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LIFEBRIDGE HEALTH, INC.

Institutional Review Board

Policies and Standard Operating Procedures

Revised as of 20 August 2008

TABLE OF CONTENTS

I. INTRODUCTION....................................................................................................................................... 1

II. STATEMENT OF AUTHORITY AND PURPOSE...................................................................................3

A. GOVERNING PRINCIPLES .................................................................................................................. 3 B. INSTITUTIONAL AUTHORITY ............................................................................................................ 3 C. IRB AUTHORITY ............................................................................................................................. 5 D. RESPONSIBILITIES OF THE IRB ......................................................................................................... 6

III. ORGANIZATION OF THE IRB................................................................................................................ 9

A. COMPOSITION OF THE BOARD .......................................................................................................... 9 B. MANAGEMENT .............................................................................................................................. 10 C. DUTIES OF IRB MEMBERS ............................................................................................................. 12 D. SCOPE OF IRB REVIEWS ................................................................................................................ 16

IV. GENERAL ADMINISTRATION............................................................................................................. 18

A. POLICIES AND PROCEDURES MAINTENANCE ................................................................................... 18 B. EDUCATION AND TRAINING ........................................................................................................... 19

V. FUNCTIONS AND OPERATIONS.......................................................................................................... 24

A. RESEARCH SUBMISSION REQUIREMENTS ........................................................................................ 24 B. EXEMPTIONS FROM IRB REVIEW .................................................................................................... 27 C. IRB MEETING ADMINISTRATION ................................................................................................... 30 D. ADMINISTRATIVE REVIEW AND DISTRIBUTION OF MATERIALS ........................................................ 35 E. DOCUMENTATION AND DOCUMENT MANAGEMENT ........................................................................ 37

VI. REVIEW OF RESEARCH........................................................................................................................ 41

A. EXPEDITED REVIEW ...................................................................................................................... 41 B. FACILITATED IRB REVIEWS (CENTRAL IRB) ................................................................................. 47 C. FULL IRB INITIAL REVIEW – CRITERIA FOR IRB APPROVAL .......................................................... 49 D. FULL IRB CONTINUING REVIEW – CRITERIA FOR RENEWAL ........................................................... 53 E. CONTINUING REVIEW – ONGOING ................................................................................................. 57 F. INVESTIGATOR REPORTING OF SERIOUS ADVERSE EVENTS IN RESEARCH SUBJECTS ........................ 65 G. SUSPENSIONS OF STUDIES .............................................................................................................. 72 H. STUDY COMPLETION ..................................................................................................................... 74 I. CATEGORIES OF ACTION BY THE IRB ............................................................................................ 75

VII. INFORMED CONSENT........................................................................................................................... 78

A. GENERAL REQUIREMENTS AND DOCUMENTATION .......................................................................... 78 B. ECONOMIC CONSIDERATIONS IN RESEARCH INVOLVING HUMAN SUBJECTS .................................... 88 C. EXCEPTIONS TO INFORMED CONSENT REQUIREMENTS ................................................................... 91 D. PROCEDURES BY WHICH RESEARCH SUBJECTS MAY VOICE COMPLAINTS OR CONCERNS ................ 94

VIII. VULNERABLE SUBJECT POPULATIONS...........................................................................................96

A. CHILDREN ..................................................................................................................................... 96 B. EMPLOYEES OR STUDENTS ........................................................................................................... 101 C. COGNITIVELY DISABLED PERSONS ............................................................................................... 101 D. PREGNANT WOMEN, FETAL RESEARCH, AND PRISONERS .............................................................. 103

IX. CATEGORIES OF RESEARCH............................................................................................................ 104

A. INVESTIGATIONAL DRUGS, BIOLOGICS AND MEDICAL DEVICES .................................................... 104

B. REVIEW OF RESEARCH INVOLVING MEDICAL DEVICES ................................................................ 104 C. HUMANITARIAN USE DEVICES (HUD) ......................................................................................... 106 D. EMERGENCY USE OF INVESTIGATIONAL AGENTS .......................................................................... 112 E. SINGLE PATIENT OR SMALL GROUP USE “COMPASSIONATE USE” OF INVESTIGATIONAL AGENTS IN

NON-EMERGENCY SITUATIONS .................................................................................................. 114 F. MEDICAL RECORDS AND CHART REVIEW .................................................................................... 117 G. GENETIC RESEARCH .................................................................................................................... 118 H. GENE THERAPY, TISSUE AND CELL TRANSPLANTATION RESEARCH .............................................. 119

X. INVESTIGATOR RESPONSIBILITIES................................................................................................120

A. REQUIRED INVESTIGATOR ACTIONS ............................................................................................. 120 B. RESPONSIBILITY .......................................................................................................................... 122 C. APPLICABLE REGULATIONS AND GUIDELINES ............................................................................... 123

XI. QUALITY ASSURANCE........................................................................................................................ 124

A. QUALITY ASSURANCE AND QUALITY CONTROL ........................................................................... 124 B. AUDITS BY REGULATORY AGENCIES ............................................................................................ 124

XII. APPENDIX............................................................................................................................................. 127

A. IRB FORMS ................................................................................................................................. 127 PROTOCOL APPLICATION CHECKLIST ................................................................................................ 127 APPLICATION FOR NEW RESEARCH ................................................................................................... 127 RENEWAL APPLICATION FOR CONTINUING RESEARCH ...................................................................... 127 REQUEST FOR EXCEPTION TO INFORMED CONSENT REQUIREMENTS FOR RESEARCH ........................... 127 IRB CO-INVESTIGATOR SIGNATURE PAGE ........................................................................................ 127 LBH INVESTIGATOR DELEGATION OF RESPONSIBILITY ...................................................................... 127 FINANCIAL INTEREST DISCLOSURE FORM .......................................................................................... 127 REQUEST FOR EXCEPTION TO INFORMED CONSENT REQUIREMENTS FOR RESEARCH ........................... 127 HIPAA AUTHORIZATION FORM FOR USE OR DISCLOSURE OF PROTECTED HEALTH INFORMATION-

OUTSIDE SPONSOR ................................................................................................................... 127 AUTHORIZATION FORM FOR USE OR DISCLOSURE OF PROTECTED HEALTH INFORMATION-INVESTIGATOR

SPONSORED………………………………………………………………………………………. 12 7 APPLICATION FOR WAIVER OF INDIVIDUAL AUTHORIZATION FOR USE OR DISCLOSURE OF PROTECTED HEALTH INFORMATION (PHI) IN A RESEARCH STUDY ............................................ 127

DISCLOSURE/USE OF DE-IDENTIFIED DATA/MATERIALS FOR RESEARCH ............................................ 127 EXEMPTION SCREENING QUESTIONS ................................................................................................. 127 CLAIM OF EXEMPTION ...................................................................................................................... 127 ADVERSE EVENT REPORT FORM ....................................................................................................... 127 CONSENT TO UNDERGO TREATMENT WITH A HUMANITARIAN DEVICE ............................................... 127 HUMANITARIAN USE DEVICE INFORMED CONSENT AND PRIVACY AUTHORIZATION FORM ................. 127 HUMAN GENE TRANSFER / RECOMBINANT DNA RESEARCH .............................................................. 127 IRB PROTOCOL REVIEW ................................................................................................................... 127 IRB PROTOCOL AMENDMENT REVIEW .............................................................................................. 127 LBH IRB INFORMED CONSENT REVIEW FORM ................................................................................. 127 CLAIM OF EXEMPTION CHECKLIST FOR IRB STAFF ........................................................................... 127 IRB MEMBER AGREEMENT ............................................................................................................... 127 IRB ALTERNATE MEMBER AGREEMENT ............................................................................................ 127 IRB MEMBER AND ALTERNATE CONFIDENTIALITY AGREEMENT ........................................................ 128 IRB MEMBER AND ALTERNATE CONFLICT OF INTEREST DISCLOSURE AND RECUSAL AGREEMENT ..... 128

B. IRB GuidelinesCASE REPORTS & CHART REVIEWS ................................................................................................. 128 DISCLOSURE / USE OF DE-IDENTIFIED DATA / MATERIALS FOR RESEARCH ........................................ 128 ADVERSE EVENT REPORTING ............................................................................................................ 128 ADVERSE EVENT AND SAFETY REPORT CONTINUING REVIEW REPORTING ......................................... 128

POLICY ON CONFLICT OF INTEREST IN RESEARCH ............................................................................. 128 CONFLICT OF INTEREST GUIDELINES FOR CLINICAL RESEARCH .......................................................... 128 HUMAN GENE TRANSFER/RECOMBINANT DNA RESEARCH ............................................................... 128 COMPASSIONATE USE OF AN UNAPPROVED DRUG, DEVICE, OR BIOLOGIC ......................................... 128 HUMANITARIAN USE DEVICES ......................................................................................................... 128 QUESTIONNAIRES BY TELEPHONE OR MAIL ...................................................................................... 128 INDEPENDENT CENTRAL INSTITUTIONAL REVIEW BOARD (CIRB) EVALUATION AND FACILITATED

REVIEW ...................................................................................................................................... 128 NCI CIRB FACILITATED REVIEW ..................................................................................................... 128 DEFINING COMMUNITY OUTREACH RESEARCH AND NON-RESEARCH PROJECTS ................................ 128 IRB MEMBER RESPONSIBILITIES AND REVIEWER DUTIES ................................................................. 128 EVALUATING AND MONITORING RISK IN HUMAN SUBJECTS RESEARCH ............................................ 128 IRB REVIEW FEES ........................................................................................................................... 128

Please refer to the LifeBridge Health Intranet for the latest version of all available forms for your use. Forms are also available at the LifeBridge Health Office.

I. INTRODUCTION

Federal regulations detailed in the Code of Federal Regulations (CFR), 21 CFR 56, 21

CFR 50, and 45 CFR 46, concerning protection of human subjects indicate the required

review process to be followed by Institutional Review Boards ("IRBs") at all facilities

conducting Federally funded research or research under the jurisdiction of the Food and

Drug Administration. Maryland State House Bill 917 applies the requirements of 45 CFR

46 (and counterpart FDA regulations) to all research conducted in Maryland, regardless of

funding source.

LifeBridge Health applies these regulations to (1) all research conducted at LifeBridge

Health facilities by LifeBridge Health faculty or others and to (2) all research conducted by

LifeBridge Health attending physicians, housestaff, LifeBridge Health employees, faculty,

and students at all LifeBridge Health affiliated sites.

These policies and procedures are issued by LifeBridge Health IRB to explain its

institutional charge, outline the process by which it operates in compliance with the

regulations, and define the obligations of Principal Investigators and their staff who

conduct human subjects research.

Suggestions on the content of the guidelines and the IRB process are encouraged and may

be directed to the IRB office.

Institutional Review BoardLifeBridge Health

Sinai Hospital of Baltimore2401 W. Belvedere Avenue

Schapiro Building, Suite 203Baltimore, MD 21215

Arthur N. Freed, Ph.D., ChairpersonPatty Lohinski, CIM, Research Coordinator

(410) 601-9021 Office(410) 601-8282 Fax

LifeBridge Health IRB Revised Date: August 20, 2008 Page 1 of 133Policies and SOPs Original Date: June 6, 2003

This version supercedes all previous versions of IRB policies for LifeBridge Health and for Sinai Hospital of Baltimore, Northwest Hospital

Principal investigators are invited to consult the IRB office prior to submitting a protocol for

review. This document has been developed to explain the review process and what is required

of investigators and research staff who submit applications to the IRB.



VII. STATEMENT OF AUTHORITY AND PURPOSE

A. Governing Principles

Institutional Review Boards (IRBs) are guided by key ethical principles applied to all

research involving humans as subjects, as set forth in the report of the National

Commission for the Protection of Human Subjects of Biomedical and Behavioral

Research, titled: Ethical Principles and Guidelines for the Protection of Human

Subjects of Research (the "Belmont Report"). These principles are defined in the

Belmont Report (See Attachments) as follows:

1) Beneficence -- The sum of the benefits to the subject and the importance of

the knowledge to be gained from the research so outweigh the risks to the

subjects as to warrant a decision to allow the subject to accept these risks

and participate in the research.

2) Autonomy -- Legally effective informed consent is obtained, so that

subjects may be fully informed of the potential risks of participation in the

research and that participation is voluntary and free of coercion.

3) Justice -- The selection of subjects is equitable and is representative of the

population that will benefit from the research.

B. Institutional Authority

The LifeBridge Health IRB is established and empowered under the auspices of the

LifeBridge Health executive administration, and, for Federally Funded research, by the

Institution’s Federal–Wide Assurance (FWA) with the Office for Human Research

Protections (OHRP) of the Department of Health and Human Services (DHHS). The

IRB's Federal-Wide Assurance Number is FWA00003667 and is renewable every 3

years. Copies of the Federal-Wide Assurance document filed with the DHHS are also

available in the IRB office.



Two IRB committees have been established (IRB-A and IRB-B) which adhere to the

same underlying principles and are responsible to the same authorities. This Institution

requires that all research projects involving humans as subjects or human material be

reviewed and approved by the IRB prior to initiation of any research related activities,

including recruitment and screening of potential subjects. The IRB is established to

review biomedical and behavioral research involving human subjects within LifeBridge

Health regardless of the source of funding or sponsorship. All research conducted on

or about human subjects, and all other activities which even in part involve such

research, unless specifically exempted, are subject to these policies and procedures if

one or more of the following apply:

1. The research is sponsored by institutional authorities of LifeBridge Health

and/or;

2. The research is conducted by or under the direction of any member of the

medical staff, employee, faculty, resident, fellow, student or agent of the

LifeBridge Health in connection with his or her institutional

responsibilities; and/or

3. The research is conducted by or under the direction of any member of the

medical staff, employee, faculty, resident, fellow, student or agent of the

LifeBridge Health using any property or facility of the Institution; and/or

4. The research involves the use of the Institution's nonpublic information to

identify or contact human research subjects.

These policies and procedures apply to any research performed on the premises of

Sinai Hospital of Baltimore, Northwest Hospital Center and Levindale Hebrew

Geriatric Center and Hospital (hereinafter referred to as LifeBridge Health) and to any

such activity performed elsewhere by LifeBridge Health medical staff, faculty, house

staff, students, or employees under LifeBridge Health auspices. Part-time and

volunteer members of the Medical Staff are subject to these rules and regulations with

respect to any research conducted under the auspices of LifeBridge Health. Research is



considered to be conducted under the auspices of LifeBridge Health when it is

supported financially or by in kind services of LifeBridge Health, when the research

will take place at LifeBridge Health, when the research will involve participation by

LifeBridge Health students or employees, or when the use of a faculty appointment or

LifeBridge Health affiliation is made in correspondence with research subjects,

agreements with research sponsors, or descriptions of the research in other contexts.

The responsibility for appointing and maintaining the IRB rests with the Senior Vice-

President of LifeBridge Health, or his designee.

C. IRB Authority

The IRB will have the authority to determine whether or not any activity is covered by

these policies and procedures and whether it requires review by the IRB or may be

exempted. The IRB has the authority to ensure that research is designed and conducted

in such a manner that protects the rights and welfare of participating subjects.

Specifically:

1. The IRB may approve, disapprove, or request modification to proposed studies

based upon consideration of the potential risks and benefits, scientific merits

and human subject protection concerns;

2. The IRB reviews, and has the authority to approve, require modification in, or

disapprove, all research activities that fall within its jurisdiction;

3. The IRB has the authority to conduct continuing review as it deems necessary

to protect the rights and welfare of research subjects, including requiring

progress reports from the Investigators and auditing the conduct of the study,

observing the informed consent process and/or auditing the progress of any

study under its jurisdiction as it deems necessary to protect the rights and

welfare of human subjects;

4. The IRB may suspend or terminate approval of a study; and

5. The IRB may place restrictions on a study or investigator, when necessary.



For Federally funded research, if the study is part of an application to a Federal

sponsoring agency, the human protocol must be reviewed by the IRB before or when

the application is processed and prior to expenditure of any grant funds. The IRB also

has a relationship to other institutional research review committees such as the Sinai

Hospital Administration Review Board (ARB). The IRB functions independently of,

but in coordination with, those other committees. Research that has been reviewed and

approved by the IRB may be subject to review and disapproval by institutional officials

or other committees. However, those officials or committees may not approve research

if it has been disapproved by the IRB.

D. Responsibilities of the IRB

1. IRB Review of Research

All research involving human subjects (as defined below), and all other activities,

which even in part involve such research, must be reviewed and approved by the

LifeBridge Health IRB. No intervention or interaction with human subjects in

research, including recruitment of prospective subjects, may begin until the IRB has

reviewed and approved the research protocol. Specific determinations as to the

definition of “research” or “human subjects,” and their implications for the

jurisdiction of the IRB under LifeBridge Health policy are determined by the IRB

(see below).

The IRB's purpose and responsibility is to protect the rights and welfare of human

subjects. The IRB reviews and oversees such research to ensure that it meets

established ethical principles and that it complies with federal regulations at 45

CFR 46 and 21 CFR 50 and 56, that pertain to human subject protection, as well as

any other pertinent regulations and guidelines, including the Good Clinical Practice

(GCP) Guideline (E6) of the International Conference on Harmonization, state and

local regulations, and institutional policy.

According to Federal regulations, the activities that require IRB review include any

activities involving the collection of data through intervention or interaction with a LifeBridge Health IRB Revised Date: August 20, 2008 Page 6 of 133Policies and SOPs Original Date: June 6, 2003


living individual, or involving identifiable private information regarding a living

individual. Specific activities that require IRB review include, but are not

necessarily limited to the following:

a. Any experiment that involves a test article (investigational or FDA

approved agents) and one or more human subjects, and that either must

meet the requirements for prior submission to the Food and Drug

Administration (FDA) under relevant investigational drug or medical device

provisions of the Food, Drug, and Cosmetic Act, or studies that need not

meet the requirements for prior submission to the FDA, but the results of

which are intended to be later submitted to, or held for inspection by, the

FDA as part of an application for a research or marketing permit.

b. Any systematic investigation involving innovative procedures or treatments,

including innovative uses of FDA approved agents in a series of subjects,

c. All Federally funded research unless specific criteria for exemption are met

(see Functions and Operations: Exemptions from IRB requirements).

d. An investigational diagnostic procedure for research purposes that is added

to a standard treatment.

e. Collection of comparative data about a series of standard procedures or

treatments for dissemination, generalization, or publication.

f. Emergency use or “compassionate use” (use outside an approved research

protocol) of an investigational drug or medical device.

g. Human cell or tissue (genetic tissue) research that involves repositories that

collect, store, and distribute human tissue materials for research purposes.

h. Investigator-initiated research, where an Investigator both initiates and

conducts, alone or with others, a clinical study. In the case of Investigator-

initiated studies, it is the Investigator's responsibility to keep the IRB

informed of unanticipated adverse events and other unexpected findings that

affect the risk/benefit assessment of the research, even if the event occurred

at a location for which the Institution’s IRB is not the IRB of record.



i. Resident or Student-conducted research, which includes all activities that

meet the definition of research with human subjects and that are conducted

by students for a class project or for work toward a degree, and for which

findings may be published or otherwise disseminated, unless such project

meets criteria for exemption from review.

j. Case studies, such as when a series of subject observations are compiled in

such a way as to allow possible extrapolation or generalization of the results

from the reported cases, when there is intent to publish or disseminate the

data or findings.

k. If personally identifiable health information is to be used in a research

protocol, compliance with the HIPAA Privacy Act requirements is required,

and may require review and approval by the IRB. (See “HIPAA Policy Use

and Disclosure of Protected Health Information in Research,”). Activities

within the institution which use patient or other human subject information

and which are generally not subject to the requirement for review and

approval by the IRB include routine activities of Quality Assurance,

Performance Improvement, or departmental statistics.

2. Failure to Submit Research for IRB Review

The implications of engaging in activities that qualify as research that is subject to

IRB review without obtaining such review are significant. Results from such

studies may not be published unless IRB approval had been obtained prior to

collecting the data. To do so is in violation of institutional policy. Data collected

without IRB approval may be rejected by FDA if the data are submitted by a

sponsor in support of a marketing application. Repeated failure to submit research

for IRB review by an investigator will result in suspension or termination of the

investigator’s ability to conduct research, as enforced by the Compliance

Subcommittee of the LifeBridge Health IRB.

VIII. ORGANIZATION OF THE IRBLifeBridge Health IRB Revised Date: August 20, 2008 Page 8 of 133Policies and SOPs Original Date: June 6, 2003


A. Composition of the Board

1. Membership Selection Criteria

a) The membership shall be diverse, and selection shall include consideration of

race, gender, cultural backgrounds, clinical experience, healthcare experience

and sensitivity to community attitudes to assess the research submitted for

review.

b) There shall be at least one member whose primary concerns are in scientific

areas and at least one member whose primary concerns are in nonscientific

areas. There shall be at least one member who has no affiliation with this

institution, either self or family member. At least one member shall be a

member of the clergy or another community representative. For reviews of

FDA-regulated research, there shall be at least one member in attendance who

is a licensed physician.

c) The committee shall have at least eight regular members. Representatives with

expertise in the medical specialties under review shall be represented on the

IRB (see III. D, Scope of IRB Reviews). Members from the following

professional areas may also be represented on the committee: pharmacy,

psychology, pastoral care, legal and administration. Copies of the IRB

membership list are maintained in the IRB office.

d) The members shall be appointed by the Chairperson with concurrence of their

department chief. The members shall each be appointed for one year, with

annual review and reappointment possible and subject to approval by the

Chairperson. Attendance at two-thirds of the meetings in a year is required in

order for a member to stay on the IRB. The Chairperson shall have the right to

remove any member; grounds for removal includes:

(i) failure to contribute to the workings of the IRB.

