HARTFORD HOSPITAL HRPP POLICIES AND PROCEDURES CONTENTS
Page
I.
INTRODUCTION ….………………………………………….………………..…..
1
II.
SCOPE ………………………………………………………………………………..
1
III.
PURPOSE ……………………………………………………………….……………
2
IV. INSTITUTIONAL REVIEW BOARD ………………………………………………
2
A. Institutional Relationship …………………………………………………………
2
B. Composition ………………………………………………………………………
3
C. Membership Appointment ……………………………………………………….
3
D. Responsibilities …………………………………………………………….……… 4
V.
OFFICE OF RESEARCH ADMINISTRATION ……………………………………..
4
Responsibilities ………………………………………………………………………
4
VI. RESEARCH STAFF ………………………………………………………………….
5
Responsibilities ……………………………………………………………………….
5
VII. RESEARCH TRAINING AND EDUCATIONAL PROGRAM …………..………….. 6
VIII. INFORMED CONSENT OF HUMAN SUBJECTS ………………………………..… 7
A. General Requirements of Informed Consent ………………………………………
7
B. Exception from General Requirements (21CFR50.23) ……………………………
7
C. Exception from Informed Consent Requirements for Emergency Research (21CFR50.24) 8
D. Elements of Informed Consent …………………………………………………..
10
E. Documentation of Informed Consent ……………………………………………
12
F. Certificates of Confidentiality …………………………………………………...
14
G. Advertisement for Research Subjects ……………………………………………
14
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Page
IX. PROCEDURES ………………………………………………………………………15
A. Research Application Process ……………………………………………………
15
B. Determination of Extent of IRB Oversight ………………………………………
15
C. Expedited Review Procedure …………………………………………………….
17
D. Full Committee Review Procedure ………………………………………………
19
E. Distribution of Information for Review ………………………………………….
19
F. Committee Meetings ……………………………………………………………..
20
G. Criteria for IRB Approval of Research …………………………………………..
21
H. Additional Considerations for Approval of Research Involving Children ………. 22
I. Additional Considerations for Approval of Research Involving Pregnant Women,
Fetuses or Neonates or Fetal Material ……………………………………………
24
J. Additional Considerations for Approval of Research Involving Prisoners……….. 26
K. Requirement for Investigational New Drug (IND) Application or Investigational
Device Exemption (IDE)…………………………………………………………... 28
L. Significant Risk and Non-Significant Risk Device Studies ……………………..
28
M. Committee Decisions …………………………………………………………….
30
N. Investigator Notification Process ………………………………………………… 30
O. Revision Review Procedure ……………………………………………………… 30
P. Adverse Event Reports ………………………………………………………….
31
Q. Emergency Use Requests ……………………………………………………….
32
R. Progress Reports …………………………………………………………………
32
S. Compliance Audits ………………………………………………………………
33
T. Approval Withdrawal ……………………………………………………………
35
U. Reporting Responsibilities ………………………………………………………
35
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Page
V. Appeal Process ………………………………………………………………….
35
W. Communications ………………………………………………………….……..
36
X. IRB Records ……………………………………………………………………… 36
Appendices
Cooperative Agreement, HH-CCMC …………………………………………….………… A
Cooperative Agreement, HH-UCHC ………………………………………………..……… B
Cooperative Agreement, HH-UConn ………………………………………………..……… C
Cooperative Agreement, HH-Windham ……………………………………………..……… D
Organizational Chart …………………………………………………………………..……. E
Reference Materials ……………………………………………………………………..….. F
SR/NSR Devices ………………………………………………………………………….…. G
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HARTFORD HOSPITAL
HUMAN RESEARCH PROTECTIONS PROGRAM
POLICIES AND PROCEDURES
I. INTRODUCTION
The mission of Hartford Hospital (HH) is to promote, restore and maintain the health of all the
people we serve. This is to be accomplished through excellence in patient care, education, and
research. Consideration for the safety and welfare of every patient or healthy volunteer who
agrees to participate in a research project is the highest concern of the Research Program, and it
was for the purpose of protecting these subjects that the Human Research Protections Program
(HRPP) was established, including an Institutional Review Board (IRB) duly constituted in
accordance with applicable federal regulations.
II. SCOPE
The Institutional Review Board will evaluate and approve:
A. All research involving patients and volunteer subjects at Hartford Hospital, including, but
not limited to, that conducted, supported, or otherwise subject to regulation by any federal
department or agency (exceptions: see attached Cooperative Agreements between Hartford
Hospital and the Connecticut Children's Medical Center, Hartford Hospital and the
University of Connecticut Health Center, and Hartford Hospital and Windham Hospital).
B. The use of all investigational drugs/devices and procedures in patients and volunteers at
Hartford Hospital (exceptions: see attached Cooperative Agreements between Hartford
Hospital and the Connecticut Children's Medical Center, Hartford Hospital and the
University of Connecticut Health Center, and Hartford Hospital and Windham Hospital).
C. All humanitarian use device and emergency (compassionate) use requests for Hartford
Hospital.
Research is defined by federal regulations as "a systematic investigation, including research
development, testing and evaluation, designed to develop or contribute to generalizable
knowledge" [45 CFR 46.102(d)].
Human subjects are defined by the regulations as "living individual(s) about whom an
investigator (whether professional or student) conducting research obtains (1) data through
intervention or interaction with the individual, or (2) identifiable private information" [45 CFR
46.102(f)]. In addition, HIPAA (Health Insurance Portability and Accountability Act)
regulations apply to data of deceased individuals used for research.
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III. PURPOSE
The purpose of the Hartford Hospital HRPP is to ensure subject safety in all investigations
covered under its scope of activities (see above). The HRPP and IRB will conduct all activities
in accordance with applicable Department of Health and Human Services (DHHS) and Food and
Drug Administration (FDA) regulations, state and local laws, and Hospital policies, as well as
the principles set forth in the Belmont Report. The HRPP works collaboratively with
investigators to achieve this purpose, and may sponsor educational programs to keep
investigators and their staff apprised of current issues and to enhance the performance of quality
research.
IV. INSTITUTIONAL REVIEW BOARD
A. Institutional Relationship
The IRB is a standing joint committee of Hartford Hospital (includes both medical staff members
and non-medical members), and is established under the auspices of the Medical Staff Council.
The IRB is indemnified by the hospital and is covered under the hospital’s liability insurance.
The IRB is supported by administrative staff in the HRPP, who report to the Director of the
HRPP. The Director and the IRB report to the Vice President for Research, who is also the
signatory official. The Vice President reports to the Vice President of Academic Affairs, who in
turn reports to the President/CEO (see Organizational Chart, attached).
To ensure the most favorable research environment for all concerned, the IRB interacts with
other pertinent hospital committees and departments, such as the Research Committee, Radiation
Safety Committee, Health Information Management, Pharmacy, and Biomedical Engineering.
Clinical departmental endorsement is required for each protocol submitted. As well as IRB
approval, all projects involving humans must have approval of the Research Committee. No
project can be instituted at the hospital without approval of this committee; however, the
Research Committee will not approve protocols involving humans that are not approved by
the IRB.
Research Committee members are required to provide a current Financial Disclosure Form (FDF)
as outlined in the Research Corporate Compliance Manual.
The IRB has a standing reservation for regular scheduled meetings for a room with space
sufficient to comfortably accommodate the full committee. Support staff members have offices
in the ORA, where all records are kept and office equipment (computers, copier, fax machine) is
used to produce meeting materials and correspondence.
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B. Composition
The composition of the committee will be consistent with federal and state requirements; i.e. at
least 5 members with varying backgrounds, and including representatives from both sexes. At
least one member's primary background will be in a scientific area, and at least one member's
primary background will be in nonscientific areas. In addition, at least one member will not be
otherwise affiliated with the institution or part of the immediate family of a person affiliated with
the institution. The IRB shall be sufficiently qualified through the experience and expertise of its
members and the diversity of its members, including consideration of race, gender, cultural
backgrounds, and sensitivity to such issues as community attitudes, to promote respect for its
advice and counsel in safeguarding the rights and welfare of human subjects. In addition to
possessing the professional competence necessary to review the specific research activities, the
IRB shall be able to ascertain the acceptability of proposed research in terms of institutional
commitments and regulations, applicable law, and standards of professional conduct and
practice. The IRB shall therefore include persons knowledgeable in these areas.
If at any time the expertise of the committee is not sufficient for review of a specific research
activity, one or more consultants may be engaged for this purpose. Such consultants may be
engaged if, at the time of assignment of a review group to a project, it is determined by Research
Administration that the field of study is not represented on the IRB, or if additional expertise may
be needed for other reasons, such as involvement in the project of the committee’s one expert, or
inclusion of vulnerable populations needing additional representation. Consultants will be
selected by the chair or his designee, and may be permanently appointed to the committee as full
members if it is anticipated that their expertise may be needed on a more frequent basis.
Consultants will be required to attend the meeting(s) at which the pertinent research activity is
discussed, both for initial and continuing review (as long as the activity continues to require full
review), or to submit a written assessment if continuing review may be expedited. They will
provide expert input as required in addition to the review of the assigned group, but the
consultants may not vote, nor will they be counted toward a quorum.
C. Membership Appointment
The committee chairman, upon recommendation by the Vice President for Research, will be
appointed by the Executive Committee of the Medical Staff Council of Hartford Hospital. The
chairman must be a physician. All other physician members are to be appointed by the Executive
Committee of the Medical Staff Council, upon recommendation by the IRB chairman. This
membership is reviewed annually. All non-physician members are to be appointed by the
chairman. The chairman, upon recommendation from primary members, will appoint alternate
members (discussed under item F of the Procedures section). Alternate members will be listed
on the IRB roster along with primary members. The roster will identify the primary member(s)
for whom each alternate may substitute.
No investigator shall have input into selection of committee members, except that member
investigators may recommend their own alternates. If the chairman is an active investigator
while holding this position, he shall not appoint or make a recommendation for appointment of
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any member that would give undue advantage to consideration of his research. Nor should he
knowingly refrain from appointing an otherwise qualified person based on potential conflict with
his own research.
The chairman or members may be removed from the committee for a justified reason; e.g., a
conflict that may affect the proper functioning of the committee, or failure to attend a minimum
of 50% of the scheduled meetings within a twelve month period. There is no limit to the length
of service of the chairman or the members. The chairman and members are not compensated for
their time.
D. Responsibilities
1. The chairman will:
a. Preside over all convened meetings or designate an acting chairman in his absence.
b. Make recommendations for appointment of physician members, and appoint nonphysician members and alternates.
c. Review or designate another experienced member to review items meeting the criteria
for expedited review, adverse event reports, emergency use requests, and reports of
injuries, unanticipated problems, or serious or continuing non-compliance.
d. Sign correspondence.
e. Complete the Hartford Hospital Research Training course and the designated modules
of the training course of the Office for Human Research Protections (OHRP).
f. Provide a current Financial Disclosure form.
2. The members will:
a. Attend a minimum of 50% of scheduled meetings in a 12-month period.
b. Review in depth all items assigned to their review group and be prepared to present
them to the committee, and be sufficiently familiar with other items in order to vote
on them.
c. Assist with review of items meeting the criteria for expedited review and other items
as requested by the chairman.
d. (Physicians only) Review emergency use requests as requested by the chairman or in
his absence.
e. Complete the Hartford Hospital Research Training course.
f. Provide a current Financial Disclosure form.
V. OFFICE OF RESEARCH ADMINISTRATION
Responsibilities
1. The Vice President for Research will:
a. Act as the Signatory Official for the institution as designated in the Federalwide
Assurance of Protection for Human Subjects (FWA).
b. Complete the Hartford Hospital Research Training course and the designated modules
of the training course of OHRP.
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c.
Provide a current Financial Disclosure form.
