Protecting Human Research Participants

1
Protecting Human Research Participants

• Dr. Rasha Salama
• PhD Community Medicine and Public Health
• Suez Canal University
• Egypt

2
Research

• Research is the systematic collection, analysis
  and interpretation of data to answer a certain
  question or solve a problem

3
What is Research About?

• Discover knowledge
• (research)
• Transfer knowledge
• (education, publication)
• Apply knowledge
• (translation, outreach extension to the
  community welfare)

4
Contribution of Research

• Research can contribute to the
• Researcher
• Individual level (patient)
• Community at large

5
Protection of Research ParticipantsWho and What?

• Who should be involved?
• Individuals involved in the design and/or conduct
  of human subjects research.
• What is the purpose?
• Preparation of investigators involved in the
  design and/or conduct of research involving human
  subjects to understand their obligations to
  protect the rights and welfare of subjects in
  research.

6
Goals and Principles of Human Subjects Protection

• Human subjects are essential to the conduct of
  research intended to improve human health. As
  such, the relationship between investigators and
  human subjects is critical and should be based on
  honesty, trust, and respect.

7
Historical Events Nazi Medical War Crimes
(19391945)

• The experiments conducted by Nazi physicians
  during World War II were unprecedented in their
  scope and the degree of harm and suffering
• Medical experiments were performed on thousands
  of camp prisoners and included deadly studies and
  tortures such as injecting people with gasoline
  and live viruses, and forcing people to ingest
  poisons.
• In December 1946, the War Crimes Tribunal at
  Nuremberg indicted 20 physicians and 3
  administrators because they hadcorrupted the
  ethics of the medical and scientific professions
  and repeatedly and deliberately
• violated the rights of the subjects

8
Historical Events The Nuremburg Code

• In the August 1947 the judges included a section
  called Permissible Medical Experiments.
• This section became known as the Nuremberg Code
  and was the first international code of research
  ethics.
• This set of directives established the basic
  principles that must be observed in order to
  satisfy moral, ethical, and legal concepts in the
  conduct of human subject research.

9
The Nuremburg CodeTEN directives for human
experimentation

• 1. Voluntary consent of the human subject is
  absolutely essential
• 2. The experiment must yield generalizable
  knowledge that could not be obtained in any other
  way and is not random and unnecessary in nature
• 3. Animal experimentation should precede human
  experimentation
• 4. All unnecessary physical and mental suffering
  and injury should be avoided
• 5. No experiment should be conducted if there is
  reason to believe that death or disabling injury
  will occur

10
The Nuremburg Code (cont.)TEN directives for
human experimentation

• 6. The degree of risk to subjects should never
  exceed the humanitarian importance of the problem
  
• 7. Risks to the subjects should be minimized
  through proper preparations
• 8. Experiments should only be conducted by
  scientifically qualified investigators
• 9. Subjects should always be at liberty to
  withdraw from experiments
• 10. Investigators must be ready to end the
  experiment at any stage if there is cause to
  believe that continuing the experiment is likely
  to result in injury, disability or death to the
  subject

11
The Syphilis Study at Tuskegee

• .
• Study of the natural history of untreated
  syphilis (1930-1972)
• involved approximately 600 African-American men
  about 400 with syphilis (cases) and about 200
  without syphilis (controls). These men were
  recruited without informed consent and were led
  to believe that some of the procedures done in
  the interest of research (e.g., spinal taps) were
  actually special free treatment.
• In the 1940s, penicillin was found to be
  effective in the treatment of syphilis. The
  Syphilis Study at Tuskegee continued, however,
  and the men were neither informed about nor
  treated with the antibiotic.
• By 1946, reports indicated that the death rate
  among those with syphilis was about twice as high
  as it was among the controls.