(ii) numerous absences from scheduled meetings.

(iii) violation of the confidentiality of IRB proceedings.



2. Membership Types

a) Regular members: The backgrounds of the regular members shall be varied in

order to promote complete and adequate reviews of the types of research

activities commonly reviewed by the IRB. Regular members must include:

1. Nonaffiliated member(s): The nonaffiliated member(s), who can be either

scientific or nonscientific reviewers, will be knowledgeable about the local

community and be willing to discuss issues and research from that

perspective. Consideration will be given to recruiting individuals who

speak for the communities from which the LifeBridge Health draws its

research subjects.

2. Scientific members: The IRB will include several physicians, representing

various medical specialties, and may also include PharmD. or Ph.D.

scientists.

3. Nonscientific members: The intent of the requirement for diversity of

disciplines is to include members whose main concerns are not in scientific

areas. Therefore, nonscientific members are individuals whose education,

work, or interests are not solely in medical or scientific areas.

b) Consultants: When the IRB encounters studies in areas beyond the expertise of

the members, the IRB may use consultants to assist in the review, as provided

by 21 CFR 56.107(f).

B. Management

1. Appointments

The IRB Chairperson shall be appointed by the Senior Vice-President of LifeBridge

Health or designee. The President of LifeBridge Health will approve the selection

of the Chairperson. The initial appointment shall be for eighteen months, and

renewable annually thereafter. A Vice-Chairperson shall be appointed by the

Chairperson to assume his or her duties in his or her absence. The term of the

Vice-Chairperson will be renewable annually. The Research Coordinator will

handle the administrative functions of the IRB.



The IRB Chairperson with the assistance of the Research Coordinator, will submit

reports of IRB activities to the administration of LifeBridge Health on a periodic

basis, as required by the Senior Vice President of LifeBridge Health or designee.

2. Member Responsibilities:

a) New members shall receive a packet of information which includes the following:

1. IRB Policies and Procedures,

2. IRB Member Agreement,

3. Relevant educational and training materials, and resources for review.

b) The members shall not be compensated for routine IRB activities. The Chairperson

and Research Coordinator will be compensated at reasonable hourly rates.

c) New members will be expected to provide information about the member's earned

degrees, position or occupation, board certification, licenses, relationship to

LifeBridge Health, his or her representative capacity, and any potential conflict of

interest (COI) disclosures. Members will be required to disclose any personal,

professional, financial or other relationship with commercial sponsors of research

and department affiliation(s) within LifeBridge Health, Inc. which may impair his

or her ability to evaluate a proposed research activity in an unbiased manner. Any

IRB member with such interest may participate in the discussion of a study for the

purpose of providing information requested by the IRB; however, he or she must be

recused from the vote. Issues involving questionable conflict of interest shall be

resolved by the Chairperson.

d) Continuing reviewer education and periodic certification will be required of all

committee members. (See Education and Training Policy). The Chairperson, staff

and other members of the IRB, will be encouraged to periodically attend relevant

continuing education meetings on human subjects protection or the responsible

conduct of research. The Chairperson and other members as designated shall make

periodic presentation of educational topics of interest to the IRB committee.



Continuing reviewer education and periodic certification will be required of all

committee members.

3. Resources

All members of the IRB will receive liability coverage in the performance of their

duties as committee members as per applicable policies of LifeBridge Health. The IRB

shall maintain written minutes and copies of all protocols reviewed, as well as

amendments and revisions to protocols and consent forms. Administrative services and

office space shall be provided to the IRB.

C. Duties of IRB Members

1. Policy

Each IRB member's primary duty is the protection of the rights and welfare of the

individuals who are serving as the subjects of that research. The IRB member must

understand that he or she is not serving on the IRB to expedite the approval of

research, but as a member of a group charged with ensuring the ethical conduct and

scientific merit of research proposals. In order to fulfill their duties, IRB members

are expected to be versed in regulations governing human subjects protection,

biomedical and behavioral research ethics, and the policies of LifeBridge Health,

Inc. germane to human subjects protection.

a) Duty to the LifeBridge Health, Inc. Organization

The IRBs are appointed as LifeBridge Health Committees. As such, the IRB

members serve the institution as a whole, rather than a particular department.

Therefore, members must not allow their own interest or that of their

department to supercede their duty to protect the rights and welfare of research

subjects.

b) Term of Duty

Regular IRB members and Chairpersons are expected to commit to a one-year

term, renewable annually and, during that time, to fulfill certain duties (see

Member Agreement). These duties will be described prior to appointment and



each IRB member is expected to fully understand the duties of IRB members

prior to accepting appointment as an IRB member.

c) Specific Duties

Regular Members:

Nonaffiliated member(s): Nonaffiliated members are expected to provide input

regarding their knowledge about the local community and be willing to discuss

issues and research from that perspective.

Non-scientific members: Nonscientific members are expected to provide input

on areas germane to their knowledge, expertise and experience, professional

and otherwise. For example, members who are lawyers should present the legal

views of specific areas that may be discussed, such as exculpatory language or

state requirements regarding consent. Non-scientific members should advise

the IRB if additional expertise in a non-scientific area is required to assess if the

protocol adequately protects the rights and welfare of subjects.

Scientific members: Scientific members are expected to contribute to the

evaluation of a study on its scientific and statistical merits and standards of

practice. These members should also be able to advise the IRB whether the

protocol and informed consent adequately protects the rights and welfare of

subjects, and to advise if additional scientific or non-scientific expertise is

required.

Chairperson: The Chairperson chairs meetings of the IRB, assigns reviews, and

sets meeting agendas with the assistance of the IRB Research Coordinator. The

Chairperson performs or delegates to an appropriate voting IRB member all

expedited reviews. The Chairperson is empowered to suspend the conduct of a

clinical trial deemed to place individuals at unacceptable risk, pending IRB

review. The Chairperson is also empowered, pending IRB review, to suspend

the conduct of a study if he/she determines that an Investigator is not following

the IRB’s requirements. LifeBridge Health IRB Revised Date: August 20, 2008 Page 13 of 133Policies and SOPs Original Date: June 6, 2003


A Vice-Chairperson is appointed to assist or act on behalf of the Chairperson in

particular IRB matters and at IRB meetings, when the Chair is not present, as a

matter of general procedure, and on a case-by-case basis. The Chairperson also

may delegate any of his/her responsibilities as appropriate to other qualified

individual(s). Such ad hoc delegation will be in writing and tracked by the IRB

Research Coordinator.

The task of making the IRB a respected part of the institutional and community

will fall primarily on the shoulders of IRB members. The IRB continually

strives to be fair and impartial, immune from pressure by the institution's

administration, the Investigators or sponsors whose protocols are brought before

it, and other professional and nonprofessional sources.

Primary Reviewers: In addition to the duties described previously, each regular

member will be expected to act as a Primary Reviewer for assigned studies at

convened meetings. Two Primary scientific reviewers will be assigned for new

protocols. One primary scientific reviewer will be assigned for continuing

review amendments and reviews of Serious Adverse Events (SAEs). The

Primary Reviewer is expected to complete the review of the prospective study

and supporting documentation prior to the IRB meeting date and to identify any

omissions, clarifications needed or potential deficiencies. At the meeting the

Primary Reviewer presents his or her findings and provides an assessment of

the soundness and safety of the protocol (leads the IRB discussion of the study)

and recommends modifications and/or specific actions to the IRB. When

approval is deferred or provisional approval is granted the Primary Reviewers

may be required to review additional material upon submission for the purpose

of determining final approval. One primary non-scientific reviewer will be

assigned for each new submission and for continuing reviews of renewal

requests, amendments or serious adverse event reports. This reviewer is



responsible for conducting an in depth review of the consent form and any

included assent forms, for leading the discussion on the consent form, and

consent process, and for making recommendations to the committee regarding

specific modifications.

d) Designated Alternate

Each Member is responsible for designating an alternate individual, preferably

from his/her department or in the same field, to perform reviews and attend

meetings when the member cannot attend (see Alternate Agreement).

Substitution of individuals other than the designated alternate is not allowed at

IRB meetings. Alternates will be subject to the same requirements for

education, training, disclosure of potential COI information, performance of

reviews and participation in meetings as regular members.

2. Administration

The IRB Research Coordinator is responsible for clearly articulating IRB members’

duties to potential and current IRB members. IRB Members are responsible for

fulfilling their duties as specified.

3. Applicable Regulations and Guidelines

45 CFR 46.l07

21 CFR 56.107

OHRP IRB Guidebook

FDA Information Sheets FAQ, section II, questions 14, 15, and 17

4. Attachments

Member Agreement

Designated Alternate Agreement

D. Scope of IRB Reviews

1. Designation of Review Authority by Medical Specialty and Department



Review authority will be designated by originating department and medical

specialty as follows, effective January 14, 2004:

a. IRB A: Pediatrics, Perinatology, Oncology, Orthopedic Surgery, Rehabilitation

Medicine, Obstetrics and Gynecology, Women’s and Children’s Services,

b. IRB B: Internal Medicine and subspecialties, General Surgery and

subspecialties, including Surgical Oncology and Ophthalmology, Pharmacy,

Pathology, Psychiatry, Social Work, Radiology.

2. Transfers of Review Authority Between IRBs A and B

New submissions will be assigned to the appropriate committee as above after the

effective date of this policy. Ongoing studies subject to continuing review and

other submissions previously reviewed may be transferred from IRB A to IRB B

and from IRB B to IRB A using the following procedure:

a. The Chairperson and Vice Chairperson of the originating IRB (A or B) will

initiate a written request (memorandum) for the other committee to accept

review responsibility for each submission to be transferred.

b. The Chairperson and Vice Chairperson of the accepting IRB (A or B) will

respond in writing (memorandum) indicating acceptance of the review

responsibility for each submission to be received.

c. The effective date of the transfer will be indicated in both the originating and

the accepting memoranda.

3. Membership

Membership of each IRB committee shall be adjusted so that appropriate expertise

is included across the specialty areas included in the committee’s scope (see III. A.

Composition of the Board).

4. AdministrationLifeBridge Health IRB Revised Date: August 20, 2008 Page 16 of 133Policies and SOPs Original Date: June 6, 2003


The Research Coordinator and IRB Chairperson are responsible for maintaining

accurate records of the protocols reviewed by each IRB, and for periodic updating

as required.


45 CFR 46.107

21 CFR 56.107



IX. GENERAL ADMINISTRATION

A. Policies and Procedures Maintenance

1. Policy

Following regulations and guidance of OHRP, FDA, and the International

Conference on Harmonization (ICH), supported by institutional policies, ensures

that the rights and welfare of the human subjects of such research will be overseen

and protected in a uniform manner, regardless of changes in personnel. Written

procedures must be in place to ensure the highest quality and integrity of the review

and oversight of research involving human subjects and for the adequate

documentation of such oversight. Standard operating policies and procedures

(SOPs) provide the framework for the ethical and scientifically sound conduct of

human research.

a. Review, Revision, Approval of Policies & Procedures

1. Changes to regulations, Federal guidelines, or research practice as well

as the policies and procedures of LifeBridge Health may require a new

SOP or a revision to a previously issued SOP.

2. Policies will be reviewed by the appropriate institutional official(s) at

intervals established by the Chairperson and IRB Research

Coordinator. (Policies and procedures will be developed and

periodically revised as needed to accommodate to changes in

regulations or institutional practices).

3. Policy development and revision will be the responsibility of the IRB

Chairperson and Vice Chairpersons, subject to concurrence by the

Senior Vice President of LifeBridge Health or designee.

4. Documentation of review and approval is required by signature of the

responsible and authorized individuals.

b. SOP Dissemination and Training



1. When new or revised SOPs are approved, they will be disseminated to

the appropriate individuals & departments as required.

2. Training will be provided to all members of the IRB and IRB staff on

any new or revised policy and/or procedure. It is the responsibility of

members to complete all required training.

3. Each new IRB member or staff employee must review all applicable

SOPs prior to undertaking their IRB responsibilities.

c. Forms

1. Forms are used to 1) ensure that policies are integrated into the daily

operations of research and review throughout the LifeBridge Health

system, and 2) enable IRB staff to manage review, tracking, and

notification functions consistently. Forms will be reviewed and

modified by the IRB staff as needed to accomplish these functions.

2. Responsibility

The Senior Vice President of LifeBridge Health is responsible for granting final

approval to new and revised IRB policies.

The IRB Chairperson in consultation with The Vice Chairpersons and The IRB

Research Coordinator (or designee) is responsible for establishing and periodically

reviewing and modifying IRB standard operating policies and procedures.

3. Applicable Regulations And Guidelines

21 CFR 56.108, 56.109, 56.113

45 CFR 46.108

B. Education and Training

1. Policy Rationale and To Whom This Policy Applies

The administration of LifeBridge Health recognizes that the requirements for

regulatory and ethical oversight of clinical research have increased in recent years,



at the Federal, state and local institutional level. To keep pace with this evolution,

and to ensure that clinical research within the LifeBridge Health system adheres to

the highest ethical standards and is fully in compliance with applicable regulations,

the LifeBridge Health administration has instituted the following policy for:

a. All Clinical Investigators and Staff who participate in clinical research within

LifeBridge Health for:

1. certification of clinical competence to perform research studies, and

2. continuing education to keep pace with changing requirements, and for

b. All Institutional Review Board members, designated alternates and staff, for

1. education in the requirements of review of research studies, and

2. continuing education to keep pace with changing requirements.

This policy applies to all members of the medical staff, medical residents and

fellows in training who are responsible for recruitment, enrollment, treatment

and/or follow-up of subjects in clinical research within the institution. This

includes research projects deemed “exempt” from IRB oversight. Department

Chiefs, administrators and others who oversee staff who conduct clinical research

studies within the institution are also encouraged to avail themselves of the

resources detailed herein.

2. The Collaborative IRB Training Initiative (CITI)

The CITI human subjects research educational program consists of a basic course

of 17 training modules for Biomedical investigators and a similar number of

modules specifically prepared for investigators conducting Social/Behavioral

research. Each module was developed by experts in the "IRB community", focuses

on different aspects of bio-ethics and human subjects research, and has an

associated quiz. Software maintained at the University of Miami compiles the quiz

scores. When the user completes the required materials (which takes ~20

min/module), the learner can print/download a Completion Report that details the LifeBridge Health IRB Revised Date: August 20, 2008 Page 20 of 133Policies and SOPs Original Date: June 6, 2003


learner’s accomplishments. A copy of the report is e-mailed to the institutional

IRB administrator. The CITI training program can be found at:

https://www.citiprogram.org/default.asp

3. Requirements

a) For Principal Investigators and Clinical Research Coordinators

(i) Individuals involved in biomedical research are required to complete The

CITI Program “Group 1” training consisting of 12 modules prior to

initiating any research activity.

(ii) Individuals involved in Social and Behavioral Research training are

required to complete The CITI Program “Group 3” consisting of 12

modules prior to initiating any research activity. .

b) For All Clinical Investigators (Co-Investigators), and Research Staff

(i) Individuals involved in biomedical research are required to complete The

CITI Program “Group 2” training consisting of 8 modules prior to

initiating any research activity.

(ii) Individuals involved in Social and Behavioral Research training are

required to complete The CITI Program “Group 4” consisting of 8

modules prior to initiating any research activity.

c) For IRB Members, Designated Alternates, and IRB Staff

(i) For new appointments, within 120 days of appointment:

1. The CITI Program “Group 1” training consisting of 12 modules is

required.

(ii) For those with current appointments, it is required that they maintain

their current educational training by completing The CITI Program within

two years of their last completed training session.

4. Alternatives and Additional Resources

a. For “Group 1 and Group 3 Training Requirements”



https://www.citiprogram.org/default.asp

The CITI Program completed at another institution may satisfy LBH IRB

training requirements within two years from the date of the documented

completed training session. Alternate coursework provided by appropriately

certified educational, regulatory or governmental entities or professional

societies may be substituted for The CITI Program, subject to approval by the

Research Office.

b. Additional Resources

The Medical Libraries will maintain the following reference collections for use

by any individuals who seek to update their knowledge at any time:

1. Federal Regulations governing Federally-sponsored and FDA-regulated

clinical research, Good Clinical Practices, investigator and IRB

responsibilities

2. FDA Information Sheets and OHRP guidance documents, “IRB Guidebook”

3. LifeBridge Health, Inc. IRB Policies and Standard Operating Procedures

4. Foundations of Human Subject Protection, c.2003, Center for Clinical

Research Practices

5. Foundations of Clinical Research, c.2002, Center for Clinical Research

Practices

6. International Conference on Harmonization (ICH) documents

7. Code of Helsinki

8. Belmont Report

9. Selected articles, documents and texts on research ethics, clinical trial

design and conduct, informed consent procedures, and other related topics

10. A listing of online resources is available on the LifeBridge Health, Inc.

Intranet site, including links to government agencies, regulations, guidance

documents, and professional societies.

5. Consequences for Failure to Comply with this Policy

Failure to complete required certification as outlined in this policy by the indicated

dates will result in the following actions:



a. Refusal to accept new research applications from the non-compliant

Investigator and staff by the IRB office, and

b. Suspension of the non-compliant Investigator and staff from participation in

further research until the requirements are met.

c. IRB Members who do not comply with deadlines imposed will have their status

changed to a non-voting member with a one-(1) month extension to fulfill the

requirements. If the requirements are not met, the member will be removed

from the IRB committee.

The above actions may be modified at the discretion of the IRB chairperson.

3. Responsibility

a. The IRB Research Coordinator will maintain certificates of completion on file

in the IRB office.

b. The Chairperson retains the authority to enforce such refusals and suspensions,

and may designate such authority to the IRB Research Coordinator, Vice-

Chairperson or other individual as appropriate.

c. Referral to the Compliance Subcommittee may be made.


21 CFR 56.107

45 CFR 46.107

OHRP IRB Guidebook

21CFR 56.102(e)

45 CFR 46.102(f)

NIH Notice: OD-00-039 “Required Education in the Protection of Human

Research Participants”



X. FUNCTIONS AND OPERATIONS

A. Research Submission Requirements

1. Policy

IRB members often rely solely on the documentation submitted by Investigators

for initial and continuing review. Therefore this material must provide IRB

members with enough information about a study to assess if it adequately meets

the IRB's criteria for approval. A submitted protocol will be scheduled for IRB

review when staff has determined that the information and materials submitted

present an adequate description of the proposed research.

1a. Submission Requirements for Initial Review

i. Required: Investigators applying for initial approval of a proposed

research protocol must submit:

1. IRB Application signed by the Principal Investigator and Department

Chief

2. Signed co-investigator forms and Conflict Of Interest disclosures

3. Study Summary Form

4. Research protocol with all appendices.

5. Investigator Brochure, package insert or device specifications for all

investigational agents, including agents which are FDA-approved but

investigational in the proposed study.

6. Questionnaires & assessment instruments if applicable

7. Proposed informed consent document and pediatric assent

document(s)

8. Investigation Delegation of Responsibility Form

9. Any other printed material to be given to subjects (instruments, quality

of life information sheets, etc).

10. Examples of recruitment and advertising materials.

11. Any other relevant supportive material (academic papers IND-

exemption letters, device risk classification statements from the

manufacturer, etc. as appropriate) LifeBridge Health IRB Revised Date: August 20, 2008 Page 24 of 133Policies and SOPs Original Date: June 6, 2003


ii. In addition, applicants may be required to submit:

1. Copies of FDA Financial disclosure statements

2. FDA Form 1572 (for studies under IND) or signed Investigator

Agreement (for studies under IDE).

3. Sample Case report forms

4. Documentation that the study has been reviewed and approved by

other committees charged with oversight of research at the LifeBridge

Health, Inc. as appropriate (radiation safety, biosafety, etc).

2. IRB Review Fee

The charge for an initial IRB review of a single protocol is $2,000. The fee

for expedited review is $1000. The cost of a review for exempt status is

$500. These are onetime upfront fees, with no additional charge for the

continuing (annual) review of a protocol, or for the processing of protocol

amendments.

Applicability

These fees apply to all industry-funded human subjects research conducted in

any LifeBridge Health (LBH) facility, including sponsor-initiated and

investigator-initiated studies. Excluded from the IRB review fees are human

research protocols funded by federal or state agencies, non-profit foundations,

or by departments/divisions/centers within the LifeBridge Health

organization. The fee should be added to the budgets of contracts that are

entered directly with for-profit companies, as well as subcontracts issued to

LBH from another institution.

Human Subjects Research Budgets

The IRB review fee is to be included in budgets that are submitted with the

LBH Administrative Review Board (ARB) application form for ARB

approval. The IRB review fee is exempt from the calculation of indirect costs

(F&A) on these projects, and therefore should be listed as a separate invoiced

item that is included in the total budget amount. Clinical trial budget



submissions are reviewed by ARB, whose staff is available to investigators

for assistance in budget preparation.

IRB Review Fee Invoice and Collections Process

The IRB review fee should be a line item in the sponsor budget, is included in

the agreement, and is therefore an obligation of the external industry sponsor.

The IRB review fees are assessments for a portion of the real costs associated

with protocol review by the IRB. Invoices for the IRB review fee are

generated and submitted to sponsors once a protocol has been submitted to the

IRB for review. The actual costs of the review process are still incurred if

subjects are never enrolled, the study terminates before milestones are met,

expenditures exceed revenue, or a contract is never finalized. The invoice is

therefore due and payable upon receipt. The investigator and/or department

will be responsible for all costs not covered by the sponsor, specifically

including the IRB review fee.

Contacts

For questions regarding IRB fee invoicing and applicability contact the LBH

Research Office at 410-601-9021.