2. The Director of the HRPP will:
a. Establish and implement the HRPP and policies
b. Develop an annual budget for the HRPP.
c. Review and evaluate reports and results of HRPP performance measurement and
quality improvement activities
d. Implement needed improvements and follow-up on actions, as appropriate
e. Monitor changes in applicable regulations, policies and guidelines that relate to
human research protection
f. Complete the Hartford Hospital Research Training course.
g. Provide a current Financial Disclosure form.
3. The administrative support staff will:
a. Process new proposals, ensuring that the application provided is complete.
b. Determine the extent of IRB oversight required, and forward items meeting the
criteria for expedited review to the chairman or his designee.
c. Schedule meetings.
d. Prepare and distribute agendas, and arrange for attendance of consultants, if
necessary.
e. Attend meetings and take minutes.
f. Prepare correspondence.
g. Maintain a schedule of continuing review due dates, and send requests for reports at
intervals determined by the committee to be appropriate for each project.
h. Maintain records, including minutes, protocols, membership roster, certificates of
training and financial disclosures, educational materials, and policies.
i. Update policies as necessary.
j. Assist investigators with preparation of applications and consent forms as requested.
k. Complete the Hartford Hospital Research Training course, and the IRB Administrator
will also complete the designated modules of the training course of the Office for
Human Research Protections (OHRP).
VI. RESEARCH STAFF
Responsibilities
1. Principal investigators will be expected to:
a. Be appropriately credentialed for the research undertaken, as indicated in a current
curriculum vitae submitted to or on file in the ORA
b. Complete all training requirements as discussed below
c. Provide a current Financial Disclosure Form
d. Be responsible for the scientific conduct of the projects and the research staff involved
in the projects they direct, including licensing/credentialing of all staff appropriate to
their responsibilities
e. When appropriate, ensure that one of the study investigators is a qualified clinician
responsible for any study-related healthcare decisions
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f. When appropriate, have provisions in place for referral of subjects for any needed
health care, both during a study, and for follow-up after a study
g. Submit all proposed research involving human participants, their tissue or data to the
ORA for review
h. Obtain informed consent in accordance with section VIII
i. Submit for review all proposed changes to protocols and consents (including changes
to improve subject protection), and reports of adverse events, unanticipated events
involving risks to subjects, and deviations from the approved protocol or applicable
policies or regulations
j. Comply with all requests of the ORA for timely reports (continuation, final), and any
additional information needed in the course of a study to conduct oversight activities
2. Research Coordinators will be expected to:
a. Complete all research training requirements as discussed below
b. Provide a current Financial Disclosure Form
c. Complete any additional training/licensing requirements to perform study-related
duties, such as certification at the annual Hospital Nursing Validation to perform CPR
if working in the Clinical Research Center.
VII. RESEARCH TRAINING AND EDUCATIONAL PROGRAM
All individuals involved in the administration, conduct, or review of research with human
subjects must complete the Hartford Hospital Research Training Course or an equivalent course,
such as one from the National Cancer Institute, and are encouraged to attend seminars and
meetings that focus on human subject research activities and current topics.
A. In addition, the Institutional Official, IRB Chairman, and IRB Administrator must
complete the designated module(s) of the OHRP training course as a requirement for
filing an FWA.
B. When they are appointed to the committee, new IRB members are expected to meet with
the chairman to review policies and duties. They also receive a copy of the HRPP
Policies and Procedures, the 45 CFR 46 regulations, and the Belmont Report. The
“Human Research Report” is distributed monthly as an item for discussion on the IRB
agenda, along with any other items of current interest.
C. Researchers involved in human subject research also receive a copy of the HRPP Policies
and Procedures and the Belmont Report when their first project is approved by the IRB.
Copies of past issues of the “Human Research Report” and all materials presented as educational
items on the agenda, as well as other periodic publications regarding human subject research are
maintained in the ORA for reference, along with pertinent regulatory and guidance documents.
A list of available reference materials is attached.
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VIII. INFORMED CONSENT OF HUMAN SUBJECTS
A. General Requirements of Informed Consent
Except as provided below (21 CFR Part 50.23 or 50.24), no investigator may involve a human
being as a subject in research unless the investigator has obtained legally effective informed
consent of the subject or the subject’s legally authorized representative. An investigator will
seek such consent only under circumstances that provide the prospective subject or the
representative sufficient opportunity to consider whether or not to participate and that minimize
the possibility of coercion or undue influence. A research subject should not be enrolled in more
than one clinical trial at a time. Investigators may generally avoid this situation by not
participating in studies simultaneously competing for the same subject population. Acceptance
of incentive payments by the hospital, investigators, or their staff, physicians or other health care
providers to encourage enrollment of patients or volunteers presents a potential conflict of
interest, and is not allowed for any Hartford Hospital sanctioned research projects.
The person presenting the study information and obtaining the prospective participant’s consent
must be on the Hartford Hospital medical staff or have HH privileges, and must have completed
the HH research training, or be a Hartford Hospital employee who has completed the training.
The information that is given to the subject or the representative should be in language
understandable to the subject or the representative. Therefore, if it is anticipated that a sizeable
percentage of the study population will speak a language other than English, the consent
document should be translated into that language. No informed consent, whether oral or written,
may include any exculpatory language through which the subject or representative is made to
waive or appear to waive any of the subject’s legal rights, or release or appear to release the
investigator, sponsor, institution or its agents from liability for negligence.
The State of Connecticut statutes permit the following people to consent as representatives for
patients incapable of providing consent:
1. a court-appointed conservator
2. an agent with documented power of attorney
3. a parent of a minor with provisions for exception for treatment of alcohol or drug
dependence, mental health problems, HIV or AIDS, or venereal disease.
Spouses and next of kin are not considered legal representatives unless so designated, except that
next of kin may consent for mentally ill patients under certain critical circumstances (State
Statute 17a-543).
The content of consent forms must be consistent with any applicable state laws regarding
research.
B. Exception from General Requirements (21CFR 50.23)
1. The obtaining of informed consent is deemed feasible unless, before the use of a test
article (except as provided in paragraph 2. of this section), both the investigator and a
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physician who is not otherwise participating in the clinical investigation certify in writing
all of the following:
a. The human subject is confronted by a life-threatening or severely disabling situation
necessitating the use of the test article.
b. Informed consent cannot be obtained form the subject because of an inability to
communicate with, or obtain legally effective consent from, the subject.
c. Time is not sufficient to obtain consent from the subject’s legal representative.
d. There is available no alternative method of approved or generally recognized therapy
that provides an equal or greater likelihood of saving the life or lessening the disability
of the subject.
2. If immediate use of the test article is, in the investigator’s opinion, required to preserve the
life of the subject, and time is not sufficient to obtain the independent determination
required in paragraph 1. of this section in advance of using the test article, the
determinations of the clinical investigator shall be made, and, within 5 working days after
the use of the article, be reviewed and evaluated in writing by a physician who is not
participating in the clinical investigation.
The documentation required in paragraph 1. or 2. of this section must be submitted to the IRB
within 5 working days after the use of the test article.
C. Exception from Informed Consent Requirements for Emergency Research (21CFR50.24)
1. The IRB may approve clinical investigations of the nature described in this section without
requiring that informed consent of all research subjects be obtained if the IRB (with the
concurrence of a licensed physician who is a member of the IRB and who is not otherwise
participating in the clinical investigation) finds and documents the following:
a. The human subjects are in a life-threatening situation, available treatments are
unproven or unsatisfactory, and the collection of valid scientific evidence, which may
include evidence obtained from randomized placebo-controlled investigations, is
necessary to determine the safety and effectiveness of particular interventions.
b. Obtaining informed consent is not feasible because:
(1) The subjects will not be able to give their informed consent as a result of their
medical condition;
(2) The intervention under investigation must be administered before consent from the
subjects’ legally authorized representatives is feasible; and
(3) There is no reasonable way to identify prospectively the individuals likely to
become eligible for participation in the clinical investigation.
c. Participation in the research holds out the prospect of direct benefit to the subjects
because:
(1) Subjects are facing a life-threatening situation that necessitates intervention;
(2) Appropriate animal and other pre-clinical studies have been conducted, and the
information derived from those studies and related evidence support the potential
for the intervention to provide a direct benefit to the individual subjects; and
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d.
e.
f.
g.
(3) Risks associated with the intervention are reasonable in relation to what is known
about the medical condition of the potential class of subjects, the risks and
benefits of standard therapy, if any, and what is known about the risks and
benefits of the proposed intervention or activity.
The clinical investigation could not be practically carried out without the waiver.
The proposed investigational plan defines the length of the potential therapeutic
window based on scientific evidence, and the investigator has committed to attempting
to contact a legally authorized representative for each subject within that window of
time and, if feasible, to asking the legally authorized representative contacted for
consent within that window rather than proceeding without consent. The investigator
will summarize efforts made to contact legally authorized representatives and make
this information available to the IRB at the time of continuing review.
The IRB has reviewed and approved informed consent procedures and an informed
consent document consistent with section D. These procedures and the informed
consent document are to be used with subjects or their legally authorized
representatives in situations where use of such procedures and documents is feasible.
The IRB has reviewed and approved procedures and information to be used when
providing an opportunity for a family member to object to a subject’s participation in
the clinical investigation consistent with paragraph 1.g.(5) of this section.
Additional protections of the rights and welfare of the subjects will be provided,
including, at least:
(1) Consultation (including, where appropriate, consultation carried out by the IRB)
with representatives of the communities in which the clinical investigation will be
conducted and from which the subjects will be drawn;
(2) Public disclosure to the communities in which the clinical investigation will be
conducted and from which the subjects will be drawn, prior to initiation of the
investigation, of plans of the investigation, and its risks and expected benefits;
(3) Public disclosure of sufficient information following completion of the clinical
investigation to apprise the community and researchers of the study, including the
demographic characteristics of the research population, and its results;
(4) Establishment of an independent data monitoring committee to exercise oversight
of the clinical investigation; and
(5) If obtaining of informed consent is not feasible and a legally authorized
representative is not reasonably available, the investigator has committed, if
feasible, to attempting to contact within the therapeutic window the subject’s
family member who is not a legally authorized representative, and asking whether
he or she objects to the subject’s participation in the clinical investigation. The
investigator will summarize efforts made to contact family members and make
this information available to the IRB at the time of continuing review.
It is the responsibility of the investigator to provide a sponsor with the information that is
publicly disclosed in g.(2) or (3), above.
If the research is not subject to FDA regulations, but is federally funded, documentation
that the above criteria have been met will be sent to OHRP. The research will not be
allowed to begin until OHRP has concurred that the waiver is appropriate.
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2.
The IRB is responsible for ensuring that procedures are in place to inform, at the earliest
feasible opportunity, each subject, or if the subject remains incapacitated, a legally
authorized representative of the subject, or if such a representative is not reasonably
available, a family member, of the subject’s inclusion in the clinical investigation, the
details of the investigation, and other information contained in the informed consent
document. The IRB will also ensure that there is a procedure to inform the subject, or if
the subject remains incapacitated, a legally authorized representative of the subject, or if
such a representative is not available, a family member, that he or she may discontinue
the subject’s participation at any time without penalty or loss of benefits to which the
subject is otherwise entitled. If a legally authorized representative or family member is
told about the clinical investigation and the subject’s condition improves, the subject is
also to be informed as soon as feasible. If a subject is entered into a clinical investigation
with waived consent and the subject dies before a legal representative or family member
can be contacted, information about the clinical investigation is to be provided to the
subject’s legally authorized representative or family member, if feasible.
3.
The IRB determinations required by paragraph 1. of this section must be maintained for a
period of 3 years after completion of the clinical investigation, and the records shall be
accessible for inspection and copying by the FDA.
4.
Protocols involving an exception to the informed consent requirement under this section
must be performed under a separate investigational new drug application (IND) or
investigational device exemption (IDE) that clearly identifies such protocols as protocols
that may include subjects who are unable to consent. The submission of those protocols
in a separate IND/IDE is required even if an IND for the same drug or an IDE for the
same device already exists. The studies may not begin until FDA approves the separate
IND/IDE.
5.
