3. Physical, mental and social well-being
Application:
Assessment of risks and benefits
Minimising the risks
Maximising the potential benefits
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* this assessment includes evaluation
of the study design and the ability of the researcher
Principal 2- Beneficence
4. A. Medical Risks:
1. Therapeutics: (Tuskegee experiment)
2. Preventive: (Trials of polio vaccine)
3. Diagnostic:
◼ Irradiation:
- Teratogenic effect to the fetus.
- Carcinogenic effect.
◼ Samplings:
- Biopsies: tissues that contain genetic information about the
participant.
- Surgical hazards.
- Too risky procedures (under anesthesia)
Forms of Harm to Human Subjects in Research
5. The Forgotten Risks
B. Social Risks:
Stigma (e.g. research on HIV-AIDS, STDs).
Social stigma –Social risks can range from loss of reputation and
social standing, to placing the individual at-risk of political or social
reprisals.
C.Emotional Risks:
On families when their children were chosen for trial of new
vaccine; research in war.
D. Psychological Risks:
Questionnaires with sensitive questions to participants
in sensitive positions, as to ask poor people about there
nutrition and houses.
Psychological harm include: anxiety, sadness, regret and emotional
distress, among others. Specially in behavioral studies.
6. Risk to the Society
❖ Manipulating environmental factors (Pathogenic organisms and
toxic chemicals).
❖ Economic risk
Economic risks may exist if knowledge of one’s participation in
research, for example, could make it difficult for a research
participant to retain a job or to find a job, or if insurance
premiums increase or loss of insurance is a result of the
disclosure of research data.
❖ Legal risks:
Vulnerable groups, e.g., prisoners, children, pregnant women.
Legal risks include the exposure of activities of a research subject
“that could reasonably place the subjects at risk of criminal or
civil liability
7. Responsibilities of Researchers
Qualification and competent
Integrity and legality
Honesty and transparency
The Investigator bears
primary
responsibility for the
protection of human
subjects in the study
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8. Risks Benefit
To Whom Individual, investigators and the community
Duration Short term, i.e., only for the study period
Long term. i.e., extends beyond the study period
Forms Major potential risks to
participants
Major potential benefits to
participants
Risk/ Benefit Ratio
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9. Benefits and risks…
Research on vulnerable groups may be justified in special
circumstances:
the health advantages clearly outweigh the minimal risks
the problem to be studied is clearly relevant to the unique health
problem of the vulnerable group
every effort is made to maximize the right of the group to self
direction and protection
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10. Ethical Obligation:
fair sharing of burdens and benefits
of research
Application:
Equitable selection of research subjects;
Fairness in inclusion and exclusion criteria
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Principal 3- Justice
11. Equity vs. Equality in Human Subjects
Research
The meanings of “equity” and “equality” not the same.
“equitably ”means to deal fairly;
“ equally ”means to deal in exactly the same way.
12. How to Apply the 3 Principles?
Ethical principle Ethical rule
Respect for persons Obtain the informed consent of prospective
research subjects
Protect the confidentiality of private
information
Beneficence Qualifications of PI
Good research design
Risk -benefit analysis
Justice Subject selection procedures must be fair
Rules Derived
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13. Belmont Report
Common Rule
informed consent
Protect the confidentiality of
private information
Qualifications of PI
Good research design
Fair Subject selection
Common Rule
The “Common Rule” is the set of regulations which were developed to ensure compliance
with the principles of the Belmont Report, which regulate human research.
14. Institutional Review Board=IRB
❑ International guidelines(DOH) require that an independent
committee
❑ performs an Ethical and Scientific review of biomedical research.
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15. Scientific review and ethical review cannot be
separated.
Scientifically
unsound
research
Exposes
subjects to risk
Unethical
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16. What Makes Good Research?
Dr. Eman Mortada
• Problem selection
• SMART objectives
• Proper methodology
• Proper analysis
Good
Study
• Fair subject selection
• Favorable Risk-
Benefit Ratio
• Independent Review
• Informed Consent
Good
Ethics
17. Mission of the IRB
The IRB is charged with providing independent, objective
review of research involving humans subject in order to:
❑ protect the rights and welfare of human research subjects,
and
❑ ensure compliance of human subject research with
established ethical standards and local regulations and
policies.
Dr. Eman Mortada
18. 18
The Primary Concern of the IRB is
the Rights and Welfare of the
Research Participants
19. From IRB perspective, the project is either
Non-human subjects research
or
Human subjects research
Does The Project Require IRB Review?
The question: “ Is an activity research
involving human subjects?”
