Justification of Research in Humans

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Justification of Research in Humans

• Impossible to reach the important conclusions
  without studying humans
• Human physiologic studies, because
• animal responses often are not the same
• Epidemiological studies, because
• they depend on human susceptibilities
• and human interactions
• Drugs for treating humans because
• animal experiments dont always predict
• results

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Justification (2)

• If youre going to treat humans, you must study
  humans
• Corollary If youre going to treat certain kinds
  of humans, then you must perform studies with
  them, for example
• Children, mentally impaired, ethnic groups,
  elderly, women, and pregnant women)

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• History of the Ethical
• Research Movement

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The Nuremberg Code (World War II)

• Informed consent is absolutely essential
• Qualified researchers must use appropriate
  research designs
• There must be a favorable risk/ benefit ratio
• Participants must be free to stop at any time

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The Declaration of HelsinkiWorld Medical
Association(1964, 1975, 1983, 1989, 1996, 2002)

• 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, especially if treatment
  is available
• Greater access to benefit once research is
  concluded

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The Belmont Report (The U.S. National Commission
for the Protection of Human Subjects of
Biomedical and Behavioral Research, 1978)

• Ethical Principles and Guidelines for the
  Protection of Human Subjects of Research
• Respect for persons
• Beneficence
• Justice

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Council for International Organizations of
Medical Science (CIOMS) Guidelines 1993, 2002

• Nuremberg gt Helsinki gt CIOMS
• Informed consent
• Research in developing countries
• Protection of vulnerable populations
• Distribution of the burdens and benefits
• Role and responsibilities of ethics committees

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• Basic Concepts for
• Ethical Research

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Definition of Ethics (1)

• The discipline of dealing with what is good and
  bad, with moral duty and obligation
• A set of moral principles or values
• The principle of conduct governing an individual
  or group
• Websters Ninth New Collegiate Dictionary

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Definition of Ethics (2)

• A Dictionary of Epidemiology, 4th ed, 2001 (J.M.
  Last (ed))
• The branch of philosophy that deals with
  distinctions between right and wrong with the
  moral consequences of human actions

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• Basic Principles of Research on
• Human Subjects (1)
• (The Belmont Report)
• Respect for persons
• Beneficence
• Justice

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Basic Principles of Research on Human Subjects (2)

• Respect for persons
• Choices of autonomous individuals should be
  respected
• People incapable of making their own choices
  should be protected
• Voluntary subjects need adequate information for
  decision-making

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Basic Principles of Research on Human Subjects (3)

• Beneficence
• Participation in research is associated with a
  favorable balance of potential benefits and harms
• Maximize possible benefits, minimize potential
  harm

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Basic Principles of Research on Human Subjects (4)

• Justice
• Participation in research is associated with a
  favorable balance of potential benefits and harms
• May not exploit or exclude vulnerable individuals
  who may benefit without good reason

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CONFLICTING PUBLIC HEALTH GOALS

• Protect the uninfected
• Protect the infected

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Summary - Principles and Foundations of Research
Ethics

• All codes and regulations advocate three
• fundamental principles
• Respect for persons
• Beneficence
• Justice
• Research is a privilege, not a right
• The well-being of the participant is paramount

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• Assessment of Benefits and Risks

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Assure That Benefits Outweigh Risks

• Research must be justified on the basis of a
  favorable benefit/risk assessment for the
  research participant. Benefits must outweigh
  risks
• This is similar to the principal of beneficence
  or do no harm. Researchers must protect
  participants from harm and maximize their
  well-being

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Risk and Benefit Defined

• A risk refers to a harm or likelihood of a
  harm. The degree of severity of a possible harm
  may be unclear
• A benefit refers to a positive value that
  accrues to the participant and/or to the society.
  The precise degree of gain that might accrue to
  the participant and/or to the society may be
  uncertain

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Types of Risks and Benefits

• Risks or harms and benefits may be physical (pain
  or injury), psychological, social, economic, or
  legal
• Risks or benefits of research may apply to
  individual participants, families, groups or
  organizations, communities, or nations
• Risks and benefits to the research participant
  usually carry the most weight

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General Principles

• There is absolutely no justification for inhumane
  treatment of participants
• Risks to participants should always be reduced to
  the maximum extent possible
• If a significant risk is involved, justification
  of the research must be examined with particular
  care
• Whenever vulnerable persons are participants, the
  need to involve them must be carefully
  demonstrated

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• Informed Consent

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What is Informed Consent?