12
Outcomes of the Syphilis Study at Tuskegee

• Outcomes included
• National Research Act of 1974
• Department of Health and Human Services (HHS)
  Policy for Protection of Human Subjects
• National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research

13
The Belmont Report

• The Belmont Report
• identified three principles
• essential to the
• ethical conduct of
• research with humans
• Respect for persons
• Beneficence
• Justice
• These three basic principles serve as the
  foundation of the current HHS regulations and
  guidelines for the ethical conduct of human
  subjects research supported by HHS.

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1. Respect for Persons
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1. Respect for Persons

• The principle of respect for persons can be
  broken down into two basic ideas
• 1. Individuals should be treated as autonomous
  agents
• An autonomous person is able to
• Consider the potential harms and benefits of a
  situation
• Analyze how those risks and potential benefits
  relate to his or her personal goals and values
• Take action based on that analysis

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1. Respect for Persons (cont.)

• 2. Persons with diminished autonomy are
  entitled to additional protections
• Special provisions may need to be made when an
  individuals comprehension is severely limited or
  when a class of research participants is
  considered incapable of informed decision making
  (e.g. children, people with severe developmental
  disorders, or individuals suffering from
  dementias).
• In some cases, respect for persons may require
  seeking the permission of other parties, such as
  a parent or legal guardian.

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Challenges

• The challenges in applying the Belmont
  principle of respect for persons are in
• Making sure that potential participants
  comprehend the risks and potential benefits of
  participating in research
• Avoiding influencing potential participants
  decisions either through (coercion) or through
  (undue influence)

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Coercion

• Influencing an individual decision about
  whether or not to do something by using explicit
  or implied threats (loss of good standing in job,
  poor grades, etc.)

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Undue Influence

• An offer of an excessive, unwarranted,
  inappropriate, or improper reward or other
  overture in order to obtain compliance
  excessive compensation
• Undue inducements are troublesome because
• offers that are too attractive may blind
  prospective subjects to the risks or impair their
  ability to exercise proper judgment and
• they may prompt subjects to lie or conceal
  information that, if known, would disqualify them
  from enrolling or continuing as participants
  in a research project.

20
Undue Influence versus Compensation

• Some types of research involve a significant
  commitment from research participants in terms of
  time or effort, and investigators may wish to
  provide compensation.
• Institutions should consider establishing
  standards for fair and appropriate compensation.
• Compensation is meant to reimburse research
  participants for their time, research-related
  inconveniences and/or research-related
  discomforts
• Compensation is not a benefit of the research.

21
Case Study Sleeping Sickness Study on Campus

• An investigator, who is a professor at a large
  university, is developing a grant application for
  submission to the NIH to study sleeping sickness
  (trypanosomiasis)
• The study will require fresh human blood daily
  for several months, and thus will require
  research participants.
• It is now time to make a decision about
  recruitment of the research participants.

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• Based on the number of students and employees in
  her classes and lab, the researcher feels
  confident that she will have enough participants
  needed for the proposed research if she simply
  recruits among them. But she knows that some
  colleagues advertise their studies through
  postings on campus.
• The investigator is faced with two possible
  options for recruiting normal, healthy research
  participants
• Recruit the students in her upper level classes
  and the technicians from her lab, and give 5
  compensation to participants per blood draw, or
• Recruit from the general university population
  (students, faculty and staff) by posting fliers
  around campus, and give 5 compensation to
  participants per blood draw

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• From which population would you advise the
  researcher to recruit?
• Recruit the students in her upper level classes
  and the technicians from her lab to participate
  in the study
• Post fliers around campus to recruit participants
  from the campus population (students, faculty and
  staff)

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Correct answer is

• Asking for study participants from a population
  over which a researcher has authority is not the
  best idea.
• It is generally agreed that students and
  employees are groups that can be vulnerable to
  coercion.
• Even though the researcher may feel confident
  that she would never let her students and
  employees decisions about participation affect
  her opinions about them, her students and
  employees might feel pressured to participate
  simply because she is in a position of authority.
• Recruiting for the study participants from the
  students, faculty and staff of the university is
  the best choice.