3. Submission Requirements for Continuing Review

a) During the approval period, Investigators must submit documentation to

inform the IRB regarding changes in the status of the study including, but

not necessarily limited to:

1. Protocol amendments or revisions

2. Deviations from the protocol (protocol violations)

3. Reports of serious and unexpected adverse events

4. For IND/IDE studies, reports of serious and unexpected adverse events

that

5. occur during the approval period as required by FDA regulationLifeBridge Health IRB Revised Date: August 20, 2008 Page 26 of 133Policies and SOPs Original Date: June 6, 2003


6. Changes to the status of Principal or Co-investigators

b) Progress Report and/or Request to Renew IRB Approval

At least sixty (60) days prior to the IRB approval expiration date,

Principal Investigators requesting renewal of an approved research project

must submit:

1. A completed Continuing Review Renewal Request Form.

2. All the required materials that are indicated on the form are also

required prior to review.

4. Action Taken If Documentation is Not Adequate or Additional

Information is Required

If the IRB or IRB staff determine that the submitted documents are

incomplete or not adequate for review, Investigators may be required to

submit additional information, and or their presence may be required at the

IRB meeting to answer questions or explain the details of the study.

Incomplete submission will not be reviewed by the IRB. Applications

missing substancial portions of documentation will be deferred from

presentation at an IRB meeting until complete.


45 CFR 46.115

21 CFR 56.108 (a)(4)

21 CFR 312, 812

ICH Good Clinical Practice (GCP) Guideline

B. Exemptions from IRB review

1. Policy

Federal regulations have exempted from review certain categories of social,

educational, and economic research activities [45 CFR 46-101(b).] Research in the

categories described in the section below is considered exempt from review by the

LifeBridge Health IRB, and is based on regulatory and institutional criteria:



a. Research conducted in established or commonly accepted educational settings,

involving normal educational practices, such as

1. research on regular and special education instructional strategies, or

2. research on the effectiveness of or the comparison among instructional

techniques, curricula, or classroom management methods.

b. Research involving the use of educational tests (cognitive, diagnostic, aptitude,

achievement), if information taken from these sources is recorded in such a

manner that subjects cannot be identified, directly or through identifiers linked

to subjects.

c. Research involving survey or interview procedures, except where any of the

following conditions exist:

1. responses are recorded in such a manner that the human subjects can be

identified, directly or through identifiers linked to the subjects,

2. the subject’s responses, if they became known outside the research, could

reasonably place the subject at risk of criminal or civil liability or be

damaging to the subject’s financial standing or employability, and

3. the research deals with sensitive aspects of the subject’s own behavior, such

as illegal conduct, drug use, sexual behavior, or use of alcohol. All research

involving survey or interview procedures is exempt, without exception,

when the respondents are elected or appointed public officials or candidates

for public office.

4. Research involving the observation (including observation by participants)

of public behavior, except where all of the following conditions exist:

a) observations are recorded in such a manner that the human subjects can

be identified, directly or through identifiers linked to the subjects,

b) the observations recorded about the individual, if they became known

outside the research, could reasonably place the subject at risk of

criminal or civil liability or be damaging to the subject’s financial

standing or employability, and



c) the research deals with sensitive aspects of the subject’s own behavior

such as illegal conduct, drug use, sexual behavior, or use of alcohol.

5. Research involving only 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.

6. Unless specifically required by statute (and except to the extent specified in

paragraph (a) below), research and demonstration projects that are

conducted by or subject to the approval of the Department of Health and

Human Services, and are designed to study, evaluate, or otherwise examine:

a) programs under the Social Security Act, or other public benefit or

service programs;

b) procedures for obtaining benefits or services under those programs;

c) possible changes in or alternatives to those programs or procedures; or

d) possible changes in methods or levels of payment for benefits or

services under those programs.

2. Responsibility

The IRB Chairperson or designee, with the assistance of the IRB Research

Coordinator, is responsible for making determinations of exemption.

3. Applicable Regulations

45 CFR 46.101

21 CFR 46.104

21 CFR 46.105

4. Attachments

See Section XIII - Forms

C. IRB Meeting AdministrationLifeBridge Health IRB Revised Date: August 20, 2008 Page 29 of 133Policies and SOPs Original Date: June 6, 2003


1. Policy

Except when an expedited review procedure is used, the IRB will review proposed

research at convened meetings at which a quorum is present. The IRB will meet

monthly, on the second and fourth Wednesday of each month. A quorum, defined

as a majority of the members, shall be required to be present to conduct business.

A. Quorum

1. A quorum is defined as a majority; that is, one half of the number of regular

members plus one.

2. A quorum may include regular and/or designated alternate members and

must include at least one member whose primary concerns are in scientific

areas, and one member whose primary concerns are in nonscientific areas.

3. When FDA-regulated research is reviewed, there shall be one member who

is a physician.

4. An alternate member may attend in the place of an absent regular member

in order to meet the quorum requirements outlined above.

5. A special consultant(s) may not be used to establish a quorum.

B. Primary Reviewers

Prior to the meeting, the Chairperson or IRB Research Coordinator will

designate primary reviewers for each research proposal.

C. Meeting Materials Sent Prior to IRB Meetings

All IRB members will be sent study documentation required for review

sufficiently in advance of the meeting to allow time for adequate review. These

include:

1. Agenda: a meeting agenda will be prepared by the IRB Research

Coordinator (or designee) and distributed to IRB members prior to each

meeting. A copy of the agenda and attached materials will be maintained

on file with the meeting minutes. Members are to declare any potential

conflict of interest they may have with research that is about to be reviewed

at the initiation of each discussion. The chair will ask the member to recuse



him/herself from deliberation and voting. The IRB minutes will specifically

document recusals as they occur during meetings.

2. All IRB members will receive:

a. A completed IRB Application, Study Summary Form with a signature

page and

b. conflict of interest statement and/or protocol synopsis

c. Proposed informed consent and/or assent document(s) and lay summary

d. Amendments, serious adverse events or DSMC reports, or relevant

background materials if appropriate to the particular review

3. Primary reviewers will receive:

a. Full Investigator’s or Sponsor’s protocol

b. A completed IRB Application, Study Summary Form with a signature

page and

c. conflict of interest statement

d. Proposed informed consent and /or assent document(s)

e. Copies of surveys, questionnaires, or videotapes (if applicable)

f. Investigator Brochure (if one exists), Package insert or Directions For

Use

g. Advertising intended to be seen or heard by potential subjects, including

email

h. solicitations and physician letters

i. IRB Review of NIH-Approved Informed Consent Documents for NIH-

Supported Multi-center Clinical Trials: For NIH-supported multi-center

clinical trials the IRB must receive and review a copy of the NIH-

approved sample informed consent document and the full NIH-approval

of the local informed consent document. Any deletion or substantive

modification of information concerning risks or alternative procedures

contained in the sample informed consent document must be justified in

writing by the Investigator, approved by the IRB, and reflected in the

IRB minutes.LifeBridge Health IRB Revised Date: August 20, 2008 Page 31 of 133Policies and SOPs Original Date: June 6, 2003


j. Copies of relevant correspondence, serious adverse events or DSMC

reports, or other documents as appropriate

4. Minutes

The Federal regulations for the protection of human subjects [45 CFR

46.115(a)(2)] detail requirements for the content of IRB minutes.

D. Recording: The IRB Research Coordinator will take minutes of each meeting.

Minutes will be written in sufficient detail to show: attendance at the meeting;

actions taken by the IRB; the vote on these actions including the number of

members voting for, against, and abstaining; the basis for requiring changes in

or disapproving research; and a written summary of the discussion of

controverted issues and their resolution.

E. Approval: Draft minutes will be distributed to members at the next IRB

meeting for review and approval.

1. Corrections requested by IRB members will be made by the IRB Research

2. Coordinator or designee and the minutes will be printed in final form and

made available to members at the following meeting.

3. The IRB Research Coordinator will maintain copies of the minutes, as well

as the agenda and pertinent materials on file in the IRB office.

4. A majority of the members present must vote in favor of an action for that

category of action to be accepted by the IRB. Only regular and alternate

members acting in place of absent regular members may vote. The vote

will be recorded in the minutes. Members with a conflict of interest will

recuse themselves from the discussion and voting and such will be noted in

the minutes.

5. Actions taken by the IRB on each agenda item requiring full IRB action,

including,

6. the basis for requiring changes in or disapproving the research;

7. Summary of the discussion of controverted issues and resolution; LifeBridge Health IRB Revised Date: August 20, 2008 Page 32 of 133Policies and SOPs Original Date: June 6, 2003


8. Voting results, including number for, against and members who recused

themselves and reason for recusal.

F. Telephone Use

1. Convened meeting using speaker phone:

Should a member not be able to be physically present during a convened

meeting, but is available by telephone, the meeting can be convened using a

speakerphone. The member who is not physically present will be connected

to the rest of the members via speakerphone. In this manner, all members

will be able to discuss the protocol even though one member is not

physically present. Members participating by such speakerphone call may

vote, provided they have had an opportunity to review all the material the

other members have reviewed.

2. Meetings Conducted Via Telephone Conference Calls:

On occasion, meetings may be convened via a telephone conference call. A

quorum (Section VC1a above) must participate for the conference call

meeting to be convened. To allow for appropriate discussion to take place,

all members must be connected simultaneously for a conference call to take

place. Telephone polling (where members are contacted individually) does

not qualify as a conference call. Members not present at the convened

meeting or participating in the conference call may not vote on issues

discussed at the meeting.

G. Voting

Members of the IRB vote upon the recommendations made by the primary

reviewers according to the criteria for approval (see SOP RR 402 and 404).

Members also will determine level of risk, the frequency of review for each

protocol whether, monitoring or audit of the investigative site is required, and

whether third party assessment and follow-up will be needed.



Applications may be:

1. Approved,

2. Provisionally approved pending minor changes in the protocol or

consent/assent forms, or

3. Deferred (not approved).

In cases where a study is deferred, the Committee will provide its rationale for

the action taken in writing to the Principal Investigator. An application for

study which is deferred with clarifications or modification requested will be

considered active for 90 days from the meeting date in which it was considered.

Failure to respond within that 90-day period will cause the study file to be

closed. The investigator may request an appearance before the Committee to

present arguments for reversal of the decision or propose a change in the

protocol based on the advice and counsel of the Committee.

H. Investigator Attendance of Meetings

Investigators may be requested to appear before the committee to respond to

questions or provide clarification regarding proposed research and should plan

to be available at the time of IRB review in the event that this is necessary.

I. Notification

Written notification of actions taken at the full Committee meeting is provided

to each Principal Investigator whose research is reviewed as soon as possible

after each convened meeting. The rationale for actions taken and modification,

additional information or clarifications requested will be communicated in

writing. For approved studies, attached to the standard approval letter is the

final approved version of the consent form with the Committee approval stamp

affixed. IRB approval of the protocol and the consent form is valid for one

year, and expires one year from the date of IRB approval regardless of when the

research begins. If the consent forms are revised in association with an interim



review, IRB approval of the revised forms is valid only until the original

continuing review date for the project.

2. Responsibility

The IRB Research Coordinator is responsible for IRB meeting procedural conduct

and documentation. The IRB Chairperson (or designee) is responsible for meeting

review conduct and leadership.


45 CFR 46.103, 46.108

21 CFR 56.108, 56.109

FDA Information Sheets, 1998

D. Administrative Review and Distribution of Materials

1. Policy

The efficiency and effectiveness of the IRB is supported by administrative

procedures that ensure that IRB members not only have adequate time for thorough

assessment of each proposed study, but that the documentation they receive is

complete and clear enough to allow for an adequate assessment of study design,

procedures, and inclusion criteria, the consent process and conditions for

participation.

a. Exemptions

The IRB Research Coordinator will review prospective studies to determine

exemption status in consultation with the IRB Chairperson. Such

determinations will be filed.

b. Incomplete Submissions

Incomplete applications will not be accepted for review until the Investigator

has provided all necessary materials as determined by the IRB Research

Coordinator or designee. The IRB Research Coordinator will notify the

submitting Investigator to obtain any outstanding documentation or additional

information before the application is scheduled for review.LifeBridge Health IRB Revised Date: August 20, 2008 Page 35 of 133Policies and SOPs Original Date: June 6, 2003


c. Scheduling for Review

Complete applications that appear to meet qualifications for expedited review

will be submitted to the Chairperson or his/her designee. If a submission meets

expedited review requirements, the review will be performed as described in

Section---(Expedited Review). All other applications will be placed on the

agenda for the earliest meeting possible for review by the full IRB as described

in Section---(IRB Meeting Administration).

d. Distribution to Members Prior to IRB Meetings

Copies of application materials described in Section---(Research Submission

Requirements) will be distributed to all IRB members, generally 7 to 10 days

prior to the meeting. Each regular member of the IRB, and any alternate

members attending the meeting in place of a regular member, will receive a

copy of the initial application material. Consultants will only receive copies of

material that pertain to their requested input.

The originals of submission materials will be retained in the IRB Office and

will be available for the IRB meeting.

e. Confidentiality

All material received by the IRB will be considered confidential and will be

distributed only to meeting participants (regular members, alternate members

and special consultants) for the purpose of review. All application materials will

be stored in a secure IRB study file with access limited to the IRB members and

staff. Consultants and visitors will be expected to maintain the confidentiality

of any written documents received and to observe confidentiality procedures

during and after convened meetings. All meeting materials are to be returned to

the IRB Research Coordinator at the end of each convened meeting.



2. Responsibility

The IRB Research Coordinator is responsible for conducting appropriate

assessment of submissions for triage purposes.

The IRB Research Coordinator is responsible for providing complete review

material packets to IRB members and other relevant parties.

The IRB Chairperson (or designee) is responsible for supporting and assisting the

IRB Manager in submission triage activities.


21 CFR 56.109

45 CFR 46.109

E. Documentation and Document Management

1. Policy

The IRB’s files will be maintained in a manner that contains a complete history of

all IRB actions related to review and approval of research protocols, including

initial and continuing reviews, amendments, adverse event reports and

correspondence.

All records regarding a submitted study (regardless of whether it is approved) will

be retained in an appropriate manner as required by regulatory requirements and/or

LifeBridge Health policy.

Records will be accessible for inspection and copying by authorized representatives

of regulatory agencies and institutional auditors at reasonable times and in a

reasonable manner.

a. Document Retention

The IRB Office will retain all records regarding an application (regardless of

whether it is approved) for at least three (3) years. For all applications that are



approved and the research initiated, the IRB Office will retain all records

regarding that research for at least three (3) years after completion of the

research.

1. Study-related documents:

Adequate documentation of each IRB's activities will be prepared,

maintained and retained in a secure location. Retained documents include:

a. Copies of all original research protocols reviewed, scientific evaluations,

subjects

b. and reported deviations from the protocol.

c. Agendas and minutes of all IRB meetings.

d. Copies of all submitted monitoring reports, site visit reports and other

continuing

e. review activities.

f. Copies of all correspondence between the IRB and the Investigators.

g. Statements of significant new findings provided to subjects.

h. Reports of any complaints received from subjects or others.

b. IRB Administration Documents

The IRB Office will maintain and retain all records regarding IRB

administrative activities that affect review activities for least three (3) years.

The IRB Office will retain all records regarding protocols that are approved and

the research initiated for at least three (3) years after completion of the research.

1. Rosters of regular and alternate IRB members identified by name, earned

degrees, representative capacity, and indications of experience sufficient to

describe each regular and alternate member's chief anticipated contribution

to the IRB’s deliberations; and any employment or other relationship

between each member and the IRB and/or LifeBridge Health (e.g., full-time

employee, part-time employee, member of governing panel or board,

stockholder, paid or unpaid consultant).



Alternate members shall be included on the complete board roster. In

addition to the above information, the roster shall indicate the regular

member for whom the alternate may substitute.

Current and obsolete membership rosters will remain in the IRB Office and

then archived according to LifeBridge Health policy.

The roster of IRB members will be submitted to OHRP, and any changes in

IRB membership will be reported to OHRP periodically.

2. Maintain current and obsolete copies of the Standard Operating Policies and

Procedures.

3. Delegation of specific functions, authorities, or responsibilities by the IRB

Chairperson not otherwise authorized by these policies will be documented

in writing and filed in the IRB Office.

c. Destruction of Copies

All material received by the IRB, which is considered confidential and in excess

of the required original documentation and appropriate forms, will be collected

at the end of the meeting and destroyed by an appropriate method (i.e.

shredding).

d. Archiving and Destruction

After 3 years, all documents and materials germane to IRB determinations will

be archived according to institutional policy. Archiving policies of LifeBridge

Health will determine when such archived records may be destroyed.

2. Responsibility

IRB Research Coordinator and Administrative Assistant are responsible for

maintaining complete files on all research reviewed by or submitted to the IRB and

for all applicable regulatory compliance requirements.




45 CFR 46.103,115

21 CFR 56.115



XI. REVIEW OF RESEARCH

A. Expedited Review

1. Policy

An expedited review procedure consists of a review of research involving human

subjects by the Chairperson or by one or more experienced reviewers designated by

the Chairperson from among members of the IRB. The categories of research that

may be reviewed by the IRB through an expedited review procedure include

research activities that

a. present no more than “minimal risk” to human subjects (see below), and

b. involve only procedures listed in one or more of the specific categories listed in

the regulations at Federal Register Volume 63, No 216, November 9, 1998 (See

“Categories of Research that May be Reviewed by the IRB Through an

Expedited Review Procedure”, Attachments).

2. Case Reports & Chart Reviews

The LifeBridge Health (LBH) Institutional Review Board (IRB) does not consider case reports and chart reviews presented in a purely descriptive manner (i.e., lacking data analysis) as research*, and as such do not require either verification of IRB exemption or IRB review. On the other hand, case reports are research if presented in a manner that states or implies application of findings to other situations, in which case verification of IRB exemption or IRB review are required. Research or not, the LBH IRB emphasizes that the most important issue is protection of the privacy and confidentiality interests of the patient-subject.

The LBH IRB recognizes 3 categories of case reports/chart reviews:

A) Single case reports meeting the following criteria are not research (whether

they are intended for publication or not), and are exempt from IRB oversight:

1. The record review is done by individuals already involved in the patient's care (insuring that no new confidentiality risks are created by this activity),

2. The information is collected, analyzed, and presented in a truly anonymous fashion meeting all requirements for the de-identification of data, and

3. No changes are made in the patient's care or diagnostic testing in relation to or as a result of the record review.



B) Chart reviews or case study series involving de-identified data (research or not), require the submission of a LBH IRB Disclosure/Use of De-Identified Data/Materials for Research form for IRB review and approval.

1. Disclosure of De-Identified Data/Materials for Research

The LifeBridge Health (LBH) Institutional Review Board (IRB) designed the De-Identified Data/Materials form to 1) inform the investigator about the unusually specific federal regulations concerning information that cannot be recorded in order to qualify for exemption under 45 CFR 46.101(b)(4) (for Existing Data, Documents, Records and Specimens), and 2) provide a means of documenting this activity. Both the individual releasing the de-identified information and the individual receiving the de-identified information must sign the completed form. The De-Identified Data/Materials form must be submitted along with your data collection form for review. Upon receipt, the Chairman of the LifeBridge Health Inc. Institutional Review Board or his designee will expedite review of these forms. If appropriate, the Chairman or his designee will approve this activity as exempt from further IRB review. However, if there are any changes to the design of the study or the data collection form, you are requested to notify the IRB in writing, as it may no longer meet the criteria for exemption from IRB review.

2. Chart reviews or case study series involving data analysis and/or application of findings to other situations (i.e., research), require the submission of a LBH IRB Application for New Research form for IRB review and approval.

Investigators are advised to contact the IRB Office for consultation on a case by case basis.

* Research as defined in 45 CFR 46.102(d), and 45 CFR 164.501 means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

3. Scope

a. Definition of Minimal Risk

Minimal risk is defined (45 CFR 46.102 and 21 CFR 56.102) as “...the

probability and magnitude of harm or discomfort anticipated in the research 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….”

b. Cautions

1. The activities listed should not be deemed to be of minimal risk simply

because they are included on the list of eligible research. Inclusion on this

list merely means that the activity is eligible for review through the

expedited review procedure when the specific circumstances of the

proposed research involve no more than minimal risk to human subjects.

2. The expedited review procedure may not be used where identification of the

subjects and/or their responses would reasonably place them at risk of

criminal or civil liability or be damaging to the subjects' financial standing,

employability, insurability, reputation, or be stigmatizing, unless reasonable

and appropriate protections will be implemented so that risks related to

invasion of privacy and breach of confidentiality are no greater than

minimal.

3. The expedited review procedure may not be used for classified research

involving human subjects.

4. Authority

a) Expedited review may be performed by the Chairperson, Vice Chair, or another

experienced IRB member (“Designated Expedited Reviewer”) as designated by

the Chairperson.

b) The IRB Chairperson (or designated reviewer) may exercise all of the

authorities of the IRB, except that he/she may not disapprove the research.

c) A research proposal may be disapproved only after review by the full IRB.



5. Notification of the IRB

When the expedited review procedure is used, all regular members shall be

informed of expedited review actions taken at the next convened meeting.

6. Documentation

a) An initial determination will be made by the intake reviewer (the IRB Research

Coordinator or Chairperson, or designee) as to whether the submission meets

the criteria for expedited review (see review qualification form). The initial

reviewer will document his/her determination.

b) The Expedited reviewer will complete a Review Form. For new protocols, this

will include a determination of risk status and designation of the interval for

continuing review.

c) The minutes of each meeting will include documentation of the studies that

were reviewed by an expedited review and any issues discussed concerning the

research reviewed.

d) The expedited reviewer will document his/her determination of whether the

research may be approved, whether further information is needed, or whether

review by the full convened committee is necessary.

