1. Ethics in Research involving Human Subjects
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS
COMMITTEE (IRB/IEC)
Gayathri Devi R
Pharm D V year
January29,2015

2. Landmark Document
• The Nuremburg Code
Permissible Medical Experiments” Trials of War Criminals before
the Nuermberg Military Tribunals under Control Council Law No.
10, 1949
• Helsinki Declaration
World Medical Association General Assembly, Edinburgh,
Scotland, October 2000
• Belmont Report of 1979
Report of the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research, DHEW, April
1979
January29,2015

3. Helsinki Declaration
The World Medical Association (WMA) has
developed the Declaration of Helsinki as a
statement of ethical principles for medical
research involving human subjects, including
research on identifiable human material and data.
The first version was adopted in 1964 and has
been amended six times since, most recently at
the General Assembly in October 2008. The
current (2008) version is the only official one.
January29,2015

4. Other International Guidelines
• 1982 - International Ethical Guidelines for
Biomedical Research Involving Human Subjects
by World Health Organization (WHO) and Council
for International Organizations of Medical
Sciences (CIOMS)
• This 2002 text supersedes the 1993 Guidelines. It is the
third in the series of biomedical-research ethical
guidelines issued by CIOMS since 1982. Its core consists
of 21 guidelines with commentaries.
January29,2015

5. The FourPrinciplesof Ethics
1- Autonomy (Respect for the person)
2 - Beneficence (Do Good)
3 - Non-malfecience (Do No Harm)
4 - Justice
January29,2015

6. Institutional Review Board
(IRB)
• Also called, Ethical Review Board (ERB) is a
committee that has been formally designated to
approve, monitor, and review biomedical and
behavioral research involving humans with the
aim to protect the rights and welfare of the
research subjects.
November14,2013

7. Composition
collectively have the qualifications and experience
to review and evaluate the science, medical
aspects, and ethics of the proposed trial.
• At least five members.
• At least one member whose primary area of
interest is in a non scientific area.
• At least one member who is independent of the
institution/trial site.
January29,2015

8. • Only those IRB/IEC members who are independent of the
investigator and the sponsor of the trial should
vote/provide opinion on a trial-related matter.
• A list of IRB/IEC members and their qualifications should
be maintained.
• The members must have enough experience,
expertise, and diversity
• If the IRB works with studies that include vulnerable
populations, the IRB should have members who are
familiar with these groups.
January29,2015

9. The IRB/IEC
• should perform its functions according to written
operating procedures
• should maintain written records of its activities and
minutes of its meetings
• should comply with GCP and with the applicable
regulatory requirement(s).
• should make its decisions at announced meetings at
which at least a quorum, as stipulated in its written
operating procedures, is present.
• may invite non members with expertise in special areas
for assistance.
January29,2015

10. Need for IRB/IEC
• Risks to study participants are minimized
• Risks are reasonable in relation to anticipated
benefits
• Selection of study participants is equitable
• Informed consent is obtained and
appropriately documented for each participant
• Adequate provisions for monitoring data
collection to ensure safety of the study
participants
• Participant privacy and confidentiality is
protected
January29,2015

11. IRB Responsibilities
• Conducting initial review
• Conducting continuing review
• Notifying the investigators about IRB decisions
• Determining which studies require review more
often than annually
• Review and approval of changes in research
activities
• Determining which device studies pose
significant or non-significant risk
January29,2015

12. IRB Responsibilities (Cont.)
• Ensuring that changes in approved research are not
initiated without IRB review and approval except
where necessary to eliminate apparent immediate
hazards
• Ensuring prompt reporting to appropriate institutional
officials, regulatory agencies and funding sources of:
• unanticipated problems involving risks to subjects or others
• serious or continuing noncompliance with federal
regulations
• suspension or termination of IRB approval
January29,2015

13. IRB Authority
 The IRB reviews, and has the authority to approve,
require modification in, or disapprove all research
activities, including proposed changes in ongoing,
previously approved, human subject research.
 The IRB has the authority to suspend or terminate
the approval of ongoing, previously approved
research that is not being conducted in accordance
with the IRB's requirements or that has been
associated with unexpected, serious harm to
subjects.
January29,2015

