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
� Poor infrastructure
� No. of proposals variable 2-
60/ meeting
� No. of proposals variable 2-
60/ meeting
� Poor infrastructure
� Part time activity
� Often Head of Institute is
Chair
� Poor infrastructure
� 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]
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
Legal requirements of a formal
consent statement [2]
Legal requirements of a formal
consent statement [2]
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.
Legal requirements of a formal
consent statement [3]
Legal requirements of a formal
consent statement [3]
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.
Legal requirements of a formal
consent statement [4]
Legal requirements of a formal
consent statement [4]
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?
Research Impropriety:
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
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%
Top 10 Scientific Misbehaviors: Likely or
Very Likely to be Sanctionable - 2
Top 10 Scientific Misbehaviors: Likely or
Very Likely to be Sanctionable - 2
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.”
Research Impropriety:
Can it be Prevented?
Research Impropriety:
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