7. Additional Submissions That May be Subject to Expedited Review

a) Provisional approval pending minor revisions, clarification: Revisions to

consent documents and other documentation or clarifications submitted in

response to full IRB review and as a condition to final approval may be

reviewed by the IRB Chairperson or his/her designee. Final approval will be

issued providing the revisions, documentation or clarifications do not result in a

change to the study that alters the relationship of risks to benefits of

participation.

b) Ongoing Review of Changes to Previously Approved Research:LifeBridge Health IRB Revised Date: August 20, 2008 Page 44 of 133Policies and SOPs Original Date: June 6, 2003


i. The IRB Chairperson may use the expedited review procedure to review

minor changes in previously approved research during the period for which

approval is authorized. This includes minor changes to revisions and/or

amendments which do not alter the risk to subjects of participation. The

LBH IRB considers minor changes to include;

(1) Administrative and editorial revisions to protocol, assent forms, and

consent forms;

(2) Corrections and clarifications to the protocol, assent forms, and

consent forms;

(3) Updates to drug monographs; and

(4) Procedural changes that do not affect the overall risk to the subject.

ii. Any protocol revision that entails more than minimal risk to the subjects

must be reviewed by the full IRB at a convened meeting.

iii. Revisions to informed consent documents: Minor changes to informed

consent documents that do not affect the rights and welfare of study

subjects, or do not involve increased risk or significant changes in study

procedures may be reviewed and approved by the Chairperson/designee.

iv. Serious adverse event and safety reports: The Chairperson will triage all

serious adverse event reports (including IND safety reports) as eligible for

expedited review or requiring full board review. The IRB Chairperson

acting for the IRB will review summaries of safety reports and serious

adverse events in a timely manner after receipt.

1. If expedited review leads to the determination that no changes in the

protocol or informed consent documents are necessary, the PI will be

informed in writing.

2. If the Chairperson feels that action is needed to protect the safety of

research subjects due to the nature or frequency of reported adverse

events, the Chairperson will make a report and recommendation to the



full IRB, which will review the adverse events and study in question to

determine action, if any, by the IRB.

3. In the event of a circumstance requiring urgent action to prevent harm to

subjects, the Chairperson or designated reviewer may correspond with

the investigator and request modifications as necessary.

v. Advertisements: The IRB Chairperson or designee may approve new or

revised recruitment advertisements or scripts.

vi. Translations: Translations of consent documents will also be submitted for

IRB approval and will be reviewed in an expedited manner. There are two

options available to obtain approval of translated consent forms.

Option #1: The IRB-approved consent form is translated by the Sponsor or

site and submitted to the IRB. If available, the IRB will have a member or

consultant fluent in the language of the consent review the translated

document for accuracy. It must match the English version.

Option #2: The Investigator (or Sponsor) may submit the IRB-approved

version of the consent to an IRB-approved, certified translator and submit

certification of such review to the IRB with the translated consent form for

approval.

vii. Questionnaires, survey documents, patient information sheets or case report

forms may be required for certain reviews.

7. Responsibility

The IRB Research Coordinator or Chairperson (or designee) is responsible for

identifying submissions that qualify for expedited review.

The IRB Research Coordinator is responsible for providing a summary of expedited

review performed to IRB members at convened meetings.

The IRB Chairperson, Vice-Chair, experienced reviewer (or other designee) is

responsible for conducting expedited review.




Expedited Review: 45 CFR 46.110

1 CFR 56.110


OHRP IRB Guidebook

B. Facilitated IRB Reviews (Central IRB)

The National Cancer Institute (NCI) Central Institutional Review Board (CIRB) is the designated review board for collaborative adult and pediatric oncology projects. The CIRB’s primary function is initial and continuing review of protocols. The LifeBridge Health IRB’s primary function is consideration of local context and oversight of local performance for these protocols. The process for initiating facilitated LBH IRB review of CIRB-approved materials and protocol review procedures are outlined below.

Submission

1. The Principal Investigator (PI) or Research Coordinator (RC) receives new protocol from an NCI CIRB-associated Community Clinical Oncology Program.

2. The PI or RC sends 5 copies of the following to the Research Office:

a) Cover letter requesting Facilitated Review of NCI CIRB protocol b) Protocol and all documentation from the Participants Area downloaded from

the CIRB website c) Completed and signed LBH IRB “Application for New Research” form d) One copy of the NCI CIRB-approved consent form(s)e) Two copies of the NCI CIRB-approved consent form(s) revised with all LBH

IRB approved language and standard statements clearly highlighted in one copy. The other revised consent form will have the LBH IRB stamp affixed after local IRB approval.

NOTE: All LBH IRB educational requirements must be satisfied prior to submitting a request for facilitated review.

LBH IRB CIRB Subcommittee Review

The purpose of the LBH IRB CIRB Subcommittee (LICS) is to conduct facilitated reviews of CIRB approved protocols concentrating on local context issues. The LICS will decide on a protocol-by-protocol basis whether to accept the review of the CIRB,



or to conduct a full board review of the protocol at the local level. The following are instructions for submitting these protocols to the IRB for facilitated review.

1. The IRB chair or vice-chair and two IRB members, one with expertise in oncology and the other with expertise in pharmacology, will review all CIRB materials. Based on this review the IRB chair will determine either that:

a) The CIRB protocol review is acceptable and the CIRB consent form is acceptable with the inclusion of all LBH consent and HIPAA form components (i.e., use of LBH letterhead and LBH boilerplate language).

or

b) The CIRB review is not acceptable. The CIRB does not allow CIRB-approved language to be deleted but does allow the institution to comply with local requirements in terms of required consent language. If consent modifications are deemed crucial, the chair/vice-chair will document the rationale for the decision to initiate the standard LBH IRB review process. The PI/RC will be notified that their CIRB application will undergo a full board review by the LBH IRB, and that the application should be submitted in time for the next appropriate IRB meeting following standard LBH IRB submission guidelines.

NOTE: If the material submitted meets all criteria for expedited review, LICS review is not required, and the chair, vice-chair, or their designee may conduct the review.

2. The LBH IRB Coordinator will report to the CIRB the decision about local acceptance/rejection of the CIRB review. The outcome will be reported using the Electronic Protocol Acceptance Form inside the Participant’s Area of the CIRB website (www.ncicirb.org). A confirmation email will be sent from the CIRB Office to the local IRB Coordinator for each protocol review accepted, and then forwarded from the Research Office to the PI/RC.

3. The NCI CIRB is now IRB of record for this protocol. This means that the local IRB no longer has to perform amendment reviews, non-local SAE reviews, or continuing (ongoing) reviews for this protocol. The CIRB will conduct these reviews and post them on the CIRB website. In addition, both the local IRB and the local PI will receive e-mail notification of these reviews.

Post-Approval Responsibilities

1. After approval, the IRB Coordinator will track the protocol status. The NCI CIRB will review amendments and continuing review applications. Once amendments and continuing review materials are approved by the CIRB, the PI, the RC, and the



IRB Coordinator will be notified and provided with updated documents. The LBH IRB Chair, Vice-Chair, or a designated IRB member will review the amendment or continuing review materials and determine if the LBH IRB will continue to accept CIRB review. If accepted, the IRB Coordinator will complete and submit a Cancer Trials Support Unit (CTSU) Certification form to the CIRB. If the LBH reviewer does not deem an amendment or continuing review acceptable, the materials in question then go to the full board for review.

NOTE: LBH IRB post-approval responsibilities should be viewed as a screening backup to insure no local issues are impacted by the proposed changes. The LBH IRB would notify the investigator if a new unexpected problem arose, and would then initiate the necessary changes to allow the study to go forward from that point.

2. The PI/RC will report adverse events that occur at a LBH facility to both the LBH IRB and the CIRB per LBH IRB guidelines (see http://lbhweb/lifebridgebody.cfm?id=822.). The IRB Chair or Vice-Chair and the oncology and pharmacology subcommittee members will review adverse events. The CIRB will be notified immediately if a CIRB approved protocol is suspended or terminated locally.

The investigator will report personnel or site changes to the LBH IRB and CIRB immediately.

3. Any locally initiated alterations/updates (e.g., advertisement/s, etc.) should be submitted to the LBH IRB and CIRB for review.

NOTE: Notification of LBH IRB review results will be communicated in the conventional manner. The LBH Research Office will maintain a hard copy file of the protocol, including subsequent reviews and other CIRB documentation.

NOTE: For existing protocols that have LBH IRB and NCI CIRB approval, the LBH IRB will rely on the CIRB as the IRB-of-Record for the annual renewal. Until that time, standard LBH IRB paperwork should be submitted following standard LBH procedure.

C. Full IRB Initial Review – Criteria for IRB Approval

1. Policy

All research proposals that intend to enroll human subjects must meet certain criteria

before study related procedures can be initiated. The criteria are based on the

principles of justice, beneficence and autonomy as discussed in the Belmont Report and

are specified below. Certain other criteria that are unique to the LifeBridge Health, Inc.

system will apply and must be met as well.



a. Minimal Criteria for Approval of Research

In order for a research project to be approved, the IRB must find that:

1) Risks to subjects are minimized:

a.By using procedures that are consistent with sound research design and which do not unnecessarily expose subjects to risk, and

b. Whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

2) 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.

a.In evaluating risks and benefits, the IRB will consider only those risks and

benefits that may result from the research (as distinguished from risks and

benefits of therapies that subjects would receive even if not participating in

the research). The IRB should 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.

3) Selection of subjects is equitable.

a. In making this assessment the IRB should take into account the purposes of

the Research and the setting in which the research will be conducted and

should be particularly cognizant of the special problems of research

involving vulnerable populations, such as children, prisoners, pregnant

women, handicapped, or mentally disabled persons, or economically or

educationally disadvantaged persons.

4) Informed consent will be sought from each prospective subject or the subject's

legally authorized representative, in accordance with and to the extent required

by appropriate local, state and federal regulations.

5) Informed consent will be appropriately documented as required by local, state

and federal regulations.LifeBridge Health IRB Revised Date: August 20, 2008 Page 50 of 133Policies and SOPs Original Date: June 6, 2003


6) Where appropriate, the research plan makes adequate provision for monitoring

the data collected to ensure the safety of subjects.

7) Where appropriate, there are adequate provisions to protect the privacy of

subjects and to maintain the confidentiality of data.

8) 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 or for subjects found at international sites, additional safeguards have

been included in the study and in the IRB review process, to protect the rights

and welfare of these subjects.

9) Studies are reviewed at periods appropriate to the degree of risk research

subject are exposed to due to their participation in the study, but at least

annually.

10) For FDA-regulated research in which some or all of the subjects are children,

research must be in compliance with 21 CFR Part 50 subpart D.

11) Compensation to the subjects for their participation is reasonable and not overly

enticing.

12) Subjects asked to participate in a research project are given a full explanation of

the procedures to be followed, especially those that are experimental in nature.

13) Subjects asked to participate in a research project are told that they may refuse

to participate, and that their refusal will not compromise their access to

services.

These same standards apply for initial approval of research studies, renewal of

approval for ongoing studies, and for review of protocol amendments. LifeBridge Health IRB Revised Date: August 20, 2008 Page 51 of 133Policies and SOPs Original Date: June 6, 2003


b. Other Criteria

The IRB may require verification of information submitted by an Investigator.

Such need may be determined by the IRB at a convened meeting or by the IRB

Chairperson/designee and/or Primary Reviewer, as required. The purpose of the

verification will be to provide necessary protection to subjects when deemed

appropriate by the IRB.

The criteria used to determine whether third-party verification is required may

include:

Investigators who conduct studies that involve a potential high risk to

subjects,

Studies that involve vulnerable populations,

Investigators that conduct studies that involve large numbers of subjects, and

Other selection criteria at the discretion of the IRB.

Projects that need third party verification from sources other than the Investigator

that no material changes have occurred since previous IRB review is determined,

will have such assessment performed as necessary.

c. Reliance on Other IRBs for Review and Approval of Research Conducted at

LifeBridge Health, Inc.

Under authority granted by the Board of Trustees of LifeBridge Health, the

LifeBridge Health IRB Chairperson or designee may enter into joint review

arrangements, rely upon the review of another qualified IRB, or make similar

arrangements for avoiding duplication of effort as allowed and upon modification

of the institutional Multiple Project Assurance/Federal-wide Assurance agreements

(MPA/FWA). This may be done on a case-by-case basis all will be limited to duly

qualified IRBs at the discretion of the IRB leadership (Chairperson, Vice-Chairs,

with LifeBridge Health administration concurrence).



d. Responsibility

The IRB Research Coordinator is responsible for ensuring that IRB reviewers have

all the tools and resources they need to complete their research reviews.

The IRB Chairperson (or designee) is responsible for providing IRB members

adequate submission review training and ongoing guidance, and for selecting

primary and secondary reviewers with the relevant expertise to perform reviews

and make necessary recommendations on approval decisions by the IRB.

The IRB Reviewer is responsible for conducting a thorough review and making all

appropriate approval recommendations for consideration by the IRB.

e. Applicable Regulations and Guidelines

45 CFR 46.111

21 CFR 56.108, 56.111

D. Full IRB Continuing Review – Criteria for Renewal

1. Policy

The IRB conducts continuing review of research taking place within its jurisdiction at

intervals appropriate to the degree of risk, but not less than once per year.

a. Interval for Review for Purposes of Renewal

The IRB must conduct continuing review of protocols for purposes of renewal of

the IRB approval period, at intervals appropriate to the degree of risk, which is

determined at the initial review, but not less than once per year. “Not less than once

per year" means that the research must be reviewed on or before the one-year

anniversary of the previous IRB review date, even though the research activity may

not have begun until some time after the IRB gave its approval.

Investigators or qualified designees are required to submit a periodic report prior to

the expiration of the study or as specified by the IRB, but at least annually. The

report should normally be filed 60 days before the study approval period ends.LifeBridge Health IRB Revised Date: August 20, 2008 Page 53 of 133Policies and SOPs Original Date: June 6, 2003


b. Extensions of Approval Period

There is no grace period extending the conduct of the research beyond the

expiration date of IRB approval. Extensions beyond the expiration date will not be

granted. If Continuing Review Report forms and other requested progress reports

are not received as scheduled, the Investigator must suspend the study and study

enrollment until reports are reviewed and approved.

However, if the Investigator is in communication with the IRB, the Continuing

Review Report or other report is forthcoming, and in the opinion of the IRB,

subjects participating is such a study would suffer a hardship if medical care were

discontinued, appropriate study-related treatment and follow-up of enrolled subjects

may continue beyond the expiration date for a reasonable amount of time.

However, new subjects cannot be enrolled. The IRB will address on a case-by-case

basis those rare instances where failure to enroll new subjects would seriously

jeopardize the safety or well being of an individual. Prospective research data

cannot be collected, and no procedures that are only being performed for the

purposes of the protocol may be performed until a Continuing Review Report is

reviewed and approved.

c. Criteria for Renewal

Continuing review must be substantive and meaningful. When considering whether

or not to renew a study, the IRB revisits the same criteria used to grant initial

approval. Therefore, the IRB (or the reviewers for protocols reviewed under an

expedited procedure) must determine that:

1. The risks to subjects continue to be minimized and reasonable in relation to the

anticipated benefits;

2. The selection of subjects continues to be reasonable in relation to anticipated

benefits;

3. Informed consent continues to be appropriately documented;

4. Additionally, there are:LifeBridge Health IRB Revised Date: August 20, 2008 Page 54 of 133Policies and SOPs Original Date: June 6, 2003


a. Provisions for safety monitoring of the data,

b. Protections to ensure the privacy of subjects and confidentiality of data, and

c. Appropriate safeguards for vulnerable populations.

Because it may be only after research has begun that the real risks can be evaluated

and the preliminary results used to compute the actual risk/benefit ratio; the IRB

can then determine whether or not the study can be renewed at the same risk/benefit

ratio, or if new information has changed that determination.

In order to determine the status of the study, the following will be revisited:

1) Consent document: The IRB shall review the currently approved consent

document and ensure that the information is still accurate and complete. Any

significant new findings that may relate to the subject's willingness to continue

participation should be provided to the subject in an updated consent document.

2) Current approved protocol including any amendments to protocol since initial

review: A copy of the protocol will be sent to the Primary Scientific Reviewer

for the continuing review. Amendments and addenda to a research protocol

should be submitted as generated during the course of the study. They also may

be submitted at the time of continuing review if not previously done. A

separate cover letter describing the changes and all appropriate documentation

(approved consent form) must accompany the continuing review application,

noting that approval of the amendment(s) is also requested.

3) Continuing IRB review is required as long as individually identifiable follow-

up data are collected on subjects enrolled in HHS-supported protocols. This

remains the case even after a protocol has been closed at all sites and protocol-

related treatment has been completed for all subjects. These renewal requests

may qualify for expedited review.



4) Continuing review of DSMB-monitored clinical trials: When a clinical trial is

subject to oversight by a DSMB whose responsibilities include review of

adverse events, interim findings and relevant literature (e.g., DSMBs operating

in accordance with the National Cancer Institute Policy for Data and Safety

Monitoring of Clinical Trials), the IRB conducting continuing review may rely

on a current statement from the DSMB indicating that it has reviewed study-

wide adverse events, interim findings and any recent literature that may be

relevant to the research, in lieu of requiring that this information be submitted

directly to the IRB. However, the IRB must still receive and review reports of

local, on-site unanticipated problems involving risks to subjects or others and

any other information needed to ensure that its continuing review is substantive

and meaningful.

5) Progress report: All IRB members shall receive a progress report prepared and

submitted by the Investigator along with the number of subjects entered to date

and since the last review. The progress report shall summarize adverse event

experiences, amendments, changes in training of personnel and new COI

disclosure as applicable, and provide a reassessment of the risk-to-benefit ratio.

d. Possible Outcomes of Continuing Review

As an outcome of continuing review, the IRB may renew approval, or may require

that the research be modified or halted altogether. The IRB may need to impose

special precautions or relax special requirements it had previously imposed on the

research protocol. Determination of the risk status of the research and the

appropriate interval are made just as for the initial review.

e. Expedited Review for Renewal

A protocol that was originally reviewed using the expedited review procedure may

receive its continuing review on an expedited basis. Additionally, a standard-

review protocol that had no accrual during the previous period, or which has not



been awarded funding, or which remains open only to data analysis may be

reviewed using an expedited review.

When conducting research under an expedited review procedure, the IRB

Chairperson or designated IRB member conducts the review on behalf of the full

IRB using the same criteria for renewal as stated above. If the reviewer feels that

there has been a change to the risks or benefits, he or she may refer the study to the

full IRB for review.

f. Applicable Regulations and Guidelines

21 CFR 56.108,111

45 CFR 46.111

OPRR Reports 95-01

g. Attachments

See Section X III - Forms

E. Continuing Review – Ongoing

1. Policy

No Investigator has a right to conduct research within this institution. Rather, it is a

privilege granted by society as a whole and the Trustees of LifeBridge Health in

particular.

IRB approval may be withdrawn at any time if warranted by the conduct of the

research. The regulations authorize the IRB to establish procedures for the concurrent

monitoring of research activities involving human subjects. Periodic review of research

activities is necessary to determine whether approval should be continued or

withdrawn. All research involving human subjects must be reviewed no less than once

per calendar year, as outlined in the previous section of this manual.



IRB approval for the conduct of a study may be withdrawn if the risks to the subjects

are determined to be unreasonably high, for example, more than an expected number of

adverse events, unexpected serious adverse events; or evidence that the Investigator is

not conducting the investigation in compliance with IRB or Institutional guidelines.

Such findings may result in more frequent review of the study to determine if approval

should be withdrawn or enrollment stopped until corrective measures can be taken or

the study terminated. Continuing review includes, but may not be limited to the

following activities:

a. Review of Serious and Unexpected Adverse Events

b. Review Amendments and changes to the study protocol or consent forms

c. Review of Significant New Findings (results from the study or other studies that

bear upon the potential risks and benefits of the study)

d. Reports from Employees, Staff and Faculty

e. Noncompliance with IRB procedures by investigators and staff

f. Site Visits, Audits and Third Party Verification Reports

1. Site Visits, Observation of Consent Process, and Third Party Verification

The IRB has the authority to observe, or have a third party observe, the

informed consent process of research it has approved, and to verify that the

study is being conducted as required by the IRB and within the Institutional

policies and procedures and site-specific procedures, as appropriate. IRB staff

or members may perform site visits or use another party, either affiliated or not

with the institution, to verify information in the study application, in any

interim or continuing review submissions, in response to specific complaints, or

at anytime deemed necessary by the chairperson or designee.

The criteria for selecting Investigators to be visited may include:

a. Investigators who conduct studies that involve a potential high risk to

subjects,

b. Studies that involve vulnerable populations,



c. Investigators who conduct studies that involve large numbers of subjects,

and

d. Investigators selected at the discretion of the IRB.

Site visits may include on-site interviews with investigators, staff and/or

research subjects, and audit of study records. Other means of verification

include questionnaires sent to investigative staff to verify information submitted

by the Investigator. Sponsors may be asked to submit copies of monitoring

reports, or may be requested to complete a questionnaire regarding the protocol

and/or the investigative site.

Investigators may be asked to submit copies of signed informed consent forms

or other documents to ensure their compliance with IRB requirements. The

IRB may conduct interviews with screened and/or enrolled subjects as deemed

necessary.

