The Informed Consent Process

Dr. Hemant Malhotra, MD, FRCP (London), MNAMS, FUICC, FICP, FIMSA

Senior Professor of Medicine & Head, Division of Medical Oncology,

SMS Medical College & Hospital, Jaipur. Email: drmalhotrahemant@gmail.com

Objectives

• Informed Consent Process • Informed Consent Interview • Informed Consent Document • Informed Consent and Vulnerable Populations

Media Uproar Over Perceived Injuries to Human Subjects in

Clinical Trials in India

Research ≠

Medical Practice

Patients vs. Subjects • When a person volunteers to participate in a

research trial, his or her status changes from patient to subject

• Subjects may not be receiving “standard of care”. The risks may be higher

• Documentation for subjects is MORE EXTENSIVE than regular clinical documentation

• The subject is the ultimate decision maker and must have complete information to assure his participation remains voluntary

History

• History reveals that in past human • subjects have been abused for “research”

without their willing consent Tuskegee Syphilis experiment Experiments on German war soldiers Milestones: • Nuremberg code - 1949 • Helsinki Declaration - 1964

• A process of shared decision making by the physician and patient

• An active communicative process

What is Informed Consent?

Why do we need consent?

• Legal and ethical considerations • Way to minimize potential harm • Avoid unfairness and exploitation • Protect patient rights.

• Disclosure

• Understanding

• Voluntariness

• Competence

• Consent

• Presenting Information to Patients What? When? How much? How?

General Elements of Informed Consent (Beauchamp & Childress -1994)

The Informed Consent Process

Informed consent is information exchange including subject recruitment materials, verbal instructions, written materials, questions and answer sessions and signature documenting consent with date. Subjects are given opportunity to choose involvement based on information, comprehension and voluntariness.

– Protecting study volunteers in research Cynthia McGuire Dunn, MD & Gary Chadwick, PHARM.D, mph 1999.

The Informed Consent Process

• Is the key to respecting autonomy • Provides a reasonable assurance that the

subject has not been deceived or coerced • Cannot be obtained from those who are

vulnerable, dependent or cognitively impaired O O’Neil J Med Ethics 2003:29:4-7

Steps in Informed Consent Process • Starts with an interview • Is an exchange of essential information about

the research • Allows an opportunity for subject to ask

questions and have them answered • Is evidenced by the signing of informed consent

document (with AV recording of the process now)

• Is documented in record • Requires giving a copy of the Informed Consent

form to the subject • Continues at each interaction by providing the

subject new information as it develops

Informed Consent Interview

Interview

• Choose a quiet, private, non-intimidating place to talk to the prospective subject – An investigator shall seek such consent only under

circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject shall be in language understandable to the subject or representative

45 CFR 46.116

Interview

• Explain the research in simple terms –Describe what is going to happen –Be clear this is a voluntary activity –Truthfully state any possible benefits

(payment is not considered benefit) –Truthfully state known possible risks –Lay out alternatives to participation –Describe how personal information will be

kept confidential » OHRP Tips for Informed Consent

Interview

• Talk about research related injury – and if there would be any compensation

• Will the subject undergo any additional direct or indirect costs?

• Make sure and explain that no legal rights will be waived

• Emphasize that the subject may quit the study at any time with NO affect on their medical care

Interview

• Explain that participation can be terminated by the investigator without subject’s permission

• Give the IRB number to the subject should they have questions about their rights as a research subjects

• Some studies require 24 hour contact numbers for the investigator

• Discuss the possible risks to pregnant women and fetus

Interview

• Tell the subject that if new information, positive or negative is discovered regarding the research that they will be informed.

• During the interview be aware of the things you might be saying that would affect voluntariness or be coercive – “free drug” “free treatment” “I think this is

best for you” “do this for me”

Interview

• Who can conduct the Interview to obtain Informed Consent? –The PI –A subinvestigator –A study staff person, listed with the IRB,

whom the investigator has documented is fully conversant with the study and is able to answer subjects questions.

The Informed Consent Document

Use the current, IRB

approved version

Informed Consent Document • The ICD should

– Contain all required elements – Describe the study in language the person can

understand – Be signed and dated by

• Subject or Legally Authorized Representative (LAR)

• Witness • Investigator • Person obtaining the consent , if not an investigator

Informed Consent Document

• The person signing as the witness cannot be the same as the person obtaining consent or the investigator

• The subject MUST be given a copy of the complete consent form.