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Informed Consent

• Definition A legally-effective, voluntary
  agreement that is given by a prospective research
  participant following comprehension and
  consideration of all relevant information
  pertinent to the decision to participate in a
  study
• The HHS regulations require that investigators
  obtain legally effective informed consent from
  prospective participants in a way that allows
  them to consider whether or not to participate
  and that minimizes the possibility for coercion
  or undue influence .

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Informed Consent (cont.)

• The Belmont principle of respect for persons is
  primarily applied by requiring that all human
  subjects research participants provide voluntary
  informed consent to participate in research.
• The three fundamental aspects of informed consent
  are
• Voluntariness
• Comprehension
• Disclosure

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Voluntariness

• Individuals decisions about participation in
  research should not be influenced by anyone
  involved in conducting the research ...consent
  must be freely given or truly voluntary.

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Comprehension

• Individuals must have the mental or decisional
  capacity to understand the information presented
  to them in order to make an informed decision
  about participation in research.
• Avoid Therapeutic Misconception

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Disclosure

• HHS regulations require that researchers
  disclose
• The purpose of the study
• Any reasonably foreseeable risks to the
  individual
• Potential benefits to the individual or others
• Alternatives to the research protocol
• The extent of confidentiality protections for the
  individual
• Compensation in case of injury due to the
  protocol
• Contact information for questions regarding the
  study, participants rights, and in case of
  injury
• The conditions of participation, including right
  to refuse or withdraw without penalty
• This disclosure must be made in such a way that
  it provides a reasonable person the information
  she or he would need in order to make an informed
  decision.

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Informed Consent (cont.)

• Investigators are responsible for providing
  information during the informed consent process
  in a manner that is understandable to the
  potential participants.
• Methods used in addition to a consent form to
  enhance individuals comprehension
• Oral presentations (opportunity to
• discuss the information and ask questions)
• Providing additional educational materials,
• such as brochures,
• Video presentations
• The informed consent process must be delivered in
  language that is understandable to the subject
  (reading levels of documents and translating
  documents into the language with which
  participants are most comfortable).

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Requirements for Documentation of Informed
Consent

• Informed consent must be documented using a
  written form that either contains all of the
  required elements or a short form that states
  that all of the required elements have been
  presented orally.
• This form must be signed
• by either the participant or
• the participants legally
• authorized representative

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Case Study Sleeping Sickness Study on Campus

• Now that your colleague studying sleeping
  sickness has decided on the method of recruitment
  for the study participants, she must write an
  informed consent document for the participants to
  sign.
• The researcher has prepared two different draft
  consent documents and must select one to submit
  to her IRB for review.
• Read the two consent documents and then choose
  the document that best informs the potential
  participants about the study in which they will
  enroll
• Consent Document 1
• Consent Document 2

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Consent Document 1

• Surface Antigen Expression in Trypanosomes
• Dr. X
• You are invited to participate in this
  study by giving blood on a voluntary basis, but
  no more than five times in an eight week period.
  The research project is anticipated to continue
  for four years.
• All blood draws will be performed by
  qualified technicians at the Medical Center Blood
  Bank. 100 ml of blood will be withdrawn from a
  vein in your arm.
• Although you will not benefit directly from
  participating in this study, you will make a
  major contribution to the information known about
  trypanosomiasis, also known as sleeping sickness.
  In the future, others may benefit because
  scientists and doctors will learn about how
  parasites cause sleeping sickness, and will
  develop vaccines to prevent it.
• You will be paid 5 for the time and travel
  required to give blood.
• Your signature on this form means that you
  understand that participation is voluntary, and
  you may withdraw from the study at any time.
• _________________________________________Signatu
  re of Participant
• Contact information for Dr. XEmail
  drx_at_university.eduphone 123-456-7890

