MULTIPLE PROJECT ASSURANCE (MPA) FOR COMPLIANCE WITH DHHS REGULATIONS FOR THE PROTECTION OF HUMAN SUBJECTS (45 CFR 46)

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DIVISION OF HUMAN SUBJECT PROTECTIONS
OFFICE FOR PROTECTION FROM RESEARCH RISKS
NATIONAL INSTITUTES OF HEALTH
DEPARTMENT OF HEALTH AND HUMAN SERVICES

SAMPLE LANGUAGE FOR A DEPARTMENT OF HEALTH AND HUMAN SERVICES (DHHS)
MULTIPLE PROJECT ASSURANCE (MPA) FOR COMPLIANCE WITH DHHS REGULATIONS
FOR THE PROTECTION OF HUMAN SUBJECTS (45 CFR 46), IN ACCORDANCE WITH
THE FEDERAL POLICY (EFFECTIVE AUGUST 19, 1991),
AND AS MAY OTHERWISE BE AMENDED.

THIS SAMPLE TEXT IS OFFERED AS A GUIDE TO PREPARERS

*****
For ease of identification, bold and italic entries apply to significant changes since initial introduction of this general MPA format in 1991. Care has been taken to avoid reordering of Part, Section, Category, and Item sequences to enable ready comparison with existing institutional text, whenever possible. This sample MPA text is electronically available by e-mail attachment upon request to cs19n@nih.gov. Use of OPRR’s electronic sample to create revised MPA text will automatically include all editorial changes in the sample.
*****

June 1999
NOTE: Please prepare this document on institutional letterhead and supply all information specific to your institution. All changes and individualized text should be highlighted to facilitate timely review and approval by OPRR.

TABLE OF CONTENTS

Preface

Glossary of Terms

Part 1 - Principles, Policies, and Applicability

I. Ethical Principles
II. Institutional Policy
III. Applicability
Footnote 1

Part 2 - Responsibilities

I. Institution
II. Office of Research Administration for Human Subject Research
III. Institutional Review Board(s)
IV. Research Investigator
V. Affiliated Institutions and Investigators
Footnote 2

Part 3 - Signatures

I. Institutional Endorsements
II. Office for Protection from Research Risks (DHHS) Approval

Part 4 - Appendices

A. Institutional Components
B. IIA Institutional Affiliates
C. Institutional Review Board List(s)
D. Abstract of Institutional Program and Organizational Line Diagram

Part 5 - Reference Documents

A. OPRR Reports - 45 CFR 46
B. The Belmont Report
C. Inter-Institutional Amendment
D. Non-institutional Investigator Agreement
E. OPRR-Recognized Cooperative Protocol Research Programs
F. Cooperative Amendment

PREFACE

On behalf of DHHS, the Office for Protection from Research Risks (OPRR) is responsible for the negotiation of assurances of compliance with Title 45 of the Code of Federal Regulations (CFR), Part 46 (45 CFR 46). OPRR has prepared this sample Multiple Project Assurance (MPA) document to assist institutions in developing their Assurances. Numerous Federal departments and agencies, including DHHS, share common basic provisions for the protection of human subjects, effective August 19, 1991. These provisions are known as the Federal Policy for the Protection of Human Subjects (56FR28003), also referred to as the Common Rule. For DHHS, provisions of the Common Rule are included in 45 CFR 46 as Subpart A. Subparts B, C, and D remain unaltered other than for cross-references to exemptions which have been renumbered in Section 101(b). Citations of CFR titles and parts for each department and agency currently participating in the Common Rule are as follows:

Central Intelligence Agency Executive Order 12333

Consumer Product Safety Commission 16 CFR Part 1028

Department of Agriculture 7 CFR Part 1c

Department of Commerce 15 CFR Part 27

Department of Defense 32 CFR Part 219

Department of Education 34 CFR Part 97

Department of Energy 10 CFR Part 745

Department of Health and Human Services 45 CFR Part 46

Department of Housing and Urban Development 24 CFR Part 60

Department of Justice 28 CFR Part 46

Department of Transportation 49 CFR Part 11

Department of Veterans Affairs 38 CFR Part 16

Environmental Protection Agency 40 CFR Part 26

National Aeronautics and Space Administration 14 CFR Part 1230

National Science Foundation 45 CFR Part 690

Social Security Administration Public Law 103-296

Citations by section (e.g., Section 110) in the sample document are intended to avoid confusion over reference to Subpart A of DHHS's regulations (45 CFR 46) as opposed to those of other Federal departments and agencies. Subparts B, C, and D of 45 CFR 46 are explicitly included in the requirements of any DHHS MPA.

MPA institutions generally elect to comply with all Subparts of 45 CFR 46 for any research conducted under their auspices (i.e., regardless of the source of support). When an institution has elected to abide by 45 CFR 46, regardless of the source of support, all Subparts of 45 CFR 46 are applicable to research even if it is not federally sponsored or sponsored by Federal departments or agencies other than DHHS. This has been taken into account in wording the sample text.

Federal departments and agencies are obligated to honor a DHHS MPA which has been approved for Federal-wide use by OPRR. When a DHHS MPA is honored by other Federal departments and agencies, reports to them which are required by the Common Rule (except certification) must also be sent to OPRR (see Section 103).

The sample Assurance will, of course, have to be adapted to the organizational structure of your institution. Additions, deletions, and alterations to the sample text should be highlighted prior to submission to OPRR.

The sample Assurance can be completed by a single signatory institution or jointly by two or more signatory institutions when appropriate changes for textual consistency, signatures, and appendices are included. In addition, some provisions of the sample MPA have been supplied as examples to illustrate how an institution might elect to manage its administrative procedures. Also, more than one Office of Research Administration for human subjects(ORA) may exist where two signatory institutions elect to rely on a common IRB but otherwise administer research initiatives independently. In such a situation, each signatory institution would be expected to have the equivalent of an ORA instead of only one ORA at the primary institution which is relied upon by all signatory institutions.

The sample DHHS MPA consists of a statement of principles, policies, and applicability (Part 1), responsibilities (Part 2), provision for signatures of all principal parties (Part 3), and appendices (Part 4). Any of the appendices that undergo change must be submitted to OPRR for approval as they occur. The appendices are as follows:

Appendix A lists all components of the signatory institution(s) that may operate under some other name (e.g., "The Warren Grant Magnuson Clinical Center" is actually a component of the National Institutes of Health). Appendix A includes only inseparable legal components of the signatory institution(s). Of those, only components that might apply for Federal human subject research support in their own names or participate in such research need to be listed in Appendix A. Appendix A does not include legally separate institutions that are merely professionally or contractually affiliated with the signatory institution(s).

