dr shariq rashid masoodi -...

Dr Shariq Rashid MasoodiMD, DM, FACP, FRCP (Edinburgh)

[email protected]@endocrinol

Objectives/

Pan of the talk

Objectives/

Pan of the talk

IRB/IECIS / ICF

History of Medical EthicsHistory of Medical Ethics

� Hippocrates ? 400 B.C.� Hippocrates ? 400 B.C.

� No mention of

experimentation

� Generally prohibits

doing harm

� No mention of

experimentation

� Generally prohibits

doing harm

History of Medical EthicsHistory of Medical Ethics

� Clinical Research/Clinical Trials were

historically part of medical practice.

� Clinical Research/Clinical Trials were

historically part of medical practice.

� People tended to do whatever their

doctor asked ? Including doing

research studies.

� People did not even know they were

part of a trial (no informed consent).

� People tended to do whatever their

doctor asked ? Including doing

research studies.

� People did not even know they were

part of a trial (no informed consent).

A California physician working

Sentinel events

A California physician working

at a leprosy hospital injected

6 girls, aged <12y with Syphilis� Hawaii, (1988)

Nazi war crimes � Nuremberg trial (1948)

Human radiation

experiments, etc.�

Declaration of Helsinki

(1963)

Tuskegee Syphilis study �National Commission

Belmont Report (1977)

Nuremberg, GermanyDec. 9, 1946 to Aug. 20, 1947

Nuremberg, GermanyDec. 9, 1946 to Aug. 20, 1947

� Any information given

is irrelevant - prisoners

were forced to

participate

� Outcome:

� Any information given

is irrelevant - prisoners

were forced to

participate

� Outcome:� Outcome:

� 23 German

scientists taken to

court; 7 acquitted,

9 imprisoned, 7

given death

sentence

� Nuremberg Code

of 1947

� Outcome:

� 23 German

scientists taken to

court; 7 acquitted,

9 imprisoned, 7

given death

sentence

� Nuremberg Code

of 1947

Nuremburg CodeNuremburg Code

� Designed to project integrity � Designed to project integrity

� Voluntary consent

� Scientific benefit

� Benefits outweigh risks

� Voluntary consent

� Scientific benefit

� Benefits outweigh risks

set of ten ethical principles

� Designed to project integrity

of research subjects.

� Delineated conditions for

ethical conduct of research

involving human subjects.

� Designed to project integrity

of research subjects.

� Delineated conditions for

ethical conduct of research

involving human subjects.

� Animal experiments first

� Avoid suffering

� No intentional death or disability

� Protection from harm

� Qualified investigator

� Subject ability to withdraw

� Stop if harm occurs.

� Animal experiments first

� Avoid suffering

� No intentional death or disability

� Protection from harm

� Qualified investigator

� Subject ability to withdraw

� Stop if harm occurs.

Declaration of Helsinki (World Medical Association)

Declaration of Helsinki (World Medical Association)

⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ 1st revision (1975) ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢

Seventh revision (2013)

1964 (11 paragraphs) ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ ⇢ 37

Tuskegee Syphilis Study

(1932 -72)

Tuskegee Syphilis Study

(1932 -72)

Research Done The Wrong Way

The Tuskeegee Syphilis Study *

Research Done The Wrong Way

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

� 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 � 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

� 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

A subject of the Tuskegee syphilis

experiment has his blood drawn, c. 1953

A subject of the Tuskegee syphilis

experiment has his blood drawn, c. 1953

�The US federal government brought

numerous violations and issues to the

forefront and in 1974 mandated the

establishment of Institutional Review

Boards (National Research Act)

�The US federal government brought

numerous violations and issues to the

forefront and in 1974 mandated the

establishment of Institutional Review

Boards (National Research Act)

Belmont Report – 1979Belmont Report – 1979

Jeff CooperAlbany Medical Center, Belmont Principles, p. 1 & 2

Applying the Principles of the

Belmont Report

Applying the Principles of the

Belmont Report

Principle Beneficence Justice

Meaning Provide benefit, protect from harm, limit risk

Equitable selection of subjects

Practice Risk-benefit assessment made Standard procedures used

Includes all groups that may benefit but does not single out one group

Objectives/

Pan of the talk

Objectives/

Pan of the talk

WHAT IS ETHICS?WHAT IS ETHICS?