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Consent Document 2

• Surface Antigen Expression in Trypanosomes
• Dr. X
• Dr. Xs
• laboratory studies the parasite which causes
  trypanosomiasis, also known as sleeping sickness.
  This study will look at the effects of different
  surface antigens (proteins) produced by the
  parasites in human blood. The goal is to identify
  how different surface antigens are expressed by
  the parasites.
• You are invited to participate in this study by
  giving blood on a voluntary basis, but no more
  than five times in an eight week period. The
  research project is anticipated to continue for
  four years.
• All blood draws will be performed by qualified
  technicians at the Medical Center Blood Bank. 100
  ml of blood will be withdrawn from a vein in your
  arm. None of the procedures are experimental.
• During the collection of blood, you may
  experience discomfort and bruising at the site of
  collection. To minimize these risks, you will be
  asked to lie down while an experienced technician
  collects the blood sample. You may feel light
  headed after having blood drawn. If you feel
  faint, you should not get up and should notify a
  nurse.
• Although you will not benefit directly from
  participating in this study, you will make a
  major contribution to the information known about
  sleeping sickness. In the future, others may
  benefit because scientists and doctors will learn
  about how parasites cause sleeping sickness and
  will develop vaccines to prevent it.
• A research assistant will keep a record of all
  blood draws in a secure database. Only the
  professional staff at the Medical Center will
  know the identity of study participants.
• You will be paid 5 for the time and travel
  required to give blood. If you feel that you have
  been injured as a direct result of participating
  in the study, please contact Dr. X at
  123-456-7890.
• Your signature on this form means that you
  understand the information presented, and that
  you want to participate in the study. You
  understand that participation is voluntary, and
  you may withdraw from the study at any time.
• _________________________________________Signatu
  re of Participant
• Contact information for Dr. XEmail
  drx_at_university.eduphone 123-456-7890

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• Which of these two consent documents would you
  choose to use?
• Choose Consent Document 1
• Choose Consent Document 2

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Consent Document 2 is the best choice

• Consent Document 2 contains all of the required
  elements of informed consent and protects against
  the perception of coercion by emphasizing the
  fact that participation is voluntary and
  explaining how someone can withdraw from the
  study if they wish.
• Consent Document 2 includes the following
  required elements of informed consent
• The purpose of the study
• Foreseeable risks/discomforts to the individual
• Potential benefits to the individual or others
• Confidentiality protections for the individual
• Compensation plan
• Contact information for questions regarding the
  study, participants rights, and in case of
  injury
• The conditions of participation, including right
  to refuse or withdraw without penalty

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Diminished Autonomy

• An individuals autonomy can be affected by
  several factors including age, cognitive
  impairment, illness, and treatments.
• An individuals capacity to consent to a
  particular study should be assessed based on
• The individuals level of capacity, and
• The complexity and risks of the study, i.e., the
  capacity needed for an individual to be able to
  understand the study well enough to consent to
  participate

38
Decisional Capacity and Legally Authorized
Representatives

• It is required that legally authorized
  representatives provide voluntary informed
  consent for individuals with diminished capacity
  to participate in research

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The HHS Regulations

• Subpart A Basic HHS Policy for Protection of
  Human Research Subjects
• Subpart B Additional Protections for Pregnant
  Women, Human Fetuses and Neonates Involved in
  Research
• Subpart C Additional Protections Pertaining to
  Biomedical and Behavioral Research Involving
  Prisoners as Subjects
• Subpart D Additional Protections for Children
  Involved as Subjects in Research
• Other vulnerable populations include mentally
  disabled persons and economically and/or
  educationally disadvantaged persons.

40
Participation of Pregnant Women in Research

• The HHS regulations prohibit
• Inducements of any kind to terminate a pregnancy
• Investigators from taking part in decisions about
  terminating a pregnancy
• Investigators from determining the viability of a
  neonate

41
Childrens Participation in Research

• Children may not have full capacity to make
  decisions in their own best interests and
  therefore
• Children are considered a vulnerable population,
  and
• Children are unable to provide legally effective
  informed consent
• Because children cannot provide informed consent,
  children provide assent to participate in
  research, to the extent that they are able, and
  parents/guardians give permission for a child to
  participate in research.
• Assent affirmative agreement to
  participate in research. Mere failure to object
  should not, absent affirmative agreement, be
  construed as assent.

