Begging the Question 10

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The Consenting Process Limiting the
Therapeutic Misconception Research
Coordinators Network February 21, 2007
Inmaculada de Melo-Martin, PhD, MS Division of
Medical Ethics Weill Cornell Medical College
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Overview

• Respect for Autonomy as grounds for Informed
  Consent
• Elements of Informed Consent
• Common Barriers to Informed Consent
• Some Strategies to Deal with Barriers

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Informed Consent

• The obligation to obtain informed consent is
  generally understood to be grounded in a
  principle of Respect for Autonomy.

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Respect for Autonomy

• This principle comes, not from the Hippocratic
  tradition, but from the tradition of Kant and
  liberal political philosophy
• Rational beings are intrinsically valuable
• They cannot be treated merely as means but as
  ends in themselves
• The principle of respect for autonomy can be
  formulated as
• Persons should be free to choose and act without
  controlling constrains imposed by others.

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Informed Consent

• Elements of Informed consent
• Disclosure
• Understanding
• Voluntariness
• Competence

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Informed Consent

• One gives free informed consent to an
  intervention if and only if
• one is competent to act,
• receives a thorough disclosure about the
  procedure,
• understands the disclosure,
• acts voluntarily,
• and consents to the intervention

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Informed Consent

• Disclosure
• Refers to the necessity of investigators to give
  information to decision-makers.
• They are obligated to disclose a core set of
  information, including
• (1) those facts or descriptions that subjects
  usually consider material in deciding whether to
  consent or refuse to the intervention purpose of
  study, risks, benefits, alternatives, costs
• (2) information the researchers believe to be
  material,
• (3) the purpose of seeking consent, and
• (4) the nature and limits of consent as an act of
  authorization.

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Informed Consent

• Understanding
• It may be the most important component for free
  informed consent.
• It requires investigators to help subjects
  overcome illness, irrationality, immaturity,
  distorted information, or other factors that can
  limit their grasp of the situation to which they
  have the right to give or withhold consent.
• People understand if they have acquired pertinent
  information and justified, relevant beliefs about
  the nature and impacts of their actions.

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Informed Consent

• Voluntariness
• It requires that subjects act in a way that is
  free from manipulation and coercion by other
  persons.
• Persuasion Influence based on facts

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Informed Consent

• Competence
• Refers to subjects' capacity to perform a task
• Subjects have capacity to consent if they are
  able to
• understand the material information,
• make a judgment about the evidence in light of
  their values,
• intend a certain outcome, and
• freely to communicate their wishes to the
  professionals.

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Informed Consent

• Competence
• Subjects might lack capacity to consent
• If they are mentally ill, have cognitive
  impairments
• Capacity is not always all or nothing
• People may have fluctuating capacity, be
  temporarily decisionally impaired
• By definition children under 18 are incompetent
  to consent

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Informed Consent

• Competence
• Persons decisionally incapacitated are vulnerable
  subjects. They require additional safeguards.
• Protections must be proportional to the severity
  of capacity impairment, or to the magnitude of
  risk, or both.
• It is necessary to
• Justify the inclusion of subjects who lack
  capacity
• Research directly related to their condition or
  circumstances
• Assessment of risks
• Assess capacity to consent
• If decisionally incapacitated, then a surrogate
  must be used
• Obtain assent from subjects where possible
• Independent monitors, or research subjects
  advocates should be used for greater than minimal
  risk protocols that involve persons with
  questionable capacity to consent

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Informed Consent

• Competence
• When enrolling children ensure that
• Children understand what is going on
• Children assent to research participation
• Assent forms are appropriate to age
• You may need more than one assent form

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Barriers to Informed Consent

• Disclosure problems
• Incomplete or unclear information
• Lack of relevant information seriously hinders
  people's abilities to make informed choices

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Barriers to Informed Consent

• Problems with Understanding
• Subjects Characteristics
• Education, illness, age
• These factors might hinder peoples ability to
  comprehend the information given to them

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Barriers to Informed Consent

• Problems with Understanding
• Consent documents
• Difficulties making sense of statistical
  information
• Difficulties understanding scientific
  methodology randomization, dosing
• Reading level ranging from the 10th to the 12th
  grade is often needed to comprehend the documents
  
• Extremely lengthy consent forms
• Incorrect translations

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Barriers to Informed Consent

• Voluntariness Problems
• Coercion Credible threat
• Undue inducement Lead people to do things to
  which they would normally have serious objections
• Manipulation Withholding evidence and misleading
  exaggerations of benefits are instances of
  manipulation inconsistent with voluntary
  decisions

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Barriers to Informed Consent

• Lack of commitment to informed consent as a
  process
• Obtaining informed consent from a subject
  involves much more than getting a signature on a
  form
• The consent document is not intended to
  substitute for
• The verbal explanation of the study
• Conversation and discussion
• Other possible tools to help subjects understand
  (videos, educational materials)
• Investigators need to assess whether subjects
  understand what is going on
• Ongoing discussion with subjects throughout the
  research process
• Consent as a process requires that we give
  subjects sufficient time to assimilate all the
  information

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Barriers to Informed Consent

• The therapeutic misconception
• The conflation between the goals of research and
  those of medical care
• The goal of medical care is to provide the best
  medical care for a particular patient
• Treating physicians have a duty of therapeutic
  beneficence to their patients
• The aim of clinical research is to answer a
  scientific question in order to provide
  generalizable knowledge that can help future
  patients
• Researchers obligations are to protect subjects
  from exploitation and unnecessary harm and to
  ensure the scientific validity of the trials.