2. Serious and Unexpected Adverse Events

Subject safety is of the greatest importance for both the individual subject and

the goals of the clinical study. If the event is serious and unexpected, prompt

reporting to the Sponsor and to the IRB is mandatory. Reports will be reviewed

by the IRB Chairperson or designee. If the Chairperson determines that action

may be needed to protect the safety of research subjects due to the nature or

frequency of reported adverse events, he/she may take such action and/or the

full IRB or designated subcommittee will review the adverse events and study

in question to determine action, if any, by the IRB. The IRB will review

summaries of all safety reports and serious adverse events as soon as possible at

a convened meeting.

a). External Adverse Events

The LifeBridge Health (LBH) Institutional Review Board (IRB) only

requires submission of an Adverse Event Report form when the external

adverse event is serious, unexpected, and related or possibly related to LifeBridge Health IRB Revised Date: August 20, 2008 Page 59 of 133Policies and SOPs Original Date: June 6, 2003


the experimental aspect of the study. In studies involving a drug or

biologic, those adverse events which require a change in protocol,

consent form, or the risk/benefit ratio for subjects must be submitted

to the IRB within 10 days following receipt of the report from the sponsor

or cooperative group (see attached Table 1 and 2C). External adverse

events that satisfy the above criteria but do not require a change in

protocol, consent form, or risk/benefit ratio for subjects should be

submitted annually along with the continuing review application (see

attached Table 1 and 2B). Adverse events that are not serious, are

expected, or are unrelated should not be reported, and will not be

reviewed or acknowledged by the IRB (see attached Tables 1 & 2A).

The Adverse Event Report for any unexpected adverse event that occurs

in a device study requiring a change in protocol, consent form, or the

risk/benefit ratio for subjects must be submitted to the IRB within 10 days

following receipt of the report from the sponsor (see attached Tables 1 &

2C). One original of the Adverse Event Report form and one copy of the

IND Safety Report and/or other information received from the outside

agency regarding the adverse event must be submitted for IRB review. If

revision to the consent form is necessary, also submit one copy of the

current IRB approved consent form, one copy of the revised consent form,

and one copy of the revised consent form with all revisions clearly high-

lighted.

b). Internal Adverse Events

The LBH IRB only requires submission of internal Adverse Event Reports

when the event is serious, unexpected, and related or possibly related to a

study drug, biologic, or device. Internal adverse events occurring in a

study which satisfy these criteria and require a change in protocol, consent

form, or the risk/benefit ratio for subjects must be submitted to the IRB



within 10 days following the time it becomes known. All fatal or life-

threatening events that occur while the subject is being treated on

protocol or occur within 30 days of completing research related

interventions, must be reported to the Division Chief within 24 hrs and to

the IRB within 3 days. One original of the Adverse Event Report form,

and one copy of the current IRB approved consent form must be

submitted (along with any other relevant information) to the IRB. If

revision to the consent form is necessary, also submit one copy of the

revised consent form, and one copy of the revised consent form with all

revisions clearly high-lighted.

Please carefully review the Adverse Event Reporting Flow Chart (Table

1) and Guideline Summary (Table 2) before filling out the LBH Adverse

Event Report form. The form must be filled out on your computer

before printing.

After reviewing these Adverse Event Reporting Guidelines and Table 1 &

Table 2, if you still have questions about whether an event constitutes an

adverse/unexpected event or questions about completing the Adverse

Event Report form, please contact the LBH Institutional Review Board in

the Department of Research at 410-601-9021.

c). Safety Reports

The LifeBridge Health (LBH) Institutional Review Board (IRB) only

requires submission of sponsor safety reports when the adverse events

summarized in those reports are serious, unexpected, and related or

possibly related to the experimental aspect of the study and require a

change in protocol, consent form, or the risk/benefit ratio for subjects.

In this case the safety report must be submitted to the IRB within 10 days

following receipt of the report from the sponsor (see attached Tables 1 &

2C). Safety reports that satisfy the above criteria but do not require a



change in protocol, consent form, or risk/benefit ratio for subjects can be

submitted annually along with the continuing review application (see

attached Table 1 and 2B). Safety reports concerning adverse events that

are not serious, are expected, or are unrelated should not be reported, and

will not be reviewed or acknowledged by the IRB (see attached Tables 1

& 2A)

3. Amendments

Changes in approved research, during the period for which approval has already

been given, may not be initiated without prior IRB review (full or expedited

review, as appropriate) and approval, except where necessary to eliminate

apparent immediate hazards to human subjects.

Investigators or Sponsors must submit requests for changes to the IRB in

writing. Upon receipt of the protocol change, the Chairperson or his or her

designee, with assistance of the IRB Administrator, will determine if the

revision meets the criteria for minimal risk. If the change represents more than

a minimal risk to subjects, it must be reviewed and approved by the IRB.

Minor changes, involving no more than minimal risk to the subject, will be

reviewed by the expedited review procedure.

4. Procedures for Amendment Review:

a. All protocol amendments will be reviewed by the Chairperson, Vice-Chair

or designee experienced reviewer to determine if an expedited review is

appropriate or if a full committee review is required.

b. If a full committee review is required, a primary reviewer will be designated

by the Chairperson. The primary reviewer will receive the protocol, the

amendment and all appropriate supporting documentation (enrollment

updates for the study overall and for the LifeBridge Health site, serious

adverse event updates, current consent and assent forms, Investigator’s



Brochure, and any relevant literature citations). The primary reviewer will

present to the committee at the next regular IRB meeting.

c. The full IRB committee will discuss and vote to either approve,

provisionally approve with modifications, or defer the amendment.

d. If expedited review criteria are satisfied, the review will be performed by

the IRB Chairperson or a designed IRB member.

e. The expedited reviewer may exercise all of the authorities of the full IRB

except he/she may not disapprove the research. A full committee review

will be necessary for disapproval as per the regulations.

f. The IRB Coordinator will send a letter to the Principal Investigator advising

of the IRB’s determination. If action other than approval is taken by the

IRB, the letter will include an itemized list of the rationale for the action

taken and any requests for additional information to be supplied for review.

g. Determination of approval of amendments will be performed according to

the same criteria for approval of research generally applied by the IRB, as

per the regulations, as detailed elsewhere in this document.

5. Significant New Findings

During the course of a study, the IRB may review reports generated from a

Data Safety Monitoring Board (DSMB), adverse event reports, current

literature, and other sources to ascertain the status of the study and assess

whether or not the risk/benefit balance is still acceptable. The IRB will

determine whether or not new information needs to be conveyed to subjects, or

if a segment of the population may be bearing an undue burden of research risk

or being denied access to promising therapy.

6. Reports From Employees, Staff and Faculty



It is the responsibility of the IRB staff and members to act on information or

reports received from any source that indicate a study being conducted at any

facility under the jurisdiction of the IRB could adversely affect the rights and

welfare of research subjects.

7. Ensuring Prompt Reporting of Any Serious or Continuing Noncompliance

with Applicable Regulations or the Requirements or Determinations of the

IRB

All credible reports of inappropriate involvement of human subjects in research

must be investigated by the IRB Chairperson or designee and referred to the

IRB. The results of the investigation will be reported to the appropriate

LifeBridge Health official(s). Regulatory authorities or Sponsors may also be

notified. Such reports of noncompliance may come from any source including

IRB members, Investigators, subjects, institutional personnel, the media,

anonymous sources or the public.

The IRB has the authority to suspend or terminate approval of research that is

not being conducted in accordance with the IRB policies, is not in compliance

with federal regulations, or has been associated with unexpected serious harm to

subjects. All such suspension and or terminations will be reported to the OHRP

and FDA as appropriate.

8. Responsibility

The IRB Chairperson and Research Coordinator are responsible for establishing

the processes for conducting ongoing reviews of research.

.The IRB Chairperson (or designee) is responsible for preliminary assessments

of adverse events, significant new findings and the need for third party

verification.




21 CFR 812.64

21 CFR 56.108, 56.109, 56.113

45 CFR 46.103, 46.109, 46.115


F. Investigator Reporting of Serious Adverse Events in Research Subjects

1. PolicySubject safety is of the greatest importance for both the individual subject and the goals

of the clinical study. It is the responsibility of the investigator to report to the

Investigator's Departmental Chairperson, the Sponsor and the IRB any unanticipated

problems or serious adverse events involving risks to patients or other human subjects

who are enrolled in an approved protocol. The occurrence of an adverse event that is

both serious and unexpected in a clinical research protocol should be promptly reported

to the Sponsor and to the IRB. Reports will be reviewed by the IRB Chairperson or

designee. If the Chairperson or designated reviewer determines that action may be

needed to protect the safety of research subjects due to the nature or frequency of

reported adverse events, the Chairperson or designated reviewer may take any actions

deemed necessary to continue to protect human subjects from unnecessary research

risks. If such action is taken outside a regular meeting of the IRB, the Chairperson

shall report it at the next meeting for discussion and action. The Chairperson or

designee may also request a full review by the IRB to determine what action, if any, is

needed by the IRB. The IRB will review summaries of all safety reports and serious

adverse events at the next convened meeting.

a. Requirements

1) Death or Life-threatening Events

The LifeBridge Health IRB must be notified by the Principal Investigator (PI)

within 72 hours of

a. any unexpected death or life-threatening event occurring in a LifeBridge

Health research subject, or



b. the investigator or research staff first becoming aware of any unexpected

death or life-threatening event occurring in a subject at another study site.

2) Notice to Department Chief

The Department Chief shall be notified by the PI within 24 hours or the next

business day of any unexpected death or life-threatening event occurring in a

LifeBridge Health research subject.

3) Unexpected Serious Adverse Events

The IRB must be notified by the Principal Investigator (PI) within 10 business

days of:

a.any unexpected serious adverse event or any serious injury or any

unanticipated adverse device effect occurring in a LifeBridge Health

research subject, regardless of the relationship to the study agent or device,

or

b. the investigator or research staff first becoming aware of any unexpected

serious adverse event or any serious injury or any unanticipated adverse

device effect, regardless of the relationship to the study agent or device,

occurring in a subject at another study site.

4) Follow-Up

Follow-up information must be submitted to the IRB as soon as the information

becomes available, in accord with the same time frames listed above.

5) Other Requirements

These requirements do not replace or override any requirements of the study

sponsor or other regulatory agencies.

b. Definitions

1. Life-threatening adverse event.

Any adverse event that places the patient or subject, in the view of the

investigator, at immediate risk of death from the reaction as it occurred, i.e., it



does not include a reaction that, had it occurred in a more severe form, might

have caused death.

2. Serious adverse event:

Any adverse event that results in any of the following outcomes:

a.Death,

b. A life-threatening adverse event,

c.Inpatient hospitalization or prolongation of existing hospitalization,

d. A persistent or significant disability/incapacity, or

e.A congenital anomaly/birth defect.

Important medical events that may not result in death, be life-threatening, or

require hospitalization may be considered a serious adverse event when, based

upon appropriate medical judgment, they may jeopardize the patient or subject

and may require medical or surgical intervention to prevent one of the outcomes

listed in this definition.

3. Unexpected adverse event:

Any adverse event in a subject treated with a drug or biologic agent in a

research study which is not described in specificity (type) or severity in the

current investigator brochure; or, if an investigator brochure is not required, in

the investigational protocol. ``Unexpected,`` as used in this definition, refers to

an event that has not been previously observed, rather than from the perspective

of such experience not being anticipated from the pharmacologic properties of

the investigational agent.

4. Unanticipated adverse device effect:

Any serious adverse effect on health or safety or any life-threatening problem

or death in a subject treated with a device in a research study, if that effect,

problem, or death was not previously identified in nature, severity, or degree of

incidence in the investigational plan or protocol, or any other unanticipated



serious problem associated with a device that relates to the rights, safety, or

welfare of subjects.

5. Serious injury: An injury or illness that:

a.Is life-threatening;

b. Results in permanent impairment of a body function or permanent damage

to body structure; or

c.Necessitates medical or surgical intervention to preclude permanent

impairment of a body function or permanent damage to a body structure.

c. Compliance

1. Single Occurrence

In the event that a PI fails to submit to the IRB a single report within the

required time frames as listed above, but no greater than 30 days after the event

or first becoming aware of the event, the IRB will issue a warning letter to the

Principal Investigator, with a copy to the appropriate Department Chief.

2. Second Occurrence or > 30 Days

In the event of a second failure to report on time by the same investigator, in

any clinical study, or if over 30 days have lapsed since the event or first

becoming aware of the event:

a.A letter will be issued to the Principal Investigator with a copy to the

appropriate Department Chief and Vice-Chair of the IRB

b. If the study is on a 12-month continuing review cycle, the next required

continuing review of the study by the IRB will be changed to 6 months. If

the study is on a 6-month continuing review cycle, the next required

continuing review will be changed to 3 months.

c.An audit of the site’s records and/or a site visit may be requested or

performed by IRB officials.

3. Third Occurrence or > 60 Days



In the event of a third failure to report on time by the same investigator, in any

clinical study, or if over 60 days have elapsed since the event or first becoming

aware of the event:

i. IRB approval will be suspended for the clinical study

ii. All provisions of the LifeBridge Health, Inc. IRB policy on Suspension of

Studies will apply.

iii. A suspension letter will be issued to the Investigator. Notification of

suspension will also be sent to the appropriate Department Chief, the Chief

Operating Officer (COO) of LifeBridge Health, and appropriate Federal

authority(ies) as required by regulations.

iv. If the study is on a 12-month continuing review cycle, the next required

continuing review of the study by the IRB will be changed to 6 months. If

the study is on a 6-month continuing review cycle, the next required

continuing review will be changed to 3 months.

v. An audit of the site’s records may be requested or performed by IRB

officials.

The investigator will be required to provide evidence of recertification of the

investigator’s competence to conduct clinical investigations, including understanding

of the requirements for adverse events reporting, within the prior 180 days or no later

than 60 days from the date of citation, by one of the following:

(i) Completion of the OHRP sponsored course “Investigator 101” if not done

within the previous year

(ii) Completion of the LifeBridge Health, Inc. Educational Series “Ethical and

Regulatory Considerations in Clinical Research” if not previously completed, or

completion of another educational course by a recognized professional

organization, subject to approval by the IRB Chair or designee.

1. Certification or training of staff may be required at the discretion of IRB

officials.



Reinstatement of IRB approval for the study will require:

(i) Submission by the investigator of a written action plan for compliance with

these IRB reporting requirements,

(ii) Review and concurrence by the full convened IRB at a regularly scheduled

meeting.

4. Repeated Non-Compliance

The IRB Chairperson, upon the recommendation of the IRB Subcommittee on

Investigator Compliance, may suspend some or all of an investigator’s clinical

research at LifeBridge Health, pending approval by the LifeBridge Health Chief

Operating Officer, for a period of time, up to one year, for non-compliance with this

policy.

Reinstatement of the investigator’s privileges will require:

(i) Submission by the investigator of a written action plan for compliance with these

IRB reporting requirements,

(ii) Evidence of certification of competence as required above,

(iii) A letter of concurrence from the Department Chief , and

(iv) Review and concurrence by the IRB Subcommittee on Investigator Compliance.

d. Subcommittee on Investigator Compliance

a) Composition

This committee will be composed of the IRB Chairperson, the two Vice-Chairs,

and an administrative or legal representative of LifeBridge Health designated by

the LifeBridge Health Chief Operating Officer, as a non-voting consultant.

b) Meetings

This subcommittee will meet ad hoc to review cases of investigator non-

compliance as described in this policy or other Standard Operating Procedures

(SOP’s) of the LifeBridge Health Institutional Review Board.

c) Authority



1. The subcommittee will report to the LifeBridge Health Chief Operating

Officer (COO) and will have exclusive authority, subject to approval by the

COO, to suspend an investigator from conducting any clinical research

within LifeBridge Health as described in above, or to reinstate an

investigator after suspension as described in above.

2. The subcommittee will address non-compliance with other LifeBridge

Health, Inc. IRB policies in similar manner, and will address other

disciplinary matters regarding clinical investigators and clinical research as

may arise.

5. IRB Review of Serious and Unexpected Adverse Events

a) Procedure

Reports of serious and unexpected adverse events will initially be reviewed by

the Chairperson or designee to determine if immediate action is required, or if a

full committee review is required.

b) Actions

If the Chairperson or designated reviewer determines that action may be needed

to protect the safety of research subjects due to the nature or frequency of

reported adverse events, the Chairperson or designated reviewer may take any

actions deemed necessary to continue to protect human subjects from

unnecessary research risks. If such action is taken outside a regular meeting of

the IRB, the Chairperson shall report it at the next meeting for discussion and

action. The Chairperson or designee may also request a full review by the IRB

to determine what action, if any, is needed by the IRB. The IRB will review

summaries of all safety reports and serious adverse events at the next convened

meeting.




21 CFR 312.32 and 312.60

21 CFR 803.30 and 812.150

21 CFR 56.108

45 CFR 46.103(B5) and 46.108

G. Suspensions of Studies

1. Regulatory Requirements

Under 21 CFR 56.109(f) and 45 CFR 46.109(e) continuing review of ongoing research

studies must be conducted by the IRB at intervals appropriate to the degree of risk, but

not less than once a year, to determine if approval may continue. IRB approval is valid

for one year, or may be granted for a shorter period in some cases at IRB discretion.

The IRB further has authority to suspend approval for

a. research “that is not being conducted in accordance with the IRB’s requirements”,

or

b. research “that has been associated with unexpected serious harm to subjects”.

Any suspension or termination of IRB approval must be promptly reported to the

investigator and appropriate institutional officials. Notification should also be made to

the Food and Drug Administration, under 21 CFR.108(b) and 21 CFR.56.113, or the

Federal Department or Agency Head under 45 CFR46.113, and must include a

statement of the reasons for the IRB’s action.

2. Suspension Procedures

Continuing review of ongoing research studies is conducted by the IRB on an periodic

basis. Renewals are to be reviewed at convened IRB meetings no less than one month

prior to expiration of the current approval. Renewal applications and supporting

documentation must be received in the IRB office no less than 60 days prior to

expiration of approval.



Suspensions will be issued for studies for which the required application and

supporting documentation has not been submitted in adequate time to permit IRB

review. The IRB will issue the suspension in writing to the Principal Investigator.

Notification will also be made in writing to the Department Chief, the appropriate

administrative official, and the appropriate Federal authority, if required, on a periodic

basis, as appropriate.

Suspensions will be issued for studies for which the determination has been made that

the study has been associated with serious and unexpected harm to subjects. This

determination must be made by the full IRB at a convened meeting, or, in an

emergency situation, may be made by the Chairperson or appropriate designee who is

acting on behalf of the committee. Notification will also be made in writing to the

Department Chief, the appropriate administrative official, and the appropriate Federal

authority, if required, on a periodic basis as appropriate.

3. Reapproval Following Suspension

The Chairperson or his/her designee may grant IRB approval following a suspension if

the application was originally evaluated via expedited review. However, if there are

significant changes in the protocol or the consent form, or the previous review was

conducted by a fully convened IRB, then the application must be reviewed by a fully

convened IRB. Approval will be issued in writing to the Principal Investigator, with

notification to the Department Chief, the appropriate administrative official, and the

appropriate Federal authority, as required by regulations.

4. Exceptions

Suspension of IRB approval requires that enrollment of new subjects cease. Treatment

and follow-up of previously enrolled subjects may be permitted to continue if the

investigator provides documentation that discontinuation of treatment would be

deleterious to the subjects’ health, subject to approval by the chairperson or designee.

5. Responsibility



The IRB Research Coordinator is responsible for maintaining IRB documentation of

renewals and expirations.


21 CFR 56.108 (b)

21 CFR 56.109 (e, f)

21 CFR 56.113

45 CFR 46.133

H. Study Completion

1. Policy

The completion or termination of a study is a change in activity and must be reported

to the IRB. Although subjects will no longer be "at risk" under the study, a final

report/notice to the IRB allows it to close its files as well as providing information that

may be used by the IRB in the evaluation and approval of related studies.

A. Determining When a Project Can be Closed

i. HHS-supported protocols: When individually identifiable follow-up data are no

longer being collected on subjects enrolled in an HHS-supported protocol and

analysis that could indicate new information is complete, the study may be

closed.

ii. Multi-site industry studies may be closed when the Investigator submits his or

her final report.

B. Completion Reports

Completion reports should be submitted within 30 days after completion or

termination of the study. Completion reports may be submitted in any format that

provides adequate information about the status of the study including total

enrollment, number of subjects completing/terminating early, and number/type of

any serious and unexpected adverse events. Completion reports may be submitted

by the Investigator's designee at the investigative site. The IRB Administrator will



review all reports of study completion and, if needed, request further information

from the Investigator to clarify any questions that may arise.

A listing of closed studies will be presented to the IRB at the next meeting with the

summary of administrative actions, and copies of the Completion Report and

supplementary information are made available to the IRB members upon request.

C. Applicable Regulations and Guidelines

21 CFR 56.108, 56.109

45 CFR 46.103, 46.109

I. Categories of Action by the IRB

1. Policy

As a result of its review, the IRB may decide to approve or disapprove the proposed

research activity, or to specify modifications required to secure IRB approval of the

research activity. Except when the expedited review procedure is used, these actions

will be taken by a vote of a majority of the regular and alternate members present, after

recusal of those members present but unable to vote in accordance with the IRB's

conflict of interest policies. When reviewed via expedited review, the Chairperson or

designee can take any of the following actions except to disapprove a study.

A. Determinations

The IRB may make one of the following determinations as a result of its review of

research submitted for initial review or for continuing review:

i. Approval: The protocol and accompanying documents are approved as

submitted. Final approval will commence on the day the study is approved by

an action of the convened IRB or Chairperson or designee and expire within

one (1) year of the meeting date, but not later than the day preceding the date of

review.



