Policies and Standard Operating Procedures

LIFEBRIDGE HEALTH, INC.

Institutional Review Board

Policies and Standard Operating Procedures

Revised as of 20 August 2008

I.INTRODUCTION......

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

A.Governing Principles......

B.Institutional Authority......

C.IRB Authority......

D.Responsibilities of the IRB......

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

A.Composition of the Board......

B.Management......

C.Duties of IRB Members......

D.Scope of IRB Reviews......

IV.GENERAL ADMINISTRATION......

A.Policies and Procedures Maintenance......

B.Education and Training......

V.FUNCTIONS AND OPERATIONS......

A.Research Submission Requirements......

B.Exemptions from IRB review......

C.IRB Meeting Administration......

D.Administrative Review and Distribution of Materials......

E.Documentation and Document Management......

VI.REVIEW OF RESEARCH......

A.Expedited Review......

B.Facilitated IRB Reviews (Central IRB)......

C.Full IRB Initial Review – Criteria for IRB Approval......

D.Full IRB Continuing Review – Criteria for Renewal......

E.Continuing Review – Ongoing......

F.Investigator Reporting of Serious Adverse Events in Research Subjects......

G.Suspensions of Studies......

H.Study Completion......

I.Categories of Action by the IRB......

VII.informed consent......

A.General Requirements and Documentation......

B.Economic Considerations in Research Involving Human Subjects......

C.Exceptions To Informed Consent Requirements......

D.Procedures by Which Research Subjects May Voice Complaints or Concerns......

VIII.Vulnerable Subject Populations

A.Children......

B.Employees or Students......

C.Cognitively Disabled Persons......

D.Pregnant Women, Fetal Research, and Prisoners......

IX.CATEGORIES OF RESEARCH......

A.Investigational Drugs, Biologics and Medical Devices......

B.Review Of Research Involving Medical Devices......

C.Humanitarian Use Devices (HUD)......

D.Emergency Use of Investigational Agents......

E.Single Patient or Small Group Use “Compassionate Use” of Investigational Agents in non-emergency situations

F.Medical Records and Chart Review......

G.Genetic Research......

H.Gene Therapy, Tissue and Cell Transplantation Research......

X.INVESTIGATOR RESPONSIBILITIES......

A.Required Investigator Actions......

B.Responsibility......

C.Applicable Regulations and Guidelines......

XI.QUALITY ASSURANCE......

A.Quality Assurance and Quality Control......

B.Audits by Regulatory Agencies......

XII. Appendix......

A.IRB Forms......

Protocol Application Checklist

Application for New Research

Renewal Application for Continuing Research

Request for Exception to Informed Consent Requirements for Research

IRB Co-Investigator Signature Page

LBH Investigator Delegation of Responsibility

Financial Interest Disclosure Form

Request for Exception to Informed Consent Requirements for Research......

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

IRB Member Agreement

IRB Alternate Member Agreement......

IRB Member and Alternate Confidentiality Agreement...... 128

IRB Member and Alternate Conflict of Interest Disclosure and Recusal Agreement...... 128

B. IRB Guidelines

Case 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 Board

LifeBridge Health

SinaiHospital of Baltimore

2401 W. Belvedere Avenue

SchapiroBuilding, Suite 203

Baltimore, MD21215

Arthur N. Freed, Ph.D., Chairperson

Patty Lohinski, CIM, Research Coordinator

(410) 601-9021 Office

(410) 601-8282 Fax

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.

II.STATEMENT OF AUTHORITY AND PURPOSE

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:

The research is sponsored by institutional authorities of LifeBridge Health and/or;
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
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
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, NorthwestHospitalCenter and LevindaleHebrewGeriatricCenter 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:

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;
The IRB reviews, and has the authority to approve, require modification in, or disapprove, all research activities that fall within its jurisdiction;
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;
The IRB may suspend or terminate approval of a study; and
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 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:

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.
Any systematic investigation involving innovative procedures or treatments, including innovative uses of FDA approved agents in a series of subjects,
All Federally funded research unless specific criteria for exemption are met (see Functions and Operations: Exemptions from IRB requirements).
An investigational diagnostic procedure for research purposes that is added to a standard treatment.
Collection of comparative data about a series of standard procedures or treatments for dissemination, generalization, or publication.
Emergency use or “compassionate use” (use outside an approved research protocol) of an investigational drug or medical device.
Human cell or tissue (genetic tissue) research that involves repositories that collect, store, and distribute human tissue materials for research purposes.
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.
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.
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.
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.

III.ORGANIZATION OF THE IRB

Composition of the Board

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.