42
Excluding Children from Research

• The NIH Policy and Guidelines on the Inclusion of
  Children in Research states that children must be
  included in all NIH-supported human subjects
  research unless there are scientific and
  ethical reasons not to include them.

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Obtaining Informed Consent from Prisoners

• Requirements specific to informed consent for
  prisoners are
• Not to be under constraints as a result of their
  incarceration that could affect their ability to
  make a truly voluntary decision about whether or
  not to participate in research.
• Adequate assurance exists that parole boards will
  not take into account a prisoners participation
  in the research in making decisions regarding
  parole, and each prisoner is clearly informed in
  advance that participation in the research will
  have no effect on his or her parole

44
Case Study Fetal ImagingWHAT DO YOU THINK?

• Indicate whether the HHS regulations require the
  investigator to provide additional protections
  for participants in the study under Subparts B, C
  or D
• A study proposes to test a novel fetal imaging
  technology designed to enhance image quality and
  allow physicians to assess more accurately
  prenatal health. This technology has been tested
  both on pregnant mammals and non-pregnant women
  with no adverse effects. Women will be recruited
  at their regularly scheduled prenatal check-ups
  and those who consent to participate will receive
  the experimental scan
• Does this study require the investigator to
  provide additional protections for participants?
• Yes, the study involves a vulnerable population
• No, the study does not involve a vulnerable
  population

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Yes, the study involves a vulnerable population

• Correct!
• This study involves a vulnerable population.
  Because the research will be conducted with
  pregnant women and fetuses, the requirements of
  Subpart B apply.

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Case Study Treatment and Prevention Research in
Adolescents

• Indicate whether the HHS regulations require the
  following studies to provide additional
  protections for the studys subject populations
  under Subparts B, C or D
• A study proposes to examine the effectiveness of
  a medical treatment and prevention program for
  adolescents in a location where the legal age for
  consent to such treatment is 12. The adolescents
  involved range from ages 12 to 17.

Does this study require additional protections
be provided for the subject population?
                           
47
Case Study Lack of Assent from a Child

• A 7-year-old child has a rare genetic disorder.
  No treatment is currently available. You have
  designed a longitudinal study that will examine
  the progression of the disorder. The study will
  involve standard physical and psychological
  examinations, including drawing 10ml of blood 4
  times per year.
• After enrollment, at which time the parents
  provided permission for the child to participate
  in the study and the child provided assent, he
  panics and screams that he doesnt want to
  participate and wants to go home when he sees the
  nurse holding a needle for the blood draw. The
  parents are present and want the child to
  participate.
• Do you need to withdraw this child from your
  study because he has withdrawn his assent?

48

• This is not an easy question because it does not
  have a clear yes or no answer. Various issues
  to consider are explored
• Is the child old enough to provide assent?
• Does the study offer the prospect of direct
  benefit to the children enrolled?
• How severe is the childs fear, and how insistent
  is he not to participate?
• Is there a way that could elevate the childs
  fear so he can participate?

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No, the study does not involve a vulnerable
population

• The correct answer is No.
• Because the location in which the research will
  be conducted allows 12-year-olds to consent to
  the treatment, the participants in this research
  are not considered children under the HHS
  regulations and can provide informed consent to
  participate in the study. While the regulations
  do not require the additional protections of
  Subpart D for children in this study, the IRB may
  require some additional protections if they feel
  that the adolescents who will be involved in the
  study are vulnerable.

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Case Study 3 Observational Study of Challenges
Returning to Work WHAT DO YOU THINK?