“Ethics is the disciplined study or “Ethics is the disciplined study or “Ethics is the disciplined study or

morality….and morality asks the

question…what should one’s

behavior be”.

“Ethics is the disciplined study or

morality….and morality asks the

question…what should one’s

behavior be”.

Jeff CooperAlbany Medical Center, Ethical Decision Making, 2001, p. 1

MEANING of Ethics?MEANING of Ethics?

�“Greek ethos ‘character’ is the

systematic study of value concepts—

�“Greek ethos ‘character’ is the

systematic study of value concepts—systematic study of value concepts—

good, bad, right, wrong and the

general principles that justify

applying these concepts”.

systematic study of value concepts—

good, bad, right, wrong and the

general principles that justify

applying these concepts”.

Joan E. Sieber

Planning Ethically Responsible Research, p. 3

An ethically INSENSITIVE researcher can

leave the research setting in pandemonium

An ethically INSENSITIVE researcher can

leave the research setting in pandemonium

�The researcher�The researcher

�The institution

�The cause that he/she seeks to

promote

�The institution

�The cause that he/she seeks to

promote

Joan E. SieberPlanning Ethically Responsible Research, p. 3

Failure to treat subjects with respect

can result in data that is:

Failure to treat subjects with respect

can result in data that is:

�Misleading

�Inconclusive

�Misleading

�Inconclusive�Inconclusive

�Biased

�Inconclusive

�Biased

Joan E. SieberPlanning Ethically Responsible Research, p. 4

Norms of Scientific ResearchNorms of Scientific Research

1.Valid research design

2.Competence of researcher

1.Valid research design

2.Competence of researcher2.Competence of researcher

3. Identification of consequences

4.Selection of subjects

5.Voluntary informed consent

6.Compensation for injury

2.Competence of researcher

3. Identification of consequences

4.Selection of subjects

5.Voluntary informed consent

6.Compensation for injury

Jeff Cooper

Albany Medical Center, Ethical Decision Making, 2001, p. 19

“The public’s perception of

research, its benefits and its

risks is shaped by the way

“The public’s perception of

research, its benefits and its

risks is shaped by the way risks is shaped by the way

research is conducted”.

risks is shaped by the way

research is conducted”.

Dunn & Chadwick, 1999Dunn & Chadwick, 1999

Objectives/

Pan of the talk

Objectives/

Pan of the talk

IRB/IECIS / ICF

IRB / IECIRB / IEC

�The role of the Institutional Review

Board (IRB) is to determine whether

�The role of the Institutional Review

Board (IRB) is to determine whether Board (IRB) is to determine whether

the rights and welfare of the subjects

are adequately protected and

whether the study adheres to sound

ethical and scientific principles

Board (IRB) is to determine whether

the rights and welfare of the subjects

are adequately protected and

whether the study adheres to sound

ethical and scientific principles

Jeff Cooper

Albany Medical Center, Ethical Decision Making, 2001, p. 4-5

IECIEC

Should :

� Develop and Follow SOPs

� Specify in writing the authority under which it is

established

Should :

� Develop and Follow SOPs

� Specify in writing the authority under which it is

establishedestablished

� Membership requirements

� Terms of reference

� Conditions of appointment of members

� Quorum requirements

� Review through formal meetings

established

� Membership requirements

� Terms of reference

� Conditions of appointment of members

� Quorum requirements

� Review through formal meetings

IEC should ensureIEC should ensure

� Scientific evaluation completed before ethical review taken up (Only

good science makes good ethics!)

� Justified risk /benefit ratio

� Scientific evaluation completed before ethical review taken up (Only

good science makes good ethics!)

� Justified risk /benefit ratio

� Adequacy of documentation

� Privacy, confidentiality and justice issues

� investigator qualifications

� Appropriate facilities

� Adequacy of documentation

� Privacy, confidentiality and justice issues

� investigator qualifications

� Appropriate facilities

Institutional Ethics Institutional Ethics Institutional Ethics

Committees in India

Institutional Ethics

Committees in India

WHO perspectiveWHO perspective

Status of Ethical Review in

India….