Appendix B lists all legally separate institutions that have or qualify for formal affiliation with the signatory institution(s) for the protection of human subjects. Such standing affiliations are entered into through an OPRR-approved Inter-Institutional Amendment (IIA). IIAs assure compliance with the DHHS regulations and acknowledge reliance on the IRB(s) of the signatory institution(s) when the IIA affiliate serves as a performance site for research conducted in the name of the MPA signatory institution(s). Please note that a research activity conducted by an IIA affiliate, when not under the auspices of the MPA institution with which it is affiliated, is not covered by the IIA and a separate Assurance document for that activity would be required. For example, a county hospital with an IIA to an MPA held by a nearby university would be covered by the IIA for federally sponsored research directly awarded to the university but would not be covered if the hospital directly applied for Federal support in its own name (whether or not the university might also be involved).

Appendix C consists of one or more IRB membership lists for all signatory institutions of the MPA. Each such list must be submitted using the sample format (or its retyped equivalent) and must be dated. If there is more than one IRB, it will be necessary to cite all signatory institutions that rely on each and the intended scope (e.g., biomedical, behavioral, both, or otherwise). Changes in membership do not require obtaining a revised signature page for the MPA. However, the list itself (which is basic to the MPA) must be signed by the IRB Chair and forwarded to OPRR as changes in IRB membership occur.

Appendix D consists of a one page abstract of the institutional program of protections (i.e., operational written procedures and reporting responsibilities) which apply to the specific MPA institution or group of institutions and an organizational line diagram that shows the interrelationships between MPA signatory officials, the ORA, the IRB, and significant components from which investigators may be expected to submit human subject proposals.

In preparing the sample, we have attempted to include all of the elements necessary for compliance with the regulations. We invite you to view this sample Assurance as an aid in developing your Assurance and would appreciate your comments as to its adequacy in assisting you in that development. A glossary of terms has been included in this preface for your convenience to help in interpreting the sample MPA document.

If you have any general questions, please contact the Adjunct Medical Officer, DHSP at 301/402-5942 (Fax: 301-402-2803; E-mail: kd41f@nih.gov) or the Chief of the Assurance Branch, DHSP at 301/402-5218 x211 (Fax: 301-402-0527; E-mail: cs19n@nih.gov).

Specific negotiations will be conducted by the OPRR staff person who is assigned review responsibilities for MPA institutions on the basis of state or country of location. Staff assignments are available by fax at 301-594-0464.

GLOSSARY OF TERMS

* Affiliate - an institution or independent investigator which legally separate from the signatory (s) to an Assurance but has a formal affiliation with the signatory institution(s) through an OPRR-approved Inter-Institutional Amendment or Assurance

*Agreement - a document (e.g., AII or NIA) which assures individual compliance with 45 CFR 46 by an independent non-institutional investigator

*Agreement for an Independent Investigator (AII) - an OPRR-approved document entered into between a signatory institution and a non-institutional affiliate investigator (e.g., private practitioner) which assures compliance with 45 CFR 46 for specified activities that are not CPRP in nature

*Amendment - any formal addition to an approved Assurance (e.g., CA or IIA to an MPA)

* Assurance - an OPRR-approved document which assures institutional compliance with 45 CFR 46(e.g., SPA, CPA, or MPA)

*Collaboration - engagement by two or more entities in human subject research by virtue of subject accrual, transfer of identifiable information, and/or in exchange of something of value, such as material support (e.g., money, drugs, identifiable specimens), coauthorship, intellectual property, or credits

* Component - any entity that is legally inseparable from the signatory institution(s)

*Cooperative Amendment (CA) - a document requiring OPRR approval (formerly referred to as a Cooperative Agreement) which is jointly agreed to by two or more MPA institutions (or otherwise with prior OPRR consultation) for the purpose of specifying arrangements for relying on one another's IRBs to avoid duplication of effort

* Cooperative Project
Assurance (CPA) - an Assurance designed to accommodate CPRP multi-protocol, multi-site research specifically recognized by OPRR

* Cooperative Protocol
Research Programs (CPRP) - DHHS multi-site, multi-protocol clinical trials which are explicitly recognized by OPRR as suited for CPAs (e.g., cooperative oncology trials of the National Cancer Institute)

* Federal - departments and agencies of the Federal government that are a party to the Federal Policy (see 56FR28003 and page I of the Preface to the MPA sample text)

* Federal Policy
(56FR28003) - minimum Federal standards for the protection of human research subjects, effective August 19, 1991 (see FR Volume 56, No. 117, Tuesday, June 18, 1991), and contained in 45 CFR 46 as Subpart A - also known as the Common Rule

* 45 CFR 46
(DHHS Regulations) - Title 45 of the Code of Federal Regulations, Part 46, which consists of Subpart A (the Federal Policy for the Protection of Human Subjects) and Subparts B, C, and D which apply to fetuses, pregnant women and in-vitro fertilization of human ova; prisoners; and children as vulnerable subject populations

* Inter-Institutional
Amendment (IIA) - an amendment to an MPA for compliance with 45 CFR 46 by affiliate institutions that do not have their own MPA, regularly serve as a performance site for research conducted by an Multiple Project Assurance signatory institution(s), and usually do not possess their own Institutional Review Boards.

* Multiple Project
Assurance (MPA) - a DHHS Assurance which applies during fixed and renewable periods to a broad spectrum of unrelated research activities

* Noninstitutional
Investigator Agreement
(NIA) - an OPRR-authorized document entered into between a signatory institution and a non-institutional affiliate investigator (e.g., private practitioner) which assures compliance with 45 CFR 46 for OPRR-recognized CPRP activities (e.g., cooperative oncology group trials)

* Office of Research
Administration for Human Subject Research (ORA) - the resources maintained by each signatory institution or the primary signatory institution (if applicable) which provides a central focus for researchers, IRB(s), and administrators in processing protocols, arranging IRB review, keeping records, reporting, and communicating pertinent information about human subject research

* Performance Site - any entity (institution or independent investigator) where human subjects are involved in research for which an MPA, IIA, SPA, CPA, AII, or NIA is required

* Primary Signatory Institution - -where applicable, the signatory institution of two or more which may be chosen to assume the function of the ORA for all signatory institutions

* Signatory Institution - an institution which OPRR finds eligible to enter into an Assurance and which has signed the Assurance

* Single Project
Assurance (SPA) - an Assurance document which is submitted to OPRR by an institution, upon request, for a specific DHHS research activity at a performance site where an MPA, IIA, or CPA, does not apply.

[Please prepare on institutional letterhead]

SAMPLE MPA TEXT

Multiple Project Assurance of Compliance with DHHS Regulations
for Protection of Human Research Subjects

(Name of Signatory Institution[s]), hereinafter known as the "institution" (see Appendix A), hereby gives assurance, as specified below, that it will comply with the Department of Health and Human Services (DHHS) regulations for the protection of human research subjects, 45 CFR Part 46, as amended to include provisions of the Federal Policy for the Protection of Human Subjects (56FR28003) as Subpart A, and as may be further amended during the approval period for this Assurance.

