Informed Consent The Process: Information, Comprehension and Decisional Capacity

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Informed Consent The Process  Information,
Comprehension and Decisional Capacity

• Robert R Conley, MD
• Professor of Psychiatry and Pharmacy Science,
  UMAB
• Chair, NIDA IRB
• Past Chair, UMAB IRB
• With thanks to
• Kathleen Palmer, RN, CCRC
• General Clinical Research Center

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The voluntary consent of the human subject is
absolutely essential.

• This means that the person involved should
• have legal capacity to give consent
• be able to exercise free power of choice, without
  any element of force, fraud, deceit, duress, or
  any form of constraint or coercion and
• have sufficient knowledge and comprehension of
  the subject matter and the elements involved as
  to enable him or her to make an informed and
  enlightened decision.
• The
  Nuremberg Code

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Respect for Persons

• Individuals should be treated as autonomous
  agents
• Consent vs. Assent
• Persons with diminished autonomy are entitled to
  increased protections and also entitled to
  participate in research when possible

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Informed Consent Process

• An ongoing exchange of information between the
  investigator and the subject beyond the consent
  interview
• Starts before enrollment and continues throughout
  the trial
• Allows an opportunity for subject to ask
  questions and have them answered
• New findings are communicated to the subject
  during the course of the study
• Voluntary participation is assessed throughout

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Components of Informed Consent

• Information
• Comprehension
• Voluntariness

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Essential Information

• Nature of the research
• Purpose of the study
• Procedures involved
• Duration
• Risks and Benefits
• Compensation

• Confidentiality
• Voluntary
• Right to Withdraw
• Alternatives
• Contacts for questions about the research,
  research- related rights and injuries

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Additional Information

• There may be unforeseeable risks
• Circumstances under which participation may be
  ended by the investigator
• Additional costs to the subject
• Consequences of a decision to withdraw
• Significant new findings will be provided
• Number of subjects participating

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Communicating Information

• Explain the research using simple terms
• Language that is understandable to subject
• Describe what is going to happen
• Be clear that participating is voluntary
• State benefits without exaggerating
• Do not minimize statement of risks
• Explain all alternatives
• Do not use exculpatory or coercive language

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Comprehension

• Elements of Understanding
• Intelligence
• Rationality
• Maturity
• Language

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Assessment of Understanding

• Responsibility of researcher
• Informally through verbal exchange using open
  ended questions
• Formal tools
• Dartmouth evaluation tool
• Evaluation to Consent
• Study specific informed consent test

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Therapeutic Misconception

• The general goal of clinical care is to provide
  benefit to an individual patient
• The general goal of research is to gain new
  knowledge
• Therapeutic Misconception can occur when subjects
  believe that research protocols are designed to
  benefit them directly rather than to test or
  compare treatment methods
• Rarely tolerable
• Understanding beneficence from overall research
  program is not a misconception

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Minimizing Therapeutic Misconception

• Explicit and clear descriptions of research
  purpose, procedures, etc.
• Careful discussion of voluntariness and
  alternatives to participation
• Evaluation plan
• Objective/neutral advocate

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Voluntariness

• Voluntary choice requires the consent process be
  free from
• Coercion threat of harm
• Undue influence offer of excessive or improper
  reward

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Voluntary Withdrawal

• A subject may discontinue participation at any
  time
• No penalty or loss of benefits
• Expected medical consequences of decision to
  withdraw
• Procedures for orderly termination

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Reconsent

• Reconsent is required when material and
  significant changes are made to the research
• Formal process solicited by a responsible
  investigator
• New consent document is signed as with initial
  consent

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Reaffirmation of Willingness to Participate

• At each interaction, the investigator should
  reassure voluntary participation continues
• Long intervals between visits or extended study
  periods
• Less formal interaction
• State the nature of upcoming visits
• Reminder of right to withdraw

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Dissent

• Should be monitored by entire research team
• Indicated by both verbal and non-verbal
  expressions

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Vulnerable Populations

• Informed consent may be obtained from those who
  are vulnerable or cognitively impaired
• Must be protected from coercion
• May have limited freedom to choose
• Additional safeguards may be required

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Vulnerable Populations 

• Children
• Impaired Cognitive or Decisional Capacity
• Prisoners
• Pregnant Women and Fetuses
• Non-English speaking persons
• Illiterate persons
• Terminally Ill

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Children (persons lt 18 years)

• Consent is obtained from the parent(s) and then
  obtain assent from the child
• Exceptions emancipated minors, wards of the state
• Assent
• Children 7 11 years of age, assent is verbally
  obtained and documented in the research records
• Minors 12 17 years of age, assent should be
  documented on an IRB approved assent form. 