• Indicate whether the HHS regulations require the
  following studies to provide additional
  protections for the studys subject populations
  under Subparts B, C or D
• A study proposes to observe the challenges for
  former prisoners returning to office jobs.
  Researchers will recruit individuals who have
  spent over ten years in prison, have completed
  their sentences, and are now interviewing for
  office jobs.
• Does this study requires additional protection
  for the subject population?
• Yes, the study involves a vulnerable population
• No, the study does not involve a vulnerable
  population

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No, the study does not involve a vulnerable
population

• Correct!
• This study does not involve a vulnerable
  population. The participants in this research are
  not considered prisoners, per Subpart C, because
  they have completed their period of involuntary
  confinement and are no longer confined or
  detained in a penal institution nor are they
  detained pending arraignment, trial, or
  sentencing.

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• In some cultures it is not appropriate to obtain
  informed consent solely from the individual
  participants, because the individuals interests
  may be considered to be intimately entwined with
  their communitys interests.
• It is often achieved through meetings with large
  groups of community representatives or community
  leaders.
• It is appropriate to consult a community before
  conducting research when the research involves
  risk to discrete, identifiable populations. For
  example, members of a community may feel
  stigmatized if a number of members of that
  community participate in research that may reveal
  unpopular or dangerous traits.

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2. Beneficence
54
2. Beneficence

• Two general rules have been articulated as
  complementary expressions of beneficent actions
• Do no harm
• Maximize possible benefits and minimize possible
  harms
• The challenge inherent in applying the
  Belmont principle of beneficence is how to
  determine when potential benefits outweigh
  considerations of risks and vice versa.

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Minimal harm

• Minimal harm is defined as
• that the probability and magnitude of harm or
  discomfort anticipated in the research are not
  greater than those ordinarily encountered in
  daily life or during the performance of routine
  physical or psychological examinations or tests.

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Risk of Research

• A. Physical
• Physical risks may include pain, injury, and
  impairment of a sense such as touch or sight.
  These risks may be brief or extended, temporary
  or permanent, occur during participation in the
  research or arise after.
• Physical risks in research can be minimized by
  carefully following protocols, by having trained
  individuals conduct research procedures, through
  careful monitoring of research participants
  health status, by recruiting appropriate
  populations, and by providing clinical care when
  needed.

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Risk of Research (cont.)

• B. Psychological
• Psychological risks can include anxiety, sadness,
  regret and emotional distress, among others.
  Specially in behavioral studies.
• Possible ways to protect against psychological
  risks include reminding participants of their
  right to withdraw from research or limit their
  participation if they become uncomfortable, and
  providing counseling or psychological support for
  participants who experience distress

58
Risk of Research (cont.)

• C. Psychological
• Social risks can range from jeopardizing the
  individuals reputation and social standing, to
  placing the individual at-risk of political or
  social reprisals.
• Minimizing social risks to participants involves
  protecting confidential data, including not only
  the data collected, but the fact of participation
  in the research project itself.

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Risk of Research (cont.)

• D. Legal
• Legal risks include the exposure of activities of
  a research subject that could reasonably place
  the subjects at risk of criminal or civil
  liability
• Protections against legal risks often involve
  protecting the confidentiality of research data.
  For studies conducted in the United States,
  investigators can apply for Certificates of
  Confidentiality, which are intended to prevent
  investigators from being forced to disclose data
  that can be linked to identifiable research
  participants in legal proceedings.

60
Risk of Research (cont.)

• E. Economic
• Economic risks may exist if knowledge of ones
  participation in research, for example, could
  make it difficult for a research participant to
  retain a job or to find a job, or if insurance
  premiums increase or loss of insurance is a
  result of the disclosure of research data.
• Protecting confidentiality of data is one method
  for protecting against economic risks, such as
  those to employability and insurability.
  Investigators may elect to keep research data
  separate from medical records in order to prevent
  employers and insurance companies from obtaining
  information that could put the participants at
  risk.