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Prevalence

• Evidence indicates that the TM is quite common
• Nearly 62 of subjects fail to distinguish the
  aims of research participation from those of
  receiving ordinary treatment
• 54 of investigators fail to recognize that the
  main reason for clinical trials is benefit to
  future patients.
• Generally find that subjects
• Are confused about randomization, dose
  escalation, placebo use, and blind trials
• Confuse standard treatment with research
• Overestimate benefits
• Underestimate risks

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Factors that Contribute to TM

• Learned expectancies
• Healthcare Experiences
• Media emphasis on new research
• Institutional emphasis on the benefits of
  participating in clinical research
• Coping mechanisms
• Therapeutic optimism
• Shortcomings in the informed consent process
• Inadequate informed consent documents
• Use of healthcare-related terms
• Problems with explanations of potential benefit
• Informed consent as discrete act rather than as
  process

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Inadequate Informed Consent Forms

• Use of health-care related terms
• Considerable inconsistency in terminology
• Forms use patient/subject doctor/researcher
  treatment/experimental intervention as
  interchangeable
• Overwhelming use of inappropriate terms
• Patient treatment physician treatment group
  therapy

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Inadequate Informed Consent Forms

• Concerns about Potential Benefits Issues
• Overstatement of potential benefits
• The hope is that we can improve your symptoms
  and prolong your life with this treatment...
• The purpose of this study is to determine
  whether this procedure is safe and to evaluate
  the effect of this treatment on your disease.
• King et al. 2005
• Vague or inconsistent language describing
  potential benefits
• "Personal benefit cannot be guaranteed"
• We do not guarantee or promise
• We hope this will help
• We hope your tumor will shrink
• "It is not known whether your participation in
  this research study will have a beneficial
  effect."
• Inattention to differences between potential
  direct benefits and collateral benefits
• Failure to mention benefits to society as main
  reason for study

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Informed Consent as Discrete Act rather than as
Process

• Insufficient explanation of research methods
• Insufficient attention to the consequences for
  subjects of such methods
• Not enough time

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Strategies for Improvement

• Ensure that the information given to subjects is
  correct, and up to date
• Ensure that the reading level is appropriate for
  subjects (maximum 8th grade reading level)
• Ensure that forms are correctly translated and
  that a qualified interpreter is present to
  facilitate conversation between the investigator
  and the potential subject
• Allow enough time for subjects to ask questions
  and understand information
• Involve subjects in discussion, ask open-ended
  questions rather than yes no questions
• Ask subjects to describe the purpose of the
  study, the risks, possible benefits

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Strategies for Improvement

• Emphasize the distinction between research and
  treatment
• Call attention to specific features of the study
  not found in routine care, i.e., randomization,
  placebo, blind-study
• Indicate that such procedures are being done to
  learn what works and what doesnt. They are not
  intended for therapeutic reasons
• Discuss these issues before discussing the
  specific risks/benefits of the study
• Be clear about direct benefits and always point
  out benefits to society
• Be Attentive to consent form and discussion
  terminology
• Use study drug, experimental procedure,
  investigator, researcher, subject
• Do not use medication, treatment, doctor,
  physician, patient
• Continually reassess understanding

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Strategies for Improvement

• When the consent form does not adequately reflect
  the study (changes in risks and benefits, new
  visits, different doses, more blood) you need to
  revise the consent and protocol and submit an
  amendment to the IRB
• Make sure you that do not change the consent
  document without IRB approval
• Ensure that only those people listed as
  co-investigators obtain consent from subjects. If
  you are going to be doing the consenting, you
  need to be listed as Co-PI
• The PI or Co-PI who is involved in the consenting
  process must be the one signing the document

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Bibliography

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  misconception in clinical research frequency and
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• Henderson GE, Davis AM, King NM, et al. Uncertain
  benefit investigators' views and communications
  in early phase gene transfer trials. Mol Ther.
  2004 Aug10(2)225-31.
• Joffe S, et al. Quality of Informed Consent in
  cancer clinical trials a cross-sectional survey,
  The Lancet Vol 358.Nov 24, 2001.
• Kimmelman J, Levenstadt A. Elements of style
  consent form language and the therapeutic
  misconception in phase 1 gene transfer trials.
  Hum Gene Ther. 2005 Apr16(4)502-8.
• King NM. Defining and describing benefit
  appropriately in clinical trials.J Law Med
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• King NM, Henderson GE, Churchill LR, et al.
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• Lidz C, Appelbaum P, et al. Therapeutic
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  (2004)
• Lidz C,Appelbaum P. The Therapeutic
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• National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research
  The Belmont Report .Ethical Principles and
  Guidelines for the Protection of Human Subjects
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• Paasche-Orlow MK, Taylor HA, Brancati FL.
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• Weinfurt KP, Sulmasy DP, Schulman KA, Meropol NJ.
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