Why Research Ethics?History and Principles

Henry Silverman, MD, MAUniversity of Maryland School of Medicine

Balancing Two Goals

Advancement of Science

Protection of Subject Welfare/Rights

History of Research Ethics Before 20th century

◦ Small scale, involving few individuals Beginning of 20th century

◦ Larger scale clinical trials◦ collect systematic data ◦ groups of individuals◦ vulnerable groups

• Prisoners• Orphans• Mentally ill

No Formal Codes of Research Ethics

World War II

Nuremburg Nazi Doctors’ Trial (1947)

Nazi doctors and scientists put on trial for the murder of concentration camp inmates who were used as research subjects

15 of 23 guilty, 7 hanged, 5 life sentences

Relevance of the Hippocratic Oath?

Expand on Hippocratic Ethics to Protect Research Subjects

In the context of researchCould not protect human welfare Could not respect human rights

Why did the Nazi doctors purposefully inflict harm?

+ Concept of Human Rights

Nuremberg Code

Do No Harm

Nuremberg Code (1947)First Codification of Research GuidelinesHuman Rights + Welfare of Subjects

The first and longest principle

Article (9)Subjects have the right to

withdraw at any time

“The voluntary consent of the human subject is absolutely essential.”

Articles (2-8, 10)• Scientific value• Favorable risk/benefit ratio• Suffering by subjects

should be avoided

Research Abuses Henry Beecher: Published

22 examples of abuses Withholding antibiotics

from patients with rheumatic fever

Purposely infecting institutionalized children with hepatitis

Injecting live cancer cells into nursing home patients

Abuses and exploitations of

humans in research continued despite

having ethics codes

Significance of Article?

Tuskegee Syphilis Study (1932 - 1972)

Tuskegee, Alabama◦ High prevalence of syphilis◦ Although treatment existed, blacks in the rural

southern town were not receiving treatment◦ Lack of funds/Lack of doctors

Study natural course of syphilis◦ Enrolled 400 black males infected with syphilis ◦ Not an experiment but rather a “study in nature”

Tuskegee Syphilis Study (1932 - 1972)

Ethical Issues

•Inadequate disclosure of information•Subjects believed they were getting free treatment•Told that spinal taps was therapy•US Gov’t actively prevented men from receiving penicillin•1972 press reports caused the U.S. Gov’t to stop the study

Balancing Two GoalsWithout an Adequate Framework of Research Ethics

Advancement of Science

Protection of Subject Welfare/Rights>>>

Response to Ethical Lapses

U.S. National Research Act (1974) The National Research Act created the National

Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

The Commission charge was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human participants

To develop guidelines which should be followed to assure that such research is conducted in accordance with those principles.

Carrying out its charge, the Commission prepared the Belmont Report in 1979.

Research Ethics Principles

ئدهالفا Beneficence

االختيا حقر

العدل Justice

Respect of persons األشخاص إحترام

Right to make a decision

Respect for Persons– Individuals should be treated as autonomous

agents– Individuals with diminished autonomy are entitled

to protections Beneficence

◦ Maximum possible benefits, and minimize potential harms

Justice◦ Fair distribution of burdens and benefits of

research◦ Do not exploit those who are readily available or

malleable

Basic Ethical Principles

The Belmont Report has served as an ethical framework for protecting human subjects for over 25 years.

To obtain a full appreciation of the Belmont Report, the report can be found @ http://www.fda.gov/oc/ohrt/IRBS/belmont.html

National Regulations◦ Force of law

Independent review of research by Institutional Review Boards (IRBs)

The Belmont Report

Declaration of Helsinki (1964)

World Medical Association - 1953 Interprets Nuremberg Code for research that

involves patients who are receiving medical care

Some risks justified by “potential therapeutic or diagnostic value for the patient”.

In case of legal incompetence, informed consent should be obtained from the legal guardian

Review of research by an independent review committee

CIOMS 2002 Council for International Organizations of

Medical Sciences: International Ethical Guidelines for Biomedical Research Involving Human Subjects

Apply Helsinki to the conduct of International Clinical Trials

1900 the Kingdom of Prussia established the Berlin Code of Ethics, a series of ethical rules regarding human experiments to test new treatments.

In 1931, the German Ministry of the Interior issued ‘‘directives for new therapies and experiments in humans’’ which incorporated the legal doctrine of informed consent.

