INFORMED CONSENT

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INFORMED CONSENT

• Jocelyne Benatar
• Cardiovascular Research Unit

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Contents

• Historical perspective
• What is informed consent
• Informed consent in the acute setting
• Informed consent some solutions
• Vigorous debate and intelligent interjections
  throughout talk from audience would be preferable
  to

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Historical perspective
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• 1939 -1945
• Nazi Experiments WWII
• 1946
• Nuremberg Doctors Trial
• 1947
• Nuremberg Code

The Nuremberg Military Tribunal's decision in the
case of the United States v Karl Brandt et al.
includes what is now called the Nuremberg Code, a
ten point statement delimiting permissible
medical experimentation on human subjects.
According to this statement, humane
experimentation is justified only if its results
benefit society and it is carried out in accord
with basic principles that "satisfy moral,
ethical, and legal concepts."
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Historical Perspective

• 1932-1972 Tuskegee Syphilis Study
• 1972 Tuskegee Study Exposed
• 1944-1974 Human Radiation Experiments

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Historical Perspective

• 1948 The Universal Declaration of Human Rights
• 1963 Jewish Chronic Disease Hospital Study
• 1963 The Willowbrook Study
• In the mid-1960s Laud Humphreys, a sociologist
• 1964 Declaration of Helsinki (recently revised
  2000)

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1979 Belmont report

• respect for persons recognizing the autonomy and
  dignity of individuals, and the need to protect
  those with diminished autonomy (i.e., impaired
  decision-making skills), such as children, the
  aged, and the disabled
• beneficence an obligation to protect persons
  from harm by maximizing benefits and minimizing
  risks
• justice fair distribution of the benefits and
  burdens of research

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• 1991 Federal Policy for the Protection of Human
  Subjects
• 2005 The European directive

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NZ Historical Perspective

• Late 80s- cervical cancer trial at NUM exposed

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What is informed consent?
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Definition

• Informed consent is a process in which a person
  agrees to participate in a trial with complete
  knowledge of all relevant facts, such as the
  risks involved or any available alternatives. It
  continues throughout the trial and is designed to
  protect individuals participating in clinical
  research trials. 1

1. The Belmont Report, Ethical Principles and
Guidelines for the Protection of Human Subjects
of Research, The National Commission for the
Protection of Human Subjects of Biomedical and
Behavioral Research, Department of Health,
Education and Welfare, April 18, 1979
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What is the Consent Form in Research?

• The information sheet and consent form are one
  document.
• Findings in FDA audits
• 75 relate to issues with informed consent
• Investigator blacklist on FDA website related to
  findings

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What is the big deal?

• If the person has not consented in writing, they
  are seen not to have consented for the trial.
• Recent case in NZ with consent signed by family
  member for a trial

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Why is the process so different in research?

• It is voluntary
• It is not necessary for patient care

• It may have unknown harmful effects

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Why is the process so different to normal
clinical practice?

• It is subject to more scrutiny.
• It is governed by strict rules and guidelines

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Why Do It Then?

• Emergency medicine needs to be evidenced based
• CAST study, recent CASINO study

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Governance of Research

• Consumer rights
• National legislation
• International Code of Harmonisation(ICH)
• Good Clinical Practice(GCP)
• Code of Federal Regulations (USA)
• European Directive on Research - coming out in May

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Which regulations do we follow in NZ?

• Always have to practice according to the code
  with the highest standard

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Informed consent-some tips

• Before any trial related procedure is carried
  out- Informed Consent MUST be obtained
• Check inclusion/exclusion criteria BEFORE
  consenting
• Informed consent is a process not a form

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Requirements - Tell patients the following

• The overall experience- including reasonably
  foreseeable, harm, discomfort, inconvenience and
  risk
• The benefits
• Any alternatives to participating in the project
• Confidentiality

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Requirements - Tell patients the following

• Compensation should injury occur
• Who to contact for more information or for
  concerns
• That the trial is voluntary and has the right to
  withdraw
• You can not waive or appear to waive any legal
  rights of subjects

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What is the Witness used for

• Impartial witness used when participant cannot
  read
• Must have no relation ship to trial.
• Signs to affirm participant has been explained
  study and consents to it.