61
Privacy and Confidentiality

• Investigators are responsible for
• Protecting privacy of individuals
• Confidentiality of data
• Privacy means being free from unsanctioned
  intrusion
• Confidentiality means holding secret all
  information relating to an individual, unless the
  individual gives consent permitting disclosure

62
Coded Private Information and Human Subjects
Research

• Research with coded private information or
  specimens does not involve human subjects if
• The private information or specimens were not
  collected specifically for the currently proposed
  research project through an interaction or
  intervention with living individuals and
• The investigator(s) cannot readily ascertain the
  identity of the individual(s) to whom the coded
  private information or specimens pertain

63
Case Study Confidentiality in Clinical Research

• After the conclusion of a clinical trial in a
  small rural community, an investigator is anxious
  to publish findings. Understanding the NIH
  policies encouraging the reporting of demographic
  differences in intervention effect, and concerned
  about protecting the confidentiality of research
  participants, the investigator publishes only
  general demographic data such as sex, age, state,
  and county.
• Is this an appropriate and acceptable way to
  protect the confidentiality of research
  participants?
• Yes, this is an appropriate and acceptable way to
  protect the confidentiality of research
  participants.
• No, this is NOT an appropriate and acceptable way
  to protect the confidentiality of research
  participants.

64
Case Study Research with Anonymized Data

• You are an investigator proposing to use data
  from a colleagues database to conduct secondary
  analyses. Your colleague will provide coded data
  for your proposed studies, and you and he enter
  into an agreement by which he will keep the key
  to the code and will have no other involvement in
  the research.
• Does this study involve human subjects?
• Yes, this study involves human subjects.
• No, this study does not involve human subjects.

65
Case Study Esophageal Cancer

• A group of investigators proposes to investigate
  genetic factors that may increase risks for
  esophageal cancer. Genetic factors in esophageal
  cancer are not well understood and esophageal
  cancer occurs in many racial and ethnic
  populations. The investigators propose to collect
  DNA from cheek swabs and administer a risk factor
  questionnaire. Both cancer patients and
  age-matched controls will be included.
• The investigators have access to a predominantly
  Caucasian sample, and have no plans to recruit
  participants outside of their available pool.
• Is this an acceptable strategy?
• Yes, this is an acceptable strategy
• No, this is not an acceptable strategy

66
Anticipated Benefits Greater than Potential Harms

• Research requires that
• Risks are minimized
• Unavoidable risks are justified as necessary for
  sound scientific design
• Research studies are anticipated to make progress
  toward important, generalizable knowledge

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Debriefing

• To Debrief or Not to Debrief
• Debriefing of research participants after the
  study involves an explanation of the incomplete
  disclosure of research steps to participants
• Debriefing is generally considered to be
  appropriate, but must depend on whether the
  disclosure will result in harm.

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Institutional Review Boards (IRB)

• IRBs determine
• the acceptability of proposed research in terms
  of institutional commitments and regulations,
  applicable law, and standards of professional
  conduct and practice

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IRB Role

• The major roles of IRBs in the oversight of
  research are
• Initial review and approval or disapproval of the
  proposed research activity
• Ensuring that the proposed informed consent
  process meets all of the requirements
• Providing continuing oversight for progress
  reports and protocols for ongoing research
  studies Data and safety monitoring

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3. Justice
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3. Justice

• Justice requires that individuals and groups be
  treated fairly and equitably in terms of bearing
  the burdens and receiving the benefits of
  research.
• The principle of justice may arise in decisions
  about inclusion and exclusion criteria for
  participation in research and requires
  investigators to question whether groups are
  considered for inclusion simply because of their
  availability, their compromised position, or
  their vulnerability rather than for reasons
  directly related to the problem being studied.

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Types of Justice
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Individual Justice and Social Justice

• Individual justice requires that investigators
  should not offer potentially beneficial research
  only to some patients who are in their favor or
  select only undesirable persons for risky
  research.
• Social justice requires that distinction be
  drawn between classes of subjects that ought, and
  ought not, to participate in any particular kind
  of research, based on the ability of members of
  that class to bear burdens and on the
  appropriateness of placing further burdens on
  already burdened persons.