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Cognitive Impairment and Impaired Decisional
Capacity

• Permanent
• Temporary
• Fluctuating
• Declining

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Assessing Decisional Capacity

• There is no standard for assessment
• Investigator judgment
• Tools
• Mini-Mental State Examination (Folstein et al.,
  1975)
• MacArthur Competence Assessment Tool-Clinical
  Research (Appelbaum and Grisso,1995)
• Evaluation to consent (Derenzo, Conley, Love,
  1998)

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MacCAT-CR-Sz
1. Present hypothetical clinical
trial 2. Procedural details, goals,
risks, benefits, and means of protocol
withdrawal are presented
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DECISIONAL CAPACITY RBANS Total vs. MacCAT
Understanding
r .82
Carpenter, et al. 2000
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Evaluation To Sign Consent 1.
Is the patient able to communicate? 2. Name at
least two potential study risks. 3. Name at
least two things that will be expected during
the study. 4. Explain what to do if he/she
no longer wishes to participate. 5. Explain
what to do if he/she is experiencing distress or
discomfort. 6. Explain how medications (or
treatments) are assigned during the study.
Evaluator
Date Witness
Date
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Decisional Capacity Judgment

• Subject can
• Engage in meaningful conversation
• Grasp relevant facts and repeat them
• Realizes that proposed research relates to
  his/her conditionis different from clinical care
• Can make personal decisions
• Reasoning not dominated by underlying
  illness/psychosis/hope for cure
• IRB review of evaluation plan
• Document assessment

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Safeguard Options

• Use of an Independent Monitor
• Use of a Surrogate
• family member
• other LAR
• Use Assent in Addition to Surrogate Consent
• Use of an Advance Directive
• Use of Informational/Educational Techniques
• Use of Waiting Periods

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Prisoners 

• Are considered vulnerable due to lack of control
  of their circumstances
• There MUST be a prisoner representative on the
  IRB if a prisoner is enrolled 

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Pregnant Women

• Obtain informed consent from both the pregnant
  woman and the father except
• The purpose of the study is to meet the health
  needs of the mother
• The identity or whereabouts of the father can not
  be reasonably ascertained
• The father is not reasonably available
• The pregnancy is the result of rape

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Human Fetuses and Neonates

• Many regulatory restrictions based upon viability
  of fetus or neonate
• Study personnel may play no part in determination
  of fetal or neonate viability 
• If anticipating this type of research, contact
  IRB during planning phases.

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Other vulnerable populations

• Non-English speaking persons
• Consent document translated in a language
  understandable to subject
• Illiterate persons
• Witness to the informed consent process
• Terminally Ill
• Be aware of therapeutic misconception
• May use neutral advocate

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Documentation

• Informed Consent Document
• Subject (or LAR) signs and dates
• Signed copy to subject and in Medical Record
• Always prior to any individual screening
  activities
• Consent discussion
• Progress note in research record
• Ongoing consent discussions

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References

• 45 CFR 46, 21 CFR 50
• Horng, S. Grady, C. Misunderstanding in Clinical
  Research Distinguishing Therapeutic
  Misconception, Therapeutic Misestimation,
  Therapeutic Optimism. Ethics Human Research,
  Jan-Feb 2003. The Hastings Center.
• Good, P.I. The Design Conduct of Clinical
  Trials. Wiley-Liss, 2002.
• International Conference on Harmonization GCP
• IRB Guidebook, OHRP
• FDA Information Sheets
• Dunn, C.M Chadwick, C. Protecting Study
  Volunteers in Research. CenterWatch, 1999.
• Wendler, D Rackoff, J. Consent for Continuing
  Research Participation. Ethics Human Research,
  May-June 2002. The Hastings Center.