PART 1 - PRINCIPLES, POLICIES, AND APPLICABILITY

I. Ethical Principles

A. This institution is guided by the ethical principles regarding 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 (entitled: Ethical Principles and Guidelines for the Protection of Human Subjects of Research [the "Belmont Report"]), regardless of whether the research is subject to Federal regulation or with whom conducted or source of support (i.e., sponsorship).

B. All institutional and non-institutional performance sites for this institution, domestic or foreign, will be obligated by this institution to conform to ethical principles which are at least equivalent to those of this institution, as cited in the previous paragraph or as may be determined by the DHHS Secretary.

II. Institutional Policy

A. All requirements of Title 45, Part 46, of the Code of Federal Regulations (45 CFR 46) will be met for all federally-sponsored research, and all other human subject research regardless of sponsorship ⁽¹⁾, except as otherwise noted in this Assurance. Federal (all departments and agencies bound by the Federal Policy) funds for which this Assurance applies may not be expended for research involving human subjects unless the requirements of this Assurance have been satisfied.

B. Except for those categories specifically exempted or waived under Section 101(b)(1-6) or 101(i), all research covered by this Assurance will be reviewed and approved by an Institutional Review Board (IRB) which has been established under a Multiple Project Assurance (MPA) with OPRR or as may be otherwise agreed to by OPRR (see Part 1, II, G). The involvement of human subjects in research covered by this Assurance will not be permitted until an appropriate IRB has reviewed and approved the research protocol and informed consent has been obtained from the subject or the subject's legal representative (see Sections 111, 116, and 117), unless properly waived by the IRB under Section 116(c),(d) or by any applicable waiver under Section 101(i).

C. This institution assures that before human subjects are involved in nonexempt research covered by this Assurance, the IRB(s) will give proper consideration to:

1. the risks to the subjects,
2. the anticipated benefits to the subjects and others,
3. the importance of the knowledge that may reasonably be expected to result, and
4. the informed consent process to be employed.

D. Certification of IRB review and approval for all Federally-sponsored research involving human subjects will be submitted to the Office of Research Administration (ORA) for forwarding to the appropriate Federal department or agency. Compliance will occur within the time and in the manner prescribed for forwarding certifications of IRB review to DHHS or other Federal departments or agencies for which this Assurance applies.

As provided for under section 118, applications and proposals lacking definite plans for involvement of human subjects will not require IRB review and approval prior to award. However, except for research exempted or waived under Section 101 (b) or (i), no human subjects may be involved in any project supported by such awards until IRB review and approval has been certified to the appropriate Federal department or agency.

As required under Section 119, the IRB will review proposed involvement of human subjects in Federal research activities undertaken without prior intent for such involvement, but will not permit such involvement until certification of the IRB's review and approval is received by the appropriate Federal department or agency.

E. Institutions that are not direct signatories to this Assurance are not authorized to cite this Assurance. This institution will ensure that such other institutions and investigators not bound by the provisions of this Assurance will satisfactorily assure compliance with 45 CFR 46, as required (see Part 2, I, D and II, K), as a prior condition for involvement in DHHS-sponsored human subject research which is under the auspices of this institution (see Part 1, III, A). Institutions that have entered into an Inter-Institutional Amendment (IIA) to this Assurance must submit a Single Project Assurance (SPA) to the Office for Protection from Research Risks (OPRR) for DHHS-sponsored research, when that research is not conducted under the auspices of a signatory institution to this Assurance.

F. This institution will ensure that any collaborating entities (i.e., those entities engaged in human subject research by virtue of subject accrual, transfer of identifiable information, and/or in exchange of something of value, such as material support [e.g., money, drugs, or identifiable specimens], coauthorship, intellectual property , or credits) materially engaged in the conduct of non-federal sponsored research involving human subjects will possess mechanisms to protect human research subjects that are at least equivalent to those procedures provided for in the ethical principles to which this institution is committed (see Part 1, I).

G. This institution will comply with the requirements set forth in Section 114 of the regulations regarding cooperative research projects. When research covered by this Assurance is conducted at or in cooperation with another entity, all provisions of this Assurance remain in effect for that research. This institution may accept, for the purpose of meeting the IRB review requirements, the review of an IRB established under another DHHS MPA. Such acceptance must be (a) in writing, (b) approved and signed by an official of this institution's Office of Research Administration(s), and (c) approved and signed by correlative officials of each of the other cooperating institutions (i.e., a Cooperative Amendment to this MPA). The original of the signed understanding will serve as an addendum to this Assurance and will be forwarded to the OPRR of DHHS by the ORA(s) for OPRR approval.

H. This institution will exercise appropriate administrative overview to ensure that the institution's policies and procedures designed for protecting the rights and welfare of human subjects are being effectively applied in compliance with this Assurance.

I. Description of this institution's policy for the protection of human subjects is contained in its internal written procedures which are available to OPRR and other Federal departments or agencies, upon request. Appendix D to this Assurance abstracts pertinent organizational, personnel, and reporting procedures sufficient to describe the substance and relative prominence conferred upon the protection of subjects.

III. Applicability

A. Except for research in which the only involvement of humans is in one or more of the categories exempted or waived under Section 101(b)(1-6) or 101(i), this Assurance applies to all research involving human subjects, and all other activities which even in part involve such research, regardless of sponsorship¹, if one or more of the following apply:

1. the research is sponsored by this institution, or

2. the research is conducted by or under the direction of any employee or agent of this institution in connection with his or her institutional responsibilities, or

3. the research is conducted by or under the direction of any employee or agent of this institution using any property or facility of this institution, or

4. the research involves the use of this institution's non-public information to identify or contact human research subjects or prospective subjects.

B. All human subject research which is exempt under Section 101(b)(1-6) or 101(i) will be conducted in accordance with: (1) the Belmont Report, (2) this institution's administrative procedures to ensure valid claims of exemption, and (3) orderly accounting for such activities.

C. Components of this institution are bound by the provisions of this Assurance. Those components which can be expected to participate in human subject research sponsored by DHHS or other Federal departments or agencies for which this Assurance applies are identified in Appendix A. Appendix A will be revised as changes occur and revisions forwarded to OPRR.

D. This Assurance must be accepted by other Federal departments or agencies that are bound by the Federal Policy for the Protection of Human Subjects when appropriate for the research in question and therefore applies to all human subject research so sponsored.1 Research that is neither conducted nor supported by a Federal department or agency but is subject to regulation as defined in Section 102(e) must be reviewed and approved, in compliance with Sections 101, 102, and 107 through 117.

Footnote

¹ Note to Preparers:
Compliance with 45 CFR 46 regardless of sponsorship is a choice elected by most institutions for internal consistency of operations. Election will require compliance with all requirements of 45 CFR 46 (Subparts A through D) and acceptance by other Federal departments and agencies without the need for preparing separate and additional Assurances.