RESEARC
H
HUMAN
SUJECTS
IRB review
Dr. Eman Mortada
20. Key Questions
Ask in the Following Order
Answer questions in proper sequence when determining whether an activity is research,
human subjects research, exempt, or can be expedited
1. Is it research?
2. If so, does it involve human subjects?
3. If so, is it exempt?
4. If it is not exempt, is it eligible for expedited review OR full review?
22. 1st step
Research
Is the project RESEARCH that
needs to be reviewed by the IRB??????
Research
is a systematic investigation
designed to develop
generalizable knowledge.
http://www.hhs.gov/ohrp/humansubjects/guida
nce/45cfr46.html#46.102
Dr. Eman Mortada
23. Results dissemination
Conclusion can be drawn
Data analysis
Data will be collected
Methodological driven
Set hypothesis to be tested
The
Research
Process
Systematic Investigation
Generalizable knowledge. Dr. Eman Mortada
24. Research: A systematic investigation, including research development,
testing and evaluation, designed to develop or contribute to generalizable
knowledge
• Systematic Investigation typically involves a predetermined method for studying a
specific topic, answering a specific question, testing a specific hypothesis, or
developing theory.
• Develop or contribute to generalizable knowledge typically requires that results (or
conclusions) of the activity are intended to be extended beyond a single individual or
an internal program.
Research Defined - DHHS
25. Key Terms*
A systematic investigation is a project that is planned in advance and that uses data
collection and analysis to answer a question
that may include:
Collection of quantitative or qualitative data
Collection of data using surveys, testing or evaluation procedures, interviews, or
focus groups
Collection of data using experimental designs such as clinical trials
Observation of individual or group behavior
26. Key Terms*
Generalizable knowledge
means that the purpose or intent of the project is to test or to develop scientific theories
or hypotheses, or to draw conclusions that are intended to be applicable and/or shared
beyond the populations or situations being studied.
This may include one or more of the following:
➢ Presentation of the data at meetings, conferences, seminars, poster presentations, etc.
➢ Publications including journals, papers, dissertations, and master’s theses
27. If the project does not meet the
definition of research (i.e. is not a
systematic investigation or does
not contribute to generalizable
knowledge), as described above,
then the project does not require
IRB review and an IRB application
is not required.
Then it is a
research
If the answer is yes
Then it isn’t a
research
If the answer is No
28. Systematic
data
collection
To test
hypothesis
Improve a
program
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When the proposed project does not involve research ?
Designed solely for internal purposes, and
Is not designed to be generalized beyond (i.e. not designed to expand scientific
understanding or knowledge of base of a scholarly field of study)
Project is Not Research if:
Case reports • Designed to
contribute to generalizable
knowledge, but NOT a systematic
investigation
• Quality Assurance • Systematic
investigation, but NOT to
contribute to generalizable
knowledge
❑ Quality improvement : Program evaluation
❑ Program evaluation
❑ Health surveillance
❑ Case reports
30. Case Scenario 1
Nader goes to Vietnam to work for WHO.
They want him to conduct an evaluation of their immunization
program, to identify effective delivery strategies.
The results of his work will be used to improve WHO programs in
Vietnam. He does not intends to use the data he collects for his
thesis or any other publication
Dr. Eman Mortada
Is this QI or Research? And why
32. A group of affiliated hospitals implements a procedure known to reduce pharmacy
prescription error rates, and collects prescription information from medical charts to
assess adherence to the procedure and determine whether medication error rates
have decreased as expected.
Case Scenario 2
Is this QI or Research? And why
34. Does the project meet the HUMAN SUBJECTS
definition???
Human
subjects
1st step
2nd step
Research
A “ human subject ” is a
living individual from
whom an investigator
conducting research
obtains either
1)data through interaction
or intervention with the
person or
2)identifiable private
information eg medical
records
http://www.hhs.gov/ohrp/humansubjects/guida
nce/45cfr46.html#46.102
Dr. Eman Mortada
35. Questions to Determine if Research
Involves Human Subjects
Does the research involve obtaining
information about living individuals?
Does the research involve an intervention or
interaction with the individuals?
Is the information individually identifiable?
Is the information private?
36. Does the research involve obtaining information about
living individuals?
Living Individual-The Specimen (s)/data/information must be
collected from live subjects.
Cadavers, autopsy specimens or specimens/ information from subjects now
deceased is not human subjects.
Not all research that involves human beings is necessarily human subjects
research according to the federal regulations.
Information that is public and involves no interaction or intervention with
living individuals is not bound by human research protections.
37. • Manipulation of the participant
• Manipulation of the participant’s environment
Intervention includes
• 1- Direct communication with the participant e.g.:
interviewing or conducting a focus group)
• 2- Interpersonal contact with the participant e.g.
• surveying
Interaction includes
Research may involve
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Does the research involve an intervention
or interaction with the individuals?