Status of Ethical Review in

India….

� SOP’s not written /followed

� Poor infrastructure

� SOP’s not written /followed


� No. of proposals variable 2-

60/ meeting

� No. of proposals variable 2-

60/ meeting


� Part time activity

� Often Head of Institute is

Chair


� Part time activity

� Often Head of Institute is

Chair

� No Legal expert

� Minutes not recorded

� Poor record keeping

� No Legal expert

� Minutes not recorded

� Poor record keeping

Usual constraints faced by ECsUsual constraints faced by ECs

� No funds allocated

� No permanent staff

� No funds allocated

� No permanent staff

� No training

� No separate room / space

� No or poor honorarium to members / staff

� No proper monitoring mechanisms, no expedited review, no ongoing

review

� No training

� No separate room / space

� No or poor honorarium to members / staff

� No proper monitoring mechanisms, no expedited review, no ongoing

review

Other areas needing attentionOther areas needing attention

� Expedited Review

� Continuing Review

� Expedited Review

� Continuing Review

� Conflicts of Interest

� Site visits

� Adverse Events

� Conflicts of Interest

� Site visits

� Adverse Events

Voluntary InformedVoluntary InformedVoluntary Informed

Consent

Voluntary Informed

Consent

Voluntary Informed Consent Voluntary Informed Consent

� Voluntary

means without threat or undue inducement. � Voluntary

means without threat or undue inducement.

� Informed

means that the subject knows what a reasonable

person in the same situation would want to know

before giving consent.

� Consent

means explicit agreement to participate.

� Informed

means that the subject knows what a reasonable

person in the same situation would want to know

before giving consent.

� Consent

means explicit agreement to participate.

Legal requirements of a formal

consent statement [1]



1. An explanation of the purpose of the research, 1. An explanation of the purpose of the research, 1. An explanation of the purpose of the research,

the expected duration of the subject’s

participation, and a description of the procedure

– details of design not needed

2. A description of any foreseeable risk or discomfort

1. An explanation of the purpose of the research,

the expected duration of the subject’s

participation, and a description of the procedure

– details of design not needed

2. A description of any foreseeable risk or discomfort





3. A description of any benefits to subjects or other 3. A description of any benefits to subjects or other 3. A description of any benefits to subjects or other

reasonably to be expected

4. A description of alternatives to participation that

aught be advantageous to the subject.

3. A description of any benefits to subjects or other

reasonably to be expected

4. A description of alternatives to participation that

aught be advantageous to the subject.





5. A description of how confidentiality or anonymity

will be assured and the limits to such assurances

if warranted—especially in sensitive research,

5. A description of how confidentiality or anonymity

will be assured and the limits to such assurances

if warranted—especially in sensitive research, if warranted—especially in sensitive research,

such AIDS research.

6. For research involving more than minimal risk, a

statement of whether compensation or treatment

for harm or Injury is available.

if warranted—especially in sensitive research,

such AIDS research.

6. For research involving more than minimal risk, a

statement of whether compensation or treatment

for harm or Injury is available.





7. An explanation of whom to contact for answers to pertinent

questions about the research and about subjects’ rights,

and whom to contact in the event of research-related

harm.

7. An explanation of whom to contact for answers to pertinent

questions about the research and about subjects’ rights,

and whom to contact in the event of research-related

harm.harm.

8. Indication that participation is voluntary, that refusal to

participate will involve no penalty or loss of benefits to

which the subject would otherwise be entitled. and that the

subject may discontinue participation at any time.

9. The subject should be given a copy of the consent

statement.

harm.

8. Indication that participation is voluntary, that refusal to

participate will involve no penalty or loss of benefits to

which the subject would otherwise be entitled. and that the

subject may discontinue participation at any time.

9. The subject should be given a copy of the consent

statement.