It was forbidden to experiment on patients who were dying, poor, or socially disadvantaged. It was also stated that proportionality of risk and benefit must be respected and that experiments should first be done in animals.

Germany Code of Ethics 1931

Why Research Ethics?Middle East and North

Africa

Henry Silverman, MD, MAUniversity of Maryland School of Medicine

Increase in Clinical Trials in Developing Countries

Research Landscape: Clinical Trials

CountryNumber (2008)

Number(2011)

Number(2013)

Iran 111 373 534

Egypt 83 261 401

Jordan 135 41 42

Kuwait 7 29 20

Lebanon 24 128 140

Sudan 9 11 16

Qatar 6 23 25

Saudi Arabia 45 164 172

UAE 14 49 53

Syria 1 8 7

www.clinical trials.gov

Outsourcing of Clinical TrialsDeveloped World to Developing World

Advantages to Host Countries

Exposure to recent technologies and drug therapies

Training to local health professionals

Incentives to local health institutions (new technology)

A road paving to upgrade of local drug/biotech industry

Advantages to Pharma

Large population Disease pattern

◦ CVD◦ Diabetes◦ Cancer

Lower costs Faster patient recruitment Avoid regulatory restrictions Avoid elaborate safety and

compensation requirements

Headlines

Panel Faults

Pfizer in

'96

Clinica

l Tria

l In

Nigeria:

Unapproved

Drug Teste

d on

Children

May, 2006

Cameroon suspends trial

AIDS drug after protests

Growth of clinical trial

outsourcing raises issues

Feb, 2009

Feb, 2005

Balancing Twin Goals

Advancement of Science

Protection of Subject Welfare/Rights

Issues in Research Ethics in the Middle East

National Guidelines

Country Regulation

Egypt None 

Jordan Clinical Research Law 2001 http://www.jfda.jo/custom/law/23.doc

Yemen None

Sudan National Guidelines for Ethical Conduct of Research (2008): http://sites.google.com/site/healthresearchlibrary/national-guidelines

Lebanon None

Syria None

Morocco None

Saudi Arabia Law of Ethics of Research on Living Things. National Committee of BioEthics http://www.kacst.edu.sa/ar/depts/bioethics/Pages/WShp.aspx

Qatar Guidelines, Regulations and Policies for Research Involving Human Subjects

UAE Guidance for Conducting Clinical Trials Based on Drugs/Medical Products & Good Clinical Practice

National Regulations

Ethical Practices in the Middle East

Confidentiality

Informed Consent

REC Revie

w

N

43)88%(

37)76%(

28)58%(

49 Biological Samples

30)100%(

19)65%(

10)33%(

30 Qualitative Studies

Confidentiality

Informed Consent

REC Revie

w

N

43)88%(

37)76%(

28)58%(

49 Biological Samples

30)100%(

19)65%(

10)33%(

30 Qualitative Studies

Ethics Review and Informed Consent is Imperfectly Realized

in the EMR

Investigators’Knowledge

Prior Ethics TrainingCairo University

0%

20%

40%

60%

Percentage of Faculty with Prior Ethics Training

20%

28%

Asem A, et. al. PRIM&R 2009

52%

Prior Ethics TrainingAin Shams and King Abdul-Aziz

Workshop/Course No prior exposure0%

10%

20%

30%

40%

50%

60%

70%

Percentage of Dental Faculty with Prior Ethics Training

38%

El-Dessouky H, et.al. International Journal of Dentistry 2011

62%

Prior Ethics TrainingAlexandria, Mansoura, Suez Canal, Ain Shams

0%

20%

40%

60%

Percentage of Faculty with Prior Ethics Training

Kandeel A. In Press 2011

52%

18%

30%

Prior Research Ethics Training

No Prior Exposure to Research Ethics

28 – 62%

Barriers to Functioning of Research Ethics Committees

RECs Face Challenges

Institutional Support

Ethics Training

Member Composition

Human/Capital Resources

Gaps in Research Ethics in the Middle East

Category Gaps in Research EthicsNational Capacity • Lack or insufficient national guidelines

• Lack of efficient NRA

Institutional Commitments

• Inadequate institutional policies (e.g., conflict of interest policies, etc.).

• Lack of degree programs in research/ethics

Research Ethics Committee Capacity

• Suboptimal administrative structures • Inadequate budgets• Inadequate Membership diversity• Lack of training

Researchers • Inadequate knowledge of research ethics.• Responsible conduct in research. 

Human Subjects • Many are not aware of their rights