Documentation of Informed Consent

• The subject record should contain a note that documents the Process

Today I discussed the ABC Drug Company hypertension study with Smt. Ram Devi. I explained the study and went over the consent form with her and her husband. They had time to ask questions and have them answered. Smt. Ram Devi voluntarily agreed to participate. She signed the informed consent form and her husband signed as a witness. She was given a copy of the signed form. Ms. Nisha, RN participated in the interview.

When Is the Informed Consent Process Finished?

• When the study is closed and final reports are issued!

• At each interaction, the investigator must reassure –Voluntary participation continues –New information is given to the subject

Informed Consent: Safeguarding the Vulnerable

populations

Vulnerable Populations

Vulnerable Populations and Informed Consent

• Persons who may not be able to make free and informed decisions about their participation in research or medical care are considered vulnerable

• Vulnerable populations may be easily coerced or have limited freedom to choose

• Persons identified as vulnerable have additional safeguards in the research informed consent process

Informed Consent & Vulnerable Populations

• Vulnerable Populations protected in regulation are: –Children and wards of the state –Prisoners –Pregnant Women and fetuses –Cognitively Impaired

Informed Consent & Vulnerable Populations

• Other accepted vulnerable populations are: –Non-English speaking persons – Illiterate persons –Financially impaired (poor patients) –Terminally Ill

Prisoners

Informed Consent & Prisoners

• Prisoners, due to the lack of control of their circumstances are considered vulnerable –DO NOT enroll prisoners unless you check

with the IRB first. There MUST be a prisoner representative on the IRB if a prisoner is enrolled

– If a person becomes a prisoner during a trial, notify the IRB immediately

Informed Consent & Prisoners

• Informed consent for a prisoner would state that participation will not be considered in parole consideration

• Must state that risks for prisoner in this study same as for a non-prisoner

• If a prisoner is treated in a research study and the IRB is not aware or does not have a prisoner advocate on the committee, federal regulatory bodies must be notified

Pregnant Women and Fetuses

Informed Consent & Pregnant Women

• Researchers should obtain informed consent from both the pregnant woman and the father

• Consent of the father is not necessary if: – The purpose of the study is to meet the health needs of

the mother. – The identity or whereabouts of the father can not be

reasonably ascertained. – The father is not reasonably available. – The pregnancy is the result of rape.

NOTE: Research targeting pregnant women as subjects does not qualify

for an exempt status.

Informed Consent in Fetal Research

• In utero fetal research –Same signature as those for pregnant

women –Study personnel may play no part in

determination of fetal viability

Informed Consent in Fetal Research

• Ex Utero Research –Study personnel may play no part in

determination of fetal viability –Many regulatory restrictions based upon

viability of fetus. –Mother and father must be legally

competent and have given their informed consent. (Consent of Father may not be required)

– If anticipating this type of research, contact IRB or ORC during planning phases.

Cognitively Impaired

Informed Consent & Cognitively Impaired

• Persons with diagnosed cognitive impairment such as mental retardation, dementia, and coma, can participate in research.

• This type of research must specifically address how an individual’s capacity to give informed consent will be determined.

• The signature of a legally authorized representative will be required

• Research with Cognitively Impaired subjects cannot be considered exempt by the IRB

Informed Consent & Cognitively Impaired

• For persons whose cognitive status is suspect, but there is no definitive diagnosis –Use the Cognitive Impairment Algorithm in

the Investigator’s Handbook to determine ability to give free informed consent

–Document the use of the algorithm

Cognitively Impaired

• Document carefully the enrollment of persons whose cognitive status is not outwardly obvious e.g. stroke patients, psychiatric patients or persons with speech or language disorders

• If a person is enrolled in a study during a period of cognitive impairment and regains his ability to give consent – he must be re-consented

Non-English Speaking

Informed Consent & Non-English Speaking Persons

• Persons must be consented in a language that is understandable to them

• Non-English speaking subjects may not be excluded on the basis of language

• If the principal investigator anticipates that consent interviews will be routinely conducted in a language other than English, the IRB requires a translated consent document be submitted with the original protocol for approval. It is the investigator’s responsibility to ensure that the translation is accurate.

Informed Consent & Non-English Speaking Persons

• A copy of the consent document must be given to each subject. While a translator may be helpful in facilitating conversation with a non-English speaking subject, verbal translation of the consent document must not be substituted for a written translation.