If the IRB determines that it cannot approve a clinical investigation because the
investigation does not meet the criteria in the exception provided under paragraph 1. of
this section, or because of other relevant ethical concerns, the IRB will document its
findings and provide these findings promptly in writing to the clinical investigator and to
the sponsor of the clinical investigation, including reasons for this determination.
D. Elements of Informed Consent
1.
Basic elements of informed consent.
In seeking informed consent, the following information shall be provided to each subject:
a. A statement that the study involves research, an explanation of the purposes of the
research and the expected duration of the subject’s participation, a description of the
procedures to be followed, and identification of any procedures which are
experimental.
b. A description of any reasonably foreseeable risks or discomforts to the subject.
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c. A description of any benefits to the subject or to others, which may reasonably be
expected from the research.
d. Disclosure of appropriate alternative procedures or courses of treatment, if any, that
might be advantageous to the subject.
e. A statement describing the extent to which confidentiality of records identifying the
subject will be maintained and that notes the possibility that the FDA may inspect the
records. This must include
(1) a description of any protected information that may be used or disclosed,
(2) the person(s) by whom the information may be used or disclosed,
(3) the person(s) to whom the information may be disclosed,
(4) the purpose(s) of the use or disclosure,
(5) an expiration date or event of permission to use or disclose the information,
(6) a statement of consequences of not giving authorization for use or disclosure of
the information,
(7) a statement advising of the subject’s right to revoke authorization,
(8) a statement advising that information that is disclosed is subject to redisclosure by
the recipient, and
(9) reference to the institution’s Privacy Notice for more complete information.
f. For research involving more than minimal risk an explanation as to whether any
compensation and an explanation as to whether any medical treatments are available if
injury occurs and, if so, what they consist of, or where further information may be
obtained.
g. An explanation of whom to contact for answers to pertinent questions about the
research and the research subject’s rights, whom to contact in the event of a research
related injury to the subject, and a number to call to discuss confidential issues with
someone not involved with research.
h. A statement that participation is voluntary, that refusal to participate will involve no
penalty or loss of benefits to which the subject is otherwise entitled, and that the
subject may discontinue participation at any time without penalty or loss of benefits to
which the subject is otherwise entitled.
2.
Additional elements of informed consent.
When appropriate, one or more of the following elements of information shall also be
provided to each subject:
a. A statement that the particular treatment or procedure may involve risks to the subject
(or to the embryo or fetus, if the subject is or may become pregnant) which are
currently unforeseeable.
b. Anticipated circumstances under which the subject’s participation may be terminated
by the investigator without regard to the subject’s consent.
c. Any additional costs to the subject or third party payers that may result from
participation in the research.
d. Any compensation a subject will receive for participation, including a plan for
prorating the amount if the study is not completed.
e. The consequences of a subject’s decision to withdraw from the research and
procedures for orderly termination of participation by the subject.
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f. A statement that any significant new findings during the course of the research which
may relate to the subject’s willingness to continue participation will be provided to the
subject.
g. The approximate number of subjects in the study.
h. Disclosure of investigators’ potential financial conflicts of interest.
i. Name of commercial sponsor and a statement that the sponsor may review a subject’s
records related to the study.
E. Documentation of Informed Consent
1.
Except as provided in paragraph 3. or 4. below, informed consent shall be documented by
the use of a written consent form approved by the IRB and signed and dated at the time of
consent by both the subject or the subject’s legally authorized representative and the
person obtaining consent. A copy of the informed consent document (ICD) shall be given
to the subject or representative.
2.
Except as provided in paragraph 3. or 4. below, the consent form may be either of the
following:
a. A written consent that embodies the elements of informed consent required in
section D. This form may be read to the subject or the subject’s legally authorized
representative, but, in any event, the investigator shall give either the subject or the
subject’s legally authorized representative adequate opportunity to read it before it is
signed.
b. A short form written consent may be used if the subject is unable to read the long
consent form, or if there is currently no version of the long consent translated into a
language understandable to the subject. The short consent document must be in
language understandable to the subject, stating that the required elements of
informed consent have been presented orally to the subject or the subject’s legally
authorized representative. When this method is used, there shall be a witness to the
oral presentation. The witness should be fluent in both English and the language of
the subject if the subject does not readily understand English. Also, the IRB must
approve a written summary of what is to be said to the subject or representative. The
English consent document may be used as the summary. Only the short form itself is
to be signed by the subject or representative. However, the witness shall sign both
the short form and a copy of the summary and the person actually obtaining the
consent shall sign a copy of the summary. A copy of the summary shall be given to
the subject or the representative in addition to a copy of the short form. These
should be included in the medical record of the subject.
3.
The requirement to obtain a signed consent form may be waived by the IRB if it finds
either:
a. That the only record linking the subject and the research would be the consent
document and the principal risk would be potential harm resulting from a breach of
confidentiality. Each subject will be asked whether the subject wants documentation
linking the subject with the research, and the subject’s wishes will govern.
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b.
That the research presents no more than minimal risk of harm to subjects and
involves no procedures for which written consent is normally required outside of the
research context.
Notification of approval will include the criteria justifying the waiver.
4.
Except as noted below, written informed consent will be required for all studies involving
patients or volunteers, or information about them, at Hartford Hospital if the data is
recorded such that the subject’s identification can be reconstructed from the collected
data. In other words, if a link is created that allows the researcher to go back to the
subject’s data, this is considered a breach in confidentiality, and not allowable unless
written informed consent is obtained from the research subject. Disclosure of subjectspecific information for research purposes without the written consent of research
subjects is not allowable for any research studies subject to FDA regulations. Therefore,
all studies requiring patient data abstracted from Health Information Management
(Medical Records) and submitted to the FDA will require written informed consent which
specifically indicates that such patient records will be made available to the FDA.
In accordance with DHHS and HIPAA regulations, the IRB may approve a consent
procedure that does not include, or which alters, some or all of the elements of informed
consent, or waive the requirements to obtain informed consent provided the IRB finds
and documents that:
a. The research, including use or disclosure of protected health information, involves no
more than minimal risk to the individuals. The determination that the risk to privacy is
no more than minimal will be based on the presence of at least the following elements:
(1) There is an adequate plan to protect the identifiers from improper use and
disclosure.
(2) There is an adequate plan to destroy the identifiers at the earliest opportunity
consistent with conduct of the research, unless there is a health or research
justification for retaining the identifiers, or such retention is otherwise required by
law.
(3) There are adequate written assurances that the protected health information will
not be reused or disclosed to any other person or entity, except as required by law,
for authorized oversight of the research project, or for other research for which the
use or disclosure of protected health information would be permitted.
b. The research could not practicably be conducted without the alteration or waiver.
c. Where applicable, the research could not practicably be conducted without access to
and use of the protected health information.
d. The waiver or alteration will not adversely affect the rights and welfare of the subjects.
e. Whenever appropriate, the subjects will be provided with additional pertinent
information after participation.
The request for waiver will be evaluated by the HRPP along with the research application, and
will be reviewed according to full committee or expedited review procedures described under
Procedures.
Notification of approval will include the criteria justifying the waiver.
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F. Certificates of Confidentiality
Where data are being collected for biomedical or behavioral research and involve sensitive,
personally identifiable information, a Certificate of Confidentiality should be sought from the
National Institutes of Health to protect the identifiable information from forced (i.e. involuntary)
disclosure. Voluntary disclosure of the information may be made as long as this is specified in
the informed consent approved by the IRB.
Sensitive information may include, but is not limited to, sexual attitudes, preferences, or
practices; information relating to the use of alcohol, drugs, or other addictive products;
information pertaining to illegal conduct; information that, if released, might be damaging to an
individual’s financial standing, employability, or reputation within the community or might lead
to social stigmatization or discrimination; information pertaining to an individual’s psychological
well-being or mental health; and genetic information or tissue samples.
G. Advertisements for Research Subjects
Direct advertising (advertising intended to be seen or heard by prospective subjects to solicit their
participation in a study) is considered to be the start of the informed consent and subject selection
process. Direct advertising includes, but is not limited to newspaper, radio, TV, bulletin boards,
posters and flyers that are intended for research subjects. Not included are communications
intended to be seen or heard by health professionals, such as “dear doctor” letters, news stories
and publicity intended for other audiences, such as financial page advertisements directed
towards prospective investors.
Advertisements should be reviewed and approved by the IRB as part of the materials submitted
for the initial review. If, after approval of a research study, an investigator desires to utilize
advertisements, these must be submitted to the IRB as an addendum to the ongoing study. The
IRB chairman or designee may review these through the expedited process unless questions are
raised which cannot be easily or clearly resolved. The following criteria should be considered
when reviewing advertisements:
1. The review should ensure that such ads are not unduly coercive, and do not state or imply
a certainty of favorable outcome or other benefits beyond those outlined in the ICD.
2. The evaluation should be of the final copy of all printed or taped ads.
3. Advertisements for recruitment into investigational drug, biologic or device studies
should not use terms such as “new treatment,” “new drug,” etc. without a phrase
explaining that the test article is investigational.
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4. Advertisements should not promise free medical treatment, when the intent is that
subjects will not be charged for taking part in the investigation.
5. Advertisements may state that subjects will be paid, but should not emphasize the
payment or amount to be paid by such means as large or bold type.
IX. PROCEDURES
A. Research Application Process
All proposed research must be submitted to the Office of Research Administration for review and
determination of the scope of review required. The ORA will evaluate all protocols for scientific
content. Only those protocols that are scientifically sound will be reviewed by the IRB.
Information required for adequate review of all research protocols must be supplied at the time of
initial submission. This material must include at a minimum the application forms signed by the
investigator (including information regarding any sponsor and support or services needed to
conduct the research), Hartford Hospital ICD, Human Studies Form (including how, where, and
by whom participants will be recruited, languages of study population, collection and use and
storage of data), investigator's brochure, if applicable, or a summary of any pre-clinical data and
any pertinent clinical data, and the full protocol developed by the local investigator and/or a
multicenter protocol (including grant application) and sample consent form. The protocol should
include the title of the study, hypothesis, purpose, research design and methods, procedures to be
followed, expected number of subjects, characteristics of the expected subject population;
specifically, gender and race, age range, and health status, and reasons for inclusion or exclusion
of any subpopulations, provisions for managing any adverse reactions, statistical analysis,
significance/benefit, references, and investigator’s experience. Signatures of the collaborative
management team (CMT) of the appropriate clinical department are also required to ensure that
the departments are aware of the research being conducted with their patients.
In addition, a certificate or other evidence of completion of the Hartford Hospital Research
Training Course for all key personnel involved in the study must be on file (described under
Research Educational Program), as well as a current Financial Disclosure Form for principal
investigators and co-investigators on externally funded studies (as outlined in the Research
Corporate Compliance Manual), prior to study initiation. Key personnel are all study personnel
working at HH in any capacity other than an advisory role. The ORA must be notified if
personnel are to be added to a study after the initial submission, and they will be required to
complete the training course and submit a current FDF as applicable (if not done previously).
The FDF will be reviewed by the Research Committee, and, if a potential financial conflict is
found to exist, a recommendation will be made to the IRB for consideration when conducting
their review. Other information which may be included with the application are advertisements,
case report forms, a request for waiver of consent, an agreement between Hartford Hospital and a
funding agency or sponsor, and updated curricula vitae of the investigators.
B. Determination of Extent of IRB Oversight
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The ORA, including at least one representative of the IRB, will be responsible for review of the
Human Studies Form and any other documentation needed to make a determination of whether
IRB oversight of the research activity is required, and, if so, whether the activity meets the
criteria for expedited review or if it must be given full committee review. Investigators do not
have the authority to make a definitive independent determination that research involving human
subjects is exempt from IRB oversight.
Research activities involving human subjects (including children except where noted, pregnant
women, fetuses, and neonates) that are exempt from IRB review are activities in which the only
involvement of the subjects will be in one or more of the following categories:
1. Research conducted in established or commonly accepted educational settings, involving
normal educational practices, such as
a. research on regular and special education instructional strategies, or
b. research on the effectiveness of or the comparison among instructional techniques,
curricula, or classroom management methods.
