Human Research: Consent, Assent, and Permission

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Human Research Consent, Assent, and Permission

• John DeBoer, M.Div, MSW
• Paul J. Reitemeier, Ph.D.
• Human Research Review Committee
• Grand Valley State University

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What is Ethics?

• A sustained conversation about what one ought to
  do in a given situation, all things considered,
  and why.

3
The Protection of Human Subjects

• Research using human subjects is intended to
  benefit them and/or society, but also imposes
  risks on research subjects.
• To help ensure that the research risks do not
  outweigh the benefits, human subjects research is
  carefully regulated.
• Regulated research must comply with
• 1) federal regulations
• 2) state and local laws
• 3) institutional policies ethics standards
• 4) codes formulated by professional groups.

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The Protection of Human Subjects

• Researchers must meet a variety of oversight
  responsibilities. This requires
• 1) knowing what research is subject to regulation
• 2) understanding and following the rules regs
• 3) obtaining training in subject protection
• 4) accepting responsibility for full compliance

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Federal Regulations

• Research preceded the regulations, at societys
  peril and harm to individuals.
• Following WWII discoveries widespread concerns
  arose re atrocities committed in the name of
  medical research.
• Legal defense at Nuremburg Doctors trial focused
  on absence of regulations or laws governing
  medical experimentation
• International codes guidelines for ethical
  human subjects research were formulated
• the Nuremburg Code (1947)
• The Declaration of Helsinki (1964)

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Federal Regulations

• The codes guidelines did not end unethical
  human subjects research. Many examples exist.
• 1950-60s ? Tuskegee AL deceptive research on
  rural males with untreated active syphilis
• Cold War era ? radiation tests on hospital
  patients, soldiers, children w/o consent or
  permission.
• Leo Alexander, MD, NEJM article (194924139-47)
  Medical Science Under Dictatorship
• Henry Beecher, MD, NEJM article
  (6/16/1966274241354-1360) Ethics and Clinical
  Research.
• Media story re Tuskeegee 1972 ?government
  regulation
• 1974 Congress required the DHEW (now HHS) to
  develop rules for the use of human subjects
  research ? 45 CFR 46

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How often did it Happen?

• 17 published clinical studies were originally
  identified, expanded to 50 from the studies own
  references.
• The 50 studies included 186 references to further
  problematic studies. Pappworth (U.K.) claimed to
  have identified 500 papers based upon unethical
  experimentation.
• Beecher reported on 22 of the 50 studies due to
  space limits.
• An experiment is ethical or not at its
  inception it does not become ethical post
  hocends do not justify means. There is no
  ethical distinction between ends and
  means. -- Henry Beecher, 1966

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How did it Happen?

• During ten years of study of these matters it has
  become apparent that thoughtlessness and
  carelessness, not a willful disregard of the
  patients rights, account for most of the cases
  encountered
• A far more dependable safeguard than consent is
  the presence of a truly responsible (sic)
  investigator. -- Henry Beecher, 1966

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Federal Regulations

• 22 federal agencies issued individual rules
• 1991 most federal agencies departments adopted
  a common set of regulations The Common
  Rule (45 CFR 46)
• Three especially vulnerable populations were
  given additional protections
• Subpart B pregnant women, fetuses neonates
  (lt1mo)
• Subpart C prisoners
• Subpart D children
• Subpart E cognitively impaired (was never
  adopted)

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Definitions

• Researchers must obtain appropriate approval from
  the subject or guardian before conducing
  research.
• Three key considerations
• 1) whether the activity qualifies as research
• 2) whether it involves live human subjects
• 3) whether it is covered research or exempt

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1st QuestionIs it Research?

• 45 CFR 46.102(d) Definition of Research
• A systematic investigation, including research
  development, testing and evaluation, designed to
  develop or contribute to generalizable knowledge.
• A project or study is research if it
• is conducted with the intention of drawing
  conclusions that have some general applicability
  dissemination, and
• uses a commonly accepted scientific method

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2nd QuestionDoes it concern human subjects?

• Definition of Human Subject 45 CFR 46.102(f)
• living individual(s) about whom an investigator
  (whether professional or student) conducting
  research obtains
• (1) data through intervention or interaction with
  the individual, or
• (2) identifiable private information

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3rd QuestionIs the research exempt?

• Definition of Exempt 45 CFR 46.102(i)
• Research that fall into the following categories
  may qualify for exemption
• Research conducted in established or commonly
  accepted educational settings involving normal
  educational practices
• Research involving the use of educational tests,
  surveys, interviews (3 involving public
  officials or candidates)
• Research involving the collection or study of
  previously existing data, documents, records,
  specimens, if publicly available or personally
  unidentifiable
• Research conducted by or subject to the approval
  of federal department or agency heads
• taste and food quality evaluation and consumer
  acceptance studies.

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Who makes these determinations?

• That it is research ? the investigator
• That it is covered research ? the IRB
• That it is in compliance with the regulations ?
  the IRB
• An Institutional Review Board (IRB) shall review
  and have authority to approve, require
  modifications in, or disapprove all research
  activities covered by this policy. 45 CFR
  46.109(a)
• The determination about whether particular
  research activities are exempt from the
  regulations must be made by an IRB, not by the
  individual investigator.

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What are the levels of review ?

