat waste, cleanup sites

contaminated by industrial activities (bioremediation), and

to produce biological weapons.

Examples of 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)• INTEGRITY & PUBLICATION ETHICS

BenefitsBenefits to research subjectsDirect Benefit

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

Collateral “indirect” Benefit Extra supervision from being in the research study (?) Access to medical care not available for economic reasons Unplanned or unanticipated benefits Payments or incentives – benefits?

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

interventions

Types of Risk…Cont.Physical (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 their nutrition and houses.

Environmental Risks:Manipulating environmental factors (Pathogenic

organisms and toxic chemicals).

Categorization of Risk

Risk 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

Clinical EquipoiseClinical 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 specialized committees should make a complete risk assessment for the use of the hazardous 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.For Psychological Risks : Sensitive questions for sensitive group like those with AIDS,

STDs, T.B, need to be asked by experiences researchers and ask the help of psychologists may be needed.

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

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

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 due to insufficient: power, intelligence, education, resources strength, or other needed attributes to protect their own

interests.” (CIOMS, 2002)

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.

Tri-Council Policy StatementEthics Review (Cont.)

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

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 Elements1. 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 tothe 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 person

needs 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 sedationCoercion involves the use of explicit or implicit

threat to ensure that the treatment is acceptedManipulation involves the deliberate distortion or

omission of information in an attempt to induce the subject’s participation

Voluntariness

Free of undue influencePersuasion: appeals to reasonManipulationCoercision: explicit or implicit threatsForce: restraint or sedation

MANIPULATION

Distortion of facts or omissionNon-coercive alternation of choicesUndue financial paymentUndue influence, government funding only at

grade eight for hpv

Practical Challenges to a "Fully Informed Consent"

Diagnostic uncertaintyComplexity of medical informationLinguistic and cultural differencesOverworked health personnelPaternalistic 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 confidentialityPRIVACY & 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 data Often Challenging in Natural Environment Can inconvenience research participants Can encounter participants in public Procedures 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 conduct

2. Doesn’t create harm to participants

3. 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 dataEncode the collected dataLimit access to dataKeep in password-protected PCDestroy the original copies after analysis, or

publicationTraining of research team on confidentialityRelease information without identification

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

Breaking Confidentiality

Court order Communicable diseasesVulnerable person abuse/neglectDriving/flying/machine safetyDangerous 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)CONFLICTS OF

INTERESTS

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 judgement 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 studies and examples