2. Research involving the use of educational tests (cognitive, diagnostic, aptitude,
achievement), survey procedures, interview procedures or observation of public
behavior, unless:
a. information obtained is recorded in such a manner that human subjects can be
identified, directly or through identifiers linked to the subjects; and
b. any disclosure of the human subjects’ responses outside the research could
reasonably place the subjects at risk of criminal or civil liability or be damaging to
the subjects’ financial standing, employability, or reputation.
This exemption cannot be applied to research with children for survey or interview
procedures, nor to observations of public behavior except when the investigator(s) do
not participate in the activities being observed.
3. Research involving the use of educational tests (cognitive, diagnostic, aptitude,
achievement), survey procedures, interview procedures, or observation of public
behavior that is not exempt according to 2. b. above, if:
a. the human subjects are elected or appointed public officials or candidates for public
office; or
b. federal statute(s) require(s) without exception that the confidentiality of the
personally identifiable information will be maintained throughout the research and
thereafter.
4.
Research, involving the collection or study of existing data, documents, records,
pathological specimens, or diagnostic specimens, if these sources are publicly available
or if the information is recorded by the investigator in such a manner that subjects
cannot be identified, directly or through identifiers linked to the subjects.
5.
Research and demonstration projects which are conducted by or subject to the approval
of department or agency heads, and which are designed to study, evaluate, or otherwise
examine:
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a.
b.
c.
d.
6.
public benefit or service programs;
procedures for obtaining benefits or services under those programs;
possible changes in or alternatives to those programs or procedures; or
possible changes in methods or levels of payment for benefits or services under
those programs.
Taste and food quality evaluation and consumer acceptance studies,
a. if wholesome foods without additives are consumed or
b. if a food is consumed that contains a food ingredient at or below the level and for a
use found to be safe, or agricultural chemical or environmental contaminant at or
below the level found to be safe, by the FDA or approved by the Environmental
Protection Agency or the Food Safety and Inspection Service of the
U. S. Department of Agriculture.
Notification to the investigators of the exempt status of a proposal will include the category
justifying the exemption.
C. Expedited Review Procedure
Expedited review may be conducted by the IRB chairman or by one or more of the experienced
IRB members designated by the chairman to conduct the review. Any member so designated
must either have been an active, voting member (attending at least 50% of scheduled meetings)
for at least one year, with a primary background in a scientific area, or have a minimum of three
years’ experience in Research Administration, and must have no known or suspected financial
conflicts with the research activity to be reviewed. The IRB member(s) conducting the expedited
review will receive all of the same materials that would be provided to primary reviewers if full
committee review were required, and may exercise all of the authorities of the full IRB except
that the reviewer(s) shall refer any research protocol that the reviewers(s) would have
disapproved to the full committee for review. The reviewer(s) may also refer other research
protocols to the full committee whenever they believe that full review is warranted, or if they do
not feel qualified to make the required determination.
The IRB may utilize an expedited review procedure to review minor changes in previously
approved research during the period for which approval is authorized, or in procedures which
involve no more than minimal risk to the subjects and in which the only involvement of human
subjects will be in one or more of the following categories:
1.
Clinical studies of drugs and medical devices only when condition a. or b. is met.
a. Research on drugs for which an investigational new drug application (21 CFR Part
312) is not required.
b. Research on medical devices for which
(1) an investigational device exemption application (21 CFR Part 812) is not
required; or
(2) the medical device is cleared/approved for marketing and the medical device is
being used in accordance with its cleared/approved labeling.
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2.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as
follows:
a. from healthy, non-pregnant adults who weigh at least 110 pounds. For these
subjects, the 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
b. from other adults and children (as defined in section H), considering the age,
weight, and health of the subjects, the collection procedure, the amount of blood to
be collected, and the frequency with which it will be collected. For these 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.
3.
Prospective collection of biological specimens for research purposes by noninvasive
means. Examples: a. hair and nail clippings in a non-disfiguring manner; b. deciduous
teeth at time of exfoliation or if routine patient care indicates a need for extraction; c.
permanent teeth if routine patient care indicates a need for extraction; d. excreta and
external secretions (including sweat); e. uncannulated saliva collected either in a nonstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute
citric solution to the tongue; f. placenta removed at delivery; g. amniotic fluid obtained
at the time of rupture of the membrane prior to or during labor; h. supra- and subgingival
dental plaque and calculus, provided the collection procedure is not more invasive than
routine prophylactic scaling of the teeth and the process is accomplished in accordance
with accepted prophylactic techniques; i. mucosal and skin cells collected by buccal
scraping or swab, skin swab, or mouth washings; j. sputum collected after saline mist
nebulization.
4.
Collection of data through noninvasive procedures (not involving general anesthesia or
sedation) routinely employed in clinical practice, excluding procedures involving x-rays
or microwaves. Where medical devices are employed, they must be cleared/approved for
marketing. Examples: a. physical sensors that are applied either to the surface of the
body or at a distance and do not involve input of significant amounts of energy into the
subject or an invasion of the subject’s privacy; b. weighing or testing sensory acuity; c.
magnetic resonance imaging; d. electrocardiography, electroencephalography,
thermography, detection of naturally occurring radioactivity, electroretinography,
ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; e.
moderate exercise, muscular strength testing, body composition assessment, and
flexibility testing where appropriate given the age, weight, and health of the individual.
5.
Research involving materials (data, documents, records, or specimens) that have been
collected or will be collected solely for nonresearch purposes (such as medical treatment
or diagnosis).
6.
Collection of data from voice, video, digital, or image recordings made for research
purposes.
7.
Research on individual or group characteristics or behavior (including, but not limited
to, research on perception, cognition, motivation, identity, language, communication,
cultural beliefs or practices, and social behavior) or research employing survey,
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interview, oral history, focus group, program evaluation, human factors evaluation, or
quality assurance methodologies.
8.
Continuing review of research previously approved by expedited review (unless the level
of risk has increased), or previously approved by the convened IRB as follows:
a. where
(1) the research is permanently closed to the enrollment of new subjects;
(2) all subjects have completed all research-related interventions; and
(3) 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;
or
c. where the remaining research activities are limited to data analysis.
9.
Continuing review of research, not conducted under an investigational new drug
application or investigational device exemption where categories 2. through 8. do not
apply but 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.
Minor changes are considered to be those that do not present the prospect of greater than minimal
risk, and meet the criteria for expedited review.
Minimal risk is defined as risk in which the “probability and magnitude of harm or discomfort
anticipated are not greater in and of themselves than those ordinarily encountered in daily life or
during the performance of routine physical or psychological examinations or tests” [45 CFR
46.102(i)].
When the expedited review procedure is used, all IRB members shall be informed via the agenda
of any items that have been approved under this procedure. At a convened IRB meeting, any
member may request that an activity which has been approved under the expedited procedure be
reviewed by the IRB in accordance with non-expedited procedures. A vote of the members shall
be taken concerning the request and the majority shall decide the issue.
Notification to the investigators of initial and continuation approval of projects by the expedited
review process will include the categories justifying the expedited review.
D. Full Committee Review Procedure
The IRB will review and have the authority to approve, require modification in, or disapprove all
research activities involving human subjects, including proposed changes in previously approved
human subject research. These policies will be the guidelines followed for all IRB business
regardless of study funding source. The IRB decisions will take into account the subject
population, institutional restraints, all applicable legal requirements and other factors that
foreseeably can contribute to a determination of risks and benefits to subjects.
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E. Distribution of Information for Review
The ORA will distribute information to the IRB prior to the meeting with sufficient time for
adequate review, generally two weeks, on proposed studies and all other issues determined to
require full committee review. A primary group reviewer system will be utilized for protocols
requiring full committee evaluation, with at least one member having responsibility for
conducting an in-depth review of the information submitted by the clinical investigator.
Assignment of the review group will be based primarily on the expertise of the members of the
group as appropriate to the research under review, and also will take into consideration, to the
extent possible, potential conflicts of the members with the research being considered. The
assignment will be made by ORA staff (generally the IRB Administrator or Coordinator) with
sufficient knowledge of the nature of the research and the areas of expertise of the reviewers.
The group will receive the application, budget, full protocol, ICD, Human Studies Form,
investigator brochure and advertisements if applicable, and any other pertinent information
available (such as questionnaires and external grant applications). All other IRB members will
receive at least a copy of the ICD and a summary of the protocol detailed enough to allow
evaluation of the ICD, including any advertisements. In addition, each member will have access
to the investigator-submitted information prior to and during the convened meeting. Any
individual present at the IRB meeting may comment on the protocol after the formal
presentation. IRB members will be notified via the agenda of research proposals and all other
items that have met the criteria for expedited approval. These items will be available for review
prior to and during the meeting. Minutes of more recent meetings are available for review during
convened meetings, and other minutes may be requested for review at any time.
F. Committee Meetings
Regular meetings of the committee will be held monthly. Additional meetings may be convened
as necessary. The IRB shall not conduct reviews of research without the presence of a majority
of the IRB membership, including one member whose primary interests are in non-scientific
areas. A physician must be present when drug or device studies are reviewed. The IRB minutes
must document that the attendance meets these requirements. If these requirements are not met,
the meeting will be cancelled. If the attendance requirements cease to be met during a meeting,
the meeting will be adjourned.
All members are full voting members, except that any member having a conflicting interest in the
research under review (i.e., as documented in the Financial Disclosure Form or is listed on the
application as an investigator or other key personnel) may not participate in the review except to
provide requested information. The member is generally expected to leave the meeting during
discussion and voting. All IRB members are required to complete a financial conflict of interest
statement on an annual basis or whenever a change in status occurs.
To help ensure that attendance requirements are met, an IRB member, if unable to attend a
meeting, may enlist his designated alternate to attend in his place. It is the responsibility of the
IRB member to inform the ORA that an alternate will be sent. If the alternate is not from the
same discipline, it is also the responsibility of the IRB member to review the agenda, and in
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particular those items which have been assigned to his review group, and to communicate any
concerns/comments to the alternate. The alternate may then present the regular member's
comments at the meeting, and will be allowed to vote on behalf of the member represented. If
the IRB member does not have the opportunity to review all of the protocols prior to the meeting
and communicate with the alternate, this system may not be utilized. If, however, the alternate
does have the same area of expertise as the regular member, he may review the items and vote on
his own behalf. Comments submitted by members prior to a meeting may not be utilized unless
the members or their alternates are present at the meeting to discuss them. In a similar manner,
telephoned comments during a meeting may be permitted only if the calling member is able to
actively participate in the discussion.
G. Criteria for IRB Approval of Research
1. In order to approve research, the IRB shall determine that all of the following requirements
are satisfied:
a. Risks to subjects are minimized:
(1) By using procedures which are consistent with sound research design, and which
do not unnecessarily expose subjects to risk, and
(2) Whenever appropriate, by using procedures already being performed on the
subjects for diagnostic or treatment purposes.
b. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects
and the importance of the knowledge that may be expected to result. In evaluating risks
and benefits, the IRB should consider only those risks and benefits that may result from
the research (as distinguished from risks and benefits from therapies that subjects
would receive even if not participating in the research). The IRB will not consider
possible long-range effects of applying knowledge gained in the research (for example,
the possible effects of the research on public policy) as among those research risks that
fall within the purview of its responsibility.
c. Selection of subjects is equitable. In making this assessment the IRB will take into
account the purposes of the research and the setting in which the research will be
conducted and will be particularly cognizant of the special problems of research
involving special populations, such as children, prisoners, pregnant women,
handicapped, mentally disabled persons, or economically or educationally
disadvantaged persons, or persons recruited or enrolled in an emergent care setting.
d. Informed consent will be sought from each prospective subject or the subject’s legally
authorized representative, as previously described.
e. Informed consent will be appropriately documented, as previously described.
f. Where appropriate, the research plan makes adequate provision for monitoring the data
collected to ensure the safety of subjects.
g. Where appropriate, there are adequate provisions to protect the privacy of subjects and
to maintain the confidentiality of their data (such as coding of data, removing or not
including identifying information, limiting access, use, and disclosure to the minimum
necessary).
h. Investigators’ potential financial conflicts will not significantly impact the safety or
outcomes of the study.