38. Is the information individually identifiable?
Private information includes information about:
◼ Behavior in which an individual can reasonably expect that no observation or recording
is taking place, and
◼ Information provided for specific purposes which the individual can reasonably expect
will not be made public (e.g., medical record)
Private information must be individually identifiable to constitute research
involving human subjects (identity of the subject is or may readily be ascertained by the
investigator or associated with the information)
39. Individually-identifiable - Data = Identifiers
1. Names
2. ALL geographic subdivisions smaller than the state
3. All elements of dates smaller than a year and all ages over 89
4. Phone numbers
5. Fax numbers
6. E-mail addresses
7. Social Security numbers (SSN)
8. Medical record number
10. Any other account numbers
13. Device identifiers and serial numbers
14. WEB URL's
15. Internet IP address numbers
41. Can this activity considered research involving
human subjects ?
Dr. Eman Mortada
A- telephone survey of 2ry school teachers in the
Riyadh city to learn about television watching habits
ANSWER: Yes,
because it is a systematic investigation with interaction between the
investigator and the subjects
42. Dr. Eman Mortada
Can this activity considered research involving
human subjects ?
Review of patients’ emergency room records to determine the
relationship between age and type of traumatic injury
ANSWER: Yes,
because it is a systematic investigation in which the investigator is
obtaining identifiable private information (from the subjects’ medical
records)
43. Dr. Eman Mortada
Can this activity considered research involving
human subjects ?
An investigator receives autopsy specimens from a pathologist
at the same institution
ANSWER: NO Research involving only specimens and data from dead
individuals is not human subjects research
Investigator is neither interacting nor intervening with living individuals for
research
44. The project does not include any interaction or intervention with human subjects or include
any access to identifiable private information, then the project does not require IRB review.
If even one of the above categories are met (interaction, intervention, access to identifiable
private information), an IRB application is required.
Example of research ‘not human subject’:
➢ Study of private information about dead people (Cadavers, autopsy specimens)
➢ Study of publicly available information in which persons are not identifiable
➢ Data generated from medical records
➢ Analysis of anonymous biological samples previously collected (for examples blood
obtained from the Red Cross)
If the answer is, no ….
45. If the answer is, yes it is….
Research Involving Human Subjects”
Submit to IRB for final
determination
Generalizable
Knowledge
IRB
REVIEW
Human
Subjects
Dr. Eman Mortada
46. 1st step
2nd step
3rd step
4th step
5th step
Research
Human
subjects
Exempt
Expedited
Full review
What is the level of review?
Dr. Eman Mortada
All research projects are
categorized into 1of 3
categories for the IRB
review process.
47. The review path is determined by:
Level of risk to subjects associated with the project
The type of research being conducted (e.g., an educational
intervention, a survey, an observation, etc.)
The sensitivity of the research questions or complexity of the research
design
The involvement of vulnerable populations as research subjects
48. Risks in Behavioral and Social Research
Invasion of privacy
Breach of confidentiality
Embarrassment
Stigma
Psychological Trauma
49. ❑ No risk
❑ Minimal Risk (MR)
❑ Greater than Minimal Risk
The IRB categorizes the risk associated with
research into:
Increasing
level of
risk
Increasing
protection,
requirements
4- Full board
3- Expedited
2- Exempt
1- non
human
50. ❑ 1st degree review= Full
❑ 2nd degree review= Expedited
❑ 3rd degree review= Exempt
The IRB levels of review
Increasing
level of
risk
Increasing
protection,
requirements
4- Full board
3- Expedited
2- Exempt
1- non
human
All research projects are categorized into one of three categories for the
IRB review process.
51. The IRB levels of review
Increasing level of risk
Increasing protection, requirements
Greater than
minimal risk
Pain, death,
suffering ,
disability
Full
review
1st degree
review
Minimal risk
Risk
encountered in
your daily
life……
Expedited
review
2nd degree
review
No risk Without risk
Exempt
from
review
3rd degree
review
52. ❖Required for research involving greater than
minimal risk
All members participate in the discussion and comments
Full review
full review
Research
=
1ST
degree
review
59. Ice Cream Evoked Headaches (ICEH) Study:
Randomized Trial of Accelerated versus Cautious Ice Cream
Eating Regimen
Maya Kaczorowski, Janusz Kaczorowski
Group 1: Given 100 ml of ice
cream and were told to eat it in
>30 seconds
Group 2: Given 100 ml of ice
cream but were instructed to eat
it in <5 seconds
60. Experiment is without risk to the participant,
researcher, and the environment
Exempt from review
Exempt
from review
‘no risk’
activities 1 reviewer= excluded from further IRB review
63. 3: Research using existing data, if publicly available
or recorded without identifiers
•
Information recorded so subject cannot readily be identified
(directly or indirectly/linked); investigator does not contact
subjects and will not re-identify the subjects
64. 4: Taste and food quality evaluation and consumer
acceptance studies.
