The Ethics of Clinical Investigation

1
The Ethics of Clinical Investigation

• Walter S. Davis, MD
• Center for Biomedical Ethics
• Research Subject Advocate
• General Clinical Research Center
• University of Virginia School of Medicine

2
Objectives

• Review the basic tenets of informed consent (IC),
  and outline how the concept is different in
  research vs. clinical medicine
• Explore and discuss the concept of vulnerability
  in human subjects research
• Discuss the changing role of IRBs in the current
  and evolving research ethics climate

3
Research Ethics The Historical Perspective

• Code of Nuremburg 1947
• Jewish Chronic Disease Hospital Case - 1963
• Beechers NEJM paper - 1966
• Willowbrook State School case revealed - 1970
• Tuskegee Syphilis Study revealed 1972
• National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research
  The Belmont Report - 1979
• Jesse Gelsinger 1999
• National Bioethics Advisory Commission Report
  and Recommendations - 2001

4
Ethical Challenges for Clinical Research

• Increasing scientific complexity of protocols
• Increasing federal, state, and institutional
  oversight of human subjects research
• A human subject population living in the
  Information Age
• Increasing attention to conflicts of interest

5
IC is a relatively new concept

• No mention of IC in the Hippocratic Oath
• Beneficence and non-maleficence sufficient
• Implied trustgtimplied consent
• The notion of questioning or refusing treatment
  foreign in some cultures
• Consent itself was (is) implied in many
  traditional societies and cultures

6
IC as evolution of pt autonomy

• Respect for pt autonomy was perhaps the most
  basic and formative principle of biomedical
  ethics, balanced by its counter-principle
  physician paternalism
• Autonomy-focused bioethics as part of 60s
• Atmosphere of challenge of authority
• The inherent worth of the individual
• Technology with the capacity to extend life in
  seriously ill patients

7
IC as process, not event

• The process involves information presented in an
  interactive educational model, rather than
  simple transfer of information
• Process requires attention beyond medical facts
  of the case
• Pts goals and understanding of quality of life
• Pts unique requirements for information
• Pts vulnerability
• Physician more than means of passing along
  information

8
Doctrine of IC implies a coexisting doctrine of
informed refusal

• A decision to withhold or withdraw treatment is
  not, necessarily a negative one
• It is virtually impossible for a physician
  familiar with a certain treatment to be
  completely unbiased
• A frank admission and discussion of bias,
  experience, and vulnerability from both
  patients and physicians is part of the process

9
Basic Elements of IC for Research

• Statement that study involves research
• Explanation of purposes of research
• Expected duration of subjects participation
• Description of procedures to be done
• Identification of any procedures that are
  experimental

10
Basic Elements of IC for Researchcontinued

• Description of risks/benefits
• Disclosure of appropriate alternatives
• Description of how confidentiality will be
  protected
• Compensation and medical treatment available if
  injury/adverse event occurs
• Contact information
• Statement that participation is voluntary, and
  that non-participation will not have penalty

11
Vulnerable Populations the usual suspects

• Children, minors
• Pregnant women
• Prisoners
• Fetuses
• Cognitively impaired persons
• Economically disadvantaged persons
• Educationally disadvantaged persons

• Military
• Students
• Elderly
• Workers
• Veterans

12
Foster et al. (2001) The Lancet 358, 1449-1453
if everyone is vulnerable, no one is entitled
to special protection
13
Problems with the Population Model of
Vulnerability (NBAC)

• The list of subparts could get unwieldy
• Unnecessary duplication of regulations
• How do you safeguard persons with multiple
  vulnerabilities?
• Status of particular groups may change
• Subparts classify certain persons as vulnerable,
  rather than situations in which individuals might
  be considered vulnerable

14
Types of Vulnerability

• Cognitive or communicative
• Institutional
• Deferential
• Medical
• Economic
• Social

15
How is the role of IRBs changing with respect to
subject vulnerability?
Two examples

• Report from NHRPAC on Informed Consent and the
  Decisionally Impaired
• Report from NHRPAC Clarifying Specific Portion of
  45 CFR 46 Subpart D that Governs Childrens
  Research

16
NHRPAC on Decisionally Impaired
recommendations

• research not otherwise approvable may be
  conducted after consultation with a panel that
  includes both experts in pertinent disciplines
  and persons knowledgeable about the experience of
  the population with the disorder or condition..
• Independent capacity assessment will likely
  become more frequent and important in protection
  of cognitively impaired subjects

17
NHRPAC on Childrens Research recommendations

• IRB must learn about the populations that will
  be potential subjects, taking into account social
  and cultural factors that may increase or
  decrease the level of risk
• procedures should only be performed by
  professionals skilled with children
• limits on number of attempts at a procedure
• appropriate methods..to orient the child to the
  research and decrease potential anxiety and
  discomfort

18
IC in research as process, not event

• The process involves information presented in an
  interactive educational model, rather than
  simple transfer of information
• Process requires attention beyond medical facts
  of the case
• Subjects goals and understanding of quality of
  life
• Subjects unique requirements for information
• Subjects vulnerability
• The Principal Investigator (and/or staff) is more
  than the means of passing along information

19
The future of clinical investigator training.

• Community consultation skills
• Decisional capacity assessment skills
• Consent conversation skills
• Literacy in the qualitative, behavioral, and
  social sciences research on their target
  population
• Dynamic view of vulnerability