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2.
When some or all of the subjects, such as children, prisoners, pregnant women,
handicapped, or mentally disabled persons, or economically or educationally
disadvantaged persons, are likely to be vulnerable to coercion or undue influence, the IRB
will ensure that additional safeguards are included in the study to protect the rights and
welfare of these subjects, and that they are adequate.
Remuneration, monetary or otherwise, offered to research participants and/or legally
authorized representatives (LAR) is an acceptable practice in so far as it fairly offsets the
incidental costs and inconveniences inherent in study participation, such as travel, meals,
parking, and time commitment. The IRB must review and approve the remuneration plan,
including type and amount of remuneration, prior to its implementation. The IRB must
determine that the remuneration is reasonable given the nature of the study and that it does
not unduly influence or coerce enrollment into or continued participation in the study.
The IRB will exercise heightened vigilance when reviewing proposed remuneration for
studies involving vulnerable populations to ensure that the decisions of the potential
participants or their LAR are not influenced by the remuneration associated with the study
(e.g., offering children toys, which may unduly influence their decision to assent, or
offering the parents or guardians monetary compensation may influence them to coerce
their children into participation).
H. Additional Considerations for Approval of Research Involving Children
Children are defined by regulations as persons who have not attained the legal age for
consent to treatments or procedures involved in the research, under the applicable law of the
jurisdiction in which the research will be conducted [45 CFR 46.402(a)]. In the State of
Connecticut the minimum age for consent is 18, with certain exceptions for emancipated
minors or for treatment of certain conditions such as AIDS.
1. The IRB may approve research involving children if it finds:
a. No greater than minimal risk is presented, and adequate provisions are made for
soliciting the assent of the children and the permission of their parents or guardians.
b. More than minimal risk is presented by an intervention or procedure that holds out the
prospect of direct benefit for the individual subject, or by a monitoring procedure that
is likely to contribute to the subject's well-being, and:
(1) the risk is justified by the anticipated benefit to the subjects;
(2) the relation of the anticipated benefit to the risk is at least as favorable to the
subjects as that presented by available alternative approaches; and
(3) adequate provisions are made for soliciting the assent of the children and
permission of their parents or guardians.
c. More than minimal risk is presented by an intervention or procedure that does not
hold out the prospect of direct benefit for the individual subject, or by a monitoring
procedure which is not likely to contribute to the well-being of the subject, and:
(1) the risk represents a minor increase over minimal risk;
(2) the intervention or procedure presents experiences to subjects that are reasonably
commensurate with those inherent in their actual or expected medical, dental,
psychological, social, or educational situations;
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(3) the intervention or procedure is likely to yield generalizable knowledge about the
subjects' disorder or condition which is of vital importance for the understanding
or amelioration of the subjects' disorder or condition; and
(4) adequate provisions are made for soliciting assent of the children and permission
of their parents or guardians.
d. The research does not meet the requirements of paragraphs a., b., or c., but presents a
reasonable opportunity to further the understanding, prevention, or alleviation of a
serious problem affecting the health or welfare of children; and adequate provisions
are made for soliciting the assent of children and the permission of their parents or
guardians.
2. Requirements for permission by parents or guardians and for assent by children:
a. In addition to the determinations required under other applicable sections, the IRB
shall determine that adequate provisions are made for soliciting the assent of the
children, when in the judgment of the IRB the children are capable of providing
assent. In determining whether children are capable of assenting, the IRB shall take
into account the ages, maturity, and psychological state of the children involved. This
judgment may be made for all children to be involved in research under a particular
protocol, or for each child, as the IRB deems appropriate. If the IRB determines that
the capability of some or all of the children is so limited that they cannot reasonably
be consulted or that the intervention or procedure involved in the research holds out a
prospect of direct benefit that is important to the health or well-being of the children
and is available only in the context of the research, the assent of the children is not a
necessary condition for proceeding with the research. Even where the IRB determines
that the subjects are capable of assenting, the IRB may still waive the assent
requirement under circumstances in which consent may be waived in accord with
section VIII.A., General Requirements of Informed Consent.
b. In addition to the determinations required under other applicable sections, the IRB
shall determine, in accordance with and to the extent that consent is required by
section VIII.A., that adequate provisions are made for soliciting the permission of
each child's parents or guardian. Where parental permission is to be obtained, the IRB
may find that the permission of one parent is sufficient for research to be conducted
under paragraph 1.a. or b., above. Where research is covered by paragraph 1.c. or d.,
and permission is to be obtained from parents, both parents must give their
permission unless one parent is deceased, unknown, incompetent, or not reasonably
available, or when only one parent has legal responsibility for the care and custody of
the child.
c. In addition to the provisions for waiver contained in section VIII, if the IRB
determines that a research protocol is designed for conditions or for a subject
population for which parental or guardian permission is not a reasonable requirement
to protect the subjects (for example, neglected or abused children), it may waive the
consent requirements in section VIII and paragraph b. of this section, provided an
appropriate mechanism for protecting the children who will participate as subjects in
the research is substituted, and provided further that the waiver is not inconsistent
with Federal, State, or local law. The choice of an appropriate mechanism would
depend upon the nature and purpose of the activities described in the protocol, the risk
and anticipated benefit to the research subjects, and their age, maturity, status, and
condition.
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d. Permission by parents or guardians shall be documented in accordance with and to the
extent required by section VIII.E., Documentation of Informed Consent.
e. When the IRB determines that assent is required, it shall also determine whether and
how assent must be documented.
3. Wards
a. Children who are wards of the State or any other agency, institution, or entity can be
included in research approved under paragraph 1.c. or d. only if such research is:
(1) related to their status as wards; or
(2) conducted in schools, camps, hospitals, institutions, or similar settings in which
the majority of children involved as subjects are not wards.
b. If the research is approved under paragraph a. of this section, the IRB shall require
appointment of an advocate for each child who is a ward, in addition to any other
individual acting on behalf of the child as guardian or in loco parentis. One individual
may serve as advocate for more than one child. The advocate shall be an individual
who has the background and experience to act in, and agrees to act in, the best
interests of the child for the duration of the child's participation in the research and
who is not associated in any way (except in the role as advocate or member of the
IRB) with the research, the investigator(s), or the guardian organization.
I. Additional Considerations for Approval of Research Involving Pregnant Women,
Fetuses or Neonates or Fetal Material
Viable neonate is defined by regulations as a neonate after delivery that is able to survive
(given the benefit of available medical therapy) to the point of independently maintaining
heartbeat and respiration [45 CFR 46.202(h)].
1. The IRB may approve research involving pregnant women or fetuses if it finds:
a. Where scientifically appropriate, preclinical studies, including studies on pregnant
animals, and clinical studies, including studies on nonpregnant women, have been
conducted and provide data for assessing potential risks to pregnant women and
fetuses;
b. The risk to the fetus is caused solely by interventions or procedures that hold out the
prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of
benefit, the risk to the fetus is not greater than minimal and the purpose of the
research is the development of important biomedical knowledge which cannot be
obtained by any other means;
c. Any risk is the least possible for achieving the objectives of the research;
d. If the research holds out the prospect of direct benefit to the pregnant woman, the
prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect
of benefit for the woman nor the fetus when risk to the fetus is not greater than
minimal and the purpose of the research is the development of important biomedical
knowledge that cannot be obtained by any other means, her consent is obtained in
accord with the informed consent provisions of section VIII;
e. If the research holds out the prospect of direct benefit solely to the fetus, then the
consent of the pregnant woman and the father is obtained in accord with the informed
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f.
g.
h.
i.
consent provisions of section VIII, except that the father's consent need not be
obtained if he is unable to consent because of unavailability, incompetence, or
temporary incapacity or the pregnancy resulted from rape or incest.
Each individual providing consent under paragraph d. or e. of this section is fully
informed regarding the reasonably foreseeable impact of the research on the fetus or
neonate;
For children as defined in section H, above, who are pregnant, assent and permission
are obtained in accord with the provisions of section H;
No inducements, monetary or otherwise, will be offered to terminate a pregnancy; and
Individuals engaged in the research will have no part in any decisions as to the timing,
method, or procedures used to terminate a pregnancy.
2. The IRB may approve research involving neonates of uncertain viability and nonviable
neonates provided that:
a. Where scientifically appropriate, preclinical and clinical studies have been conducted
and provide data for assessing potential risks to neonates.
b. Each individual providing consent under paragraph e.(2) or f.(5) of this section is
fully informed regarding the reasonably foreseeable impact of the research on the
neonate.
c. Individuals engaged in the research will have no part in determining the viability of a
neonate.
d. The requirements of paragraph e. or f. of this section have been met as applicable.
e. Until it has been ascertained whether or not a neonate is viable, a neonate may not be
involved in research unless the following additional conditions have been met:
(1) The IRB determines that:
(a) The research holds out the prospect of enhancing the probability of survival
of the neonate to the point of viability, and any risk is the least possible for
achieving that objective, or
(b) The purpose of the research is the development of important biomedical
knowledge which cannot be obtained by other means and there will be no
added risk to the neonate resulting from the research; and
(2) The legally effective informed consent of either parent of the neonate or, if
neither parent is able to consent because of unavailability, incompetence, or
temporary incapacity, the legally effective informed consent of either parent's
legally authorized representative is obtained in accord with section VIII, except
that the consent of the father or his legally authorized representative need not be
obtained if the pregnancy resulted from rape or incest.
f. After delivery, a nonviable neonate may be involved in research only if all of the
following additional conditions are met:
(1) Vital functions of the neonate will not be artificially maintained;
(2) The research will not terminate the heartbeat or respiration of the neonate;
(3) There will be no added risk to the neonate resulting from the research;
(4) The purpose of the research is the development of important biomedical
knowledge that cannot be obtained by other means; and
(5) The legally effective informed consent of both parents of the neonate is obtained
in accord with section VIII, except that the waiver and alteration provisions of
section VIII.E.4. do not apply. However, if either parent is unable to consent
because of unavailability, incompetence, or temporary incapacity, the informed
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consent of one parent of a nonviable neonate will suffice to meet the
requirements of this paragraph, except that the consent of the father need not be
obtained if the pregnancy resulted from rape or incest. The consent of a legally
authorized representative of either or both of the parents of a nonviable neonate
will not suffice to meet the requirements of this paragraph.
3. The IRB may approve research involving viable neonates only to the extent permitted by
and in accord with the requirements pertaining to general human subjects (45 CFR 46
Subpart A) and as permitted by and in accord with the requirements pertaining to
children (45 CFR 46 Subpart D).
4. The research does not meet the requirements of paragraphs 1., 2., or 3., but the IRB finds
that:
a. The research presents a reasonable opportunity to further the understanding,
prevention, or alleviation of a serious problem affecting the health or welfare of
pregnant women, fetuses or neonates; and
b. informed consent will be obtained in accord with the informed consent provisions of
Section VIII and other applicable parts of this section.
5. Research involving, after delivery, the placenta, the dead fetus, macerated fetal material,
or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord
with any applicable Federal, State, or local laws and regulations regarding such
activities.
If information associated with material described in the previous paragraph is recorded
for research purposes in a manner that living individuals can be identified, directly or
through identifiers linked to those individuals, those individuals are research subjects
and all pertinent parts of this section are applicable.
J. Additional Considerations for Approval of Research Involving Prisoners
Prisoner is defined as any individual involuntarily confined or detained in a penal institution.
The term is intended to encompass individuals sentenced to such an institution under a
criminal or civil statute, individuals detained in other facilities by virtue of statutes or
commitment procedures which provide alternatives to criminal prosecution or incarceration in
a penal institution, and individuals detained pending arraignment, trial, or sentencing.
1.