• Exempt review Research does not fall under HHS
  or FDA required review categories. Still subject
  to GVSU ethics standards.
• Expedited review Research subject to HHS
  and/or FDA required review categories. Reviewed
  by 2 HRRC members, ongoing review schedule. All
  regulation review elements apply.
• Full Board Review 12 committee members review,
  analyze and discuss toward consensus to assure
  that
• All research subjects interests are protected
• risk of harm is minimized,
• full compliance with federal regulations ethics
  standards

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• Moral wisdom is exercised not by those who stick
  to a single principle come what may, absolutely
  and without exception but rather by those who
  understand that in the long run, no principle,
  however absolute, can avoid running up against
  another equally absolute principle.
• The key virtue therefore is practical wisdom or
  judgment (phronesis) the ability to discern the
  right and good thing to do in a given situation
  in terms of a particular moral choice.
• --- Aristotle

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What ethical principles guide these
determinations?

• Nuremberg Code (1947)
• Rules for permissible medical experimentation
• voluntary consent
• benefits outweigh risks
• Subject able to terminate participation at any
  time without penalty or loss of privileges

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What ethical principles guide these
determinations?

• The National Commissions Belmont Report (1979)
• 1. Respect for Persons
• the right to make decisions about themselves
  (consent) without undue influence or coercion
  from someone else
• 2. Beneficence/Nonmaleficence
• the obligation to maximize benefits reduce
  risks of harm to the subject
• 3. Justice
• the obligation to distribute benefits risks
  equally and without prejudice to individuals or
  groups, e.g. the mentally disadvantaged or
  members of a particular race or gender.

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Respect for Persons

• Autonomy self-directed living. Freedom, power
  authority to make choices that are important to
  oneself.
• Autonomy is respected supported via process of
  Informed Consent sufficient information about
  the research to determine whether it is in ones
  interests to participate, all things considered.

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Informed Consent

• IC is a process not an outcome,
  not a document, not a signature.
• IC refers to the ongoing process of exchanging
  information (subject ?? researcher) to effect a
  shared understanding of the research project in
  all matters of material relevance.
• Requires positive/meaningful input from both
  parties.

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Informed Consent

• Material relevance information that might
  reasonably be expected to make a difference to
  the subject concerning whether or not to
  participate in the research.
• Most common categories of materially relevant
  information include

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Informed Consent

• It is expected that ALL research subjects will be
  fully informed about research in which they
  participate and will give their consent before
  they enroll.
• Some subjects cannot give ethically valid consent
  due to age (children) or temporary or permanent
  cognitive impairment (mentally ill or impaired,
  intoxicated, extreme emotional upset, etc).
• It may not be easy to decide when an individual
  should be allowed to give consent or how it
  should best be obtained.

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Informed Consent

• Only competent adults can give CONSENT
• Children 7-17 years can give ASSENT
• Parents or Guardians give PERMISSION
• Consent and Permission are usually required to be
  documented in writing
• Assent is usually required, but not its
  documentation

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Informed Consent

• Some waivers of consent, assent or permission, or
  alterations to the usual requirements, are
  allowed under 45 CFR 46.116
• Some waivers of documentation or use of alternate
  forms of information re consent or permission
  are allowed under 45 CFR 46.117

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Informed Consent

• Waivers alterations of IC elements require 4
  separate findings by the HRRC in response to a
  request from the investigator
• Research involves no more than minimal risk
• Subjects rights welfare will not be adversely
  affected
• Could not practicably be carried out without the
  waiver or alteration
• When appropriate, subjects will be provided
  pertinent information after participation

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General Requirements for Informed Consent

• Legally effective informed consent shall
• Be obtained directly from the subject or the
  subjects legally authorized representative
• Be in a language understandable to the subject or
  representative
• Be obtained under circumstances that provide
  subject opportunity to consider whether to
  participate, and that minimizes coercion
  influences
• Not include language waiving subjects legal
  rights or which releases investigator, sponsor or
  institution from liability for negligence.

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8 Basic Elements of Informed Consent

• Statement that study involves research
  explanation of purposes of research expected
  duration of subjects participation description
  of procedures to be followed and identification
  of any procedure that are experimental.

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8 Basic Elements of Informed Consent

• Description of the potential risks or discomforts
  to the subject.
• Description of the potential benefits to subject
  or others, including society (general welfare).
• Disclosure of alternative procedures, if
  appropriate.
• Description of the extent to which
  confidentiality will be maintained.

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8 Basic Elements of Informed Consent

• For research involving more than minimal risk,
  explanation as to whether compensation medical
  treatments are available if injury occurs.
• Explanation of whom to contact if questions arise
  about the research, the subjects rights or whom
  to contact if research-related injury occurs.

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8 Basic Elements of Informed Consent

• Statement that participation is voluntary, that
  refusal to participate or decision to withdraw
  involves no penalty or loss of benefits.

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Additional Elements of Informed Consent 45 CFR
46.116(b)

• When required by the HRRC, one or more of the
  following elements shall be provided to each
  subject
• Statement that procedure may involve
  unforeseeable risks
• Description of circumstances under which
  subjects participation may be terminated by the
  investigator without subjects consent

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Additional Elements of Informed Consent 45 CFR
46.116(b)

• Additional costs to subject resulting from
  participation in research
• Consequences of subjects decision to withdraw
  from research
• Statement that significant new findings developed
  during research which may relate to subjects
  willingness to continue will be provided to
  subject
• Approximate number of subjects involved in study

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How do I start?

• GVSU home page Search term HRRC
• Human Subjects Review
• Special forms, links, etc.
• The Faculty Research and Development Center 301-C
  DeVos
• 331-3197 or hrrc_at_gvsu.edu
• Ms. Kelly Snyder, Grad Asst.