PATIENT INFORMATION SHEET

Essential points of information

PATIENT INFORMATION SHEET

Essential points of information

1. Identification of the researcher.

2. Explanation of the purpose of the study.

1. Identification of the researcher.

2. Explanation of the purpose of the study.

7. Mention of the subjects right of refusal without penalty.

8. Mention of right to withdraw own data at end of session.

7. Mention of the subjects right of refusal without penalty.

8. Mention of right to withdraw own data at end of session.the study.

3. Request for participation, mentioning right to withdraw at any time with impunity.

4. Explanation of research method.

5. Duration of research participation.

6. A description of how confidentiality will be maintained.

the study.

3. Request for participation, mentioning right to withdraw at any time with impunity.

4. Explanation of research method.

5. Duration of research participation.

6. A description of how confidentiality will be maintained.

own data at end of session.

9. Explanation of any risks.

10.Description of any feedback and benefits to subjects.

11. Information on how to contact the person designated to answer questions about subjects’ rights or injuries.

12. Indication that subjects may keep a copy of the consent

own data at end of session.

9. Explanation of any risks.

10.Description of any feedback and benefits to subjects.

11. Information on how to contact the person designated to answer questions about subjects’ rights or injuries.

12. Indication that subjects may keep a copy of the consent

Objectives/

Pan of the talk

Objectives/

Pan of the talk

IRB/IECIS / ICF

Special Caution:

Age

Poor

Stu-dents

Mili-Emp-

Uneducated

Ment-ally ill

Caution: Vulnerable Groups

Mili-tary

Child-ren

Prison-ers

Tribes

Preg-nant

Institu-tionali

zed

Emp-loyee

Objectives/

Pan of the talk

Objectives/

Pan of the talk

IRB/IECIS / ICF

“Exempt” From Ethical Approval*“Exempt” From Ethical Approval*

Within the definition of research, the following are not considered to

be 'research' and would be exempt:

� Service evaluation

Within the definition of research, the following are not considered to

be 'research' and would be exempt:

� Service evaluation� Service evaluation

� Performance reviews

� Testing within normal education requirements

� Literary or artistic criticism

� Quality assurance/audit projects that do not involve access to or

collection of private or sensitive data

� Service evaluation

� Performance reviews

� Testing within normal education requirements

� Literary or artistic criticism

� Quality assurance/audit projects that do not involve access to or

collection of private or sensitive data

*Doesn’t not apply to research involving vulnerable participant, particularly children and young people, those with a learning disability or cognitive impairment or individuals in a dependent or unequal relationship.

Objectives/

Pan of the talk

Objectives/

Pan of the talk

IRB/IECIS / ICF

Research Impropriety: What is it?

Multitude of Terms

Research Impropriety: What is it?

Multitude of Terms

� Research or Scientific

� Impropriety

� Misconduct

� Misbehavior

� Research or Scientific

� Impropriety

� Misconduct

� Misbehavior� Misbehavior

� Noncompliance

� Fraud

� Sloppy science / research

� Junk science / research

� “Egregious abrogation of investigator responsibilities”

� “Scientists behaving badly”

� Misbehavior

� Noncompliance

� Fraud

� Sloppy science / research

� Junk science / research

� “Egregious abrogation of investigator responsibilities”

� “Scientists behaving badly”

Research ImproprietyResearch Impropriety

� Why does it occur?

� What is it?

� Why does it occur?

� What is it?� What is it?

� How should it be managed?

� Can it be prevented?

� Is there any good news?

� What is it?

� How should it be managed?

� Can it be prevented?

� Is there any good news?

Research Impropriety:

Why does it occur?


Why does it occur?

� Why wouldn’t it happen? It happens in all other

human activities.

� Pressure to publish.

� Why wouldn’t it happen? It happens in all other

human activities.

� Pressure to publish.� Pressure to publish.

� Inadequate training. Not taught good practice.

Indeed, sometimes taught the opposite.

� Does sloppy behavior spill over to fraud?

� You can get away with it. The system works on

trust.

� Pressure to publish.

� Inadequate training. Not taught good practice.

Indeed, sometimes taught the opposite.

� Does sloppy behavior spill over to fraud?

� You can get away with it. The system works on

trust.