14. Continuing Review
 The IRB conducts continuing review of ongoing,
approved research at intervals appropriate to the
degree of risk, but not less than once per year.
 For approved research, the IRB determines which
activities require continuing review more frequently
than every twelve months.
 Continuing IRB reviews are preceded by receipt of
appropriate progress reports from the investigator,
including available, study-wide findings.
 Continuing review must be substantive and
meaningful.
January29,2015

15. The IRB/IEC should obtain the following
documents
–Trial protocol(s)/amendment(s),
– Written informed consent form(s)
–Consent form updates that the investigator
proposes for use in the trial
–subject recruitment procedures (e.g.,
advertisements), written information to be
provided to subjects, Investigator's Brochure (IB),
January29,2015

16. – Available safety information,
– Information about payments and
compensation available to subjects, the
investigator's current curriculum vitae
and/or other documentation evidencing
qualifications,
– Any other documents that the IRB/IEC
may need to fulfill its responsibilities.
January29,2015

17. Procedures
The IRB/IEC should establish, document in writing, and
follow its procedures, which should include:
• Determining its composition(names and qualifications of
the members) and the authority under which it is
established.
• Scheduling, notifying its members of, and conducting its
meetings. Conducting initial and continuing review of
trials. Determining the frequency of continuing review,
as appropriate
January29,2015

18. • Providing, according to the applicable regulatory
requirements, expedited review and approval/favourable
opinion of minor change(s) in ongoing trials that have the
approval/favourable opinion of the IRB/IEC, Specifying
that no subject should be admitted to a trial before the
IRB/IEC issues its written approval/favourable opinion of
the trial.
• Specifying that no deviations from, or changes of, the
protocol should be initiated without prior written IRB/IEC
approval/favourable opinion of an appropriate
amendment, except when necessary to eliminate
immediate hazards to the subjects
January29,2015

19. Specifying…
Investigator should promptly report to the IRB/IEC:
• Deviations from, or changes of, the protocol to
eliminate immediate hazards to the trial subjects
• Changes increasing the risk to subjects and/or
affecting significantly the conduct of the trial
• All adverse drug reactions (ADRs) that are both
serious and unexpected.
• New information that may affect adversely the
safety of the subjects or the conduct of the trial.
January29,2015

20. Ensuring that…
The IRB/IEC promptly notify in writing the
investigator/institution concerning:
(a) Its trial-related decisions/opinions.
(b) The reasons for its decisions/opinions.
(c) Procedures for appeal of its decisions/opinions.
January29,2015

21. IRB Documentation
• All correspondence (e.g. e-mails, submission…)
between investigators /study staff and HRC
• IRB Initial approval
• IRB continuing review
• Amendments
• Violations/deviations (including sponsor-
approved protocol deviations)
January29,2015

22. IRB Minutes
Minutes of IRB meetings must include:
• attendance at the meetings
• actions taken by the IRB
• the vote on these actions including the number of
members voting for, against, and abstaining
• the basis for requiring changes in or disapproving
research
• documentation of specific findings required by the
regulations, and
• a written summary of the discussion of debated issues
and their resolution
January29,2015

23. IRB Records
 copies of all research proposals reviewed, scientific
evaluations, if any, that accompany the proposals, approved
sample consent documents, progress reports submitted by
investigators, and reports of injuries(if any) to subjects;
 minutes of IRB meetings;
 records of continuing review activities;
 copies of all correspondence between the IRB and the
investigators;
 a list of IRB members;
 written procedures for the IRB
 statements of significant new findings provided to
subjects
January29,2015