• If a Non-English speaking subject is unexpectedly encountered, and a written translation of the consent document is not available. Investigators should carefully consider the ethical/legal ramifications of enrolling subjects when a language barrier exists

Informed Consent & Illiterate Persons

• An investigator may enroll individuals, who can speak and understand English, but cannot read or write. The potential subject must be able to place a written mark on the consent form.

• The subject must also be able to: – Comprehend the concepts of the study and understand the

risks and benefits of the study as it is explained verbally, and.

– Be able to indicate approval or disapproval for study enrollment.

Informed Consent & Illiterate Persons

• The PI has to ensure that the subject – literate or illiterate – understands what is written and is being said

• The PI & the subject should be on the ‘same page’.

Informed Consent & Illiterate Persons

• Additional items to document –what method was used to communicate the

information about the study –Who was present during the Informed

Consent Interview –The specific ways that the subject

communicated agreement to study participation

Special Issues

Informed Consent Issues

• Groups where coercion is a serious concern –Terminally ill are desperate for any type of

cure. These are probably the persons MOST vulnerable to coercion. Beware the therapeutic misconception

–Poor – the poor can be coerced by “free care” and re-imbursements can substantially affect the voluntariness of the decision to participate.

Informed Consent Issues

• Beware the Therapeutic Misconception “What goes awry is that the ill subject does

not grasp that what she has volunteered for really is research; It can be enormously hard to shake the erroneous belief that the intervention is designed to make the volunteer better, rather than contribute to anything as faceless as the medical welfare of future patients”

James Lindemann Nelson

Summary

• The Informed Consent Process begins with an interview and continues through the study

• Participation in research must begin as a voluntary activity and remain voluntary

• Persons who are vulnerable may not be able to freely consent, and require special protections in the informed consent process.

Summary

• The Investigator is primarily responsible for the ethics and practice of informing persons about their participation in research

Summary

The Investigator should communicate the importance of the Informed Consent Process to the research staff and expect them to maintain high ethical standards.

Regulators

Investigator

I admire the way you’re coping with the new regulations

Informed Consent Process AV recording

Dr. Hemant Malhotra, MD, FRCP (London), MNAMS, FUICC, FICP, FIMSA

Senior Professor of Medicine & Head, Division of Medical Oncology,

SMS Medical College & Hospital, Jaipur. Email: drmalhotrahemant@gmail.com

Audio Visual recording of Informed consent process

1. Background 2. Information for prospective study subjects 3. Principle of privacy and confidentiality 4. Consent of the subjects for a-v recording 5. Procedure of recording 6. Quality of recording 7. Storage & archival of A-V recordings

1.Background

• Case W.P. (C) No. 33/2012 of Swasthya Adhikar Manch, Indore & Anr Vs. Ministry of Health and Family Welfare &Ors. with WP(C) No. 779/2012 regarding clinical trials

• 21.10.2013: Supreme court order “5 Global Clinical Trials for which approval was given by CDSCO after 01.01.2013 till 31.08.2013,

• 19. 11. 2013: DCGI has issued direction that in all clinical

trials, in addition to the requirement of obtaining written informed consent, audio-visual recording of the informed consent process of each trial subject, including the procedure of providing information to the subject and his/her understanding on such consent is required to be done while adhering to the principles of confidentiality. Such audio-visual recording and related documentation would be preserved. This is applicable to the new subjects to be enrolled in all clinical trials including Global Clinical Trials.

Current Indian requirements • As per the passed order on

19 Nov 2013, AV consenting made mandatory in India for all clinical trials irrespective Indian or global including 5 global trials approved from Jan to Aug. 2013.

• 16. 01. 2014: DCGI issued DRAFT GUIDELINES ON AUDIO-VISUAL RECORDING OF INFORMED CONSENT PROCESS IN CLINICAL TRIAL

Current international requirements

• Apart from India, no where else Audio Video Consenting is mandatory.

2. Information for prospective study subject

• Essential elements • Additional elements • Role of Legally acceptable representative (LAR)/Impartial

witness (IW) • The process of signing/putting thumb impression by the

subject/LAR/IW should also be video recorded.

