ethical clinical research

8/8/2019 Ethical Clinical Research

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Urmila Thatte

Seth GS Medical College

[email protected]

Ethical Clinical Research


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ETHICS

Moral code of conduct defining the right and

wrong behavior in a civil society and comes from

within.

It is different from Law which regulates external

behavior.

11/14/20102 UG Certificate Course


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What is Clinical Research?

A systematic investigation in human beings

designed to produce generalisable knowledge



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Practice vs. Research

Prac

tice:

Interventions thatare designed solely

to enhance thewell-being of anindividual patientthat has a

reasonableexpectation ofsuccess

Resea

rch:

Activity designedto test an

hypothesis, permitconclusions to bedrawn; andthereby develop or

contribute togeneralizableknowledge



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Patients vs. Participant

Therapeutic misconception

Vulnerability of the patient

Doctor-patient vs. Investigator-participantrelationship and heirarchy



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Ethics in Biomedical Research

Right of thehumanparticipant

tounderstand

the nature of research,

risks & benefitsinvolved

to agree or not agree

to participate.



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14th May 1796

Jenner approached a farmer called Phipps

Asked if he could inoculate his son James against smallpox

Explained that if his theory was correct, James would never contract smallpox.

Surprisingly, the farmer agreed.

Jenner made two small cuts on James's left arm. He then poured the liquid from amilkmaids cowpox sores into the open wounds

James went down with cowpox but was not very ill.

Six weeks later when James had recovered, Jenner vaccinated him again, this time withthe smallpox virus.

To Jenner's relief James did not catch smallpox. His experiment had worked.

11/14/2010UG Certificate Course7


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1900

United States Army Yellow Fever Commission: how doesyellow fever get transmitted (Walter Reed) conducted in

experimental stations just outside Havana

Paid $100 in US gold to participants to allow themselvesto be bitten by infected mosquitoes (yellow fever)

Additional $100 if they consequently contracted the viraldisease

Payable to family in case of death

11/14/2010UG Certificate Course8


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Medical science must advance, but individual physician has special

duty and major responsibility for life and health of patient-subject

Risks proportionate to anticipated benefits

Tested in advance on animals Unambiguous consent Special caution if minors

Exploitation of social hardship is unethical

Academic training should stress special obligations when conducting

research or publishing


Regulations on New Therapy and HumanExperimentation from the Reich Minister of the

Interior, Feb 1931


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End point of experiments - DEATH

10 11/14/2010UG Certificate Course


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Defendants and Defense Counsel15 of 23 guilty, 7 hanged, 5 life sentences



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Nuremberg Code 1949: 10 points

voluntary (informed) consent must be obtained:investigators responsibility



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Clinical Trial Ethics: Nuremberg CodeThe code

specifies that:

volunteers have the

right to withdrawat any time

experiments mustprovide benefits

for society

avoid unnecessaryinjury



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Thalidomide Trial

Thalidomide was approved as a sedative

No danger to mother but extremely damagingto the foetus

Drug given to cure morning sickness

Subjects were not informed of experimental

drugs

Subjects were not asked to give their consent


Harris-Kefauver Amendment to Food,Drugs and Cosmetics Act, 1962


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Declaration of Helsinki: 1964

Adopted by the 18th World Medical Assembly

Revised 6 times

Latest version 2008, Seoul, South Korea

Para 13: protocols must be submitted to an Ethics Committee for

review, which must be independent of the investigator, the sponsor

or any other kind of undue influence.



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Tuskegee Syphilis Study

American medical research

project conducted by the

U.S. Public Health Servicefrom 1932 to 1972,

Examined the natural course

of untreated syphilis in black

American men.

Taliaferro Clark,Head of the

Public HealthService at thebeginning of theTuskegeeExperiment

http://images.google.co.in/imgres?imgurl=http://www.cynical-c.com/archives/bloggraphics/Tuskeegee_study.jpg&imgrefurl=http://www.cynical-c.com/archives/cat_wikipedia.html&h=297&w=400&sz=20&hl=en&start=1&um=1&tbnid=1bu5XQ7aQkshdM:&tbnh=92&tbnw=124&prev=/images%3Fq%3DTuskeegee%2BStudy%26svnum%3D10%26um%3D1%26hl%3Den%26rlz%3D1T4HPAA_enIN251IN252


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Tuskegee SyphilisStudy

Results:

28 deaths,

100 cases of disability,

19 cases of congenital

syphilisLack of informed consent, putting subjects and their

families to risk, exploitation of vulnerable population,

deception, withholding information, no benefit to subjects

11/14/201017

UGCertificate
http://images.google.co.in/imgres?imgurl=http://www.usrf.org/uro-video/Tuskegee_2004/Article_Header.jpg&imgrefurl=http://www.usrf.org/uro-video/Tuskegee_2004/Tuskegee_Intro.html&h=653&w=500&sz=125&hl=en&start=11&um=1&tbnid=4Yn1lsXgr6J_XM:&tbnh=138&tbnw=106&prev=/images%3Fq%3DTuskeegee%2BStudy%26svnum%3D10%26um%3D1%26hl%3Den%26rlz%3D1T4HPAA_enIN251IN252


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11/14/2010UG Certificate Course

1

8

Tuskegee 1997


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The Belmont Report

Ethical Principles and Guidelines for the Protection ofHuman Subjects of Research