PART 2 - RESPONSIBILITIES²

I. Institution

A. This institution acknowledges that it bears full responsibility for the performance of all research involving human subjects, covered by this Assurance, including complying with Federal, state, or local laws as they may relate to such research.

B. This institution will require appropriate additional safeguards in research that involves: (1) fetuses, pregnant women, or human ova invitro fertilization (see 45 CFR 46 Subpart B), (2) prisoners (see 45 CFR 46 Subpart C), (3) children (see 45 CFR 46 Subpart D), (4) the cognitively impaired, or (5) other potentially vulnerable groups.

C. This institution, including all its named components (see Appendix A), acknowledges and accepts its responsibilities for protecting the rights and welfare of human subjects of research covered by this Assurance.

D. This institution is responsible for acquiring appropriate Assurances or Amendments, when requested, and certifications of IRB review and approval for federally sponsored research from all its standing affiliates (see Appendix B) and Assurances or Agreements for all others, domestic or foreign, which may otherwise become affiliated on a limited basis in such research.

E. This institution is responsible for ensuring that no performance site cooperating in the conduct of federally sponsored research for which this Assurance applies does so without Federal department or agency approval of an appropriate assurance of compliance, in whatever appropriate form, and satisfaction of IRB certification requirements.

F. In accordance with the compositional requirements of Section 107, this institution has established the IRB(s) listed in the attached roster(s) (see Appendix C). Certain research supported by the U.S. Department of Education will be reviewed in accordance with the requirements of Title 34 CFR Parts 350 and 356 which require that the IRB(s) include at least one person who is primarily concerned with the welfare of handicapped children or mentally disabled persons.

G. This institution will provide both meeting space and sufficient staff to support the IRB's review and record-keeping duties.

H. This institution recognizes that involvement in research activities of any OPRR-recognized Cooperative Protocol Research Programs (CPRPs) will involve additional reporting and record-keeping requirements related to human subject protections.

I. This institution is responsible for ensuring that it and all its affiliates comply fully with all applicable Federal policies and guidelines, including those concerning notification of seropositivity, counseling, and safeguarding confidentiality where research activities directly or indirectly involve the study of human immunodeficiency virus (HIV).

II. Office of Research Administration for Human Subject Research (ORA)

[Please complete for each ORA if more than one signatory institution possesses an ORA]

A. The ORA(s) will receive from investigators, through their supervisors, all research protocols which involve human subjects, keep investigators informed of decisions and administrative processing, and return all disapproved protocols to them.

B. The ORA(s) is responsible for reviewing the preliminary determinations of exemption by investigators and supervisors and for making the final determination based on Section 101 of the regulations. Notice of concurrence for all exempt research will be promptly conveyed in writing to the investigator. All nonexempt research will be forwarded to the appropriate IRB.

C. The ORA(s) will make the preliminary determination of eligibility for expedited review procedures (see Section 110). Expedited review of research activities will not be permitted where full board review is required.

D. The ORA(s) will review all research (whether exempt or not) and decide whether the institution will permit the research. If approved by the IRB, but not permitted by the ORA, the ORA will promptly convey notice to the investigator and the IRB Chair. Neither the ORA nor any other office of the institution may approve a research activity that has been disapproved by the appropriate IRB.

E. The ORA(s) will forward certification of IRB approval of proposed research to the appropriate Federal department or agency only after all IRB-required modifications have been incorporated to the satisfaction of the IRB.

F. The ORA(s) will designate procedures for the retention of signed consent documents for at least three years past completion of the research activity.

G. The ORA(s) will maintain and arrange access for inspection of IRB records as provided for in Section 115.

H. The ORA(s) is responsible for ensuring constructive communication among the research administrators, department heads, research investigators, clinical care staff, human subjects, and institutional officials as a means of maintaining a high level of awareness regarding the safeguarding of the rights and welfare of the subjects.

I. The ORA(s) will arrange for and document in its records that each individual who conducts or reviews human subject research has first been provided with a copy of this Assurance, as well as with ready access to copies of 45 CFR 46, regulations of other Federal departments or agencies as may apply, the Belmont Report, and all other pertinent Federal policies and guidelines related to the involvement of human subjects in research.

J. The ORA(s) will report promptly to the IRB(s), appropriate institutional officials, the Office for Protection from Research Risks (OPRR), and any other sponsoring Federal department or agency head:

1. any unanticipated injuries or problems involving risks to subjects or others,
2. any serious or continuing noncompliance with the regulations or requirements of the IRB, and
3. any suspension or termination of IRB approval for research.

K. The ORA(s) will ensure (a) solicitation (or confirmation where applicable assurances to comply already exist), receipt, and management of all assurances of compliance (whatever the appropriate format), and (b) certifications of IRB review (where appropriate) for all performance sites to this institution (including those listed in Appendix B) and subsequent submission of new documents to the proper Federal department or agency authorities (e.g., OPRR for DHHS) as a condition for involvement of each site in human subject research activities sponsored by DHHS or any other Federal department or agency for which this Assurance applies.

L. The ORA will ensure that all affiliated performance sites that are not otherwise required to submit assurances of compliance with Federal regulations for the protection of research subjects at least document mechanisms to implement the equivalent of ethical principles to which this institution is committed (see Part 1, I).

M. When an IRB of this institution accepts responsibility for review of research which is subject to this Assurance and conducted by any independent investigator who is not otherwise subject to the provisions of this Assurance, the ORA will either: (a) obtain and retain an Noninstitutional Investigator Agreement (NIA) for CPRP activities (with copy to the investigator and the authorizing CPRP) or (b) obtain an Agreement for an Independent Investigator (AII) for review and approval by the appropriate Federal department or agency for non-CPRP activities to document the investigator's commitment to abide: (1) by the same requirements for the protection of human research subjects as does this institution(s) and (2) the determinations of the IRB(s).

N. The ORA(s) assumes responsibility for ensuring conformance with special reporting requirements for any OPRR-recognized CPRPs in which the signatory institution(s) participate(s).

O. The ORA(s) will be responsible for procedural and record-keeping audits not less than once every year for the purpose of detecting, correcting, and reporting (as required) administrative and/or material breaches in uniformly protecting the rights and welfare of human subjects as required at least by the regulations and as may otherwise be additionally required by this institution(s).

P. The ORA(s) will ensure compliance with the requirements set forth in this Assurance and Section 114 regarding cooperative research projects. In particular, where the IRB of another institution with a DHHS MPA is relied upon, the ORA(s) will ensure thatdocumentation of this reliance will be (a) in writing, (b) approved and signed by the ORA(s), (c) approved and signed by the correlative officials of each of the other cooperating institutions, and (d) retained by the ORA for at least three years past completion of the research project, if limited in scope to a specific research project or retained as a permanent addendum to the MPA if not restricted to a specific project. For all Cooperative Amendments (CAs), the ORA(s) will forward the original of the required signed understanding to OPRR for approval and inclusion in this Assurance as an addendum.