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The participant is keen, now what?

• They must
• SIGN AND DATE the consent in their own hand.
• Fill in all answers themselves
• Get a copy of the information sheet and consent
  form

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The standard ICF-who is it serving- regulatory
bodies/sponsors or participants?

• Long ICF- up to 16 pages long
• Language often complex and legalistic
• Message lost in all the words
• Designed to fulfil legalistic requirements rather
  than focused on participants needs

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Emphasis on mitigating risk

• Long list of adverse events including animal
  studies
• Very little on positive aspect of trial
• Should we be able to talk about benefits of being
  in research?

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And.

• Every time there is any change , you need to
  repeat the whole consent process- takes time,
  participants feel it is over the top, diminishes
  the consent form

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Conclusion

• Regulatory bodies require all elements to be
  incorporated into ICF- but want ICFs to be
  easily understood
• ICFs have become focused on mitigating risk

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Acute trial setting
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Issues with Acute Trials

• Drugs given in the acute setting may affect the
  ability to comprehend the information given.
• Patients in pain may feel that signing that
  piece of paper will allow treatment to be
  instituted more quickly.
• Patients are in distress and are in a vulnerable
  position

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Issues with Acute Trials

• When patients are admitted to hospital, they are
  bombarded with information and questions from a
  whole variety of people which can be confusing
  and overwhelming.
• Physicians may perceive that a long consent
  process which affects their ability to quickly
  institute treatment is not in the patients best
  interest, thereby denying patients their right to
  be involved in a research project..

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Issues with Acute Trials

• Delay door to needle times
• Expectation it may be all too much for patient
• Relative cannot sign on behalf of participant
• Participant is expected to sign and date form,
  what about drips, monitors, pain , etc. !!
• Studies1,2 shows few remember or comprehend the
  study

• Williams BF, French JK, White HDfor the HERO-2
  consent substudy investigators. Informed consent
  during the clinical emergency of acute myocardial
  infarction (HERO-2 consent substudy) a
  prospective observational study. Lancet 2003 361
   918-922.
• Yuval R, Halon DA, Flugelman MY, Lewis BS.
  Perceived patient comprehension in acute and
  chronic cardiovascular clinical trials.
  Cardiology 2003 99 68-71.

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Issues with Acute Trials

• In acute setting, doctor who consents often seen
  to be saving the life of the patient
• The Stanley Milgram's experiment

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Issues with Acute Trials

• All that paperwork and patient needs acute care!!
• Lots of procedures and protocol
• Just easier to stick to normal management-
  someone else can do the research

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Issues with Acute Trials- conclusion

• The participants comprehension of the
  information provided and their competence to
  autonomously give consent may be less than
  optimal, so that whilst the consent form is
  signed, it is neither truly legal nor ethical.

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Possible Solutions

• Change law for proxy consents?
• Exclude all incapacitated patients?
• Have two step consent process?

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Two step consent process

• Short ICF with all relevant points highlighted
• Easy simple language
• Drawing of trial design
• Followed up with normal consent when patient is
  more stable and one can sit down and spend time
  with a participant

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Two attempts to incorporate this process into a
study have failed

• Main reason
• Sponsors/steering committee are worried
  participants might refuse second time round
• They are risk adverse

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What is really needed in ICF

• Simple English
• A diagram to show trial design
• Less information- at present hard to focus on the
  really important bits.

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Some suggestions..

• More focus on what the trial is about and the
  risk/benefit to participant, the fact that it is
  voluntary and what alternatives are available.
• Simple statement on cover , is it ACC or RMI
• Maybe a handout with contact details, RMI
  guidelines ( in understandable language), health
  advocate number - standard for each hospital

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Need to address real concerns raised by
participants

• Is this study to get a drug on market or to
  improve health care?
• Should the drug have major life changing
  effects- is it ethical to stop it in participants
  sorry the trial is over- go back on your old
  medication?

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Need to address real concerns

• How much information is given when trial is
  stopped prematurely- commercial/safety reasons
• Ensure that participants get study results
• All trials get published/ presented in a peers
  review setting

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Any other solutions???
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OR.

• Stick to the way weve practised medicine before
  evidence became important