• Informed consent is consent given by a
• competent individual who
• has received the necessary information
• has adequately understood the information
• after considering the information, has arrived at
  a decision without having been subjected to
  coercion, undue influence or inducement, or
• intimidation

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Informed Consent as a Process

• Informed consent is a communication process
• Between the researcher and the participant
• Starts before the research is initiated
• Continues throughout the duration of the study

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Essential Elements of Informed Consent (1)

• Study involves research
• Purpose of study
• Duration of subjects participation
• Description of the procedures
• Foreseeable risks and discomforts
• Reasonably expected benefits to subject or others
• Alternatives, if any

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Essential Elements of Informed Consent (2)

• Confidentiality
• Compensation for injury (gtminimal risk)
• Contacts for information about the research,
  research-related injury, subjects rights
• Voluntary participation, refusal without loss of
  benefits, can withdraw at any time

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Essential Elements of Informed ConsentDescriptio
n of the Research

• That it is a research study
• Objectives of the study
• Expected responsibilities of participant
• Procedures involved
• Study duration (and possibility of early
  termination)
• Explanation of features of the research design,
  such as randomization or placebo

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Essential Elements of Informed ConsentDescriptio
n of Benefits

• Benefit to subject or others reasonably expected
  to result from the research (Common Rule)
• This can include direct medical benefit to
  participants and expected benefits of the
  research to the community or larger society, or
  contributions to scientific knowledge
• Whether, when and how any products or
  interventions proven by the research to be safe
  and effective will be made available to subjects
  once research is ended, and whether they will be
  expected to pay for them

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Essential Elements of Informed ConsentDescriptio
n of Risks

• Includes physical, social, and psychological
  risks
• Anticipated or foreseeable risks, pain or
  discomfort, or inconvenience to the individual
  (or others) associated with the research
• Include risks to health or well being of
  subjects spouse, partner, and/or family
• Culturally appropriate format

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Essential Elements of Informed ConsentConfidenti
ality

• Provisions that will be made to ensure respect
  for privacy of subjects and confidentiality of
  records in which subjects are identified
• Limits of confidentiality, what persons or
  organizations may have access to the information,
  and possible consequences of breaches of
  confidentiality
• When appropriate, policies about disclosure of
  results of genetic tests e.g., certificate of
  confidentiality
• Special cultural circumstances

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Essential Elements of Informed ConsentCompensati
on

• Available compensation in case of
  research-related injury, and whether there is any
  uncertainty about funding whether there is
  compensation for death or disability
• What treatment is available and cost
• Whether payment will be provided for
  participation, and if so, how much (fair payment
  for time, travel or inconvenience)
• Must not be coercive

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Essential Elements of Informed ConsentContacts
for information

• Provide contact for research-related questions
• Provide contact for concerns about rights as a
  participant
• Contacts must be realistic and viable

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Essential Elements of Informed ConsentVoluntary
Participation

• Absolutely voluntary
• Right to discontinue at any time
• No penalty for refusal

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Circumstances Must

• Give subject sufficient opportunity to consider
  the decision
• Minimize possibility of coercion or undue
  influence

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Language Must

• Be understandable to subject or representative
• Language must NOT
• Waive subjects rights
• Release investigator, sponsor, or institution
  from liability
• Need to test for comprehension

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Available Alternatives

• Alternative procedures or treatment
• Advantages and disadvantages
• Availability

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Additional Elements from CIOMS (1)

• Must include
• The nature and sources of funding of the
  research, the sponsors of the research, the
  institutional affiliation of the investigators,
  and financial incentives to the investigators
• The possible research uses, direct or secondary,
  of the participants medical records and of
  biological specimens taken in the course of
  clinical care whether commercial products will
  be developed
• Whether it is planned that biological specimens
  collected in the research will be destroyed at
  its conclusion, and, if not, details about their
  storage and possible future use, and that
  participants have the right to decide about such
  future use, to refuse storage, and to have the
  material destroyed

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Additional Elements from CIOMS (2)

• That, after the completion of the study,
  participants will be informed of the results
• Whether the researcher is serving only as a
  researcher or as both researcher and the
  subjects health-care professional
• The extent of the researcher's responsibility to
  provide medical services to the subject
• That the research protocol has been approved by
  an ethical review committee

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PRIVACY, CONFIDENTIALITY AND STIGMATIZATION
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DEFINITION OF PRIVACY

• PRIVACY FREEDOM FROM
  UNSANCTIONED INTRUSION
• (American Heritage Dictionary, 7th edition, 1992)

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PRIVACY

• Respect for persons guarantees the participants
  RIGHT to privacy
• Lack of privacy causes unwillingness to
  participate in research
• Assertion of investigator that privacy is
  guaranteed is insufficient
• Participant must perceive that privacy is
  guaranteed

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CONFIDENTIALITY VS. ANONYMITY
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CONFIDENTIALITY

• Name and identifying information are recorded
• Investigator guarantees that identifying
  information will not be shared with unauthorized
  persons
• Guarantee of confidentiality is only as good as
  the integrity and care of the investigator and
  staff

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ANONYMITY

• Name and identifying information are not recorded
• Impossible to trace back results to informant

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DEFINITION OF STIGMATIZATION

• Stigmatization characterizing or branding (a
  person) as disgraceful or ignominious
• (American Heritage Dictionary, 7th Edition,
  1992)

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STIGMATIZED GROUPS (1)

• Marginalized groups
• The poor
• Ethnic minorities
• Sex workers
• Drug users
• The uneducated (illiterate)
• Men who have sex with other men

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STIGMATIZED GROUPS (2)

• HIV-infected persons
• Persons infected with sexually transmitted
  organisms
• Sexually promiscuous persons

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• Lack of confidentiality creates a risk of
  stigmatization
• Investigator has the responsibility to guarantee
  freedom from stigmatization as a result of the
  research for all participants