III. Institutional Review Board (IRB)

A. The IRB(s) will review, and have the authority to approve, require modification in, or disapprove all research activities, including proposed changes in previously approved human subject research. For approved research, the IRB will determine which activities require continuing review more frequently than every twelve months or need verification that no changes have occurred if there was a previous IRB review and approval.

B. IRB decisions and requirements for modifications will be promptly conveyed to investigators and the ORA, in writing. Written notification of decisions to disapprove will be accompanied by reasons for the decision with provision of an opportunity for reply by the investigator, in person or in writing.

C. Initial and continuing convened IRB reviews and approvals will occur in compliance with 45 CFR 46 and provisions of this Assurance for each project unless properly found to be exempt (Section 101[b] or [i]) by the Office of Research Administration. Continuing reviews will be preceded by IRB receipt of appropriate progress reports from the investigator, including available study-wide findings.

D. The IRB(s) will observe the quorum requirements of Section 108(b). This institution's IRB(s) has effective knowledge of subject populations, institutional constraints, differing legal requirements, and other factors which can foreseeably contribute to a determination of risks and benefits to subjects and subjects' informed consent and can properly judge the adequacy of information to be presented to subjects in accordance with requirements of Sections 103(d), 107(a), 111, and 116.

E. The IRB(s) will determine, in accordance with the criteria found at 45 CFR 46.111 and Federal policies and guidelines for involvement of human subjects in HIV research, that protections for human research subjects are adequate.

F. The IRB(s) will ensure that legally effective informed consent will be obtained and documented in a manner that meets the requirements of Sections 116 and 117. The IRB will have the authority to observe or have a third party observe the consent process.

G. Where appropriate, the IRB(s) will determine that adequate additional protections are ensured for fetuses, pregnant women, prisoners, and children, as required by Subparts B, C, and D of 45 CFR 46. The IRB(s) will notify OPRR promptly when IRB membership(s) is modified to satisfy requirements of 45 CFR 46.304 and when the IRB fulfills its duties under 45 CFR 46.305(c).

H. Scheduled meetings of the IRB(s) for review of each research activity will occur not less than every 12 months and may be more frequent, if required by the IRB on the basis of degree of risk to subjects. The IRB may be called into an interim review session by the Chairperson at the request of any IRB member or institutional official to consider any matter concerned with the rights and welfare of any subject.

I. The IRB(s) will prepare and maintain adequate documentation of its activities in accordance with Section 46.115 and in conformance with Office of Research Administration requirements.

J. The IRB(s) will forward to the Office of Research Administration any significant or material finding or action, at least to include the following:

1. any unanticipated injuries or problems involving risks to subjects or others,
2. any serious or continuing noncompliance with the regulations or requirements of the IRB, and
3. any suspension or termination of IRB approval.

K. In accordance with Section 113, the IRB(s) will have the authority to suspend or terminate previously approved research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects.

L. The IRB(s) for this institution will ensure effective input (consultants or voting or nonvoting members) for all initial and continuing reviews conducted on behalf of performance sites where there will be human research subjects. IRB minutes will document attendance of those other than regular voting members. The IRB list(s) in Appendix C includes those who are identified as knowledgeable about any affiliate institution having entered into an Inter-Institutional Amendment or other institutional performance site for which an Assurance is required when relying on one or more of the IRBs of this institution.

M. The IRB(s) will act with reasonable dispatch, upon request, to provide full board review of protocols of OPRR-recognized Cooperative Protocol Research Programs (CPRP). The IRB will not employ expedited review procedures for CPRP protocols when they are to be entered into for the purpose of research. Although emergency medical care based on such protocols is permitted without prior IRB approval, patients receiving emergency care under these conditions will not be counted as research subjects and resultant data will not be used for research purposes.

N. Certifications of IRB review and approval will be forwarded through the ORA to the appropriate Federal department or agency for research sponsored by such departments or agencies.

IV. Research Investigator

A. Research investigators acknowledge and accept their responsibility for protecting the rights and welfare of human research subjects and for complying with all applicable provisions of this Assurance.

B. Research investigators who intend to involve human research subjects will not make the final determination of exemption from applicable Federal regulations or provisions of this Assurance.

C. Research investigators are responsible for providing a copy of the IRB-approved >informed consent document to each subject at the time of consent, unless the IRB has specifically waived this requirement. All signed consent documents are to be retained in a manner approved by the Office of Research Administration.

D. Research investigators will promptly report proposed changes in previously approved human subject research activities to the IRB. The proposed changes will not be initiated without IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subjects.

E. Research investigators are responsible for reporting progress of approved research to the Office of Research Administration, as often as and in the manner prescribed by the approving IRB on the basis of risks to subjects, but not less than once per year.

F. Research investigators will promptly report to the IRB any injuries or other unanticipated problems involving risks to subjects or others.

G. No research investigator who is obligated by the provisions of this Assurance, any associated Inter-Institutional Amendment, or Noninstitutional Investigator Agreement will seek to obtain research credit for, or use data from, patient interventions that constitute the provision of emergency medical care without prior IRB approval. A physician may provide emergency medical care to a patient without prior IRB review and approval, to the extent permitted by law (see Section 116[f]). However, such activities will not be counted as research nor the data used in support of research..

H. Research investigators will advise the IRB, Office of Research Administration and the appropriate officials of other institutions of the intent to admit human subjects (e.g., into a hospital) who are involved in research protocols for which this Assurance or any related Inter-Institutional Amendment or Noninstitutional Investigator Agreement applies. When such admissions are a planned part of DHHS-supported research, those institutions must possess an applicable OPRR-approved Assurance prior to involvement of such persons as human subjects in those research protocols at those institutions.

V. Affiliated Institutions and Investigators
(i.e., all performance sites, with or without IIAs)

A. Each performance site to this institution that is involved in federally sponsored research activities must provide to the Office of Research Administration an appropriate written assurance of compliance with the Belmont Report and the Federal Policy, to include Subparts B, C, and D or 45 CFR 46 where appropriate (or equivalent protections if a foreign site), for review and approval, as specified by the sponsoring Federal department or agency (e.g., by OPRR for DHHS), prior to involvement of human subjects or expenditure of funds or other support to do so.

B. Each institutional performance site must respond to a request by the Office of Research Administration of this institution for an Inter-Institutional Amendment, SPA, or CPA (as appropriate), whichever is most suited to the circumstances.

C. Each non-institutional performance site (e.g., a private practice physician not otherwise an employee of this institution or who otherwise would not ordinarily be bound by the provisions of this Assurance or any other applicable institutional Assurance) who is involved in human subject research of this institution must respond to a request by the Office of Research Administration of this institution for either an Agreement for an Independent Investigator or a Noninstitutional Investigator Agreement, as appropriate,depending on the nature of the research activity.