Approvals are always considered conditional. The conditions for continued

approval, and the time frame (if any) within which they must be met will be

clearly stated in the approval letter. If the conditions of the approval are not

met, approval may be withdrawn.

ii. Provisional Approval: Minor modification of, or addition to, a protocol or

accompanying document(s) is required. Changes will be voted upon during the

IRB’s meeting, as well as the terms of approval. The Investigator will be

informed in writing of the required changes and requested information and must

provide the IRB with the changes or information.

The IRB Chairperson or his/her designee has the authority to review the

information via expedited review unless the IRB requires that the material or

information be reviewed by the full IRB, the primary reviewer or another

individual delegated by the IRB to review the response. Upon satisfactory

review, approval will be issued as of the date that the requested information or

materials are approved. However, the expiration date of IRB approval will be

based on the anniversary date of the initial IRB review. Subjects must not be

recruited into the study until final approval has been issued.

iii. Deferral: This applies to research for which either:

(i) Significant questions are raised by the proposal requiring its reconsideration

after additional information is received from the Sponsor and/or

Investigator, or

(ii) The proposal fails to meet one or more criteria used by the IRB for approval

of research. Deferral for this reason may only be decided by majority vote at

a convened meeting of the IRB.

B. Applicable Regulations and Guidelines

21 CFR 56.109, 56.111, 56.113

45 CFR 46.109



VII. INFORMED CONSENT

A. General Requirements and Documentation

1. Policy

Informed consent for research must be legally effective (granted by the individual

or legally authorized representative in accord with applicable laws and regulations

as described herein) and prospectively obtained (well enough in advance of any

research-related activities to permit an unbiased decision by the participant). No

investigator may involve a human being as a research subject unless he or she has

prospectively obtained legally effective informed consent of the subject or the

subject’s legally authorized representative (see 1.8, Cognitively Impaired

Subjects, below). Consent shall be sought 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.

The IRB requires documentation of informed consent by use of a written

informed consent form approved by the IRB and signed and dated by the subject

or the subject's legally authorized representative (LAR).

Specific Policies1.1 Acceptable Consent Forms

The Consent Form must take the form of one of the following. In most cases only the first option will be appropriate.

a) A written consent document that embodies the elements of informed consent

described in 21 CFR 50.25 and 45 CFR 46.116(a). This should serve as the

basis for the discussion of the proposed research with the prospective subject

or LAR. The Investigator shall give either the subject or the LAR adequate

opportunity to read it and ask questions before it is signed. The subject or

LAR must also be given a copy of the signed form. This form may be read to

the subject or the subject's legally authorized representative if the subject is



not able to read.

b) A "short form" written consent document stating that the elements of

informed consent as required above have been presented orally to the subject

or the subject's legally authorized representative as per 21 CFR 50.27. The

IRB must approve, in advance, the text of the short form, which is to include

a written summary of the full consent form, i.e. what is to be said to the

subject or representative. The subject or the representative signs only the short

form itself. When this method is used, there shall be an impartial witness to

the oral presentation. The witness shall sign both the short form and a copy

of the summary, and the person 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.

1.2 Informed Consent Process

a) Informed Consent for clinical research may only be obtained from prospective

subjects by:

(i) the Principal Investigator (PI) ,

(ii) an IRB-approved Co-Investigator, or

(iii) an appropriately trained individual who is so designated in writing

by the PI and approved in advance by the IRB. Designation of individuals

to obtain informed consent must be included in the initial application to

the IRB for approval of the research, and updated at the time of each

continuing review.

b) The PI or Co-Investigator should discuss the research with the prospective

subject well in advance of the individual’s expected signing of the consent

form and agreement to participate. Except in the case of urgent or emergency

research, the consent process should be initiated days or weeks prior to

anticipated enrollment so as to allow the prospective subject an opportunity to

review and discuss the information with family members or their private



physician, if they so wish. These discussions should be documented in the

subject’s medical records.

c) Informed consent must be obtained prior to beginning any study-related

activities for a subject, including screening.

d) The signed informed consent document serves as the written record of the

consent interview. The consent document should be used during the

interview and should serve as the basis for the information that is discussed

with prospective participants.

e) Study subjects are to be given a copy of the consent document to be used as a

reference document, to reinforce their understanding of the study, and, if

desired, to be used as an aid to consult with their physician or other family

members about the study.

f) Informed consent is not simply a document, but an ongoing process. Subjects

should be kept informed of new information that may affect their safety or

their decision to continue to participate on an ongoing basis after they have

been enrolled.

1.3 Required Elements of Informed Consent Documents

All of the following elements must be included in written informed consent

documents:

a) A statement that the study involves research, an explanation of the purposes

of the research, 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, including an estimate of the likelihood and magnitude (severity) of

such risks, based on a summary of available data.

c) A description of any benefits to the subject or to others that may reasonably

be expected from the research.

d) A disclosure of appropriate alternative procedures or courses of treatment, if LifeBridge Health IRB Revised Date: August 20, 2008 Page 80 of 133Policies and SOPs Original Date: June 6, 2003


any, which might be advantageous to the subject.

e) A statement describing the extent to which, if any, confidentiality of records

identifying the subject will be maintained and, for research involving FDA-

regulated agents, a statement that notes the possibility that the FDA may

inspect the records.

f) For research involving more than minimal risk, an explanation as to whether

any compensation is provided if injury occurs and an explanation as to

whether any medical treatments are available for injury, 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 research subjects' rights, and whom to contact in the event of

a research-related injury to the subject.

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.

1.4 Additional Elements Generally Required

The following elements of information should also be included in the consent

form; unless determined to be inapplicable to a particular study:

a) Reproductive Risk statement: 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). This should include risks 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 that may result from participation in the

research. This should include an explanation of all costs and who will be

responsible.

d) Compensation: a statement of whether any compensation is to be provided



for participation in the research (see also VII. B. 2, Guidelines for

Compensation to Human Subjects in Research Protocols).

e) The consequences of a subject's decision to withdraw from the research and

procedures for orderly termination of participation by the subject.

f) A statement that significant new findings developed 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 involved in the study, at the site and

overall.

1.5 Other Requirements for Consent Documentsa) LBH Template: The PI should follow the guidelines in the LBH IRB-

approved consent form template [available on the LBH Intranet] for

preparation of the consent form document(s) for individual studies. An

alternative format provided by the research sponsor may be substituted (for

example, for some multicenter or pharmaceutical company-sponsored

studies), as long as (i) all of the required elements and other requirements

listed in this policy are included, (ii) the language and readability

requirements of this policy are met, and (iii) the instructions provided with the

template document are followed in adapting the alternative form for use at

LBH.

b) Second person: The language of the consent document should be in the

second person style so the consent form conveys a dialogue with information

being provided and that there is a choice to be made by the subject rather than

presumption of the subject’s consent with the use of the first person style.

c) Language should be simple: The information provided in the informed

consent documents must be in language understandable to the subject. Writing

at a 6th to 8th grade level is generally considered appropriate. The Flesch-

Kincaid scale (available in word processing programs) should be used to

check the readability level. The informed consent document should not LifeBridge Health IRB Revised Date: August 20, 2008 Page 82 of 133Policies and SOPs Original Date: June 6, 2003


include complex language or medical terminology that would not be

understandable to all subjects. All technical and scientific terms should be

adequately explained using common or lay terminology. If necessary,

consent forms for individual studies may be individualized to the reading

level of prospective subjects (for example, a lower reading level may be

used). If subjects will be enrolled who cannot read but who are capable of

understanding the information, the consent form may be read to the subjects.

d) Exculpatory language: Informed consent documents may not contain any

exculpatory language through which the subject is made to waive or appear to

waive legal rights, or releases or appears to release the Investigator, the

Sponsor, or LifeBridge Health from liability for negligence.

e) FDA-regulated investigational agents: For all research involving

investigational agents regulated by the FDA, informed consent documents

must include a statement that the purpose of the study includes evaluation of

both the safety and the effectiveness of the investigational agents. The

consent form must also include a statement that the FDA has access to the

subject's medical records.

f) Identification of the institution: the first page of the consent form should be

on LifeBridge Health letterhead or letterhead identifying the appropriate LBH

institution or entity where the research will be conducted.

g) Evidence of IRB Approval: Only informed consent documents with a current,

valid IRB stamp of approval may be used. The IRB stamp must be affixed to

the signature page of the document. The expiration date of IRB approval

must be shown clearly on the same page.



1.6 Documentation of Informed Consent and Retention of Records The signed informed consent document serves as a written record of the consent

interview, and documents that the information within was discussed with the

prospective participant or their legally authorized representative.

a) Each subject or his/her legally authorized representative must sign and date a

copy of the current IRB-approved consent form prior to enrollment or any

participation in any phase of the study, including screening, unless the

requirement is waived by the IRB.

b) The original, signed copy must be placed in the subject's research record and

maintained by the Principal Investigator.

c) A duplicate copy of the signed consent form must be given to the subject or to

the person signing the form.

d) A duplicate copy should be placed in the subject’s outpatient or inpatient

medical record.

e) A duplicate copy should also be kept on file by the Principal Investigator.

For studies with outside research sponsors, copies should be provided to the

sponsor in accord with their requirements.

1.61 Use of Facsimile or Mail to Document Informed Consenta) The IRB may approve a process that allows the informed consent document to

be delivered by mail or facsimile to a prospective subject or the prospective

subject’s legally authorized representative (LAR) and to conduct the consent

interview by telephone when the subject or the legally authorized

representative can read the consent document as it is discussed.

b) All other applicable conditions for the process and documentation of informed

consent as described in this policy must also be met when using this

procedure.

c) A proposal to utilize this procedure must be submitted to and approved by the

IRB prior to utilizing such a procedure. Application to the IRB should

include the rationale to support the use of this procedure, and an explanation

of why an in person interview is not practical. LifeBridge Health IRB Revised Date: August 20, 2008 Page 84 of 133Policies and SOPs Original Date: June 6, 2003


d) A written record of the interview must be kept with the study records and the

patient’s medical record by the investigator or the person conducting the

interview.

1.7 Oral Presentation Using Short Form As an alternative to standard written informed consent documents, oral

presentation of informed consent information may be used in certain limited

circumstances.

In such cases, the subject must be provided with both:

A short form written informed consent document stating that the elements of

informed consent have been presented orally to the subject or the LAR, and

A written summary of the information that is presented orally.

a) A witness to the oral presentation is required. The witness must sign

both the short form written informed consent document and a copy of

the written summary.

b) The subject or the legally authorized representative must sign the short

form written consent document.

c) The person obtaining consent (e.g., the Investigator) must sign a copy of

the written summary of the information that is presented orally. The

person obtaining consent may not be the witness to the consent.

d) For non-English speaking subjects, the written informed consent

document should embody, in language understandable to the subject, all

the elements necessary for legally effective informed consent. The

following procedure should be used: (i) the oral presentation and the

short form written informed consent document should be in a language

understandable to the subject; (ii) the IRB-approved English language

informed consent document may serve as the summary; and (iii) the

witness should be fluent in both English and the language of the subject.



The IRB must receive all foreign language versions of the short form

document as a condition of approval. Expedited review of these versions

is acceptable if the convened full IRB has already approved the protocol,

the full English language informed consent document, and the English

version of the short form document.

1.8 Subjects Who Do Not Speak English

Subjects who do no understand English should be presented with an informed

consent document written in a language understandable to them. When the

prospective subject population includes non-English speaking individuals, an

informed consent document that has been translated into the necessary language

may be used. The translated consent document must be IRB-approved prior to

use. The translated document may be either:

(i) submitted to the IRB for review by a member who is fluent in the language of

the translation, or

(ii) a certified translation service may be used to prepare the document and

certification submitted with the document to the IRB with a request for

approval. Expedited or full board review procedures may be used in accord

with IRB policies.

1.9 Cognitively Disabled Persons Informed consent can only be obtained from prospective subjects who are

competent to understand the research, risks, benefits, and alternatives and to make

a voluntary decision if they wish to participate. For prospective research subjects

who are deemed to be incompetent to give voluntary informed consent, a

substituted decision-maker must be sought to serve as the subject’s “Legally

Authorized Representative”.

Maryland State law states that the following individuals may be considered to be

a substitute decision-maker and to serve as the subject’s Legally Authorized



Representative for health care decisions. This listing is considered to be

applicable for clinical research, in the following order:

1. Legal guardian, or if not reasonably available,

2. Spouse, or if not reasonably available,

3. Adult child, or if not reasonably available,

4. Parent, or if not reasonably available,

5. Adult sibling, or if not reasonably available,

6. A friend or other relative may serve in this capacity with an appropriately

documented affidavit

(See also Policy VIII. C., Vulnerable Subjects: Cognitively Disabled Persons).

Studies involving subjects who are decisionally-impaired may take place over

extended periods. The IRB should consider whether periodic re-consenting of

individuals should be required to ensure that a subject’s continued involvement is

voluntary. The IRB may require that Investigators re-consent subjects after

taking into account the study’s anticipated length and the condition of the

individuals to be included (e.g., subjects with progressive neurological disorders).

2. Scope

These policies and procedures apply to all research submitted to the IRB.

3. Responsibility

The IRB Research Coordinator is responsible for reviewing all incoming

informed consent documents for completeness at the time of triage of incoming

submissions. The full IRB or the Chairperson is responsible for substantive

review of consent forms and procedures for compliance with the required

elements, using the full board or expedited review procedures. The IRB



Chairperson is responsible for communicating with Investigators to bring

documents into compliance when deficiencies are noted.


21 CFR Part 50

45 CFR Part 46.116, 117

FDA Information Sheets, 1998, Informed Consent Process and Informed Consent

Document Content

Maryland Code Ann., Health-General, Sec. 5-605

A. Attachments


B. Economic Considerations in Research Involving Human Subjects

1. Avoidance of Economic Risks to Patients:

In recent years, the IRB has been made aware of possible financial burden

as an increasing problem with regard to patient participation in research

protocols. Third party payers have been denying payment for activities

they believe are "experimental" in nature. Denial of payment either for

hospitalization required for study participation, for an investigational

product (device, drug, or biologic), or for a procedure mandated by a

protocol would place the subject/patient at economic risk. By regulation,

the consent form must inform a subject of "Any additional costs to the

subjects that may result from participation in the research".

The Committee believes subjects who participate in the process of clinical

investigation to further the aims of advancing medical knowledge and

therapy should not be responsible for costs associated with their

participation, unless the investigator can provide convincing arguments to

the contrary. Therefore, protocols that are submitted indicating that

funding is not available from a sponsor or the department must include

justification for submission of charges to third party payers to cover



research-related tests, drugs, or procedures. Such applications should

explain what plans are available if denial of payment should occur.

To avoid problems in this area, investigators are encouraged to obtain

departmental review of possible payment problems before submitting a

proposal to the IRB.

In addition, LifeBridge Health is concerned with the issue of coverage of

possible medical care costs from unanticipated side effects caused by

investigational drugs or devices used as part of a research study. Patients

or volunteers who participate in human subjects research protocols should

not be placed at risk of incurring medical care bills should they require

treatment for an unanticipated adverse event. Therefore, commercial

sponsors of research protocols must provide an indemnification agreement

which states that the sponsor will provide the cost of reasonable medical

care for treatment of a research-related injury caused by the

investigational product.

2. Guidelines for Compensation to Human Subjects in Research

Protocols

It is the obligation of the IRB to ensure that compensation offered for

participants in research protocols is fair and not so great as to induce the

subject to participate against his/her usual judgment and values. The

following guidelines are provided as an aid to investigators in developing

compensation arrangements.

a. Compensation should be reasonable and similar to amounts paid in

other research projects involving similar time, effort and

inconvenience. Maximum payment amounts must be sufficiently

modest so as not to constitute an undue inducement to participate in a

risky or uncomfortable procedure. For studies in which financial



compensation is a major reason for participation, compensation may

be sufficient to engage participants.

b. For short research studies (e.g., involving one visit), it is acceptable to

provide subject reimbursement contingent upon completion of the

study, provided that subjects disqualified through no fault of their own

are compensated fairly for the time and effort expended.

c. For longer research studies (e.g., involving multiple visits or lengthy

or repeated participation), partial payment should be provided to

research subjects who withdraw, are discharged early from a study by

the investigator, or otherwise fail to complete the study as agreed

upon. Partial payment should be related to the amount of time, effort

or discomfort involved. Pay schedules may be based on a per-day,

per-visit, or per-procedure rate, or some combination thereof. The

terms for partial compensation must be described in the protocol and

in the consent form.

d. End-loaded incentives (completion bonuses) are permissible to

encourage completion of a project. The amount of such incentives

should depend on the risk and duration of the study procedures. In

general, the range for a completion bonus should not exceed 50% of

the total compensation for studies. However, studies which involve

increased risks or discomfort to the subject or require a long-term

commitment by the subjects should not include such a large bonus.

e. The consent document should discuss the compensation to be provided

and when it will be dispensed. It is acceptable to withhold some or all

compensation until a study is complete. However, once participation

is completed or withdrawal or discharge has occurred, payment should



be provided promptly, unless a delayed payment plan has been

approved and is described to the subject in the consent document.

f. Advertisements for subject recruitment should be careful neither to

inflate expectations of the amount of compensation to be paid to

volunteers, nor to obscure the research nature of the study.

Compensation amounts used in advertisements should be those which

can be realistically expected by most subjects. Listing a theoretical

maximum that individuals are unlikely to receive should be avoided.

g. In general, compensation already earned for participation in research

studies should not be subject to penalties for poor compliance, unless

approved by the IRB.

C. Exceptions To Informed Consent Requirements

1. Policy

The IRB may approve a consent procedure that does not include, or which

alters, some or all of the elements of informed consent (such as written

documentation). The IRB may waive the requirement to obtain informed

consent if the IRB finds that the research meets specific criteria.

Specific Policies

1.1 Exemptions – IRB Waiver of One or More Requirements of

Informed Consent

a) The IRB may approve a consent procedure that does not include, or

which alters, some or all of the elements of informed consent (see

SOP VII. A.), or waive the requirement to obtain informed consent

provided the IRB finds and receives documentation that:

(i) The research or demonstration projects is to be conducted by

or subject to the approval of state or local government officials

and is designed to study, evaluate, or otherwise examine:

1. for Public benefit or service programs;LifeBridge Health IRB Revised Date: August 20, 2008 Page 91 of 133Policies and SOPs Original Date: June 6, 2003


2. Procedures obtaining benefits or services under those

programs;

3. Possible changes in or alternatives to those programs or

procedures; or possible changes in methods or levels of

payment for benefits or serviced under those programs; and

(ii) The research could not practicably be carried out without the

waiver or alteration, as in prospective emergency research

conducted under the provision of 21 CFR 50.24.

b) The IRB may also approve a consent procedure that does not

include, or which alters, some or all of the elements of informed

consent (see SOP VII. A.), or waiver the requirement to obtain

informed consent provided the IRB finds and receives

documentation of all of the following:

(i) The research involves no more than minimal risk to the

subjects; and

(ii) The waiver or alteration will not adversely affect the rights and

welfare of the subjects; and

(iii) Whenever appropriate; the subjects will be provided with

additional pertinent information after participation; and

(iv) The research could not practicably be carried out without the

waiver or alteration.

c) The IRB may waive the requirement for the Investigator or obtain a

signed consent form for some or all subjects in an approved research

protocol if the IRB finds either;

1. 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;

Note: When the IRB waives the requirement for

documentation under this condition, each subject must be



asked whether the subject wants documentation linking the

subject with the research, and the subject’s wished will govern.

Or

2. 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.

In case in which the documentation requirement is waived, the

IRB may required the Investigator to provide subjects with a

written statement regarding the research.

1.2 An Emergency Situation Prior to IRB Review and Approval

Obtaining informed consent shall be deemed feasible in all

circumstances for clinical research except:

a. In certain emergency situations where the Investigator has

adequately documented the necessary exception under the guidelines

described in the regulations, 21 CFR 50.23 and 45 CFR 116, and in

the LBH policy IX. C., “Emergency Use of Investigational Agents”,

and

b. Has documented that time was not sufficient to obtain consent from

the subject or the subject’s legal representative.

2. Scope

Applies to specific categories of research as permitted by Federal

regulations.

3. Responsibility

The IRB Chairperson (or designee) is responsible for determining

whether informed consent exemptions are applicable and appropriate

and for follow-up with Investigators as indicated from the exemption

assessment. Referral to the full IRB may be made as necessary. For

emergency research proposed to be conducted under the informed



consent exemption provisions of 21 CFR 50.24, review and approval by

the full convened IRB will be necessary.


21 CFR 50.23, 50.24

21 CFR 56. 109©, 56.109(d)

45 CFR 116(d)

5. Attachments


D. Procedures by Which Research Subjects May Voice Complaints or Concerns

Consent forms approved by the IRB for use in clinical investigation at

LifeBridge Health should contain the following:

1. The Subject should be instructed to contact the Principal Investigator of

the protocol (whose name and phone number are listed in the space

provided to voice a complaint concern regarding suspected injury.

2. Subjects should be instructed to contact the IRB office (whose name and

number is listed) if he/she has questions, complaints or concerns about

their rights as a research subject.

Typically the consent forms explain that LifeBridge Health does not have any

program to provide financial compensation for persons participating in

research projects who may experience injury that is not due to the fault of the

investigators. A statement should also be included attesting that treatment for

research-related injury will be provided by the study sponsor with out charge

to the research subject.

Any inquiry or complaint received by the IRB will be investigated pursuant to

IRB and LifeBridge Health policies and procedures. Any such inquiries or

complaints received will be documented in the IRB file for the referenced



study. Additional action, including but not limited to a site visit, audit, and

interviews with investigators, research staff or subjects and referral to the

compliance sub-committee and/or responsible institutional authorities, as

appropriate.