24. Universal Ethics Committee
c/o Aurous HealthCare R&D India Private Limited,
No. G2 RR Villa, 180/109 Rangarajapuram Main Road,
Kodambakkam, Chennai - 600024. India.
Phone: +91 9551050612; +91 9840909155
EMail id: sriraamvt@gmail.com, universalethicscommittee@gmail.com
Website: uec.auroushealthcare.com
About Us
Universal Ethics Committee, a Chennai based, OHRP registered (Office of
Human Rights Protection, United States - No. IORG0007234)
It is a unit of Aurous HealthCare Research and Development India Pvt. Ltd,
has commenced its operations since early 2012, Initiated by Dr. V.T. Sriraam,
MD (Pharmacology), a medical graduate, researcher and the founder of
Aurous HealthCare, who has over 10 years of experience in clinical research.
The committee is chaired by Dr. C. ARUN BABU MS(Gen.Sur.), MRCS (Edin.)
January29,2015

25. • Institutional Ethics Committee
IC& SR Building 2nd Floor,
IIT Madras, Chennai 600 036
Phone: +91 (44) 2257 4929
EMail: iec@iitm.ac.in
• Dr. Anju Chadha
Member Secretary, IEC
Professor, Laboratory of Bioorganic Chemistry
Department of Biotechnology and National Center for
Catalysis Research
IIT Madras, Chennai 600 036
Phone: +91 (44) 2257 4106; Fax 4102
January29,2015

26. Helpful Websites
• FDA - http:// www.fda.gov
• NIH - http:// www.nih.gov
• OHRP- http://ohrp.osophs.dhhs.gov
• FDA IRB Guidance document - http://
www.fda.gov/oc/oha/IRB/toc.html
• Code of Federal Regulations - http://
www.access.gpo.gov/nara/cfr/cfr-table-
search.html
January29,2015

27. The Relationship B/w the
Investigator and the IRB
The IRB
More supporting
documents needed!!!
App/disapp/app with
changes
Oh joy!
The P.I.
January29,2015

28. Then….
Have a nice trip!
See you next time!!
Finally!The IRB
The P.I.
January29,2015

29. Principal Investigator:
FDA Regulations
• An individual who actually conducts a clinical
investigation, i.e.,
under whose immediate direction the
test article is administered or dispensed to or used
involving, a subject, or,
in the event of an investigation
conducted by a team of individuals, is the
responsible leader of that team.
January29,2015

30. INVESTIGATOR
Investigator's Qualifications and Agreements
- The investigator(s) should be qualified by
education, training, and experience to assume
responsibility for the proper conduct of the trial,
should meet all the qualifications specified by
the applicable regulatory requirement, and
should provide evidence of such qualifications
through up-to-date curriculum vitae and/or other
relevant documentation requested by the sponsor,
the IRB/IEC, and/or the regulatory authority(is).
January29,2015

31. Investigators’ Responsibilities
• Regulatory Documentation
• Medical care of subjects
• IRB Correspondence
• Informed Consent Process
• Recruitment Procedures
• Subject Selection Criteria
• SAE Reporting
• Drug/Device Accountability
• CRF/Source Documentation
• Record Keeping
• Allocation of Responsibilities
January29,2015

32. Medical Care of Trial Subjects:
• A qualified physician (or dentist, when appropriate),
who is an investigator or a sub-investigator for the
trial, should be responsible for all trial-related
medical (or dental) decisions.
• -During and following a subject's participation in a
trial, the investigator/institution should ensure that
adequate medical care is provided to a subject for
any adverse events, including clinically significant
laboratory values, related to the trial.
• The investigator/institution should inform a subject
when medical care is needed for intercurrent
illness(es) of which the investigator becomes aware.
January29,2015

33. Compliance with protocol:
• The investigator should conduct the trial in
compliance with the protocol agreed to by the
sponsor and, if required, by the regulatory
authorities and which was given
approval/favourable opinion by the IRB/IEC.
• The investigator/institution and the sponsor
should sign the protocol, to confirm
agreement.
• Investigator, or person designated by the
investigator, should document and explain any
deviation from the approved protocol.
January29,2015

34. Drug Dispensing and CRF
Drug/Device Dispensing
Accountability:
• Dispensing log
• Shipping/receiving
CRF/SD:
• Consistency
• Dated signature
/initials
• Cross-outs
January29,2015