D. Performance sites that are legally separable from this institution (whether an institutional or non-institutional performance site) are not authorized to cite this Assurance.

Footnote
² Note to Preparers:
This Part contains several administrative provisions that may be handled differently from one institution to another. Discretionary changes are expected. Please remember to highlight any changes to help speed review and approval.

PART 3 - SIGNATURES

I. Institutional Endorsement(s)

The officials signing below assure that any research activity conducted, supported, or otherwise subject to DHHS or other Federal departments or agencies that are authorized to rely on this Assurance (Parts 1, 2, 3 and Appendices) or any other sources provided for in this Assurance, will be reviewed and approved by the appropriate IRB(s) in accordance with the requirements of all applicable Subparts of Part 46, Title 45 of the Code of Federal Regulations, with this Assurance, and the stipulations of the IRB(s).

A. Primary Signatory Institution (if any)

1. AUTHORIZED INSTITUTIONAL OFFICAL

Signature: _____________________________Date: ________

Name: _____________________________

Title: _____________________________

Institution and
Address:
[This item must be completed for
each additional signatory institution
to this proposed DHHS MPA
document in Part 3,I,B below.]

Phone: _________________

Fax: _________________

E-Mail: _________________

2. PRIMARY CONTACT (If same, write "SAME")

Signature: _____________________________Date: ________

Name: _____________________________

Title: _____________________________

Institution and
Address:
[This item must be completed for
each additional signatory institution
to this proposed DHHS MPA
document in Part 3,I,B below.]

Phone: _________________

Fax: _________________

E-Mail: _________________

B. Other Signatory Institutions [complete as many times as needed]

1. AUTHORIZED INSTITUTIONAL OFFICIAL

Signature: _____________________________Date: ________

Name: _____________________________

Title: _____________________________

Institution and
Address:

_____________________________

_____________________________

_____________________________

_____________________________

_____________________________

Phone: _________________

Fax: _________________

E-Mail: _________________

2. PRIMARY CONTACT (If same write "SAME")

Signature: _____________________________Date: ________

Name: _____________________________

Title: _____________________________

Institution and
Address:

_____________________________

_____________________________

_____________________________

_____________________________

_____________________________

Phone: _________________

Fax: _________________

E-Mail: _________________

********************************************************************************

FOR DHHS USE ONLY

II. Office for Protection from Research Risks (DHHS) Approval

A. DHHS RECOMMENDING OFFICIAL

Signature: _____________________________Date: ________

Title: Assurance Coordinator

Address: Division of Assurances and Quality Improvement

Office for Human Research Protections (OHRP )

1101 Wootton Parkway, Suite 200

Rockville, Maryland 20852

Phone: 301-496-7005

Fax: 301-402-0527

EFFECTIVE DATE OF ASSURANCE: __________________

EXPIRATION DATE OF ASSURANCE: ___________________

B. DHHS APPROVING OFFICIAL

Signature: _____________________________Date: ________

Name: ________________________________

Title: Assurance Coordinator

Address: Division of Assurances and Quality Improvement

Office for Human Research Protections (OHRP)

1101 Wootton Parkway, Suite 200

Rockville, Maryland 20852

Phone: 301-496-7005

Fax: 301-402-0527

E-Mail: _______________

[Please Submit with MPA# and Signatory Institution Names and Resubmit as Changes Occur]

DHHS MPA# ____________

Date: ________________

Appendix A

COMPONENTS WHICH ARE LEGALLY INSEPARABLE FROM EACH DESIGNATED SIGNATORY INSTITUTION
AND PARTICIPATE IN HUMAN RESEARCH OF THE SIGNATORY

MPA Signatory Institution #1(i.e., Primary):

Components that Participate in Human Research

Name: City: State:

MPA Signatory Institution #2:

Components that Participate in Human Research

Name: City: State:

MPA Signatory Institution #3:

Components that Participate in Human Research

Name: City: State:

MPA Signatory Institution #4:

Components that Participate in Human Research

Name: City: State:

MPA Signatory Institution #5:

Components that Participate in Human Research

Name: City: State:

Please check here if there are no suitable components for entry.

[Please Submit with MPA# and Signatory Institution Names and Resubmit as Changes Occur]

DHHS MPA #: ________
Date: ________________

Appendix B

STANDING AFFILIATES WHICH ARE LEGALLY SEPARATE FROM EACH DESIGNATED SIGNATORY INSTITUTION AND POSSESS OPRR-APPROVED INTER-INSTITUTIONAL AMENDMENTS

MPA Signatory Institution #1 (Primary):

Name: City: State:

Affiliate Institutions:

MPA Signatory Institution #2:

Name: City: State:

Affiliate Institutions:

MPA Signatory Institution #3:

Name: City: State:

Affiliate Institutions:

MPA Signatory Institution #4:

Name: City: State:

Affiliate Institutions:

MPA Signatory Institution #5:

Name: City: State:

Affiliate Institutions:

Please check here if there are no suitable standing affiliates for entry.

Appendix C, Institutional Review Board (IRB) Membership Roster

Appendix D

ABSTRACT OF INSTITUTIONAL PROGRAM FOR HUMAN SUBJECT PROTECTIONS

Appendix D consists of both a one page narrative and an organizational line diagram. It is intended to be an abstract of more complete written procedures that reside at your institution and are available, on a need-to-know request basis, by any Federal department or agency to which this MPA applies.

Please prepare a brief one page description which outlines the salient aspects of institutional policy and procedure for the protection of human subjects. Please includeattention to required operational written procedures (Section 103[b][4]) and reporting responsibilities (Section 103[b][5] and Section103[f]) which apply to your specific MPA institution or group of institutions. An accompanying organizational line diagram will permit showing the vertical and other interrelationships between MPA signatory officials, the ORA, the IRB, and significant components from which investigators may be expected to submit human subject proposals.

The purpose of this abstract is to identify and highlight operational responsibilities and relationships between parties who play a role in ensuring administrative compliance with procedures for review, critical decision-making, approvals, correspondence and record-keeping, and reporting to both institutional personnel and sponsoring officials. Reporting includes: (1) changes in IRB membership or MPA signatory officials, (2) certification of IRB review and approval, and (3) problems, noncompliance, and suspensions or terminations of IRB approval. It is important to include audit and training responsibilities and how they relate to investigators, IRB personnel, and institutional staff in direct support of the IRB and indirect support of human subject protections by all institutional staff. The process of identification and diagramming will help confirm and conceive operational aspects of a sound conceptual program.

