Informed Consent

Dr. Naresh Kumar Rapolu

What is Informed consent? History Guidelines Requirements Informed Consent Contents of Informed Consent Development of Informed Consent Form Informed Consent Process Documentation of Informed Consent Process

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

History

German physicians conducted medical experiments on thousands of concentration camp prisoners without their Consent. Most of the subjects of these experiments died/permanently crippled as a result of deadly studies and tortures such as injecting people with live viruses, immersing people in ice water, and forcing people to ingest poisons.

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

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 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

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

Developed after the horrors of Nazi experiments on humans became public A set of 10 principles on research involving humans In the August 1947 verdict, the section known as the Nuremberg Code came into existence. First international document which advocated voluntary participation and informed consent. Informed consent is essential. Research should be based on prior animal work. Benefits should be greater than the risks. Research must be conducted by qualified scientist.

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

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

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

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 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

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

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

Identifies three elements of the process

Information Comprehension Voluntariness

Information

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

Comprehension

Voluntariness

Ethical guidelines for research involving humans

Ethical Guidelines for Biomedical Research on Human Subjects

Published by the Indian Council of Medical Research in 2000

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)

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

What Is Informed Consent Process

Acc to ICH-GCP Guidelines 1.28

Process by which a subject voluntarily confirms his/ her willingness to Participate in a particular trial, after having been informed of all aspects of the Trial that are relevant to the Subjects decision to participate. Informed Consent is Documented by means of a written, signed and dated informed consent form. Indian GCP Informed Consent Voluntary written assent of a subjects willingness to participate in a particular study and in its documentation. The confirmation is sought only after information about the trial including an explanation of its status as research, its objectives, potential benefits, risks and inconveniences, alternative treatment that may be available and of the subjects rights and responsibilities has been provided to the potential subject.

General Requirements

MUST...

Practical, Non-technical style. Subject language. Explain medical/technical terms. Don't causes the subject to waive any legal rights. Must provide ample of time to Consider. Not be written in language which conveys any particular advantage for the study drug. Not use language that implies the study drug is safe for the purposes for which it is under investigation. Investigator should answer the questions or queries.

Contents of Informed Consent Form.

Contents of ICF

Statement that the study involves research and explanation of the purpose of the research Expected duration of the Subjects participation Description of the procedures to be followed, including all invasive procedures Description of any reasonably foreseeable risks or discomforts to the Subject Description of any benefits to the Subject or others reasonably expected from research. If no benefit is expected Subject should be made aware of this. Disclosure of specific appropriate alternative procedures or therapies available to the Subject. Statement describing the extent to which confidentiality of records identifying the Subject will be maintained and who will have access to Subjects medical records Trial treatment schedule's and the probability for random assignment to each treatment (for randomized trials)

Contents of ICF

Compensation and/or treatment(s) available to the Subject in the event of a trial-related injury An explanation about whom to contact for trial related queries, rights of Subjects and in the event of any injury The anticipated prorated payment, if any, to the Subject for participating in the trial Subjects responsibilities on participation in the trial Statement that participation is voluntary, that the subject can withdraw from the study at any time and that refusal to participate will not involve any penalty or loss of benefits to which the Subject is otherwise entitled Any other pertinent information

Contents of ICF

Statement of foreseeable circumstances under which the Subjects participation may be terminated by the Investigator without the Subjects consent. Additional costs to the Subject that may result from participation in the study. The consequences of a Subjects decision to withdraw from the research and procedures for orderly termination of participation by Subject. Statement that the Subject or Subjects representative will be notified in a timely manner if significant new findings develop during the course of the research which may affect the Subjects willingness to continue participation will be provided. A statement that the particular treatment or procedure may involve risks to the Subject (or to the embryo or fetus, if the Subject is or may become pregnant), which are currently unforeseeable Approximate number of Subjects enrolled in the study

Format of informed consent form for subjects participating in clinical trial

Study Title: XXXX Study Number : 00000 Subject Initials :___________ Date of births / age ________ 1. 2. 3.

Subjects Name :____________

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.

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

Development of the Informed Consent Form.

Development of the ICF

Development of masterICF in English MasterICF provided to CRO

CRO reviews and adapts ICF for local use

Country specific requirements Translation(s)Back-translation and translation statement ICF sent to sites for IEC submission CRA forwards IEC approved ICF to TMF

The NormalConsent Process An Overview

Explain study before study procedures are carried out; enter into source documents Give sufficient time for Question and answers.
Subject signs and dates the IEC-approved ICF Explain the significance of signing and dating the ICF Investigator (designee) signs and dates the ICF

Subject given a copy of the signed and dated ICF

Original filed at site

Consent in Special Situation

Special Situation
Children. Mentally retarded People Incurable disease / Emergency Accidents/Trauma, Stroke Condition Homeless, Refugees

In these situation Legally Acceptable Representative (LAR) is required.

Legally Acceptable Representative

Legally Acceptable Representative (LAR)

A LAR is an individual or other body authorised under applicable local laws to make decision about the study about subjects healthcare and who agrees to consent, on behalf of a prospective subject, to the subjects participation in the clinical study eg. Close relative).

LAR Consent

Inform about trial adequate to understanding Obtain dated signature, if possible. Legally acceptable representative to sign and date IC Legally acceptable process

Impartial Witness

Impartial Witness

If subject / subject LAR is not able to read, then Impartial witness should be present there as the witness of consent.
Eg: An illiterate adult patient. Patient for an ophthalmic study/blind patient. Patient with severe arthritis / severe burns in their hand. Acute mental states.

Witness Consent-Process

Written ICF to be explained to the subject or the subjects LAR Subject or the subjects LAR has orally consented to the subjects participation in the trial. Then subject/ LAR should made thumb impression on the informed consent form in relevant sections Witness should sign and personally date the consent form. Signing the consent form, the witness attests that the information in the consent form and any other written information was explained to, and apparently understood by, the subject or LAR Informed consent was freely given by the subject or the subjects LAR.

WAIVER OF INFORMED CONSENT

Minimal

risk

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

Informed Consent Documentation

Informed Consent Documentation

Process & Timing Persons involved Risk and Benefits explained All Queries discussed Voluntary Participation A Copy given to the Patient

INVESTIGATOR Should Record in subjects source document...

Who conducted process. Date ICF signed. Signed before study-related procedures. Signed/dated copy to subject. If ICF signed on same day as procedures, the time of ICF completion and time of commencing procedures.

Revisions to the Informed Consent Form

When are revisions required?

When significant new information comes to light that affects the safety of the subjects and/or might have influenced the subjects original decision to take part. Protocol Amendments may require the ICF to be revised E.g. Changes in study procedures, entry criteria, patient numbers etc Sponsor decides whether the ICF needs to be modified

Actions:

The sponsor/CRO will provide sites with an amended version of the ICF. Revised ICF must receive IEC approval before implementation, unless there is an amendment that removes an immediate hazard to the subjects. Re-consent on-going subjects. Inform completed subjects as necessary.

Therefore, INFORMED CONSENT ........Is not just a piece of paper ..Is not just a signature It is a PROCESS by which we ......Ensure that our subject right to be informed & right to consent to research, is protected.