INFORMED CONSENT

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INFORMED CONSENT

• Dr. I. Manorama Thomas
• B.Sc. (Hons.), MBBS M.S F.A.M.S.
• Emeritus Professor, St. Johns Medical College,
• Chairperson Independent Ethics Committee,
  Bangalore

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Why Informed Consent ?
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Research Done The Wrong Way IThe Tuskeegee
Syphilis Study

• Longest non-therapeutic experiment on human
  beings in medical history The progress of
  untreated syphilis (1932-72).
• 399 poor African-American sharecroppers in rural
  Macon County, Alabama, USA.
• The men were told they were being treated for
  bad blood.
• Even after penicillin was discovered and found to
  be a miracle cure, the men were not treated or
  even told what they had.
• US government officials went to extreme lengths
  to insure that they received no therapy from any
  source.
• Presidential apology, May 1997
• Tuskegee Syphilis Study Legacy Committee Final
  Report of May 20, 1996

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Research Done The Wrong Way IINazi Prisoner
Research During World War II

• Objectives of various trials
• Effect of cold, heat, chemicals on men, women and
  children
• Time to death testing in response to stressors
  in healthy volunteers
• Organ transplant experiments on healthy
  volunteers
• Any information given (some?) is irrelevant
  because prisoners were forced to participate
• Outcome
• 23 German scientists taken to court, 7 acquitted,
  9 imprisoned, 7 given death sentence
• Nuremberg Code of 1947

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Informed Consent in Human ResearchThe Origins

• Before the 20th century, guidelines required
  physicians need to adhere to acceptable medical
  standards
• Issue of patients agreement to the research
  never discussed
• Most requirements arose after the Nuremberg
  trials

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Informed Consent in Human ResearchThe Origins

• Emerges from the ethical principle of Respect for
  Persons
• Individuals be treated as capable of taking
  decisions for themselves (autonomy)
• Those with diminished autonomy be protected

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What is informed consent?

• Informed consent is a PROCESS
• Involves
• Providing all relevant information to the
  volunteer/ patient
• The patient/ volunteer understanding the
  information provided
• Voluntarily agreeing to participate
• A basic right

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Biomedical Research in HumansGuidelines for
Informed Consent

• The Nuremberg Code, 1947
• The Declaration of Helsinki, 1964 (2000)
• The Belmont Report, 1979
• ICH GCP, 1997
• ICMR Guidelines, 2000

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The Nuremberg CodeWhat is it?

• A set of 10 principles on research involving
  humans
• Developed after the horrors of Nazi experiments
  on humans became public
• Published in 1947

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The Nuremberg Code and Informed Consent

• The voluntary consent of the human subject is
  absolutely essential
• Person must have legal capacity to consent
• Should have sufficient knowledge and
  comprehension to make an understanding and
  enlightened decision
• Must be able to exercise free power of choice

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The Nuremberg Code and Informed Consent

• Inform the subject of
• The nature, duration and purpose
• The method and means
• All inconveniences and hazards
• Possible effects on health
• There should be no force, fraud, deceit, duress,
  coercion

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The Declaration of Helsinki What is it?

• A statement of ethical principles on research
  involving humans
• Published by the World Medical Association
• Developed from the Nuremberg Code
• Made by physicians
• First adopted at Helsinki in 1964

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The Declaration of Helsinki andInformed Consent

• Subjects must be
• Volunteers
• Informed participants
• Consent be obtained, preferably in writing
• If subject in a dependent relationship with the
  physician, consent be obtained by an independent
  physician

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The Declaration of Helsinki andInformed Consent

• Consent from legally acceptable representative
  required if subject
• Minor
• Incapable of giving consent
• Physical or mental disability
• If subject is a minor, assent be taken, where
  possible

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The Declaration of Helsinki andInformed Consent

• When consent not possible prior to participation
  in research
• Approved by the review committee
• Consent must be obtained as soon as possible from
  the subject or a legally acceptable representative

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The Belmont ReportWhat is it?

• Ethical principles and guidelines for protecting
  humans in clinical research
• Developed by a commission set up in the US in the
  aftermath of the Tuskeegee Study becoming public
• Published in 1979

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The Belmont Report and Informed Consent

• Identifies three elements of the process
• Information
• Comprehension
• Voluntariness

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The Belmont Report and Informed Consent

• Information
• All information be provided
• Conditions under which information provided also
  important (rapid/ disorganized manner?)
• Comprehension
• Adapt presentation of information to subjects
  capacities
• Investigators must ascertain comprehension
• Special provisions immaturity, mental
  disability
• Voluntariness
• There must be no coercion or undue influence

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ICMR GuidelinesWhat are they?

• Ethical guidelines for research involving humans
• Ethical Guidelines for Biomedical Research on
  Human Subjects
• Published by the Indian Council of Medical
  Research in 2000

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ICMR Guidelines and Informed Consent

• Participation must be voluntary
• Participants must be fully apprised of the
  research
• The investigator must obtain informed consent
• Responsibilities and information that must be
  provided
• Assent be obtained, where possible, for minors
• Requirement for consent can be waived by an
  ethics committee if risk is minimal (e.g.
  collecting data from subjects records)

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Summary

• Guidelines require
• All relevant information be provided to subjects
• Ascertaining they understand what their
  participation means for them
• Voluntary consent
• Protecting vulnerable subjects with additional
  safeguards

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Various terms
Informed Consent

• Patient Information Sheet
• Provides only the information
• Informed Consent Form
• Used to document consent
• Both integrated in to one document called the
  informed consent form

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WHAT IS INFORMED CONSENT ?