35. Informed Consent of Trial
Subjects:
• In obtaining and documenting informed consent, the
investigator should comply with the applicable
regulatory requirement(s), and should adhere to GCP
and to the ethical principles that have their origin in
the Declaration of Helsinki.
• Prior to the beginning of the trial, the investigator
should have the IRB/IEC's written
approval/favourable opinion of the written informed
consen form and any other written information to be
provided to subjects.
January29,2015

36. • The written informed consent form and any other
written information to be provided to subjects
should be revised whenever important new
information becomes available that may be relevant
to the subject’s consent.
• The subject or the subject’s legally acceptable
representative should be informed in a timely
manner if new information becomes available that
may be relevant to the subject’s willingness to
continue participation in the trial. The
communication of this information should be
documented.
January29,2015

37. Contd…
• None of the oral and written information concerning the
trial, including the written informed consent form,
should contain any language that causes the subject or
the subject's legally acceptable representative to waive
or to appear to waive any legal rights.
• The language used in the oral and written information
about the trial, including the written informed consent
form, should be as non-technical as practical and should
be understandable to the subject or the subject's legally
acceptable representative and the impartial witness,
where applicable.
January29,2015

38. Contd…
• Before informed consent may be obtained, the
investigator, or a person designated by the
investigator, should provide the subject or the
subject's legally acceptable representative ample
time and opportunity to inquire about details of
the trial and to decide whether or not to
participate in the trial. All questions about the
trial should be answered to the satisfaction of
the subject or the subject's legally acceptable
representative
January29,2015

39. Both the informed consent discussion and the written
informed consent form and any other written
information to be provided to subjects should include
explanations of the following:
• That the trial involves research.
• The purpose of the trial, trial treatment(s) and the
probability for random assignment to each
treatment.
• The trial procedures to be followed, including all
invasive procedures.
• The subject's responsibilities.
January29,2015

40. • The reasonably foreseeable risks or inconveniences
to the subject and, when applicable, to an embryo,
fetus, or nursing infant.
• The alternative procedure(s) or course(s) of
treatment that may be available to the subject, and
their important potential benefits and risks.
• The compensation and/or treatment available to the
subject in the event of trial-related injury.
• The anticipated expenses, if any, to the subject for
participating in the trial.
January29,2015

41. • That the subject's participation in the trial is
voluntary and that the subject may refuse to
participate or withdraw from the trial, at any time,
without penalty or loss of benefits to which the
subject is otherwise entitled.
• That the monitor(s), the auditor(s), the IRB/IEC, and
the regulatory authority(ies) will be granted direct
access to the subject's original medical records for
verification of clinical trial procedures and/or data,
without violating the confidentiality of the subject, to
the extent permitted by the applicable laws and
regulations.
January29,2015

42. • That records identifying the subject will be kept
confidential and, to the extent permitted by the
applicable laws and/or regulations, will not be
made publicly available. If the results of the trial
are published, the subject’s identity will remain
confidential.
• That the subject or the subject's legally
acceptable representative will be informed in a
timely manner if information becomes available
that may be relevant to the subject's willingness
to continue participation in the trial.
January29,2015

43. • The person(s) to contact for further information
regarding the trial and the rights of trial subjects, and
whom to contact in the event of trial-related injury.
• The foreseeable circumstances and/or reasons under
which the subject's participation in the trial may be
terminated.
• The expected duration of the subject's participation
in the trial.
• The approximate number of subjects involved in the
trial.
January29,2015

44. Safety reporting
All serious adverse events (SAEs) should be reported
immediately to the sponsor except for those SAEs that the
protocol or other document (e.g., Investigator's Brochure)
identifies as not needing immediate reporting.
• The immediate reports should be followed promptly by
detailed, written reports. The immediate and follow-up
reports should identify subjects by unique code numbers
assigned to the trial subjects .
• The investigator should also comply with the applicable
regulatory requirement(s) related to the reporting of
unexpected serious adverse drug reactions to the
regulatory authority(ies) and the IRB/IEC.
January29,2015

