Seyed E. Hasnain

Ethical, Legal and Social Issues arising out of

Advancements in New Biology

Importance of Ethics in Infectious Diseases/Clinical

Research

Ethics: separate right from wrong as a principle of human duty When applied to systematic studies in biology : Bioethics

Why infectious diseases warrant more of bioethics’ attention?

Infectious means contagious

Contagious means isolation of patient from the rest

Isolation means discrimination

Discrimination means seclusion, loneliness, embarrassment, humiliation, loss of physical and mental health

No isolation means threat to rest of the society

BORDERLINE ZONE BETWEEN INFECTIOUS DISEASES RELATED RESEARCH AND HUMAN RIGHTS

Moral issues in doing research involving infectious diseases

• Primary Goal : generation of useful knowledge about human health and disease, its likely spread and extent of damage possible

• The Human Subjects:o Are means to gather information and knowledge about

understanding the disease o Immediate health benefit to participants is not the purpose

of such studies

…therefore may be at risk of exploitation

Ethics in clinical research

– Minimize exploitation– Protect rights– Maintain dignity – Respect confidentiality – Ensure welfare

….while the subjects contribute to the generation of knowledge

Research in infectious diseases• Starts with field observations involving human

subjects• Mimic similar situation in a laboratory• In vitro studies, identification of targets• Check polymorphism of the target in population• Make a intervention molecule• Studies involving cell culture and animal model• Ends with human clinical trials

Some successful studies we can’t call ethical

– Jenners’ experiment with a young boy of 8 years using Cow Pox (1796)

– Tuskegee Syphilis Study (1932-72)

The Tuskegee Syphilis Experiment: A clear example of ethically unacceptable research by present standards

Source:http://en.wikipedia.org/wiki/File:Syphilis-posster

• What do we do with the results of immoral research?– “the Tuskegee study was and remains

a key source of information about …syphilis.” (Caplan, 419)

Codes of Research Ethics

• Nuremberg Code (1947)– informed consent, societal value, unacceptable levels

of risk• Declaration of Helsinki (orig. 1964)

– added written protocol, independent review• Belmont Report (1979)

– added justice, fair subject selection• Council for International Organizations of

Medical Sciences (CIOMS) International Ethical Guidelines for Biomedical Research (1993, Updated 2002)

Ethical framework while working with human subjects: 9 principles• Valuable scientific question• Valid scientific methodology• Favorable risk-benefit evaluation• Fair subject selection• Informed consent• Confidentiality• Respect for enrolled subjects • Scientific integrity• Independent reviewAdapted from: Emanuel E, Wendler D, Grady C. What makes clinical research ethical? Journal of the

American Medical Association 2000; 283(20):2701-11

Valuable scientific questionIs the research outcome a burden

or benefit?

Research as ‘burden’

Subjects need protection

Research as ‘benefit’

Subjects need access

Benefit-Risk-Balance• Minimize risks to subjects• Maximize benefits to individual subjects and to society• Enough preliminary evidence before commencement of

clinical trials• Start with case control studies

RISKS

Benefit to society

?

Cease . . . investigation if:the risks are found to outweigh the potential benefits, or there is conclusive proof of positive and beneficial results (Helsinki Declaration)

Fair Subject SelectionSelection of subjects related to the purpose of the study, not because they are readily available, vulnerable, or otherwise easily exploited, or are favoured.

Do not exclude subjects without a good reason of science, vulnerability, or susceptibility to risk or burden.

Choice of control population for proper conclusions from the study

Vulnerability• There is an order of preference in selecting subjects, for

instance, adults before children (Belmont Report)• Exclude vulnerable subjects unless their participation is

needed for scientific reasons (CIOMS)

Vulnerable group

Research group

A human subject should be at liberty to bring the experiment to an end . . .

Psychological harm Social stigmaCultural effects Economic repercussions

… or even without reasons

Informed Consent:Respect for Persons

Voluntary agreement to participate: After weighing the objectives, risks, benefits, and alternatives of

the research.

•Nuremberg Code•CIOMS guidelines•The Belmont Report

Extra protections for those with limited capacity to consent

What happens when consent can’t be taken

“When it is not possible to request informed consent from every individual to be studied, the agreement of a representative of a community or group should be sought, but the representative should be chosen according to the nature, traditions and political philosophy of the community or group.”

CIOMS

Epidemiological studies may involve genetic information

• Not only information about an individual, but also about those to whom the individual is related

• If genetic testing is involved for any study a non-directive, culturally adapted genetic counselling should be made available

• Clear directions for sharing such informationUNESCO Int’l Declaration, Art. 11

–Is there a duty to warn family members of being at risk?

THE SUBJECT HAS A RIGHT TO BE, OR NOT TO BE INFORMED OF

RESULTS

UNESCO Int’l Declaration, Art. 10

Independent Review: Institutional Review Board

Ensure:Risks are minimizedRisks are justified by expected benefits and knowledge to be gainedJustifiable subject selection Fair treatment to subjectsInformed consent is adequate

Suggest:Possible methodology before

commencement of the study

Biosafety is also an integral part of Bioethics

• Proper waste disposal– Proper decontamination– Proper segregation– Proper packing

Reporting Ethics in Infectious Diseases

- Is it research or audit or clinical practice?- Disclose if similar studies have been performed

earlier- Disclose if it differs from earlier reports- Should not alter or ignore some data to make the

results look statistically better- Patients’ identity and other relevant medical

details should remain confidential– Important to report exceptional cases

REGISTRATION A prerequisite for all Clinical Trials

•Trials must register at or before the onset of patient enrollment.

•Selective reporting distorts clinical decision-making.

•Financial benefits may hide important trials

•Right to information of trials

•Undue importance to some clinical trials for benefit of selected pharmaceutical companies

•Biased publications: Positive trials are more likely to be submitted for publication and also published quickly than negative trials

JAMA 2002;287:2825-2828. Stern and Simes BMJ 1997;315:640-645

As they say….There are three ethical injunctions….

Show Respect, Do Good, Be Fair

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Acknowledgements

Sharmistha Bannerjee, Univ of Hyderabad