65. for research involving children under age 18
Sensitive topics are used and
results are not anonymous
Exception to Exemption
66. Implied Consent
When using an anonymous survey or questionnaire to collect data, you
may fulfill requirements by providing subjects with a cover page or letter
that explains the following items:
purposes of the research and expected duration of the subject's
participation
whom to contact for answers
anonymity of the results; the subject cannot be identified
participation is voluntary,
Dr. Eman Mortada
71. (a) from healthy, non-pregnant adults who weigh at
least 110 pounds. Amounts drawn may not exceed
550 ml in an 8 week period and collection may not
occur more frequently than 2 times per week; or
from other adults and children2, considering the
age, weight, and health of the subjects, the amount
drawn may not exceed the lesser of 50 ml or 3 ml
per kg in an 8 week period and collection may not
occur more frequently than 2 times per week.
2.) Collection of blood samples by finger stick, heel stick, ear
stick, or venipuncture as follows:
74. hair and nail clippings in a non disfiguring manner;
excreta and external secretions (including sweat);
Saliva collected either in an unstimulated fashion or stimulated by chewing gumbase
or wax or by applying a dilute citric solution to the tongue;
placenta removed at delivery;
amniotic fluid obtained at the time of rupture of the membrane prior to or during
labor;
mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth
washings;
sputum collected after saline mist nebulization.
e.g.
75. 4: Collection of data through noninvasive procedures routinely
used in clinical practice
Not involving
general anesthesia or
sedation
excluding procedures
involving x-rays.
76. 5: Research involving materials such as Data, Documents, that
have been collected, solely for non-research purposes, such as
diagnosis and ttt
77. e.g.:
MRI: magnetic resonance imaging;
ECG: electrocardiography, electroencephalography, thermography,
detection of naturally occurring radioactivity, electroretinography,
ultrasound, diagnostic infrared imaging, doppler blood flow, and
echocardiography;
Moderate exercise, muscular strength testing, body composition
assessment, and flexibility testing where appropriate given the age,
weight, and health of the individual.
78. 6: Collection of data via audio/visual recordings made for
research purposes
80. Case Scenario
An investigator obtains individually identifiable information on the
treatment outcomes of patients treated for arthritis with either Drug A or
Drug B by viewing patients’ existing individually identifiable medical
records at the clinics where the patients were treated.
The investigator records only patient age, sex, diagnosis, treatment, and
health status at the end of 6 months of treatment so that the investigator
cannot link the recorded information back to the patients.
Answer: Exempt
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Exempt or Expedited?
82. Case Scenario?
An investigator obtains individually identifiable information on the treatment
outcomes of patients treated for arthritis with either Drug A or Drug B by viewing
patients’ existing individually identifiable medical records at the clinics where the
patients were treated. The investigator records the patients’ treatment outcomes in a
coded manner that could permit the identification of the patients.
ANSWER: Expedited?
Dr. Eman Mortada
Exempt or Expedited?
84. Case Scenario
Dr. Amal, plans to survey researchers at her institution to assess satisfaction
with the IRB review process. Approximately 50 researchers will be
randomly selected to complete an online survey.
Dr. Amal and her colleagues at other sites believe there is a correlation
between satisfaction with the IRB and departmental support. Each site will
send surveys to 50 researchers. The surveys will be anonymous.
Exempt Review Dr. Amal plans to retain identifiers
on the surveys so that he can send
out a second survey to those
researchers who score extremely
high on the dissatisfaction scale
Expedited Review
Dr. Eman Mortada
85. 8th, 9th and 10th
Case scenario
Dr. Eman Mortada
86. Case Scenario
Dr. Richards has a freezer of blood samples that were
originally collected for a research study which ended several
years ago. Patient codes (which can be linked to the Medical
Record) remain on the samples. The consent form originally
signed by the subjects of Dr. Richards indicated whether or not
their stored blood could be used for future research.
Dr. Richards gives the research
the samples with the patient
code. The research immediately
removes the code upon receipt of
the samples.
Exempt Review
The researcher retains the
patient code just in case she
needs to contact the patient
for follow-up information
Expedited Review
RESEARCH
87. The IRB has the authority to:
o Approve
-Unconditioned approval
Conditioned approval, after
clarifications, modifications.
o Disapprove all research activities Study
does not meet criteria
Disapprove
Defer
Approve
o Defer till more information be available
Dr. Eman Mortada
88. ✓ Risks to subjects are minimized. *
✓ Reasonable risk/benefit relationship= Risks to subjects are
reasonable in relation to anticipated benefits.
✓ Equitable subject selection
✓ Informed consent will be appropriately documented.
✓ Confidentiality/privacy maintained
✓ Vulnerable populations protected
Core Requirements for Approval of Research
Dr. Eman Mortada
