INFORMED CONSENTINFORMED CONSENT

Dr. I. Manorama ThomasDr. I. Manorama ThomasB.Sc. (Hons.), MBBS; M.S; F.A.M.S.

Emeritus Professor, St. Johns Medical College, Emeritus Professor, St. Johns Medical College,

Chairperson Independent Ethics Committee, BangaloreChairperson Independent Ethics Committee, Bangalore

Why Informed Consent ?Why Informed Consent ?

Research Done The Wrong Way – IResearch Done The Wrong Way – IThe Tuskeegee Syphilis Study *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 – IIResearch Done The Wrong Way – IINazi Prisoner Research During World War 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

Informed Consent in Human ResearchInformed Consent in Human ResearchThe OriginsThe Origins

Before the 20th century, guidelines required physician’s need to adhere to acceptable medical standards

Issue of patient’s agreement to the research never discussed

Most requirements arose after the Nuremberg trials

Informed Consent in Human ResearchInformed Consent in Human ResearchThe OriginsThe 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?What is informed consent?

Informed consent is a PROCESSInvolves

– 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 HumansBiomedical Research in HumansGuidelines for Informed ConsentGuidelines for Informed Consent

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

The Nuremberg CodeThe Nuremberg CodeWhat is it?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 The Nuremberg Code and Informed ConsentInformed 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 The Nuremberg Code and Informed ConsentInformed 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 The Declaration of Helsinki What is it?What is it?

A statement of ethical principles on research involving humans

Published by the World Medical AssociationDeveloped from the Nuremberg CodeMade by physiciansFirst adopted at Helsinki in 1964

The Declaration of Helsinki andThe Declaration of Helsinki andInformed ConsentInformed Consent

Subjects must be – Volunteers– Informed participants

Consent be obtained, preferably in writingIf subject in a dependent relationship with the

physician, consent be obtained by an independent physician

The Declaration of Helsinki andThe Declaration of Helsinki andInformed ConsentInformed 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 andThe Declaration of Helsinki andInformed ConsentInformed 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 ReportThe Belmont ReportWhat is it?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 The Belmont Report and Informed ConsentInformed Consent

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

The Belmont Report and The Belmont Report and Informed ConsentInformed Consent Information

– All information be provided– Conditions under which information provided also important

(rapid/ disorganized manner?) Comprehension

– Adapt presentation of information to subject’s capacities– Investigators must ascertain comprehension– Special provisions – immaturity, mental disability

Voluntariness– There must be no coercion or undue influence

ICMR GuidelinesICMR GuidelinesWhat are they?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 ICMR Guidelines and Informed ConsentInformed 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)

SummarySummary

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

Various termsVarious 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

Informed ConsentInformed 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

WHAT IS INFORMED CONSENT ?

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 consentInformation in informed consent

Provided in writing – The informed consent form

Discussed with the subject Consent must be in a language the

subject understands

CounselingCounseling

Who does the counseling.?Clinical Investigator—Preferably a

senior who has experience or at least trained in counseling .

PROCESS OF INFORMED CONSENT

Nature of research project

Timing Before screening

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

What must a subject know?What must a subject know?TreatmentsTreatments

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”

• What is subject’s 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

Study procedures

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 / subject’s legally acceptable representative to waiveany legal rights or release investigator / sponsor /institution from liability for negligence

Circumstances for termination of subject’s participation by investigator

• Clear, simple, non technical• Sufficient time to make decision• Give written information

• Translations written / verbal• Thumb impressions allowed• All signatures should be dated

Any questions, further informationwhom to ask rights of research subject, AEs

Language

ljy, Li”V

Monitor / auditor/IRB/IEC/ regulatory authority have direct access to records without violating confidentiality to extent permitted & subjectauthorizes such access by signing consent

Publication, identity will remain confidential

Confidentiality, privacyadverse consequences of information eg. psychiatric illness, sexual preferences, substance abuse, to employers, insurance, legal authorities, HIV stigma

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 trialStudy Title:Study Number :Subject Initials :___________ Subject’s Name :____________Date of births / age ________

Please initial

box (Subject)

1. I confirm that I have read and understood the information sheet date [ ]for the above study and have had the opportunity to ask questions

2. 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 mymedical care or legal rights being affected.

3. I understand that the Sponsor of the clinical trial, others working on the [ ]Sponsor’s behalf, the Ethics Committee and the regulatory authorities willnot 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 relationto it, even if I withdraw from the trial. I agree to this access. However, Iunderstand that my identity will not be revealed in any information released to third parties or published.

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 acceptableRepresentative :_______________Date : Signatory’s NameSignature of the Investigator : DateStudy Investigator’s NameSignature of the witness

Date

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

Resource Material

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 ExperienceOur Experience

InsuranceDosage of drugs, expiry dates of drugs.Compensation amount.ICF Different languages. ADVERSE EVENTS . Diet

Our Experience contd