The National Commission for the Protection of Human Subjects of Biomedicaland Behavioral ResearchApril 18, 1979



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The Belmont Report: 3 principles

Respect forPersons-

autonomy of

individuals

Special protectionfor those with

diminished

autonomy

Beneficence

maximize the

possible benefits

minimize possible

harm

Justice

subjects should be

selected fairly to

ensure that the

benefits and

burdens of medicalresearch are

evenly distributed



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ICH - International Conference onHarmonization, 1996

Joint initiative by regulators and

industry from three regions - US, EU &

Japan

Three observers:

WHO

Canada

IFPMA (International Federation of

Pharmaceutical Manufacturers

Association)



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GCP = Good Clinical Research Practice

A standard for the

design,

conduct,

monitoring,

recording,

auditing,

reporting

of clinical trials

22


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International

Scientific &Ethical quality

Standard

DESIGN

COLLECT

Patient Safety Credibility of Data

Good Clinical Practice

23


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India

2001 Indian GCP

2005 Schedule Y of Drugs and

Cosmetics Act Amendment:pertinent to clinical trials


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ICMR Guidelines

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UGCertificate
http://images.google.co.in/imgres?imgurl=http://www.khaitan.org/mt/archives/indian_flag.jpg&imgrefurl=http://www.khaitan.org/mt/archives/cat_india.html&h=400&w=500&sz=20&hl=en&start=5&um=1&tbnid=EY155NV88cxN2M:&tbnh=104&tbnw=130&prev=/images%3Fq%3DIndian%2BFlag%26svnum%3D10%26um%3D1%26hl%3Den%26rlz%3D1T4HPAA_enIN251IN252%26sa%3DN


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An erosion ofpublic trust...



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Informed Consentndependent Review11/14/201027 UG Certificate Course

Twin pillars of human

protection


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Informed consent

A process by which a participant voluntarily confirms his or her

willingness to participate in a particular trial, after having been

informed of all aspects of the trial that are relevant to the participants

decision to participate.

Informed consent is documented by means of a written, signed and

dated informed consent form.

ICH- GCP 1.28



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Part I : ParticipantInformation Sheet

(PIS)

Provides informationabout the study.

Part II : Consent form

Consent documented

Both integrated in toone document called

the Informed Consent

Document (ICD)

Informed Consent Document



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Informed consent

Consent given by a competent individual who

Has received the necessary information

Has understood the information

And having understood the information has arrived

at a decision without having been under any

coercion, undue influence or inducement or

intimidation



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Informed consent

Written informed consent

Voluntary

from every subject

before any study related procedure

and documented on EC approved form

Signed copy given to participant



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Who gives the consent?

Participant

if subject unable to giveconsent (minor, dementia

etc.) then -

Legally

acceptablerepresentative

(LAR)

subject should be informed

to the extent compatiblewith his/herunderstanding and consentsought and documented.



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How should the consent be documented?

Signed anddated by

Subject / subjectslegally acceptable

representative

Person conductingthe informed

consent discussionIf illiterate, an

impartial witness



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Informed Consent: Non-English speaking

Summaryand

consent inthe

vernacular

Written

translation

Thumbimpressions

allowedWitness

Documentmethod in

source



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Informed Consent: Children

Approval of older children:understand the concepts: assent

Consent from parents/legallyacceptable representative



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. . . is not a piece of paper.

. . . is not a signature.

It is a PROCESS by which we . . .. . . ENSURE that our subjects right to be informed, and right to consent to

research, is protected.

. . . DOCUMENT our efforts to protect the subjects rights to the satisfaction ofindependent observers.

Informed Consent . . .



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Informed ConsentIndependentReview


Twin pillars of human

protection


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Ethics Committee

review,

approve the initiation ofand

conduct periodic review

of biomedical researchinvolving human subjects.

Any board,committee

or othergroup

formally

designatedby aninstitution to



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All proposals onbiomedical research

involving humansubjects must be

cleared by an

Ethics Committee



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An objectivereview of researchactivities involving

human subjects

by a group ofdiverse

individuals is

most likely toprotect human

subjects and

promote ethicallysound research

Ethics Committees: Why?



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Composition of the EC

A reasonable

number of

members who

collectively have

the

qualifications and

experience

the science,

medical aspects

and

ethics of the

proposed trial

to review and

evaluate



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What does an EC do for Clinical Research?

Before thestudy begins:

Review andapproval of

research proposal

Decision makingprocess

Record keeping

During thestudy:

Review ofamendments

(Protocol, ICD)

Review of

Serious AdverseEvents

Protocoldeviations

Monitoringprogress

(reports, on-site)

Record keeping

After thestudy:

Study report,

Post trialmanagement

Publishing

Record keeping



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Criteria For Approval

Suitability ofInvestigator,Protocol and

informed consentprocesses

EquitableSelection Of

Subjects

Time Provision Confidentiality ofsubjects and data



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No study can be started without EC approval

No changes made without prior written ECapproval

EC may revoke any prior approval dependingon ongoing review

EC : Approval



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Challenges

If studies areNOT submittedfor review, thenthe safeguard of

ECs ismeaningless!



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14 November 2010Pharmatech 20084

The Road Not TakenRobert Frost

Two roads diverged in a yellow wood, I could not travel both

. long I stood

I shall be telling this with a sighSomewhere ages and ages hence:

Two roads diverged in a wood, and I,I took the one less traveled,And that has made all the difference.

ethical clinical research

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