1. Ethical Review Process
by the IRB
_________________________________
Presented By-MANISH KUMAR SHARMA
D.PHARMA,B.PHARMA, PGDCR
DEPARTMENT OF CLINICAL RESEARCH
SHARDA UNIVERSITY, GREATER NOIDA,UP

2. IRB Function
The purpose of an IRB is to
Review research and to Ensure
the rights and welfare of human
subjects involved in research
are adequately protected.

3. Why Do Human Research Subjects
Need Protection?
Trigger Events Ethical Milestones
The Nazi Experiments Nuremberg Code 1947
Tuskegee Syphilis Study National Commission for
the Protection of Human
Subjects of Biomedical &
Behavioral Research 1974
* Belmont Report 1978
* Common Rule 1991

4. The Basic Principles of the
Belmont Report
1. Respect for Persons
3. Beneficence
5. Justice

5. Regulatory Requirements for IRB
Approval
 Risks to subjects are minimized
 Risks are reasonable in relation to anticipated benefits – if any
 Selection of subjects is equitable
 Informed consent will be sought and appropriately documented
 When appropriate, the research plan makes adequate provision for
monitoring the data collected to ensure the safety of subjects

6. Regulatory Requirements for IRB
Approval
 When appropriate, there are adequate provisions to protect the
privacy of subjects and to maintain the confidentiality of data
 When some or all of the subjects are likely to be vulnerable to
coercion or undue influence, such as children, prisoners, pregnant
women, mentally disabled persons, or economically or educationally
disadvantaged persons, additional safeguards have been included to
protect the rights and welfare of these subjects.

7. IRB Review of Research
All research projects are categorized into one of three categories for
the IRB review process. Each category is different in the level of
scrutiny and submission procedures. The IRB is responsible for
making the final decision of which category a research project falls
under.
 Full
 Expedited
 Exempt
 Research Not Involving Human Subjects

8. Full Review
 One or more Committee member(s) are assigned to review the
complete protocol or amendment, consent form, Investigational
Drug/Device Brochure and any other protocol materials.
 These Primary & Secondary Reviewers summarize the protocol or
amendment to the Full Committee at a convened meeting and
answer questions during the discussion.
 All other committee members are provided with summary
information, for example the Protocol Cover Form and informed
consent document. This stresses the importance of the accuracy
and details provided in these documents, since the majority of voting
members only see these 2 documents!

9. Expedited Review
 Protocols, amendments, or continuing reviews that
meet specific federal criteria qualify for an expedited
review.
 The complete protocol, consent form, and any other
protocol materials receive review and approval by a
Committee Chair.
 Expedited does not mean “fast” it is a regulatory term
used for research that must meet specific criteria

10. Some Common
Expedited Review Categories
 Continuing Review when: the research is permanently
closed to the enrollment of new subjects; (ii) all subjects
have completed all research-related interventions; and (iii)
the research remains active only for long-term follow-up
of subjects; or
 (b) where no subjects have been enrolled and no
additional risks have been identified; where the remaining
research activities are limited to data analysis.

11. Some Common
Expedited Review Categories
 And when the IRB has determined and documented at a
convened meeting that the research involves no greater
than minimal risk and no additional risks have been
identified.

12. Exempt from IRB Review
 Committee review is not required for certain categories
of research activities that involve little or no risk to
human subjects.
 To determine if your research qualifies for exemption
from formal committee review, complete the “Protocol
Exemption Review and Determination Checklist.”
 Only the IRB can make the determination of
Exempt, this cannot be determined by researchers!

13. What about pilot studies?
 Whether or not a pilot study requires IRB approval
depends on the nature of the data collected in the pilot
 For example, we have a study of drug use among high
school students in Kenya
 If the pilot study involves testing the research instruments on high
school students, asking them questions about drug use – then this
DOES require IRB approval
 If the pilot involves asking students to give views on the the
questionnaire design/ content then this DOES NOT require IRB
approval

14. IRB Review and Determination of “Research
Not Involving Human Subjects”
 There is some research that involves coded private information or
specimens that do not involve human subjects.
 When conducting research using data or specimens, the level of
review by the IRB depends primarily on one factor: whether the
data or specimens are identifiable to the principal investigator or
key personnel.
 Determinations of whether research involving coded private
information or biological specimens is considered to be
“human subjects research” must be made by the IRB, not the
investigator.

15. The IRB submission packet must
include
The protocol and any amendments, informed consent,
and the investigator brochure. The Investigator’s
Undertaking; CVs (curriculum vitae) can verify the
investigators' qualifications. All advertising materials also
require approval. Payments to subjects require approval
and may be a source of contention between the investigator
and IRB.

16. Types of Review
 Initial
 Continuing Review
 Amendments
 Safety Information or Unanticipated Problems to
Subjects or Others
 Noncompliance

17. While Review the IRB checks…
• Risks are Minimized (Consistent with a sound research design and does
not unnecessarily expose subjects to risk)
• Risks are Reasonable in Relation to Benefits
• Selection of Subjects is Equitable
• Informed Consent will be Sought for Each Prospective Subject
• Informed Consent will Be Documented
• Research Plan Adequately Provides for Monitoring the Data Collected to
Ensure Safety of the Subjects
• Research Plan Adequately Protects the Privacy of Subjects and
Maintains Confidentiality
• When some or all of the subjects are likely to be vulnerable to coercion or
undue influence, additional safeguards need to be included in the protocol
to protect the rights and welfare of these subjects.

18. The IRB has the authority to:
oApprove
oRequire modifications prior to
approval
oDisapprove all research activities
including proposed changes in
oTable
previously approved human
subject research.