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Equity vs. Equality in Human Subjects Research

• The meanings of equity and equality are
  similar, but not the same.
• To treat equitably means to treat fairly
• To treat equally means to treat in exactly the
  same way.

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Equitable Distribution

• In order to achieve an equitable distribution of
  the risks and potential benefits of the research,
  investigators must determine the distribution of
  different groups (men and women, racial or ethnic
  groups, adults and children, age, etc.) in the
  populations that
• May be affected by the disease or condition under
  study, and
• That are anticipated to benefit from the
  knowledge gained through the research

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Case Study Migraine Intervention Trial

• A researcher seeks to improve treatment for
  severe migraines that are partially responsive to
  oral medication. He proposes to test whether
  acupuncture, in addition to a sufferers oral
  medication, is more effective treatment than oral
  medication alone. Because women are three times
  more likely to experience migraines than men, he
  proposes to enroll three times as many women as
  men. They will be recruited from racially and
  ethnically diverse communities.
• Does this study design fulfill the principle of
  justice?
• Yes, this study design does fulfill the principle
  of justice
• No, this study design does not fulfill the
  principle of justice

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Yes, this study design does fulfill the principle
of justice

• Correct!
• The research includes women and men in proportion
  to the rates of severe migraines experienced by
  each sex, and is designed to have racial and
  ethnic diversity.
• The study provides both sexes and racial/ethnic
  communities with the opportunity for benefits
  from the clinical trials, and does not unfairly
  burden any single group with the risks of
  research. Its design is fair.

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Justice and the Use of Placebos

• A researchers duty is not to exploit or
• deceive research participants and to treat
  them fairly.
• The informed consent process must disclose
  sufficient information to ensure that potential
  research participants
• Understand what placebos are
• Understand the likelihood that they will receive
  a placebo
• Are able to provide their fully informed consent
  that they are willing to receive a placebo
• Misleading research participants about the
  research purpose or procedures

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Review
Investigators should allow Individuals to make
their own decisions
Justice
Investigators should design research studies as
to maximize benefit and minimize risk to
individuals
Respect
Individuals who are less able to take decisions
for themselves require additional protection
Beneficence
The burdens and benefits of research should be
fairly distributed among individuals and society
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Fairness in International Research

• A few of the many issues that demand careful
  consideration with respect to justice, as well as
  beneficence and respect for persons, include
• How can research conducted in resource-poor
  setting avoid exploiting participants?
• What is owed to participants in clinical research
  and to the population of the host country after
  studies are complete?
• In addition to following the HHS regulations,
  what standards and assurances to protect research
  participants should investigators and non-US
  institutions use when conducting research abroad?
  
• How can regional or cultural differences be
  negotiated?
• For settings where cultural values impact
  informed consent, how should processes be
  altered?

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Sustaining Benefits Locally

• Investigators should
• Think about how benefits to individual research
  participants and the local population may be
  sustained after the study is complete
• Consider how any effective treatment emerging
  from the research could be provided to the rest
  of the population

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Standards and Assurances for International
Research

• The HHS Office for Human Research Protections
  (OHRP) has set the expectation that the HHS
  regulations, as well as any additional
  institutional and local standards, will be
  followed in all research conducted or supported
  by HHS.

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IRB Review for Research in International
Settings

• Knowledge of the local context may be provided
  by
• Specialists with personal, direct knowledge of
  the local research context who participate in IRB
  discussions and provide insight on achieving
  protections for research participants
• An IRB representative situated within the local
  research context

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Research Ethical Committee (REC) in HMC

• Hamad Medical Corporation in Qatar, parallels a
  similar approved protocols of IRB
• Research Ethical Committee (REC) in HMC is based
  upon IRB regulations and terms

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References

• National Institute of Health. NIH Office of
  Extramural Research. Protecting Human Research
  Participants

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Thank you
Thank you