VIII. VULNERABLE SUBJECT POPULATIONS

For several subject populations there are additional review requirements mandated by the

Federal human subject regulations. In addition, the institution has in place additional

requirements when employees, students or cognitively disabled subjects are to be

enrolled in research protocols. These special requirements are outlined herein:

A. Children

The IRB is responsible for compliance with DHHS and FDA regulations governing

children as research subjects as per 21 CFR Part 50 subpart D and 45 CFR 46. When

children are to be enrolled as research subjects, they must be informed of the purpose

and voluntary nature of their participation. The research-related procedures they

must undergo that are in addition to standard care must be explained.

Those under the age of eighteen years are considered children. The exception is that

under Maryland law a minor has the same capacity as an adult to consent "to

treatment for or advice about... venereal disease... [and] contraception other than

sterilization." Pregnant adolescents who seek prenatal care may provide consent

without parental consent when the research relates to that prenatal care.

Each proposal involving children as subjects must include either a co-investigator or

consultant who has medical experience with children or has been actively involved in

obtaining consent from parents and assent from children. This person may be a

pediatrician, pediatric surgeon, child psychiatrist, child psychologist, pediatric nurse

practitioner, or another individual with relevant experience in dealing with children.

The Committee believes that it is preferable for this person to be actively involved in

the execution of the study, especially as far as subject recruitment and enlistment are

concerned. Approval of the entire proposal will be predicated on the approval of the

research plan, the parental consent statement, child assent statement, and the

proposed method of obtaining assent from the children.



The proposal should contain background information explaining whether or not

preliminary studies have been conducted in animals and in adults prior to initiating a

project in children. If previous studies in adults have not been conducted, the

necessity of recruiting children into the project has to be justified. To the extent

allowed by the purpose of the research, the initial subjects should be older children

who are capable of giving assent to the project.

If a project involves greater than minimal risk to the children, but it presents the

prospect of direct benefit to the individual subjects, the Risks Section of the proposal

must demonstrate that:

1. The risk of the child's participation in the protocol 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.

If a project involves greater than minimal risk to the children and no prospect of

direct benefit to individual subjects, but the study is likely to yield generalizable

knowledge about the subject's disorder or condition, the Risks Section must

demonstrate that:

1. The risk of the child's participation in the protocol presents a minor increase over

minimal risk;

2. The intervention or procedure presents experiences to the children that are

reasonably commensurate with those inherent in their actual or expected medical,

dental, psychological, social or educational situations; and

3. The intervention or procedure is likely to yield generalizable knowledge about the

subject's disorder or condition which is of vital importance for the understanding

or amelioration of the subject's disorder or condition.



A) Determination of risk:

When reviewing research conducted on children, risk is defined in terms of

minimal and greater than minimal risk, and may only be approved by the

IRB as follows:

Risk determination Benefit assessment IRB action

Minimal With or without direct benefit

Approvable

Greater than minimal risk* Potential benefit to child Approvable

Greater than minimal risk No direct benefit to individual offers general knowledge about the child’s condition or disorder

Approvable case-by-case*

Greater than minimal risk No direct benefit to child offers potential to, “understand, prevent, or alleviate a serious problem affecting the health and welfare of subjects”

Not approvable**

* Risk may not be more than a minor increase over minimal risk, consent of both parents required under normal circumstances.

**Approval to proceed with this category of research must be made by the Secretary of the HHS with input from selected experts, and following opportunity for public review and comment.

B. Children may be subjects of research only if informed consent is obtained

from the parents or legal guardian. Children over the age of 12 must

agree to participate in the research and provide written assent and separate

assent forms should be provided based on reasonable age ranges for

comprehension i.e. 512, 13-17, 18 years of age and over.

The IRB recognizes that the formulation of consent and assent forms for

children to be universally applied is challenging. We suggest different LifeBridge Health IRB Revised Date: August 20, 2008 Page 98 of 133Policies and SOPs Original Date: June 6, 2003


approaches for each of the age ranges listed. Judgment should be applied

in the preparation and use of these forms on an individual basis as needed.

i. Children younger than 5 years:

A simple oral explanation of the study should be offered to the child

before study-related procedures are conducted, with reassurance of

parental support. An explanation of what to anticipate should be

offered in terms the child can understand in addition to obtaining

parental consent.

ii. Children between the ages of 5 and 12 years:

Informed voluntary assent should be obtained without pressure from

parents or investigators. The proposed application should include an

example of the explanation to be offered to the child. Assent from the

child should be solicited in the presence of a parent, and the consent

form should include the following statement from the investigator:

"This project has been explained to my child in my presence, in

language he/she can understand. He/She has been encouraged to ask

questions, both now and in the future, about the research study."

After the child has voiced assent, the parent and investigator (and

witness, if appropriate) should sign the consent form. Documentation

should also be placed in the medical record that the assent of the child

has been obtained.

iii. Children between the ages of 13 and 17 years:

Investigators may choose to handle the consent/assent requirements

for this group in one of two ways. They may either submit a consent

form that is written at a level simple enough for both parent and child

to read meaningfully (i.e., about a 5th grade reading level), or they

may choose to submit a consent form for the parents and a separate



assent form for the child to read and sign. If a consent form is

designed for both the parent and child, the form should be signed by

each after the study has been explained.

An assent form should be written as simply as possible and cover the

following points:

1. What the study is about

2. An explanation that the study involves research

3. Why he/she qualifies for the study

4. What procedures will be done

5. Potential benefit

6. Potential risks, including the possibility of unforeseen risks

7. An assurance that he/she will still receive medical treatment,

whether or not he/she agrees to join the study

8. An invitation to ask questions

9. An assurance that he/she may withdraw from the study after dis-

cussion with his/her parents.

The assent form should contain signature lines for the child and the

investigator. Documentation should also be placed in the medical

record that the assent of the child has been obtained. If the written

assent form is not used, documentation that verbal assent was obtained

from the child and the reason that written assent was not obtained

must also be documented.

iv. Children between the ages of 16 and 18 years:

A consent form written in language that is easily understandable for

both the parents and the child may be sufficient for this age group,

depending on the maturity of the child. A separate assent form need

not always be used. The parent and child should both sign the consent

form. For an emancipated minor, parental signature is not required

before agreeing to join the study.LifeBridge Health IRB Revised Date: August 20, 2008 Page 100 of 133Policies and SOPs Original Date: June 6, 2003


These guidelines are meant to assist investigators in preparing consent

and assent forms when children are to be recruited as research

subjects. They are not meant to make research on children more

difficult to conduct, but rather are designed to provide assurances that

the rights of children are respected. When permission is obtained

from parents, both parents must assent to the participation, unless one

parent is deceased, unknown, incompetent or not reasonably available,

or when only one parent has legal responsibility for care and custody

of the child. The consent form shall document the basis for the

consent of only one parent.

B. Employees or Students

The Committee requires adequate justification for recruitment of employees or

students as normal controls or volunteers. To avoid any perception that subtle

coercion may be applied to subordinate employees, the preferred mechanism for

recruiting normal subjects is placement of a notice on Hospital bulletin boards and/or

in the publications of the institution; email notification is acceptable. All advertising,

including email notices, requires review and approval by the IRB prior to initiation.

C. Cognitively Disabled Persons

To participate in a research protocol, documented informed consent must be obtained

from all potential subjects. By definition, valid informed voluntary consent may only

be granted by individuals deemed to be mentally competent (able to understand the

research protocol, the potential risks and benefits of the research, and the alternative

treatments). If a potential research subject has been determined by a medical opinion

not to be mentally competent, a substituted decision maker may be appointed.

Maryland State law states that the following individuals may be considered to be a

substitute decision-maker and to serve as the subject’s Legally Authorized



Representative for health care decisions. This listing is considered to be applicable

for clinical research, in the following order:

1. Legal guardian, or if not reasonably available,

2. Spouse, or if not reasonably available,

3. Adult child, or if not reasonably available,

4. Parent, or if not reasonably available,

5. Adult sibling, or if not reasonably available,

6. A friend or other relative may serve in this capacity with an appropriately

documented affidavit

(See also Policy VII A., Informed Consent: Cognitively Disabled Persons).

Studies involving subjects who are decisionally-impaired may take place over

extended periods. The IRB should consider whether periodic re-consenting of

individuals should be required to ensure that a subject’s continued involvement is

voluntary. The IRB may require that Investigators re-consent subjects after taking

into account the study’s anticipated length and the condition of the individuals to be

included (e.g., subjects with progressive neurological disorders).

If the substitute decision maker consents to the subject's participation in the research

project, the subject may be enrolled. Although incapable of providing valid informed

consent, some patients may resist participating in a research protocol approved by

their substitute decision-maker. Under no circumstances may subjects be forced to

participate against their will. In addition, if an investigator or co-investigator

becomes aware of another family member who objects to the subject's participation,

an attempt must be made by the Principal Investigator to resolve this conflict. If the

objection is not resolved, the subject may not be enrolled in the research study.

D. Pregnant Women, Fetal Research, and Prisoners

Research involving pregnant women, fetal research, and research involving prisoners:

no such studies are currently anticipated to be conducted at LifeBridge Health. Any LifeBridge Health IRB Revised Date: August 20, 2008 Page 102 of 133Policies and SOPs Original Date: June 6, 2003


such research which may be proposed must be conducted in accord with applicable

Federal regulations and adhering to the ethical standards of LifeBridge Health.



IX. CATEGORIES OF RESEARCH

A. Investigational Drugs, Biologics and Medical Devices

The use of investigational or experimental drugs, biologics and devices is governed

by Federal regulations. These agents may be administered only if the following

conditions are satisfied.

1. A signed legally effective and properly obtained informed consent has been

obtained that meets the requirements of 21 CFR 50.25 and set forth in these

policies.

2. The subject meets all of the eligibility criteria as defined by the clinical protocol,

3. An IND or IDE application has been filed with the appropriate Center, office

and/or Division within the United States FDA, as required by regulatory

requirements.

4. IRB approval has been granted in writing for the proposed research.

B. Review Of Research Involving Medical Devices

1. Policy

Upon review of an application for a research study involving a medical device,

the IRB is required by the FDA to make a determination of the risk classification

of the device. Risk classification determines whether an Investigational Device

Exemption (IDE) is required to be submitted to FDA for research involving the

device. The IRB committee (or Chairperson/designee if expedited review is

appropriate) will determine whether, in the context of the study or by the nature

of the investigational medical device, the research presents a significant risk (SR)

or a non-significant risk (NSR) of harm to study subjects. This assessment will

be based on the information provided by the Investigator and/or the Sponsor, and

consideration of the proposed use of the device, characteristics of the subject

population, instructions for use, data on adverse effects, complication rates, the

training and skills of the operator of the device, and other factors that may affect

the relative risks associated with use of the device in the proposed study.



The Primary Reviewer(s) (or Expedited Reviewer, if expedited review is

permitted) will complete the attached worksheet, and will make a

recommendation to the IRB committee at the meeting at which the research is

reviewed. The IRB’s device risk determination will be documented in the IRB

meeting minutes at which the research is reviewed (or reported, if expedited

review was performed).

If an Investigator submits a device research protocol that is claimed to be NSR

and is determined by the IRB to be an SR device study, the Investigator and the

sponsor will be notified in writing by the IRB. The research will not be allowed

to proceed until the Sponsor or Investigator has met the requirements for a

Significant Risk Device study described in 21 CFR 812 (Investigational Device

Exemption regulations) for review of an IDE application by the FDA Center for

Devices and Radiological Health.

Certain devices are categorized by the FDA; a copy of this listing of documented

NSR and SR devices is attached.

2. Applicable Federal Regulations and Guidance

21 CFR 56.111

21 812.66

FDA Information Sheets: “Medical Devices”, “Significant Risk and

Nonsignficant Risk Medical Device Studies”, ”Frequently Asked Questions About

IRB Review of Medical Devices”, in “Guidance for IRBs and Clinical

Investigators—1998 Update”

FDA Center for Devices and Radiological Health website “Device Advice”, as

updated November 21, 2002, at http://www.fda.gov/cdrh/devadvice/3132.html



http://www.fda.gov/cdrh/devadvice/3132.html

C. Humanitarian Use Devices (HUD)

I. Overview

A Humanitarian Use Device (HUD) is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects fewer than 4,000 individuals per year in the United States. FDA regulations (21 CFR 814.124: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=814.124) provide for the submission of a Humanitarian Device Exemption (HDE) in which the manufacturer is not required to provide the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose prior to marketing. This regulation was developed to provide an incentive for the development of devices for use in the treatment or diagnosis of diseases affecting these populations. When the manufacturer submits the HDE it must provide sufficient information in order for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury to the patient and that the probable benefits to health outweigh the risk of injury or illness from its use.

II. Physician Responsibilities for the Use of a HUD

A physician may utilize a HUD when agreeing to the following:

The HUD will be utilized for treatment, diagnosis, or research in accordance with the labeling of the device, intended purpose, and in the designated population for which the FDA approved its use; The patient must be informed that the HUD is a device authorized under Federal law for use; however, the effectiveness of the device for a specific indication has not been demonstrated;

and

The informed consent of the patient or the patient’s legally authorized representative will be obtained when the use of the HUD involves research or when required by the IRB. LBH IRB approval of informed consent is not required before a HUD is used clinically because an HDE, which provides for temporary marketing approval, does not constitute research. Nevertheless, the LBH IRB requires that a clinical informed consent form for HUD use be signed by the patient prior to use of the HUD at LBH, when practicable.

III. Policy

A. Initial and Continuing Review of a HUD

A HUD may only be used in facilities that have established IRBs constituted and acting in accordance with FDA’s regulations governing IRBs (21 CFR part 56: http://www.fda.gov/oc/ohrt/irbs/appendixc.html), including



responsibility for continuing review of use of the device. For initial review of a HUD, full committee review is required. For continuing review, however, an IRB may use the expedited review procedures in 21 CFR 56.110, unless the IRB determines that full committee review is necessary. The LBH Institutional Review Board (IRB) will determine at the time of the fully convened meeting whether the HUD continuing review may be expedited.

B. IRB Approval of HUD Use

A HUD may only be administered to, or implanted in, a patient located at a facility if such use has been approved by the IRB at the facility. IRB approval of the use of a HUD cannot exceed the scope of the FDA approved indication(s), but may limit the scope of the FDA approved indications if the IRB feels such limitation is appropriate. The LBH IRB reserves the right to limit such FDA approved indications when appropriate. For example, the LBH IRB may limit use of the HUD to a particular medical specialty, prior use and failure of any alternative treatment modalities, and/or reporting requirements to the IRB or IRB chair.

C. IRB Review/Approval of Each Individual Use of a HUD

The LBH IRB does not require review/approval of each individual use of a HUD as long as the use of the HUD falls within the FDA approved indication and IRB limitation(s), if applicable. HUD uses, which fall within FDA approved indication(s) and IRB limitation(s) (if applicable), must be reported to the LBH IRB at the next continuing review of the HUD. Alternatively, HUD uses, which fall outside the FDA approved indications and IRB limitation(s), if applicable, must be reported to the LBH IRB in accordance with Section IV E below.

D. Clinical Informed Consent for use of a HUD

LBH IRB approval of informed consent is not required before a HUD is used because an HDE, which provides for temporary marketing approval, does not constitute research. Nevertheless, the LBH IRB requires that a clinical informed consent form for HUD use be signed by the patient prior to use of the HUD at LBH, when practicable. See section IV A4. under the Procedures section below. Please become familiar with the procedures set out below before initiating clinical use of a HUD at LBH.

IV. ProceduresLifeBridge Health IRB Revised Date: August 20, 2008 Page 107 of 133Policies and SOPs Original Date: June 6, 2003


A. IRB Submission Requirements for Use of a HUD

Regardless of the intended use, a HUD requires prospective IRB review and approval by the full Committee. The use of a HUD does not constitute research unless the physician or health care provider intends to collect data from its use.

The physician must submit an IRB Application for review at a convened meeting. All potential users within a particular LBH facility (i.e., Department or Division) must be listed as co-investigators. The primary physician (i.e., Principal Investigator) must include the following information in the application:

1. The HUD product labeling, clinical brochure, and/or other pertinent manufacturer informational materials;

2. The FDA HDE approval letter;

3. Written clinical use statement(s) from the LBH physician/health care provider specifying how the HUD will be used at LBH (i.e., who will be administering/implanting the HUD, for what clinical indication(s), etc). The(se) statement(s) must specify that the use of the HUD will be limited to the clinical indication(s) listed in the FDA- approved product labeling; and

4. HUD Clinical Consent Form. This consent form shall address the proposed clinical use of the HUD. The HUD clinical consent forms should be modeled after other clinical consent forms to include, at a minimum, the following information:

a. A description of the HDE/HUD approval process.

b. A description of the HUD and how the HUD will be used in the clinical setting. This information can be obtained from the FDA HDE Approval Letter and/or the HUD device labeling, clinical brochure, and/or other manufacturer informational materials, and LBH IRB limitations, if any. Based on this description, it should be clear to the patient why he/she is a candidate for the use of the device.

c. A discussion of possible risks, side effects, and/or adverse events associated with the HUD and its proposed clinical use;

d. A discussion of the possible benefits associated with the clinical use of the HUD;

e. A discussion of any alternative treatments or procedures (if any) that the patient may wish to consider in lieu of clinical use of the HUD;

f. Voluntary consent statement(s) with patient signature and date of signature; and



g. Physician/health care provider certification statement with physician/health care provider signature and date of signature.

A HUD Informed Consent form template for clinical applications has been developed for your use [see IRB REVIEW Form 10A (HUD - Clinical Consent)]. A second HUD Informed Consent form template for research applications also has been developed for your use [see IRB Review Form 10B (HUD for Research).

B. Continuing Review Requirements

The physician is responsible for fulfilling continuing review requirements to the IRB at least annually. At the time of continuing review, the physician must report the HUD activities for the previous 6 months for all non-LBH performance sites. In addition, the following information must be provided to the IRB in summary form for each HUD at LBH or affiliated sites. This report must include the following:

1. A cover letter signed by the responsible physician/healthcare provider requesting continuation of IRB approval of the HUD. The cover letter should identify the HUD, specify the clinical use statement(s) of the HUD, and, if applicable, summarize any known FDA action(s) taken regarding the HUD since last initial or continuing review;

2. A summary of all correspondence received from the holder of the humanitarian device exemption (HDE) since last initial or continuing review, if applicable;

3. A copy of the current FDA-approved product labeling for the HUD;

4. A copy of the current clinical informed consent form;

5. For each patient in whom the HUD has been used during the previous 6 months provide a summary of:

a. The clinical indications for the use of the HUD;

b. Any adverse events felt to be related or possibly related to the use of the HUD; and

c. The clinical outcome of the use of the HUD.

C. Adverse Events and Unanticipated Problems.

Adverse events and unanticipated problems that result from the use of a humanitarian device are subject to LBH IRB Adverse Events reporting requirements [IRB Guide 3 (Adverse Events)]. FDA regulations require that



if a physician or health care provider receives or otherwise becomes aware of information, from any source, that reasonably suggests that a HUD has or may have caused or contributed to the death or serious injury of a patient, the physician or health care provider must report such findings (using FDA form 3500A) to the FDA as soon as possible, but no later than 10 working days after the Investigator first learns of the effect or problem. This reporting is in addition to, not a substitute for, FDA and/or manufacturer reporting requirements in accordance with 21 CFR 803.30.

The physician or health care provider is required to promptly report any FDA action(s) regarding the HUD to the IRB.

D. Prompt Reporting of FDA Action(s) on the HUD.

The physician/health care provider who requested use of the HUD at LBH must promptly report to the LBH IRB any FDA action(s) taken regarding the HUD for which he/she has become aware. This report, which shall be in the form of a memorandum to the Chair of the LBH IRB, shall be forwarded to the Chair within 10 days of receiving knowledge of such FDA action. Depending on the FDA action taken, the Chair may elect to initiate an immediate IRB action (e.g., withdraw IRB approval of use of the HUD because FDA rescinded the HDE due to the availability of a comparable device) or await action until the full IRB has discussed the FDA action taken on the HUD (e.g., modifying the clinical use of the HUD because FDA has done so). Any immediate action taken by the Chair of the IRB will be discussed and voted on at the next IRB meeting.

E. Modifications to the HUD or the Clinical Use of the HUD.

LBH IRB approval is required for any modifications of the HUD and/or of the proposed clinical use(s) of the HUD. A physician/health care provider requesting modification to either the HUD or the clinical use(s) of the HUD must submit one copy of the following:

1. A cover letter signed by the responsible physician/healthcare provider, describing the modification to the HUD and/or the proposed clinical use(s) of the HUD and the rational for such modification(s);

2. A copy of the HUD manufacturer’s amendment to the HUD product labeling, clinical brochure, and/or the pertinent manufacturer informational materials corresponding to the requested modification(s);

3. A copy of any FDA HDE amendment/supplement approval letters; and



4. A copy of the revised clinical use statement(s) and clinical consent form with the modifications highlighted.

F. Emergency Use of a HUD

1. A HUD may be used off-label (outside its approved indications for use) in an emergency situation, i.e., to save the life or protect the physical well being of a patient.

2. The treating LBH physician/health care provider should ensure that the following patient protection measures are followed before and after the emergency use occurs:

a. Before the HUD emergency use occurs. If possible, the physician should obtain the following:

1. Concurrence of the LBH IRB chairperson;

2. Informed consent from the patient or his/her legal representative;

3. An independent assessment by an uninvolved physician; and

4. Authorization from the HDE holder before emergency use of the HUD.

b. After the HUD emergency use occurs. The treating LBH physician/health care provider shall submit a follow-up report on the patient’s condition and information regarding the patient protection measures that were followed to both the LBH IRB and the HDE holder.