An Institutional Review Board reviewing research involving prisoners shall meet the
following requirements:
a. A majority of the Board (exclusive of prisoner members) shall have no association
with the prison(s) involved, apart from their membership on the Board.
b. At least one member of the Board shall be a prisoner, or a prisoner representative with
appropriate background and experience to serve in that capacity, except that where a
particular research project is reviewed by more than one Board only one Board need
satisfy this requirement.
2.
The IRB may approve research involving prisoners if it finds that:
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a. The research represents one of the following categories:
(1) study of the possible causes, effects, and processes of
incarceration, and of criminal behavior, provided that the study
presents no more than minimal risk and no more than
inconvenience to the subjects;
(2) study of prisons as institutional structures or of prisoners as
incarcerated persons, provided that the study presents no more than
minimal risk and no more than inconvenience to the subjects;
(3) research on conditions particularly affecting prisoners as a class
(for example, vaccine trials and other research on hepatitis which is
much more prevalent in prisons than elsewhere; and research on
social and psychological problems such as alcoholism, drug
addiction, and sexual assaults); or
(4) research on practices, both innovative and accepted, which have the intent
and reasonable probability of improving the health or well-being of the
subject.
b. Any possible advantages accruing to the prisoner through his or her
participation in the research, when compared to the general living conditions,
medical care, quality of food, amenities and opportunity for earnings in the
prison, are not of such a magnitude that his or her ability to weigh the risks of
the research against the value of such advantages in the limited choice
environment of the prison is impaired;
c. The risks involved in the research are commensurate with risks that would be
accepted by non-prisoner volunteers;
d. Procedures for the selection of subjects within the prison are fair to all
prisoners and immune from arbitrary intervention by prison authorities or
prisoners. Unless the principal investigator provides to the Board justification
in writing for following some other procedures, control subjects must be
selected randomly from the group of available prisoners who meet the
characteristics needed for that particular research project;
e. The information is presented in language which is understandable to the
subject population;
f. Adequate assurance exists that parole boards will not take into account a
prisoner's participation in the research in making decisions regarding parole,
and each prisoner is clearly informed in advance that participation in the
research will have no effect on his or her parole; and
g. Where the Board finds there may be a need for follow-up examination or care
of participants after the end of their participation, adequate provision has been
made for such examination or care, taking into account the varying lengths of
individual prisoners' sentences, and for informing participants of this fact.
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K. Requirement for Investigational New Drug (IND) Application or Investigational Device
Exemption (IDE)
Investigational use of approved, marketed products, when the intent is to develop information
about the product’s safety or efficacy, may require submission of an IND or IDE unless all of
the following conditions are met:
1) Not intended to be reported to FDA in support of new indication or other significant
change of labeling
2) Not intended to support a significant change in advertising
3) Risks not significantly increased by different route of administration, dosage, or
population
4) Conducted in compliance with 21 CFR 50 and 56 [requirements for IRB review and
consent]
5) Conducted in compliance with 21 CFR 312.7 [promotion and sale of drugs]
6) Not intended to invoke 21 CFR 50.24 [exception from informed consent requirements for
emergency research]
Use of a marketed product for an indication not in the approved labeling, when the intent is
the “practice of medicine,” does not require an IND application (“Off-label use”).
L. Significant Risk and Non-Significant Risk Device Studies
Investigational Device Exemption regulations (21 CFR part 812) describe two types of device
studies, “significant risk” (SR) and “non-significant risk” (NSR). An SR device study is defined
as a study of a device that presents a potential for serious risk to the health, safety or welfare of a
subject and a. is intended as an implant; or b. is used to support or maintain life; or c. is of
substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents
impairment of human health; or d. otherwise presents a potential for serious risk to the health,
safety or welfare of a subject. An NSR device investigation is one that does not meet the
definition of a significant risk study. Examples of SR/NSR devices are described by the FDA
and are attached at the end of this Policies and Procedures document.
SR device studies are governed by IDE regulations (21 CFR part 812). NSR device studies have
fewer regulatory controls than SR studies and are governed by the abbreviated requirements (21
CFR 812.2(b), with the major differences being in the approval process and reporting
requirements. If an investigator or a sponsor proposes the initiation of a claimed NSR
investigation to the IRB, and the IRB agrees that the device study is NSR and approves the study,
the investigation may begin immediately, without submission of an IDE to the FDA.
If the IRB, sponsor, or FDA determines that a device study is SR, the investigation may not begin
until both the IRB and the FDA approve the study. The IRB will review information such as
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reports of prior investigations conducted with the device, the proposed investigational plan, and a
description of subject selection criteria, as well as monitoring procedures. The sponsor should
provide the IRB with a risk assessment and the rationale used in making its risk determination.
1.
If the IRB determines that the study is Significant Risk:
a. The IRB is responsible for notifying the sponsor and investigator of the SR decision
(if the initial designation was NSR).
b. After an IDE is obtained by the sponsor, the IRB will proceed to review the study
according to 21 CFR 56.111 (as described in section G).
c. The sponsor is responsible for submitting an IDE to the FDA, or, if electing not to
proceed with the study, notify FDA of the SR determination.
d. The study may not begin until the FDA approves the IDE, and the IRB approves the
study.
e. The sponsor and investigator must comply with IDE regulations (21 CFR part 812),
as well as informed consent and IRB regulations (21 CFR parts 50 and 56)
f. If the sponsor submits the IDE, there is no requirement for the sponsor to notify the
FDA of the SR determination.
2. If the IRB decides the study is Non-significant Risk:
a. The IRB will proceed to review the study applying requisite criteria.
b. If the study is approved by the IRB, the sponsor and investigator must comply with
“abbreviated IDE requirements” (21 CFR 812.2(b), and informed consent regulation.
The abbreviated requirements are as follows:
(1) The device must be labeled in accordance with 21 CFR 812.5. The label should
include information on the manufacturer, packer, or distributor, the quantity of
contents, if appropriate, and the following statement “CAUTION –
Investigational Device. Limited by Federal (or U.S.) law to investigational use.”
The label shall describe all relevant contraindications, hazards, adverse effects,
interfering substances or devices, warnings, and precautions. The labeling of
the device shall not bear any statement that is false or misleading and shall not
represent that the device is safe or effective for the purpose investigated.
(2) Obtain IRB approval of the investigation after presenting a brief explanation of
why the device is not SR, and maintain such approval.
(3) Ensure that each investigator participating in the investigation obtains informed
consent from each subject and documents it, unless such documentation is
waived by the IRB.
(4) Comply with monitoring requirements described in 812.46, concerned with
reporting of all unanticipated adverse events.
(5) Maintain the records required under 812.140(b)(4) and (5) and make the reports
required under 812.150(b)(1) through (3) and (5) through (10). These are all
sponsor responsibilities.
(6) Ensure that participating investigators maintain the records required by
812.140(a)(3)(i) (regarding documentation of informed consent, or written
concurrence of a physician and brief description of the failure to obtain
informed consent, if such an occurrence exists), and make the reports required
under 812.150(a)(1), (2), (5), and (7), regarding unanticipated adverse events
and withdrawal of IRB approval, if such situations occur.
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(7) Comply with the prohibitions in 812.7 against promotion, commercialization
and other practices.
M. Committee Decisions
Decisions of the full committee will be by majority vote of those present. A majority of the
membership will constitute a quorum. The minutes shall record the numerical results of votes on
all protocol reviews and other actions, such as approval of progress reports and emergency use
requests.
N. Investigator Notification Process
IRB decisions and modification requirements will be promptly conveyed to principal
investigators in writing. It is the investigators’ responsibility to notify sponsors of IRB decisions.
The IRB's written notifications to investigators will indicate the type of review (exempt,
expedited or full) and the status of the research (approved, pending minor modifications, or
tabled). When the status is “approved,” the notification will include the approval date and
expiration date of the approval, and when the first or next progress report will be due. A copy of
the approved ICD, if applicable, stamped with the approval and expiration dates, will be enclosed
with notification of approval, and the investigator will be advised that use of this stamped form is
required for obtaining consent until another approved consent supercedes it.
The notification shall remind the investigators that prior IRB approval is required for changes in
approved and ongoing research, unless such changes are necessary to eliminate apparent
immediate risks and that the IRB should be notified promptly of such changes. In addition, at the
time of written approval of the project, the IRB will notify principal investigators of their
responsibility to provide the IRB with timely reports of unexpected risks to human research
subjects, as well as reports of unusual events that may impact research subjects.
O. Revision Review Procedure
When the IRB requests revisions in proposed protocols or consent documents, the completed
revisions must be reviewed and approved by the IRB before the investigator is notified that the
study may begin or continue. If the committee approves a protocol during a meeting with only
minor revisions recommended, and all that is required of the investigator is concurrence and
formal revision of the documents, the IRB chairman or his designee may determine that the
documents have been accurately corrected. The investigator will be notified at that time that the
study may be initiated with Research Committee approval. The minutes of the next meeting
shall document that the IRB members were informed that the specified changes were made and
the study was allowed to begin.
If, on the other hand, the revisions require composition by the investigator, the study will be
tabled, and the principal investigator will be notified in writing. Any revisions required to secure
approval must be provided to the full committee for review at a subsequent convened meeting.
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The revisions will be assigned to the same review group that reviewed the proposal initially. All
members will receive a copy of the revisions.
Revisions initiated by the investigator/sponsor will be evaluated by the ORA, and will be
processed according to the full committee or expedited review procedures described previously.
If full review is determined to be required, the revisions will be assigned to a review group. This
may include revisions to the protocol or consent, and changes made to improve the protection of
the subjects.
Revised versions of protocols, consent forms, or investigator brochures shall be clearly marked
as such, and will replace or supercede earlier versions.
P. Adverse Event Reports
The IRB must be notified of all serious adverse events and unanticipated problems that occur
during a research study that involves human subjects; it must also be provided notification on
trends of less serious adverse events that may indicate a serious safety concern while the
individual events are not classified as serious.
An Adverse Event Report must be submitted within 7 days of any serious or unanticipated event
involving risk to subjects or others if the event occurred at Hartford Hospital or another
institution overseen by the Hartford Hospital IRB. The report should include an assessment of
severity and relationship of the event to the study. An event is considered unanticipated if the
severity or specificity is not consistent with the information provided for IRB review (e.g.,
investigator brochure) or in the ICD. A serious event is one that is fatal, a life-threatening
adverse drug experience, persistent or significantly disabling, requiring hospitalization or
prolongation of hospitalization, or is a congenital anomaly/birth defect.
Anticipated events (i.e., described in the protocol and ICD), and those of mild or moderate
severity may be reported as they occur or at the time of review for continuation. Moderate
severity means sufficient discomfort is present to cause interference with usual activity. Mild
severity means an awareness of signs or symptoms that are easily tolerated.
Unusual events and protocol deviations or violations of regulations or policies, also, must be
reported promptly. An unusual event is one that may not be directly related to the research, but
may have an effect on the research subject, such as breach of confidentiality or inappropriate
consent documentation. A protocol deviation is any event that is not specified in the approved
protocol.
These reports, as well as any summary reports from a data safety monitoring board (DSMB) or
other safety monitoring body should be forwarded to the ORA for subsequent review by the IRB.
The IRB chairman or his designee will determine if full committee review is warranted. If so, all
members will receive a copy of the report. The IRB will determine if any changes to the protocol
or ICD will be required as a result of this event or a pattern of similar events. If full review is not
deemed necessary, the members will be notified of the review via the agenda. Notification will
be made to appropriate authorities if warranted, according to section U.
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Q. Emergency Use Requests
Proposed emergency use of an investigational drug, device, or biologic should be reviewed by the
full IRB prior to use, but may proceed without prospective committee approval if the subject is in
a life-threatening or severely debilitating situation in which no standard acceptable treatment is
available and in which there is not sufficient time to obtain full IRB approval. (However, the
subject may not be included in the research project.) The IRB must be notified of any emergency
use within five working days. Any subsequent use must be approved by the full IRB. However,
if use of the same article is necessary before it is possible for the committee to review the request
at a convened meeting, the subsequent use may be allowed. If multiple uses are anticipated, a
full protocol should be submitted for review according to the standard process.