• Statement that the study involves research

• Purpose of the research

• Expected duration

• Description of the procedures

• Foreseeable risks or discomforts

• Benefits to the subject

• Alternative procedures or therapies

• Extent of confidentiality of records & identification

• Financial compensation and medical management

• Treatment schedule(s) and randomization

• Contact details for query • Anticipated prorated payment • Subject's responsibilities on

participation • Statement that participation

is voluntary • Any other pertinent

information

Essential elements

Additional elements

• Termination of participation by investigator • Additional costs to the subject • Consequences of a subject’s decision to withdraw • Notification of subject or subject's representative in case of

new finding • Risks to the subject which are currently unforeseeable • Approximate number of subjects enrolled

• Identity and records of the trial subjects

• Prevent from subject from hardship, discrimination or stigmatization

• Define and allocate the activities of A-V recording

• Disclosure :

court of law under the orders of the judge

To communicate to Drug regulatory/Health autho.

3. Principle of privacy and confidentiality

4. Consent of the subjects for A-V recording

Before starting the informed consent process (and the AV recording of the same)

a. Consent for AV recording

b. Equipments should be functional.

c. Inform the potential participant/LAR/ IW

Process of obtaining AV consenting

5. Procedure of audio-visual recording of ICP

• Duties of PI/Co-I/Designee • Introduction • Role in research • Current time and date • Title of the protocol • Screening no. of participant • Photo ID of subject/LAR/IW documentation

Role of Participant/LAR /IW

• Name, age and address

• LAR should clearly state relation to actual reason why the participant cant give consent • State the language she/he understands best and is

literate

• In case participant/LAR is illiterate then an impartial witness is needed

• Recording should be checked by PI/Co-I / medically qualified person delegated

• No editing • Security of computer and CD/ hard drive • Hard drive will remain with the PI which could be

accessed by the delegated study team members on request for transferring and storage. The CD should be filed in the participant binder.

6.Quality of audio-visual recording

a. The informed consent process should be carried out in the designated area (unless patient is on a bed )

Following conditions should be met, that is 1. Free from disturbance 2. Well lit 3. Ensures privacy & Comfort of the participant

b. Camera having video facility with (Preferred) Good resolution (at least 1280x720 pixels) Sufficient memory (at least 4 GB) Sufficient battery back up (at least 2 hrs) Show non editable date & time on video c. Mike system d. Computer with CD/DVD writer e. Blank CDs/DVDs with cover, Hard disc(1TB)

7.Storage & archival

• After completion / termination of the study for at least a period of 5 years

• One CD per participant (Preferred) • The soft copies of the recordings will also be stored

in a password protected hard drive. • The original recording in the laptop will be deleted

when study is closed out

Forum for Ethics Review Committees in India

Template on its website for guidance www.ferci.org

Advantages

• Safeguarding the stakeholders • Simplification of the consent process • Reliability • Transparency • Improvement in informed consent

documents • Confirmation of informed decision

Challenges(1/2)

• Infrastructure • Indian culture • Dilemma regarding ongoing research participants • Recording of a “process”; not an “event” • Willingness to discuss ailment over camera

Challenges (2/2)

• Interpretation of behavior on camera • Confidentiality at stake • Language barrier • Cost implication • Special populations • Risk of tampering the records

Common Questions

• What if subject want to take ICF home for reading and then he/she will confirm the participation on next day?

• Who can see the recorded Audio Video ?

• What is the ideal time for AV consenting?

• Can Group AV Consenting be allowed?

• What if subject is ready for ICF but not for Audio Video

Consenting?

Common Questions • What if the device stops in between? • Do we need to provide recorded AV to subject? • Can we upload the recorded AV on the social media or any

website so it can help others to understand the process? • If CD will get corrupt within 2 years and if it won’t play on

the day of Audit, who will be responsible for this? • For how long AV consenting has been archived?

Responsibilities of the Tripartite

EC plays a major role in ensuring the proper AV consenting in the institute. EC must ensure that the investigator is properly trained on the AV consenting and EC should inspect the AV ICF process on interval basis to ensure the proper conduct of AV Consenting.

CRO/Sponsor should provide proper training to

investigator along with study team members regarding AV consenting during or prior to SIV.

Example of AV Consenting form

Applicable rules, regulations and guidelines

• http://cdsco.nic.in/Office%20Order%20dated%2019.11.2013.pdf)

• http://cdsco.nic.in/html/scheduley%20(amended%20version

-2005)%20original.htm) • http://icmr.nic.in/ethical_guidelines.pdf) • http://www.ich.org/fileadmin/Public_Web_Site/ICH_Produc

ts/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf)

• http://cdsco.nic.in/html/GCP.htm)

Thank You

Thank You

I admire the way you’re coping with the new regulations

Questions???

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