3. Please note that the above referenced emergency use reporting to the LBH IRB is an addition to, not a substitute for, the LBH Hospital Emergency Use Reporting Policy. Emergency Use Reporting of a HUD to the LBH Hospital is the responsibility of the physician/health care provider who requested use of the HUD.

4. For further guidance on emergency use of a HUD, please see ‘Emergency Use of Unapproved Medical Devices’ within Chapter III, Expanded Access to Unapproved Devices of the “IDE Policies and Procedures Guidance” at: http://www.fda.gov/cdrh/ode/idepolcy.html.

G. Compassionate Use of a HUD

1. A HUD may be used off-label for compassionate use, i.e., when a HUD is the only option available for a patient(s) faced with a serious, non-life threatening condition.



http://www.fda.gov/cdrh/ode/idepolcy.html

2. Before compassionate use of a HUD occurs, the treating LBH physician/health care provider shall:

a.) Provide the HDE holder with the following:

1. A description of the patient’s condition and the circumstances necessitating treatment with the device;

2. A discussion of why alternative therapies are unsatisfactory; and

3. Information addressing the applicable patient protection measures outlined in Section F2. above. The HDE holder should, in turn, submit this information in an HDE amendment for FDA approval before the use occurs.

b.) Ensure that FDA approval of compassionate use of the HUD is obtained prior to its use.

c.) Obtain LBH IRB Approval for compassionate use of the HUD.

3. If the FDA approves the HUD compassionate use request, the physician/health care provider shall devise an appropriate schedule for monitoring the patient, taking into consideration the limited information available regarding the potential risks and benefits of the device and the specific needs of the patient.

4. For further guidance regarding Compassionate Use of a HUD see ‘Individual Patient Access to Investigational Devices Intended for Serious Diseases’ within Chapter III of the “IDE Policies and Procedures Guidance” at http://www.fda.gov/cdrh/ode/idepolcy.html.

D. Emergency Use of Investigational Agents

An investigational agent (“test article”) may be used in an emergency prior to IRB

review, provided that the patient is in a life-threatening situation for which no

standard acceptable treatment is available, and in which there is not sufficient time to

obtain IRB approval.

The treating physician must obtain permission from the sponsor or manufacturer of

the investigational agent, concurrence form the FDA Center, office or Division

responsible (in review) and an IND or IDE number prior to use of the agents.



Such emergency use must be reported to the IRB within 5 working days, and any

subsequent use of the test article will then be subject to prior IRB review

requirements.

In such a situation, obtaining informed consent shall be considered feasible except in

certain emergency situations where the Investigator has adequately documented the

necessary exception under the guidelines described in 21 CFR 50.23. The

Investigator must submit documentation to the IRB for review within 5 working days

after emergency use of the test article. In review of the documentation, the IRB will

ensure that the Investigator and a physician not otherwise participating in the clinical

investigation have adequately certified the following in writing prior to use of the test

article:

1. The human subject was confronted by a life-threatening situation necessitating the

use of the test article.

2. Informed consent could not be obtained from the subject because of an inability

to communicate with, or obtain legally effective consent from, the subject.

3. Time was not sufficient to obtain consent from the subject's legal representative.

4. There was no alternative method of approved or generally recognized therapy

available that provided an equal or greater likelihood of saving the life of the

subject.

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, prior to administering the

test article, to obtain an independent physician's opinion, the determinations of the

Investigator must be reviewed in writing within 5 days after the use of the test article

by a physician not otherwise participating in the clinical investigation. In this event, a

copy of the independent review must be submitted to the IRB within 7 working days

after the use of the test article.



Whenever emergency care is initiated without prior IRB review and approval, the

patient may not be considered to be a research subject for HHS regulations do not

permit research activities to be started, even in an emergency, without prior IRB

review and approval.

For DHHS-supported or conducted research, the physician may, without prior IRB

approval, treat the patient/subject using a test article (if the situation meets the FDA

requirements), but the subject may not be considered a research subject and data

derived from use of the test article may not be used in an ongoing study.

E. Single Patient or Small Group Use “Compassionate Use” of Investigational Agents in non-emergency situations

1. Policy

Requests from a LifeBridge Health licensed practitioner for treatment of an

individual subject with an investigational agent outside an ongoing clinical

research study will be considered by the IRB providing that the investigator and

sponsor/manufacturer follow the procedures outlined in 21 CFR 312.35

(“Treatment IND” for drugs or biologics) or 21 CFR 812.35 (“compassionate

Use” for medical devices) for obtaining FDA approval to allow the

sponsor/manufacturer to release the agent to the practitioner. This provision

allows access for patients who do not meet the requirements for inclusion in an

ongoing clinical investigation but for whom the agent may provide a benefit in

treating their disease or condition. This provision is typically approved for

individual patients but may be approved to treat a small group.

This applies to subjects who meet the following criteria:

1. Individuals who have a serious disease or condition

2. No satisfactory alternative treatment is available.

Prior FDA approval is needed before use occurs. The IND application or IDE

supplement should include:



1. A description of the patient's condition and the circumstances necessitating

treatment;

2. A discussion of why alternative therapies are unsatisfactory and why the

probable risk of using the investigational agent is no greater than the probable

risk from the disease or condition;

3. A treatment protocol meeting the criteria outlined in the above-cited

regulations. A treatment protocol is required to contain the following:

(i) The intended use of the drug.

(ii) An explanation of the rationale for use of the drug, including, as

appropriate, either a list of what available regimens ordinarily should be

tried before using the investigational drug or an explanation of why the

use of the investigational drug is preferable to the use of available

marketed treatments.

(iii) A brief description of the criteria for patient selection.

(iv) The method of administration of the drug and the dosages.

(v) A description of clinical procedures, laboratory tests, or other measures

to monitor the effects of the drug and to minimize risk. Or

4. If an approved clinical research protocol will be followed, identification of

any deviations in the approved clinical protocol that may be needed in order

to treat the patient; and

5. An informational brochure for each treating physician including the technical

information that is relevant to safety and effectiveness of the agent for the

intended treatment purpose;

6. A copy of the proposed informed consent document. This may be based on

the consent form in use for the ongoing clinical study, and modified to



include a discussion of the potential risks and benefits to the individual

subject.

7. An independent assessment from an uninvolved physician should be

submitted, documenting concurrence that the subject is an appropriate

candidate for the proposed treatment.

8. The treating physician should devise an appropriate schedule for monitoring

the patient, taking into consideration the investigational nature of the agent

and the specific needs of the patient. The patient should be monitored to

detect any possible problems arising from the use of the agent.

Authorization from the sponsor or manufacturer of the investigational agent

should accompany the IRB application. The physician may not initiate

treatment until the appropriate reviewing division within FDA approves use

of the agent under the proposed circumstances, and IRB approval has been

obtained. In reviewing this type of request, the IRB will consider the above

information as well as whether the evidence of safety and effectiveness

provided justifies such use in the individual.

The treating physician will be responsible for reporting of adverse events as

per IRB and FDA regulations for investigational agents, and will also be

responsible for fulfilling the “sponsor” obligations if a treatment IND goes

into effect in the individual practitioner’s name.

A follow-up report should be submitted to FDA and to the IRB within a

reasonable time after treatment and follow-up have been completed, in which

summary information regarding patient outcome is presented. If any problems

occurred as a result of use of the agent, these should be discussed in the

report.

2. ResponsibilityLifeBridge Health IRB Revised Date: August 20, 2008 Page 116 of 133Policies and SOPs Original Date: June 6, 2003


The individual practitioner will be responsible for providing a complete package

to the IRB for review, and for fulfilling the obligations of a clinical investigator

with respect to the proposal.

The IRB Chairperson or designee will review requests under this policy and

determine if a full board review is necessary. There may be some instances in

which an expedited review is appropriate.

3. Applicable Regulations and guidance

21 CFR 312.35

21 CFR 312.32

21 CFR 812.35

21 CFR 812.32

21 CFR 50 and

21 CFR 56

“Device Advice”, Expanded Access/Compassionate Use of Medical Devices, at http://www.fda.gov/cdrh/devadvice/ide/print/early.html#compassionateuse, last updated 7-21-03

F. Medical Records and Chart Review

Studies involving the use of existing public or privately held records only may

qualify for exempt status or expedited review. However, if the nature of the research

could put subjects' confidentiality at risk, the study will be reviewed by the full IRB.

Studies that involve only chart and record review can sometimes pose significant risk

to patients.

The most common breach of confidentiality is exposure of possible embarrassing

information without the knowledge or consent of the patient. The present policy is to

require IRB review of studies involving chart review or data collection and analysis

where protected health information (PHI) may be used or disclosed, as per the



http://www.fda.gov/cdrh/devadvice/ide/print/early.html#compassionateuse

LifeBridge Health HIPAA Policy “Use or Disclosure of Protected Health Information

for Research (see Attachments).

If identifiers were to be recorded, the research would require IRB review to ensure

that, among other things, procedures for protecting privacy and confidentiality are

adequate. The LifeBridge Health HIPAA Research policy describes procedures for

individual authorization, waiver requirements, and use of de-identified information to

meet HIPAA Privacy Rule requirements.

G. Genetic Research

As genetic research technology has become more widely available, obtaining samples

of blood or tissue for genetic studies has become a popular add-on to may clinical

studies.

Some of this research may meet the criteria for expedited review.

However, these studies may create a vulnerable population if subjects' autonomy is

compromised and they are not able to make a free choice as to whether or not to

participate. Informed consent for genetic studies must be obtained separately from

the consent to participate in the main study. As separate consent form should be used

for the consent to participate in a genetic study. When the genetic study is a sub-

study, the subject must be given an opportunity to “opt out” of the genetic study

without compromising his/her enrollment in the main study. The form should outline

who will have access to the information and the extent to which confidentially will be

maintained. The IRB must also examine whether the samples will be used for any

additional studies not made explicit at the time of donation, or if the samples will be

destroyed after a specified, one-time use. This should be described in the insert

forms. The consent should also disclose whether the donor will be informed of any

or all results obtained from his or her DNA or will be informed of the results of the

entire study, and whether other family members be advised of the studies.

H. Gene Therapy, Tissue and Cell Transplantation Research



Gene therapy research (administration of recombinant vectors), in which genetic

material which is transferred in an attempt to provide treatments for genetic diseases,

presents unique questions, including the considerations of delivery methods, target

population, and required follow-up for latent complications. Any project involving

gene therapy to human subjects for research purposes, must be reviewed and

approved by the National Institutes of Health Recombinant DNA Advisory

Committee (RAC) and have concurrence from the responsible FDA review division

prior to IRB submission. Independent monitoring must be in place, and an

independent DSMB will be required. Institutional Biosafety Review will also be

required. Such protocols may require use of external consultants to provide

independent guidance to the IRB.

Protocols involving transplantation of tissues or cells must have concurrence from the

FDA CBER office of Cell, Tissue and Gene Therapy prior to IRB submission and are

subject to all relevant Federal regulatory requirements. Because regulatory guidance

is still evolving there are relatively few ethical precedents, this type of research will

require close scrutiny, and perhaps the use of consultants by the IRB in this area.



X. INVESTIGATOR RESPONSIBILITIES

A. Required Investigator Actions

1. Policy

The LifeBridge Health Principal Investigator is responsible for providing the IRB

with a complete and accurate presentation of the proposed research when

submitted with an application in time to meet established deadlines for review.

Between IRB initial approval of a protocol and the time of continuing review of a

study, it is the Investigator's responsibility to keep the IRB informed in a timely

manner of unexpected serious adverse events and other findings that could affect

the risk/benefit ratio of the research.

i. Compliance:

The LifeBridge Health Principal Investigator is responsible for ensuring

compliance of all co-investigators and research staff with the policies and

procedures of the IRB and with Federal state and local regulations.

ii. Conflict of Interest:

The LifeBridge Health. Principal Investigator and all co-investigations are

responsible for providing accurate and timely disclosure of any significant

personal, professional, or financial interest in or relationship with commercial

sponsors of research in which they participate. This information should be

updated at the time of each continuing review or at any time that relevant

changes occur.

iii. Delegation of Responsibilities:

The Principal Investigator and all co-investigators are responsible for

performing, or delegating to, responsible and qualified individuals, all

research related activities.



iv. Informed Consent:

All Investigators must obtain informed consent from subjects prior to their

enrollment into the research. The Investigator must use the informed consent

document approved by the IRB. Approval and expiration dates are indicated

on the signature page of the consent document. Consent documents are valid

only during the dates indicated on the form; and the Investigator may use the

forms only during the period for which they are valid. Investigators must

follow LifeBridge Health guidelines for obtaining informed consent.

LifeBridge Health Principal Investigator are responsible for ensuring that

consent procedures conducted by all co-investigators and are conducted in

accord with these requirements.

v. Adverse Event Reporting:

The LifeBridge Health Principal Investigator is responsible for ensuring

timely reporting of any serious, unexpected or alarming adverse events that

occur during the approval period. An IRB form or an FDA MedWatch form

may be used with a summary completed by the investigator. Investigators

must also submit Sponsor-generated reports of adverse events occurring at

other investigative sites in accord with LifeBridge Health policy.

An Investigator is responsible for the accurate documentation, investigation

and follow-up of all adverse events and other outcomes data on subjects in

clinical research protocols.

vi. Changes in Approved Research

Changes in approved research, during the period for which approval has

already been given, may not be initiated without IRB review (or expedited

review, where appropriate) and approval, except where necessary to eliminate

apparent immediate hazards to human subjects. The LifeBridge Health

Principal Investigator is responsible for ensuring that requests for changes are



submitted to the IRB in writing in adequate time to meet review deadlines

established by the IRB.

vii. Periodic Reports

The length of time approval is given to a research protocol will be no more

than one year, and is dependent on the risk involved with the research.

Investigators are responsible for requesting renewal in anticipation of the

expiration of the approval period. Investigators or their designees and/or

Sponsors are required to provide a periodic report (DSMC reports or other, as

required) regarding their investigation prior to the end of the approval period,

and upon completion of the study.

The IRB Continuing Review Report/Renewal Request Form must be

completed by the Principal Investigator or designee, and signed by the

Principal Investigator.

viii. Resident, Fellow and Student-Conducted Research

All activities that meet the definition of research with human subjects and that

are conducted by students for a class project or for work toward a degree that

are not exempted must be reviewed by the IRB. For example, activities that

must be reviewed and approved by the IRB include: (i) Master’s theses and

doctoral dissertations that involve human subjects; and (ii) All projects that

involve human subjects, and for which findings may be published or

otherwise disseminated. All residents/fellows applying for IRB review must

name and obtain signature of a faculty sponsor on the IRB Application and

Renewal Request Form., who is responsible for meeting the obligation of the

LifeBridge Health Principal Investigator.

B. Responsibility

The IRB Research Coordinator is responsible for tracking Investigator compliance

with IRB requirements stipulated during the IRB’s review of the Investigator’s



research, and for engaging appropriate Investigator sanctions or referral to the

Compliance Subcommittee as appropriate when Investigators are not in compliance

with IRB requirements.

The IRB Chairperson (or designee) is responsible for facilitating Investigator

compliance with IRB requirements through his/her management of IRB deliberations,

and providing Investigators clear guidelines through IRB communications.

C. Applicable Regulations and Guidelines

21 CFR 56.109, 56.111

21 CFR 54

45 CFR 46.109, 46.111

OHRP COI Policy Draft



XII. QUALITY ASSURANCE

A. Quality Assurance and Quality Control

1. Policy

Quality assurance and control of the daily operations of the IRB ensure effective

support of the IRB's mandate. Therefore, the QA/QC program consists of three

components:

a. Training and continuing education of IRB staff

b. Interactions with the IRB community outside the LifeBridge Health

c. Regular review and assessment of procedures

The IRB Chairperson has the authority to implement a QA/QC program and to

act on identified deficiencies by implementing corrective action via revisions to

the Standard Operating Policies and Procedures.

2. Responsibility

The IRB Research Coordinator is responsible for the establishment,

implementation and oversight of the QA/QC program.

3. Applicable Regulations And Guidelines

None

4. Attachments

None

B. Audits by Regulatory Agencies

1. Policy

LifeBridge Health acknowledges that certain regulatory agencies have the

authority to audit the operations of IRBs, and supports such audits as part of its

continuing effort to maintain high standards for human research protections.

Entities that may audit IRBs include: FDA, OHRP, JCAHO, and appropriate

certified auditors of foreign counties where data from clinical research has been LifeBridge Health IRB Revised Date: August 20, 2008 Page 124 of 133Policies and SOPs Original Date: June 6, 2003


submitted in an application for drug or device approval. Sponsors or funding

entities of research may also be authorized to audit specific documents and

procedures.

a) Preparing for an Audit

(i) For external audits involving OHRP or FDA, the following must be

notified immediately:

1. Senior Vice President, LifeBridge Health or designee

2. IRB Chairperson, Vice-Chairperson

3. The IRB staff designated to participate in the audit are required to

follow the steps outlined by this institution for preparing the site for an

audit.

b) Participating in an Audit

(i) IRB staff are expected to know and follow the procedures outlined by this

Institution for the conduct of a regulatory audit.

(ii) Prior to being granted access to IRB documentation, inspectors or auditors

must exhibit proof of their authority or authorization to conduct the

audit and to access IRB documents, and no entity other than those listed

on the consent forms may have access to any document that includes

subject identifiers.

(iii) Auditors will be provided with adequate working area to conduct

an audit and IRB staff and members must make every reasonable effort to

be available and to accommodate and expedite the requests of such

auditors.

(iv)Documents may be copied and taken off-site only by individuals

authorized in writing by the IRB Chairperson or designee to do so.



c) Follow-up After an Audit

Reports of the audit, either verbal or written, should be addressed by the IRB

Chairperson or designee (with the assistance and support of LifeBridge Health

Administration), as soon as possible after the audit.

2. Responsibility

The Senior Vice President of LifeBridge Health (or designee) is responsible for

serving as the responsible institutional official in all regulatory agency matters

regarding regulatory compliance, participating as needed in regulatory agency

audits, and providing support in responding to and correcting audit findings.

The IRB Chairperson and Research Coordinator are responsible for all formal

regulatory agency correspondence and interactions, establishing logistical support

during regulatory agency audits, serving as key institution contact during such

audits, and drafting responses to regulatory agency correspondence received

following such audits.

The IRB Chairperson, Members and Staff are responsible for participating in

regulatory agency audits and in fully cooperating with government officials

during their participation in such audits.

The IRB Chairperson is responsible for preparing formal responses to regulatory

agency audits and in implementing policy and procedure changes indicated by

such audits.


21 CFR 56.115

45 CFR 46.115

FDA Compliance Program Guidance Manual 7348.809, Institutional Review

Boards



XIII. APPENDIX

A. IRB Forms

Protocol Application Checklist

Application for New Research

Renewal Application for Continuing Research

IRB Co-Investigator Signature Page

LBH Investigator Delegation of Responsibility

Financial Interest Disclosure Form

Request for Exception to Informed Consent Requirements for Research

LBH IRB Informed Consent Template

HIPAA Authorization Form for Use or Disclosure of Protected Health Information-Outside Sponsor

Authorization Form for Use or Disclosure of Protected Health Information-Investigator Sponsored

Application for Waiver of Individual Authorization for Use or Disclosure of Protected Health Information (PHI) in a Research Study

Disclosure/Use of De-Identified Data/Materials for Research

Exemption Screening Questions

Claim of Exemption

Adverse Event Report Form

Consent to Undergo Treatment with a Humanitarian Device

Humanitarian Use Device Informed Consent and Privacy Authorization Form

Human Gene Transfer / Recombinant DNA Research

IRB Protocol Review

IRB Protocol Amendment Review

LBH IRB Informed Consent Review Form

Claim of Exemption Checklist for IRB Staff

LBH IRB Member Agreement

LBH IRB Alternate Member Agreement



http://lbhweb/workfiles/hipaa/research_appendixB.doc

http://lbhweb/workfiles/hipaa/research_appendixB.doc

http://lbhweb/workfiles/hipaa/Authorization_Form_for_Investigator_Sponsored_Research.doc

http://lbhweb/workfiles/hipaa/Authorization_Form_for_Investigator_Sponsored_Research.doc

http://lbhweb/workfiles/hipaa/Authorization_Form_for_Outside_Sponsored_Research.doc

http://lbhweb/workfiles/hipaa/Authorization_Form_for_Outside_Sponsored_Research.doc

LBH IRB Member and Alternate Confidentiality Agreement

LBH IRB Member and Alternate Conflict of Interest Disclosure and Recusal Agreement

B. IRB Guidelines

Case Reports & Chart Reviews

Disclosure / Use of De-Identified Data / Materials for Research

Adverse Event Reporting

Adverse Event and Safety Report Continuing Review Reporting

Policy on Conflict of Interest in Research

Conflict of Interest Guidelines for Clinical Research

Human Gene Transfer/Recombinant DNA Research

Compassionate Use of an Unapproved Drug, Device, or Biologic

Humanitarian Use Devices

Questionnaires by Telephone or Mail

Independent Central Institutional Review Board (CIRB) Evaluation and Facilitated Review

NCI CIRB Facilitated Review

Defining Community Outreach Research and Non-Research Projects

IRB Member Responsibilities and Reviewer Duties

Evaluating and Monitoring Risk in Human Subjects Research

IRB Review Fees

Please refer to the LifeBridge Health Intranet for the latest version of all available forms for your use. Forms are also available at the LifeBridge Health Office.