A signed consent must be obtained unless the criteria in section VIII.B. can be met. The
physician making the emergency use request should submit a copy of the signed consent to the
ORA along with a summary letter with the patient’s initials and a brief patient history, including
justification for the request. A protocol from the sponsoring agency/pharmaceutical company
providing background information and the treatment plan should be submitted when it becomes
available.
R. Progress Reports
The IRB will apply the same criteria for approval (as outlined in section G) when conducting
continuing review as for initial review, and will consider the relative risks, subject population,
enrollment criteria, and any other relevant factors of the proposed research to determine the
frequency of continuing review. For those studies determined to involve a high degree of risk,
subsequent review will be required more frequently than annually. The exact interval will be
decided at the time of the review. The time interval between approval of reports must not exceed
one year. The due date for progress report submissions will be communicated to the principal
investigator at the time of notification of approval. The minutes shall record such decisions. The
Hartford Hospital Project Renewal Form should be utilized, with responses required to all items
pertaining to human subjects. As part of the report, each investigator will indicate the number of
subjects enrolled in the study and any subjects withdrawn since its initiation or the previous
report, and will provide a copy of all signed informed consents or whatever is requested by the
ORA for review. The report should also include any complaints received, a summary of all
adverse events, protocol deviations, and unanticipated events involving risk occurring within the
report period, and a summary of any recent relevant literature and any interim findings.
Requests for reports generally are sent to investigators three months prior to expiration of the
previous approval period. Reports are due two months prior to approval expiration. Exceptions
to this schedule are made when the approval period is considerably shorter than one year.
All progress reports should be forwarded to the ORA for subsequent distribution to the IRB.
These progress reports as well as any reports generated from multicenter trials (e.g. from a
DSMB) will be evaluated along with the original protocols and any modifications previously
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approved by the IRB, as well as any proposed modifications to the protocol or ICD or any newly
proposed consent form. Those determined to require full committee review will be assigned in
accordance with the primary group reviewer system described in section E. The group will
receive all of the material described above. All other members will receive at least the report, a
copy of the current and/or proposed ICD, and a summary of the project in sufficient detail to
allow evaluation of the ICD. The complete protocol is available for review prior to and during
the meeting. Reports that meet the criteria for expedited review will be processed according to
the expedited review procedure described in section C. Notification of approval will include the
categories justifying the expedited review. If the reviewer finds that the project no longer meets
the criteria for expedited review, or if he does not have sufficient expertise to evaluate a study in
a particular area, the study may be referred for full committee review. Any study that a reviewer
would have disapproved will be referred for full committee review.
The IRB may approve, require modification in, or suspend previous approval of a continuing
project. Upon acceptance of a progress report, the committee will decide when the next report is
due. Modifications will be handled in the same manner as revisions required upon initial review.
If a project is suspended, the investigator will be notified that no further activity will be allowed
other than any deemed necessary to prevent harm to subjects previously enrolled. The
appropriate authorities may be notified of the suspension as outlined in section U.
If the investigator does not submit the requested progress information in sufficient time for
review prior to expiration of the previous approval period, or if a project does not receive final
approval for continuation before the approval period expires, the project will be suspended until
approved, and may be terminated if this does not occur. The responsibility for submitting timely
progress reports will be communicated to the investigator at the time of notification of approval
of the research project. No work may be done on a suspended project until approval is received,
except as necessary to prevent risk to the subjects.
The IRB will be notified via the agenda of projects terminated due to failure to submit a report.
Projects for which all clinical and follow-up work has been completed and the use of PHI is
completed, or in which no subjects were enrolled may be approved for termination upon request
by the investigator. The IRB will be informed of this action via the agenda. The investigator
will be notified that the project will be terminated, and, if one was not already submitted, a final
report will be requested. The report should include copies of manuscripts and abstracts. If this
work has resulted in a publication, attachment of the manuscript will be considered acceptable for
the final report. Abstracts alone are not considered acceptable, and must be accompanied by a
written report. This report should include a detailed description of the research question, what was
done, and any difficulties that impeded progress. Conclusions reached as a result of this research
must be described, and must include the statistical tools utilized to analyze the data. Ideally, the
report should be in publication format, even if the work is not intended for publication.
Based on information provided in the progress report or from other sources, a project may be
audited if concerns are raised about possible noncompliance, such as material changes occurring
without prior IRB approval or inappropriate activity such as while a project is under suspension.
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S. Compliance Audits
HRPP quarterly audits of at least three randomly selected projects involving human subjects will
be conducted in accordance with the procedure outlined in the Research Corporate Compliance
Manual. Included in the audit will be a determination that no material changes have occurred
since the previous IRB review and that no inappropriate activity has occurred (i.e. without prior
IRB approval). Projects of investigators who have a history of non-compliance will be targeted
for periodic audit. Any projects about which a significant concern has been raised also may be
audited. Concerns or complaints may be reported to any of the following:
Study contact person listed on consent form
IRB Chairman, 545-3034
Research Corporate Compliance Officer, 545-0088
Institutional Official, 545-2197
Vice President for Academic Affairs, 545-2036
Compliance Helpline, 1-800-431-5572 (English) or 1-800-297-8592 (Spanish)
Patient Relations (anonymous if desired), 545-1400
Receipt of a complaint from research subjects (patients or volunteers) and allegations of noncompliance will be acknowledged (unless submitted anonymously), and findings will be
documented and reported to the IRB and addressed as appropriate.
If scientific misconduct is suspected or alleged, the matter will be referred to the Research
Committee in accordance with the Hartford Hospital Research Policy for Dealing with and
Reporting Possible Misconduct in Science as follows:
1. Upon receiving an allegation of scientific misconduct or other evidence of possible
misconduct, the chairman of the Research Committee will appoint a subcommittee
comprised of three experts who will be responsible for conducting an inquiry of the
allegations or other evidence of possible scientific misconduct. The chairman, in
appointing investigators, will take precautions against real or apparent conflicts of interest
on the part of those involved in the inquiry or investigation.
2. A written report shall be prepared that states what evidence was reviewed, summarizes
relevant interviews and includes the conclusion of the inquiry. The report shall contain
sufficiently detailed documentation of the inquiry to permit a later assessment of the
reasons for determining that an investigation was not warranted. The individual(s) against
whom the allegation was made shall be given a copy of the report of the inquiry.
3. If findings from the inquiry provide a sufficient basis for conducting an investigation, it
will be initiated within 30 days following completion of the inquiry. Whenever possible,
as part of the investigation, interviews should be conducted with all individuals involved
who might have information regarding key aspects of the allegations. Complete
summaries of these interviews should be prepared, provided to the interviewed party for
comment or revision, and included as part of the investigatory file.
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Affected individual(s) will be afforded confidential treatment to the maximum extent
possible, a prompt and thorough investigation, and an opportunity to comment on
allegations and findings of the inquiry and/or the investigation.
The Research Committee, as appropriate and to the best of its ability, will protect both
the reputations of the individuals who in good faith make allegations of scientific
misconduct and those against whom allegations of misconduct are not confirmed.
4. When the allegations of misconduct have been substantiated, the Research Committee will
impose appropriate sanctions on individuals, and/or where appropriate will make reports
and recommendations for action to the proper hospital administrative and medical staff
bodies.
Misconduct, as defined by the Office of Research Integrity, is “fabrication, falsification, plagiarism,
or other practices that seriously deviate from those that are commonly accepted within the scientific
community for proposing, conducting, or reporting research.”
T. Approval Withdrawal
The committee has the authority to suspend or terminate previously approved research that is not
being conducted in accordance with the committee's requirements.
U. Reporting Responsibilities
Upon receiving knowledge of any of the following, the ORA will forward a written report to the
IRB chairman, who may determine the action to be taken if the incident is minor, or will present
the item to the full committee for consideration:
1. Injuries or any other unanticipated problems involving risks to subjects or others.
2. Serious or continuing non-compliance with state or federal regulations or decisions of
the committee.
3. Suspension or termination of IRB approval for reasons as cited above in 1. or 2..
If the matter is presented to the committee, all members will receive a copy of the report.
Otherwise, it will be noted on the agenda for the information of the committee.
Upon review, if the chairman believes it is warranted to prevent risk to subjects or others, he may
immediately suspend a project. If, on the other hand, the incident is found to be minor or not
likely to recur, there may be nothing required of the investigator, or he may be required to modify
either the protocol or ICD or both, or the frequency of progress reports may be increased. The
committee may also decide to suspend a project or to continue a suspension imposed by the
chairman. A letter with recommendations for action will be sent to the investigator, and a copy
will be sent to the Institutional Official. Within 10 days the Institutional Official will notify the
FDA and OHRP as well as any other appropriate authorities in writing.
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V. Appeal Process
If for any reason an investigator wishes to appeal a decision of the IRB, he must submit a letter to
the chairman stating the reasons justifying his request. The chairman may accept the appeal and
reverse all or part of the committee’s previous decision, or may forward the appeal to the full
committee for consideration. The committee may then reverse all or part of the previous
decision, or may uphold the previous decision, in which case the matter may be considered
closed. No external committee or individual can overrule IRB disapproval.
W. Communications
All official communications by the IRB to the investigators as well as to all other authorities will
be in writing.
X. IRB Records
1. Minutes of committee meetings will indicate those members present (or their alternate),
absent members, and guests. Minutes will show that attendance and quorum
requirements were met when action was taken on any item requiring full review. If an
item was assigned to a primary review group, this will be indicated, and the current
group membership list will be attached to the minutes. Votes on each item will be
recorded to show the total number of members present at that time, the number of
members voting in favor of the motion, the number opposed, and the number abstaining.
The minutes will document that any member with a conflicting interest in a project
abstained or was not present when action was taken on that item. A summary of the
discussion and outcome of any controverted issues will be included, as well as the
reasons for not approving a project or for requiring changes to a protocol or ICD.
The minutes will also document the appropriate findings when the committee approves a
procedure waiving any or all of the requirements for written consent or when approving
research involving vulnerable classes of subjects, such as pregnant women or neonates,
that require extra protections.
2. Protocol-specific materials will be maintained for a minimum of three years following
completion of the project. These may include the application, budget, full protocol,
scientific evaluations, if any, approved ICD, revisions and amendments, progress
reports, adverse event reports, investigator brochure, advertisements, and
correspondence between the IRB and investigators, as well as any significant new
findings provided to participants. In addition, documentation required by the Privacy
Rule will be retained for six years from the date of creation or the date when it last was
in effect, whichever is later.
Protocols are stored in lockable file cabinets in the Research Administration wing, which
is locked at all times. All requests to view or copy any part of a file by anyone other
IRBpap06.doc
36
than documented study personnel must be authorized by the principal investigator in
writing or in person (e.g., via telephone). A log will be kept of any such requests,
including date, files viewed, name of reviewer, and reason for review.
Records maintained by the ORA should not contain names or other readily identifiable
information of research participants. Any such information will be deleted or otherwise
concealed at the first possible opportunity.
Any confidential records to be discarded, including protocol-related documents, should
be placed in one of the hospital’s locked confidential waste containers.
3. Other records maintained by the ORA include the HRPP Policies and Procedures,
membership roster, Federalwide Assurance, reports of inspections, educational
materials, certificates of completion of the Hartford Hospital Research Training Course
and current Financial Disclosure forms.
Minutes and other IRB records that are not protocol specific may be maintained
indefinitely, but for no less than three years.
The HRPP Policies and Procedures will be reviewed on an annual basis by the ORA, and
will be updated as necessary to reflect current practices.
All records will be made accessible for inspection and copying by authorized representatives of
the FDA and DHHS and other appropriate agencies at reasonable times and in a reasonable
manner.
Signature/Date:__________________________
Signature/Date:_______________________
Robert D. Siegel, M.D.