The narrative on this page and the accompanying organizational line diagram should be sufficiently detailed to identify: (1) specific persons by name and title who have singularly essential roles (e.g., IRB Administrator), (2) other persons by role where more than one person serves the same function (e.g., Department Heads), and (3) how they organizationally relate (e.g., reporting channels) for at least the following procedures, requirements, and/or responsibilities:

consideration by investigators of human subject proposals
submission of appropriate proposals for IRB review
management of proposals for which IRB review is intended
written communication of IRB actions
delineation to investigators of their responsibilities for continuing progress reports
compliance by all collaborators in federally sponsored human subject research
timely continuing review
required record-keeping
required reporting
communication with investigators, IRB members, IRB staff, institutional personnel and subjects
training of investigators, IRB members, IRB staff, and other appropriate institutional personnel, and
institutional self-audit.

Changes in internal policy and procedures that are abstracted in Appendix D will require an update of this Appendix and forwarding to OPRR, as changes occur.

Footnotes

1.

Note to Preparers: Compliance with 45 CFR 46 regardless of sponsorship is a choice elected by most institutions for internal consistency of operations. Election will require compliance with all requirements of 45 CFR 46 (Subparts A through D) and acceptance by other Federal departments and agencies without the need for preparing separate and additional Assurances.

2.

Note to Preparers: This Part contains several administrative provisions that may be handled differently from one institution to another. Discretionary changes are expected. Please remember to highlight any changes to help speed review and approval.

Policy | Assurances | OHRP Home Page

If you have questions about human subject research, click ohrp@osophs.dhhs.gov
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Updated August 26, 2002

		Central Intelligence Agency	Executive Order 12333
		Consumer Product Safety Commission	16 CFR Part 1028
		Department of Agriculture	7 CFR Part 1c
		Department of Commerce	15 CFR Part 27
		Department of Defense	32 CFR Part 219
		Department of Education	34 CFR Part 97
		Department of Energy	10 CFR Part 745
		Department of Health and Human Services	45 CFR Part 46
		Department of Housing and Urban Development	24 CFR Part 60
		Department of Justice	28 CFR Part 46
		Department of Transportation	49 CFR Part 11
		Department of Veterans Affairs	38 CFR Part 16
		Environmental Protection Agency	40 CFR Part 26
		National Aeronautics and Space Administration	14 CFR Part 1230
		National Science Foundation	45 CFR Part 690
		Social Security Administration	Public Law 103-296

* Affiliate	-	an institution or independent investigator which legally separate from the signatory (s) to an Assurance but has a formal affiliation with the signatory institution(s) through an OPRR-approved Inter-Institutional Amendment or Assurance
*Agreement	-	a document (e.g., AII or NIA) which assures individual compliance with 45 CFR 46 by an independent non-institutional investigator
*Agreement for an Independent Investigator (AII)	-	an OPRR-approved document entered into between a signatory institution and a non-institutional affiliate investigator (e.g., private practitioner) which assures compliance with 45 CFR 46 for specified activities that are not CPRP in nature
*Amendment	-	any formal addition to an approved Assurance (e.g., CA or IIA to an MPA)
* Assurance	-	an OPRR-approved document which assures institutional compliance with 45 CFR 46(e.g., SPA, CPA, or MPA)
*Collaboration	-	engagement by two or more entities in human subject research by virtue of subject accrual, transfer of identifiable information, and/or in exchange of something of value, such as material support (e.g., money, drugs, identifiable specimens), coauthorship, intellectual property, or credits
* Component	-	any entity that is legally inseparable from the signatory institution(s)
*Cooperative Amendment (CA)	-	a document requiring OPRR approval (formerly referred to as a Cooperative Agreement) which is jointly agreed to by two or more MPA institutions (or otherwise with prior OPRR consultation) for the purpose of specifying arrangements for relying on one another's IRBs to avoid duplication of effort
* Cooperative Project Assurance (CPA)	-	an Assurance designed to accommodate CPRP multi-protocol, multi-site research specifically recognized by OPRR
* Cooperative Protocol Research Programs (CPRP)	-	DHHS multi-site, multi-protocol clinical trials which are explicitly recognized by OPRR as suited for CPAs (e.g., cooperative oncology trials of the National Cancer Institute)
* Federal	-	departments and agencies of the Federal government that are a party to the Federal Policy (see 56FR28003 and page I of the Preface to the MPA sample text)
* Federal Policy (56FR28003)	-	minimum Federal standards for the protection of human research subjects, effective August 19, 1991 (see FR Volume 56, No. 117, Tuesday, June 18, 1991), and contained in 45 CFR 46 as Subpart A - also known as the Common Rule
* 45 CFR 46 (DHHS Regulations)	-	Title 45 of the Code of Federal Regulations, Part 46, which consists of Subpart A (the Federal Policy for the Protection of Human Subjects) and Subparts B, C, and D which apply to fetuses, pregnant women and in-vitro fertilization of human ova; prisoners; and children as vulnerable subject populations
* Inter-Institutional Amendment (IIA)	-	an amendment to an MPA for compliance with 45 CFR 46 by affiliate institutions that do not have their own MPA, regularly serve as a performance site for research conducted by an Multiple Project Assurance signatory institution(s), and usually do not possess their own Institutional Review Boards.
* Multiple Project Assurance (MPA)	-	a DHHS Assurance which applies during fixed and renewable periods to a broad spectrum of unrelated research activities
* Noninstitutional Investigator Agreement (NIA)	-	an OPRR-authorized document entered into between a signatory institution and a non-institutional affiliate investigator (e.g., private practitioner) which assures compliance with 45 CFR 46 for OPRR-recognized CPRP activities (e.g., cooperative oncology group trials)
* Office of Research Administration for Human Subject Research (ORA)	-	the resources maintained by each signatory institution or the primary signatory institution (if applicable) which provides a central focus for researchers, IRB(s), and administrators in processing protocols, arranging IRB review, keeping records, reporting, and communicating pertinent information about human subject research
* Performance Site	-	any entity (institution or independent investigator) where human subjects are involved in research for which an MPA, IIA, SPA, CPA, AII, or NIA is required
* Primary Signatory Institution	-	-where applicable, the signatory institution of two or more which may be chosen to assume the function of the ORA for all signatory institutions
* Signatory Institution	-	an institution which OPRR finds eligible to enter into an Assurance and which has signed the Assurance
* Single Project Assurance (SPA)	-	an Assurance document which is submitted to OPRR by an institution, upon request, for a specific DHHS research activity at a performance site where an MPA, IIA, or CPA, does not apply.