19. How the IRB System Works
 Primary and Secondary Reviewers
 Assignments made 1 week ahead of meeting
 Discussion by Full Committee
 Reviewers lead discussion
 Everyone contributes
 Committee Vote
 Approve
 Conditional Approval
 Deferral
 Disapprove

20. Determining an Action
 Approval – the criteria for approval are met.
 Conditional approval – IRB stipulates specific revisions requiring
simple concurrence by the investigator, then the IRB Chair or another
IRB member designated by the Chair subsequently approve the
revised research protocol on behalf of the IRB.
 Deferral - substantive clarifications or modifications required that are
directly relevant to the criteria for approval.
 Disapproval – major ethical or scientific issues – PI can respond to
the IRB or start over.

21. Review Strategy
 Review application
 Look for special issues such as kids, radiation, emergency use issues, new
drugs/devices, genetics, storing samples for future use
 Read protocol summary
 Look for site specific issues; can we logistically perform the study here?
 Read detailed protocol
 Look also at any study specific tools, letters, ads, extras

22. Review Strategy
 Prepare your comments
 Written and submitted are wonderful
 Emailed is even better
 Editing the consent form
 Edit right on the document
 Use legible handwriting
 Submit marked up document

23. Background and Specific Aims
 Should contain a convincing summary of previous
work and rationale for the study
 References should be included
 There should be clear aims and endpoints

24. Subject Selection and
Enrollment
 How are subjects identified?
 Ads, charts, RPDR, referrals, PI’s own clinic, support groups, public
records.
 How, when and by whom are subjects for
contacted about study?
 In person? Should be by someone who has reason to know confidential
medical information.
 Letters? Letters should be co-signed by the MD know to the patient-
subject.
 No cold calls

25. Subject Selection and Enrollment
 Inclusion/Exclusion Criteria
 Should be a concisive list
 Should include appropriate laboratory parameters
 Should include appropriate medical exclusions
 Should not/rarely exclude non English speakers
 Who obtains consent? Who gives consent?

26. Study Procedures
 Should include sufficient detail to ascertain what
subjects will actually experience while in study
 Time commitment.
 Setting or site where study procedures occur.
 Any “routine” agents to be used – such as sedation.
 Consent form with detail in lay terms.

27. Biostatistics
 A formal sample size is generally necessary.
 Why does the PI need this many subjects?
 Are there enough subjects to answer the study
question?
 How are the data to be analyzed?
 Just because the PI says it is a pilot study doesn’t
mean they don’t need statistics.

28. Risks and Discomforts
 Should be listed clearly, quantitatively and in order of
seriousness.
 Should include risks of withdrawal from current medications.
 Non medical risks? Social, legal, financial or psychological risks?
 Is loss of confidentiality a legitimate risk or concern?
 What about loss of privacy?
 Is there a complete list of adverse events in the drug or device
brochure?
 Any foreseeable but maybe still theoretical risks – for example
tumorigenesis?

29. Benefits
 Compensation is not a benefit
 If there are benefits to the individual subjects these should
be discussed first, then any potential benefits to future
society
 A common error we see is the “overstatement” of benefits.
Example of good benefit statement: There will be no direct
health benefits to you as a result of your participation in
this study.

30. Safety Monitoring
 How are the data to be monitored and by whom?
 All studies involving more than minimal risk require a data and
safety monitoring plan.
 Not all studies require a DSMB but if one is necessary who does it
involve? Is it independent? Should it be?
 Are there objective criteria for withdrawal of subjects when safety
is in question?
 Are there stopping rules?
 Is there a plan for reporting to the IRB?

31. Common Review Issues
 PI has failed to provide information about
reasonable clinical context or apparent withholding
of standard of care.
 Failure to minimize risk.
 Inadequate information about collaborating sites,
especially when international sites are involved.
 Poor preparation of materials – cutting and pasting
errors.
 Poor writing skills, no proof reading.

32. Lets do it together
CASE STUDIES

33. Scenario 1
Karen goes to work for the Population Council in
Nairobi, Kenya on a research project.
The project was conceived and designed by the PC,
the PI is a member of the PC staff, who is not IRB
Staff.
Karen will be designing research instruments,
implementing the survey and managing the
project. While in the field, Karen decides she
wants to bring the data back to the US to use for
her thesis.
.

34. Analysis
 Karen does NOT need IRB approval for her survey.
Responsibility for IRB approval lies with the PI, so the PC
should be seeking it’s own IRB approval. Karen will need to be
added to their existing IRB approval as study staff
 To use the data for her thesis, Karen needs to apply for IRB
approval for secondary data analysis & DE identify the data
before bringing it back to the US. She can only apply for
approval for secondary data analysis once the data collection is
complete, and cannot bring the data to the US until she has IRB
approval

35. Scenario 2
Jack 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

36. Analysis
 Jack does NOT need IRB approval. An
internal evaluation, in which the data/
results are not intended to be published or
generalized is not considered research, and
is thus exempt from IRB review

37. Scenario 3
Jasmine travels to West Bengal to study infant feeding practices
among refugees. Although she submits all her IRB documents
in advance, she does not hear from the IRB before her project
is due to start. Frustrated, Jasmine decides to go ahead and
collect the data, and to apply for retrospective approval once
she returns

38. Analysis
 Data collection cannot begin without IRB approval. The
instruments can be designed & sampling can begin – but
you cannot start collecting data from human subjects
without IRB approval. Jasmine cannot apply for
retrospective approval or for permission for secondary
data analysis. The data cannot be used for any research
purposes.