• Informed consent is consent given by a
• competent individual who
• has received the necessary information
• has adequately understood the information
• after considering the information, has arrived
• at a decision without having been subjected
• to coercion, undue influence or inducement,
• or intimidation.
• CIOMS International Ethical Guidelines
• 
  

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INFORMED CONSENT AS A PROCESS

• Informed consent is a communication process
• between the researcher and the participant
• starts before the research is initiated
• continues throughout the duration of the study

FHI, Research Ethics Training Curriculum
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Information in informed consent

• Provided in writing
• The informed consent form
• Discussed with the subject
• Consent must be in a language the subject
  understands

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Counseling

• Who does the counseling.?
• Clinical InvestigatorPreferably a senior who has
  experience or at least trained in counseling .

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PROCESS OF INFORMED CONSENT
Timing Before screening
Nature of research project

• Explicitly state that it is research
• How subjects will be recruited
• Purpose / aim of research
• Investigators names affiliations

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What must a subject know?Treatments

• Trial treatment(s)
• Treatments
• Investigational product and placebo
• Investigational product and active comparator
• Investigational product in different doses
• Probability for random assignment of treatments
• flipping a coin/ drawing a card
• What chance that the subject would be assigned to
  a particular treatment
• equal chance

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Study procedures

• What is subjects involvement
• Duration of study
• Explain about sample collections (not just names
  
• of tests)
• Procedures which are research / experimental
• If treatment, how different from conventional
• Randomization / blinding
• No. of subjects in study

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• Potential risks Benefits

• Medical, social, psychological, economic
• Probability, magnitude

Participation

• Voluntary
• Can withdraw
• No penalty, no loss of benefits

• No coercion
• No statement / information that causes subject /
• subjects legally acceptable representative to
  waive
• any legal rights or release investigator /
  sponsor
• /institution from liability for negligence
• Circumstances for termination of subjects
• participation by investigator

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Any questions, further information

• whom to ask rights of research subject, AEs

Language

• Clear, simple, non technical
• Sufficient time to make decision
• Give written information
• Translations written / verbal
• Thumb impressions allowed
• All signatures should be dated

ljy, LiV
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• Confidentiality, privacy
• adverse consequences of information eg.
  psychiatric
• illness, sexual preferences, substance abuse,
• to employers, insurance, legal authorities, HIV
  stigma

• Monitor / auditor/IRB/IEC/ regulatory authority
• have direct access to records without violating
• confidentiality to extent permitted subject
• authorizes such access by signing consent
• Publication, identity will remain confidential

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WAIVER OF INFORMED CONSENT

• Minimal risk
• Rights and welfare of participants protected
• Research not possible without a waiver
• Appropriate information provided

FHI, Research Ethics Training Curriculum
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SUMMARY-INFORMED CONSENT

• Moral, not just legal requirement
• Comprehensibility essential
• Cultural influences
• Support information helpful
• Pre-testing
• Free of coercion

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• Format of informed consent form for subjects
  participating in clinical trial
• Study Title
• Study Number
• Subject Initials ___________ Subjects Name
  ____________
• Date of births / age ________
• Please initial
• box (Subject)
• I confirm that I have read and understood the
  information sheet date
• for the above study and have had the opportunity
  to ask questions
• I understand that my participation in the study
  is voluntary and that I
• am free to withdraw at any time, without giving
  any reason, without my
• medical care or legal rights being affected.
• I understand that the Sponsor of the clinical
  trial, others working on the
• Sponsors behalf, the Ethics Committee and the
  regulatory authorities will
• not need my permission to look at my health
  records both in respects of
• the current study and any further research that
  may be conducted in relation
• to it, even if I withdraw from the trial. I
  agree to this access. However, I
• understand that my identity will not be revealed
  in any information
• released to third parties or published.

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4. I agree not to restrict the use of any data or
results that arise from this study
provided such a use is only for scientific
purpose(s) 5. I agree to take part in the above
study Signature (or
Thumb impression) of the Subject/Legally
acceptable Representative _______________ Date
Signatorys Name Signature of the
Investigator Date Study Investigators Nam
e Signature of the witness Date
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Resource Material

• 1. Ethical guidelines for Biomedical Research on
  Human
• Subjects, Indian Council of Medical
  Research (ICMR)
• New Delhi 2000
• 2. The Gazette of India Extraordinary Part II
  Section 3(I)
• Research Ethics Training Curriculum R.Rivera,
• D. Borasky, R. Rice, Family Health
  International, 2001.
• http//www.fhi.org
• Designing Clinical Research An Epidemiologic
  Approach
• Ed Stephen, B Hulley, Steven R. Cummings
  Williams
• Wilkins, Batlimore

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Our Experience

• What IEC/IRBs should look for
• Inspect facility in C.R.Os/ Hospitals/otherplaces
  , especially, Space, ICU facilities, No. of beds,
  whether bunker beds, Food-Hygiene ,Recreation
  Toilet Facilities.
• DCGI permission.

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Our Experience contd

• Insurance
• Dosage of drugs, expiry dates of drugs.
• Compensation amount.
• ICF Different languages.
• ADVERSE EVENTS .
• Diet

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Thank you