Dr. Richard Smith Former Editor,

British Medical Journal

Top 10 Scientific Misbehaviors: Likely or

Very Likely to be Sanctionable - 1



1. Falsifying or ‘cooking’ research data 0.3%

2. Ignoring major aspects of human subject 0.3%2. Ignoring major aspects of human subject requirements

0.3%

3. Not properly disclosing involvement in firms whose products are based on one’s research

0.3%

4. Relationships with students, research subjects or clients that may be interpreted as questionable

1.4%

5. Using another’s ideas without permission or due credit

1.4%





6. Unauthorized use of confidential information in connection with one’s own research

1.7%

7. Failing to present data contradicting one’s own previous research

6.0%

own previous research

8. Circumventing minor aspects of human subject requirements

7.6%

9. Overlooking others’ flawed data or questionable interpretation of data

12.5%

10. Changing the design, methodology or results

of a study in response to pressure from a funding source

15.5%

Research Impropriety - Definition Research Impropriety - Definition

�“Research impropriety is any ethical lapse

or other impropriety involving or occurring

�“Research impropriety is any ethical lapse

or other impropriety involving or occurring or other impropriety involving or occurring

in connection with research other than

research misconduct…” as defined in the

Federal Policy on Research Misconduct

or other impropriety involving or occurring

in connection with research other than

research misconduct…” as defined in the

Federal Policy on Research Misconduct

VHA Handbook 1058.2 “Research Misconduct”

Research Misconduct

IMPROPRIETY

Research Misconduct

IMPROPRIETY

Research MisconductResearch Misconduct

�Research misconduct is defined as

fabrication, falsification, or plagiarism in

proposing, performing, or reviewing

�Research misconduct is defined as

fabrication, falsification, or plagiarism in

proposing, performing, or reviewing proposing, performing, or reviewing

research, or in reporting research results.

�Research misconduct does not include

honest error or differences of opinion.

proposing, performing, or reviewing

research, or in reporting research results.

�Research misconduct does not include

honest error or differences of opinion.

Federal Register Notice Vol. 65, No. 235, Dec. 6, 2000

Research Misconduct: DefinitionsResearch Misconduct: Definitions

Fabrication

� Making up data or results and recording or reporting them

Falsification

Fabrication

� Making up data or results and recording or reporting them

FalsificationFalsification

� Manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record

Plagiarism

� Appropriation of another person’s ideas, processes, results, or words without giving appropriate credit

Falsification

� Manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record

Plagiarism

� Appropriation of another person’s ideas, processes, results, or words without giving appropriate credit

“All Other” Research Impropriety:

Definitions

“All Other” Research Impropriety:

Definitions

�“Examples of research impropriety include,

but are not limited to, conflicts of interest,

�“Examples of research impropriety include,

but are not limited to, conflicts of interest, but are not limited to, conflicts of interest,

misallocation of funds, sexual harassment,

discrimination, and breaches of human

subjects protections and animal welfare

requirements.”

but are not limited to, conflicts of interest,

misallocation of funds, sexual harassment,

discrimination, and breaches of human

subjects protections and animal welfare

requirements.”


Can it be Prevented?


Can it be Prevented?

� Educate - Training

– GCP, HRP, HIPAA, Privacy

� Verify - Monitoring and Audits

� Educate - Training

– GCP, HRP, HIPAA, Privacy

� Verify - Monitoring and Audits� Verify - Monitoring and Audits

–Routine

–For-cause

� Provide a compliant environment

–Accreditation

–Exemplary Leadership

–Culture of Responsible Research

–Culture of Compliance

� Verify - Monitoring and Audits

–Routine

–For-cause

� Provide a compliant environment

–Accreditation

–Exemplary Leadership

–Culture of Responsible Research

–Culture of Compliance

Finding the BalanceFinding the Balance

Effective assurance of

“responsible conduct

of research”

Vs.

Suffocating oversight

and bureaucracy

of research”

Doing

it

Right

vs.

Not

Doing

it

THANK YOUTHANK YOUTHANK YOU

Dr Shariq R. Masoodi MD, DM, FACP, FRCPE

[email protected]@endocrinol

dr shariq rashid masoodi -...

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