Chairman, IRB
Hartford Hospital
Tiffany M. Rowe
Director, HRPP
Hartford Hospital
Rev. 05/16/06
IRBpap06.doc
37
APPENDIX E
Hartford Hospital
IRB Administrative Organizational Chart
Mr. John Meehan
President & CEO
Neil Yeston, MD
Vice President, Academic Affairs
Laurine M. Bow, Ph.D.
Vice President for Research
FWA Signatory Official
Institutional Review Board
Robert D. Siegel, M.D., Chairman
Ms. Tiffany Rowe
Director, HRPP
Ms. Susan Hughes
IRB Administrator/Support Staff
IrbOrg06.doc
APPENDIX F
IRB/Study References
Books
Fundamentals of Clinical Trials
Guide to Clinical Trials
Informed Consent: The Consumer’s Guide to the Risks and Benefits of Volunteering for Clinical
Trials
The Investigator’s Guide to Clinical Research
Periodicals
ARENA Newsletter
Clinical Trials Advisor
Human Research Report
IRB Advisor
Guidances
Coordinating a Clinical Research Study
Ethical and Policy Issues in Research Involving Human Participants
FDA Information Sheets
Protecting Human Research Subjects: Institutional Review Board Guidebook
Regulations
21 CFR 50/56
21 CFR 312
21 CFR 812
45 CFR 46
45 CFR 160/164
Clinical Research Federal Rules & Regulations Manual (including CD)
IRCRefs.doc
7/26/02
APPENDIX F
Other
Belmont Report (Ethical Principles and Guidelines for the Protection of Human Subjects of
Research)
Declaration of Helsinki
International Conference on Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH): Good Clinical Practice
Nuremberg Code
Articles
Are Placebo Controls Ethical in Antidepressant Clinical Trials?, Psychiatric Times, by Arif
Khan, M.D. and Shirin Khan, April 2000
Federal agency opens probe into death in asthma experiment; ‘Everybody’s distressed’, by
Jonathan Bor, Gary Cohn and Tom Pelton, Baltimore Sun, June 15, 2001
Jesse’s Intent, presentation by Paul Gelsinger, October 31, 2000, at PRIM&R Meeting, San
Diego
Symptom Reduction and Suicide Risk Among Patients with Placebo in Antipsychotic Clinical
Trials: An Analysis of the Food and Drug Administration Database, Am. J. Psychiatry,
September 2001, by Arif Khan, M.D., Shirin R. Khan, Robyn M. Leventhal, Walter A. Brown,
M.D.
Trials and Tribulation: A Special Report, Johns Hopkins Magazine, by Dale Keiger and
Sue De Pasquale, February 2002
Volunteer in Asthma Study Dies after Inhaling Drug, The New York Times, by Lawrence K.
Altman, June 15, 2001
CD-ROM
Investigator 101
IRCRefs.doc
7/26/02
APPENDIX G
SAMPLE SR/NSR DEVICES
NONSIGNIFICANT RISK DEVICES (NSR)
Low Power Lasers for treatment of pain
Caries Removal Solution
Daily Wear Contact Lenses and Associated Lens Care Products not intended for use directly in
the eye (e.g., cleaners; disinfecting, rinsing and storage solutions)
Contact Lens Solutions intended for use directly in the eye (e.g., lubricating/rewetting solutions)
using active ingredients or preservation systems with a history of prior ophthalmic/contact lens
use or generally recognized as safe for ophthalmic use
Conventional Gastroenterology and Urology Endoscopes and/or Accessories
Conventional General Hospital Catheters (long-term percutaneous, implanted, subcutaneous and
intravascular)
Conventional Implantable Vascular Access Devices (Ports)
Conventional Laparoscopes, Culdoscopes, and Hysteroscopes
Dental Filling Materials, Cushions or Pads made from traditional materials and designs
Denture Repair Kits and Realigners
Digital Mammography [Note: an IDE is required when safety and effectiveness data are collected
which will be submitted in support of a marketing application.]
Electroencephalography (e.g., new recording and analysis methods, enhanced diagnostic
capabilities)
Externally Worn Monitors for Insulin Reactions
Functional Electrical Neuromuscular Stimulators
General Biliary Catheters General Urological Catheters (e.g., Foley and diagnostic catheters)
Jaundice Monitors for Infants
Magnetic Resonance Imaging (MRI) Devices within FDA specified parameters
Manual Image Guided Surgery
Menstrual Pads (Cotton or Rayon, only)
Menstrual Tampons (Cotton or Rayon, only)
Nonimplantable Electrical Incontinence Devices
Nonimplantable Male Reproductive Aids with no components that enter the vagina
Ob/Gyn Diagnostic Ultrasound within FDA approved parameters
Transcutaneous Electric Nerve Stimulation (TENS) Devices for treatment of pain
Wound Dressings, excluding absorbable hemostatic devices and dressings (also excluding
Interactive Wound and Burn Dressings)
SIGNIFICANT RISK DEVICES (SR)
General Medical Use
Catheters:
 Urology - urologic with anti-infective coatings
 General Hospital - except for conventional long-term percutaneous, implanted,
subcutaneous and intravascular
 Neurological - cerebrovascular, occlusion balloon
 Cardiology - transluminal coronary angioplasty, intra-aortic balloon with control system
IRCRefs.doc
7/26/02
APPENDIX G




Collagen Implant Material for use in ear, nose and throat, orthopedics, plastic surgery,
urological and dental applications
Surgical Lasers for use in various medical specialties
Tissue Adhesives for use in neurosurgery, gastroenterology, ophthalmology, general and
plastic surgery, and cardiology
Anesthesiology
Breathing Gas Mixers
Bronchial Tubes
Electroanesthesia Apparatus
Epidural and Spinal Catheters
Epidural and Spinal Needles
Esophageal Obturators
Gas Machines for anesthesia or analgesia
High Frequency Jet Ventilators greater than 150 BPM
Rebreathing Devices
Respiratory Ventilators
Tracheal Tubes
Cardiovascular
Aortic and Mitral Valvuplasty Catheters
Arterial Embolization Devices Cardiac Assist Devices: artificial heart (permanent implant and
short term use), cardiomyoplasty devices, intra-aortic balloon pumps, ventricular assist devices
Cardiac Bypass Devices: oxygenators, cardiopulmonary non-roller blood pumps, closed chest
devices
Cardiac Pacemaker/Pulse Generators: antitachycardia, esophageal, external transcutaneous,
implantable
Cardiopulmonary Resuscitation (CPR) Devices
Cardiovascular/Intravascular Filters
Coronary Artery Retroperfusion Systems
Coronary Occluders for ductus arteriosus, atrial and septal defects
Coronary and Peripheral Arthrectomy Devices
Extracorporeal Membrane Oxygenators (ECMO)
Implantable Cardioverters/Defibrillators
Laser Coronary and Peripheral Angioplasty Devices
Myoplasty Laser Catheters
Organ Storage/Transport Units
Pacing Leads
Percutaneous Conduction Tissue Ablation Electrodes
Peripheral, Coronary, Pulmonary, Renal, Vena Caval and Peripheral Stents
Replacement Heart Valves
RF Catheter Ablation and Mapping Systems
Ultrasonic Angioplasty Catheters
Vascular and Arterial Graft Prostheses
Vascular Hemostasis Devices
Dental
Absorbable Materials to aid in the healing of periodontal defects and other maxillofacial
applications
Bone Morphogenic Proteins with and without bone, e.g., Hydroxyapatite (HA)
IRCRefs.doc
7/26/02
APPENDIX G
Dental Lasers for hard tissue applications
Endosseous Implants and associated bone filling and augmentation materials used in conjunction
with the implants
Subperiosteal Implants
Temporomandibular Joint (TMJ) Prostheses
Ear, Nose, and Throat
Auditory Brainstem Implants
Cochlear Implants
Laryngeal Implants
Total Ossicular Prosthesis Replacements
Gastroenterology and Urology
Anastomosis Devices
Balloon Dilation Catheters for benign prostatic hyperplasia (BPH)
Biliary Stents
Components of Water Treatment Systems for Hemodialysis
Dialysis Delivery Systems
Electrical Stimulation Devices for sperm collection
Embolization Devices for general urological use
Extracorporeal Circulation Systems
Extracorporeal Hyperthermia Systems
Extracorporeal Photopheresis Systems
Femoral, Jugular and Subclavian Catheters
Hemodialyzers
Hemofilters
Implantable Electrical Urinary Incontinence Systems
Implantable Penile Prostheses
Injectable Bulking Agents for incontinence
Lithotripters (e.g., electrohydraulic extracorporeal shock-wave, laser, powered mechanical,
ultrasonic)
Mechanical/Hydraulic Urinary Incontinence Devices
Penetrating External Penile Rigidity Devices with components that enter the vagina
Peritoneal Dialysis Devices
Peritoneal Shunt
Plasmapheresis Systems
Prostatic Hyperthermia Devices
Urethral Occlusion Devices
Urethral Sphincter Prostheses
Urological Stents (e.g., ureteral, prostatG)
General and Plastic Surgery
Absorbable Adhesion Barrier Devices
Absorbable Hemostatic Agents
Artificial Skin and Interactive Wound and Burn Dressings
Injectable Collagen
Implantable Craniofacial Prostheses
Repeat Access Devices for surgical procedures
Sutures
IRCRefs.doc
7/26/02
APPENDIX G
General Hospital
Implantable Vascular Access Devices (Ports) - if new routes of administration or new design
Infusion Pumps (implantable and closed-loop - depending on the infused drug)
Neurological
Electroconvulsive Therapy (ECT) Devices
Hydrocephalus Shunts
Implanted Intracerebral/Subcortical Stimulators
Implanted Intracranial Pressure Monitors
Implanted Spinal Cord and Nerve Stimulators and Electrodes
Obstetrics and Gynecology
Antepartum Home Monitors for Non-Stress Tests
Antepartum Home Uterine Activity Monitors
Catheters for Chorionic Villus Sampling (CVS)
Catheters Introduced into the Fallopian Tubes
Cervical Dilation Devices
Contraceptive Devices:
 Cervical Caps
 Condoms (for men) made from new materials (e.g., polyurethane)
 Contraceptive In Vitro Diagnostics (IVDs)
 Diaphragms
 Female Condoms
 Intrauterine Devices (IUDs)
 New Electrosurgical Instruments for Tubal Coagulation
 New Devices for Occlusion of the Vas Deferens
 Sponges
 Tubal Occlusion Devices (Bands or Clips)
Devices to Prevent Post-op Pelvic Adhesions
Embryoscopes and Devices intended for fetal surgery
Falloposcopes and Falloposcopic Delivery Systems
Intrapartum Fetal Monitors using new physiological markers
New Devices to Facilitate Assisted Vaginal Delivery
Thermal Systems for Endometrial Ablation
Ophthalmics
Class III Ophthalmic Lasers
Contact Lens Solutions intended for direct instillation (e.g., lubrication/rewetting solutions) in
the eye using new active agents or preservatives with no history of prior ophthalmic/contact lens
use or not generally recognized as safe for ophthalmic use
Corneal Implants
Corneal Storage Media
Epikeratophakia Lenticules
Extended Wear Contact Lens
Eye Valve Implants (glaucoma implant)
Intraocular Lenses (IOLs) [21 CFR part 813]
Keratoprostheses Retinal Reattachment Systems: fluids, gases, perfluorocarbons,
perfluorpropane, silicone oil, sulfur hexafluoride, tacks
Viscosurgical Fluids
IRCRefs.doc
7/26/02
APPENDIX G
Orthopedics and Restorative
Bone Growth Stimulators
Calcium Tri-Phosphate Hydroxyapatite
Ceramics Collagen and Bone Morphogenic Protein Meniscus Replacements
Implantable Prostheses (ligament, tendon, hip, knee, finger)
Computer Guided Robotic Surgery
Radiology
Boron Neutron Capture Therapy
Hyperthermia Systems and Applicators
IRCRefs.doc
7/26/02