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

Why Informed Consent ?

Research Done The Wrong Way I

The 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

Research Done The Wrong Way II

Nazi 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


Informed Consent in Human Research The 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


Informed Consent in Human Research The 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

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

Biomedical Research in Humans

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


The Nuremberg Code What 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


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

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

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


The Declaration of Helsinki and Informed 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


The Declaration of Helsinki and Informed 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

The Declaration of Helsinki and Informed 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

The Belmont Report

What 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

The Belmont Report and Informed Consent



Identifies three elements of the process

Information Comprehension Voluntariness

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

ICMR Guidelines
What 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

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)

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

Informed Consent
Various terms
  

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

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

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

Information in informed consent

 

Provided in writing
The informed consent form

Discussed with the subject  Consent must be in a language the subject understands

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


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

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

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

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

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

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

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

SUMMARY-INFORMED CONSENT Moral, not just legal requirement

Comprehensibility essential Cultural influences Support information helpful Pre-testing Free of coercion

Format of informed consent form for subjects participating in clinical trial

Study Title: Study Number : Subject Initials :___________ Date of births / age ________ Subjects Name :____________ Please initial box 1. 2. (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. ] ]

3.

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 Name Signature of the witness Date

] ]

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) 3. Research Ethics Training Curriculum R.Rivera, D. Borasky, R. Rice, Family Health International, 2001. http://www.fhi.org 4. Designing Clinical Research An Epidemiologic Approach Ed Stephen, B Hulley, Steven R. Cummings Williams & Wilkins, Batlimore

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.

Our Experience contd

Insurance  Dosage of drugs, expiry dates of drugs.


Compensation amount.  ICF Different languages.  ADVERSE EVENTS .  Diet