45. • Adverse events and/or laboratory abnormalities
identified in the protocol as critical to safety
evaluations should be reported to the sponsor
according to the reporting requirements and within
the time periods specified by the sponsor in the
protocol.
• For reported deaths, the investigator should supply
the sponsor and the IRB/IEC with any additional
requested information (e.g., autopsy reports and
terminal medical reports).
January29,2015

46. Progress Reports
• The investigator should submit written
summaries of the trial status to the IRB/IEC
annually, or more frequently, if requested by the
IRB/IEC.
• The investigator should promptly provide written
reports to the sponsor, the IRB/IEC and, where
applicable, the institution on any changes
significantly affecting the conduct of the trial,
and/or increasing the risk to subjects.
January29,2015

47. Records and reports
1. Source Documentation
2. Lab Documentation
3. Investigator Brochure
4. NIH Progress Report/DSMB
5. Curriculum Vitae (CVs)
6. Study Logs
7. Eligibility Criteria Checklist
8. Consent Form Issues
9. Protocol deviations, violations
10. Record Keeping
January29,2015

48. Records and reports
• The investigator should ensure the accuracy,
completeness, legibility, and timeliness of the data
reported to the sponsor in the CRFs and in all
required reports.
• Data reported on the CRF, that are derived from
source documents, should be consistent with the
source documents or the discrepancies should be
explained.
January29,2015

49. • Any change or correction to a CRF should be dated,
initialed, and explained (if necessary) and should not
obscure the original entry (i.e. an audit trail should
be maintained); this applies to both written and
electronic changes or corrections .
• Sponsors should provide guidance to investigators
and/or the investigators' designated representatives
on making such corrections. Sponsors should have
written procedures to assure that changes or
corrections in CRFs made by sponsor's designated
representatives are documented, are necessary, and
are endorsed by the investigator. The investigator
should retain records of the changes and corrections.
January29,2015

50. Premature Termination or
Suspension of a Trial
• If the trial is prematurely terminated or
suspended for any reason, the
investigator/institution should promptly inform
the trial subjects, should assure appropriate
therapy and follow-up for the subjects, and,
where required by the applicable regulatory
requirement(s), should inform the regulatory
authority(ies).
January29,2015

51. Contd..
• If the investigator terminates or suspends a trial
without prior agreement of the sponsor, the
investigator should inform the institution where
applicable, and the investigator/institution
should promptly inform the sponsor and the
IRB/IEC, and should provide the sponsor and the
IRB/IEC a detailed written explanation of the
termination or suspension.
January29,2015

52. Contd..
• If the IRB/IEC terminates or suspends its
approval/favourable opinion of a trial , the
investigator should inform the institution where
applicable and the investigator/institution
should promptly notify the sponsor and provide
the e sponsor with a detailed written
explanation of the termination or suspension
January29,2015

53. Helpful Websites (Cont.)
• OHRP Compliance Oversight
• http://ohrp.osophs.dhhs.gov/compovr.htm
• OHRP Compliance Findings & Guidance
• http://ohrp.osophs.dhhs.gov/references/findings.pdf
• OHRP Education Materials
• http://ohrp.osophs.dhhs.gov/educmat.htm
• FDA Warning Letters
• www.fda.gov/foi/warning.htm
• ICH HARMONISED TRIPARTITE GUIDELINE ; GUIDELINE FOR GOOD
CLINICAL PRACTICE E6(R1)
Current Step 4 version dated 10 June 1996
January29,2015

54. Helpful Websites (Cont.)
• Registration of Ethics Committees to become mandatory for
clinical trials; Ramesh Shankar, Mumbai, Thursday, October 13,
2011, 08:00 Hrs [IST]
• FDA Information Sheets
• http://www.fda.gov/oc/oha/irb/toc3.html#contrevie
w
• FDA MedWatch (AE Reporting)
• http://www.fda.gov/medwatch/report/desk/tpcfinal.htm#toc
• PRIM&R
• http://www.primr.org/
• Bioethics Resources
• http://www.nih.gov/sigs/bioethics/
January29,2015

55. Thanks for your endurance!!!!
January29,2015