I.		Ethical Principles
	A.	This institution is guided by the ethical principles regarding 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 (entitled: Ethical Principles and Guidelines for the Protection of Human Subjects of Research [the "Belmont Report"]), regardless of whether the research is subject to Federal regulation or with whom conducted or source of support (i.e., sponsorship).
	B.	All institutional and non-institutional performance sites for this institution, domestic or foreign, will be obligated by this institution to conform to ethical principles which are at least equivalent to those of this institution, as cited in the previous paragraph or as may be determined by the DHHS Secretary.
II.		Institutional Policy
	A.	All requirements of Title 45, Part 46, of the Code of Federal Regulations (45 CFR 46) will be met for all federally-sponsored research, and all other human subject research regardless of sponsorship ⁽¹⁾, except as otherwise noted in this Assurance. Federal (all departments and agencies bound by the Federal Policy) funds for which this Assurance applies may not be expended for research involving human subjects unless the requirements of this Assurance have been satisfied.
	B.	Except for those categories specifically exempted or waived under Section 101(b)(1-6) or 101(i), all research covered by this Assurance will be reviewed and approved by an Institutional Review Board (IRB) which has been established under a Multiple Project Assurance (MPA) with OPRR or as may be otherwise agreed to by OPRR (see Part 1, II, G). The involvement of human subjects in research covered by this Assurance will not be permitted until an appropriate IRB has reviewed and approved the research protocol and informed consent has been obtained from the subject or the subject's legal representative (see Sections 111, 116, and 117), unless properly waived by the IRB under Section 116(c),(d) or by any applicable waiver under Section 101(i).
	C.	This institution assures that before human subjects are involved in nonexempt research covered by this Assurance, the IRB(s) will give proper consideration to:
		1. the risks to the subjects, 2. the anticipated benefits to the subjects and others, 3. the importance of the knowledge that may reasonably be expected to result, and 4. the informed consent process to be employed.
	D.	Certification of IRB review and approval for all Federally-sponsored research involving human subjects will be submitted to the Office of Research Administration (ORA) for forwarding to the appropriate Federal department or agency. Compliance will occur within the time and in the manner prescribed for forwarding certifications of IRB review to DHHS or other Federal departments or agencies for which this Assurance applies.
		As provided for under section 118, applications and proposals lacking definite plans for involvement of human subjects will not require IRB review and approval prior to award. However, except for research exempted or waived under Section 101 (b) or (i), no human subjects may be involved in any project supported by such awards until IRB review and approval has been certified to the appropriate Federal department or agency.
		As required under Section 119, the IRB will review proposed involvement of human subjects in Federal research activities undertaken without prior intent for such involvement, but will not permit such involvement until certification of the IRB's review and approval is received by the appropriate Federal department or agency.
	E.	Institutions that are not direct signatories to this Assurance are not authorized to cite this Assurance. This institution will ensure that such other institutions and investigators not bound by the provisions of this Assurance will satisfactorily assure compliance with 45 CFR 46, as required (see Part 2, I, D and II, K), as a prior condition for involvement in DHHS-sponsored human subject research which is under the auspices of this institution (see Part 1, III, A). Institutions that have entered into an Inter-Institutional Amendment (IIA) to this Assurance must submit a Single Project Assurance (SPA) to the Office for Protection from Research Risks (OPRR) for DHHS-sponsored research, when that research is not conducted under the auspices of a signatory institution to this Assurance.
	F.	This institution will ensure that any collaborating entities (i.e., those entities engaged in human subject research by virtue of subject accrual, transfer of identifiable information, and/or in exchange of something of value, such as material support [e.g., money, drugs, or identifiable specimens], coauthorship, intellectual property , or credits) materially engaged in the conduct of non-federal sponsored research involving human subjects will possess mechanisms to protect human research subjects that are at least equivalent to those procedures provided for in the ethical principles to which this institution is committed (see Part 1, I).
	G.	This institution will comply with the requirements set forth in Section 114 of the regulations regarding cooperative research projects. When research covered by this Assurance is conducted at or in cooperation with another entity, all provisions of this Assurance remain in effect for that research. This institution may accept, for the purpose of meeting the IRB review requirements, the review of an IRB established under another DHHS MPA. Such acceptance must be (a) in writing, (b) approved and signed by an official of this institution's Office of Research Administration(s), and (c) approved and signed by correlative officials of each of the other cooperating institutions (i.e., a Cooperative Amendment to this MPA). The original of the signed understanding will serve as an addendum to this Assurance and will be forwarded to the OPRR of DHHS by the ORA(s) for OPRR approval.
	H.	This institution will exercise appropriate administrative overview to ensure that the institution's policies and procedures designed for protecting the rights and welfare of human subjects are being effectively applied in compliance with this Assurance.
	I.	Description of this institution's policy for the protection of human subjects is contained in its internal written procedures which are available to OPRR and other Federal departments or agencies, upon request. Appendix D to this Assurance abstracts pertinent organizational, personnel, and reporting procedures sufficient to describe the substance and relative prominence conferred upon the protection of subjects.
III.		Applicability
	A.	Except for research in which the only involvement of humans is in one or more of the categories exempted or waived under Section 101(b)(1-6) or 101(i), this Assurance applies to all research involving human subjects, and all other activities which even in part involve such research, regardless of sponsorship¹, if one or more of the following apply:
		1. the research is sponsored by this institution, or
		2. the research is conducted by or under the direction of any employee or agent of this institution in connection with his or her institutional responsibilities, or
		3. the research is conducted by or under the direction of any employee or agent of this institution using any property or facility of this institution, or
		4. the research involves the use of this institution's non-public information to identify or contact human research subjects or prospective subjects.
	B.	All human subject research which is exempt under Section 101(b)(1-6) or 101(i) will be conducted in accordance with: (1) the Belmont Report, (2) this institution's administrative procedures to ensure valid claims of exemption, and (3) orderly accounting for such activities.
	C.	Components of this institution are bound by the provisions of this Assurance. Those components which can be expected to participate in human subject research sponsored by DHHS or other Federal departments or agencies for which this Assurance applies are identified in Appendix A. Appendix A will be revised as changes occur and revisions forwarded to OPRR.
	D.	This Assurance must be accepted by other Federal departments or agencies that are bound by the Federal Policy for the Protection of Human Subjects when appropriate for the research in question and therefore applies to all human subject research so sponsored.1 Research that is neither conducted nor supported by a Federal department or agency but is subject to regulation as defined in Section 102(e) must be reviewed and approved, in compliance with Sections 101, 102, and 107 through 117.

	A.	This institution acknowledges that it bears full responsibility for the performance of all research involving human subjects, covered by this Assurance, including complying with Federal, state, or local laws as they may relate to such research.
	B.	This institution will require appropriate additional safeguards in research that involves: (1) fetuses, pregnant women, or human ova invitro fertilization (see 45 CFR 46 Subpart B), (2) prisoners (see 45 CFR 46 Subpart C), (3) children (see 45 CFR 46 Subpart D), (4) the cognitively impaired, or (5) other potentially vulnerable groups.
	C.	This institution, including all its named components (see Appendix A), acknowledges and accepts its responsibilities for protecting the rights and welfare of human subjects of research covered by this Assurance.
	D.	This institution is responsible for acquiring appropriate Assurances or Amendments, when requested, and certifications of IRB review and approval for federally sponsored research from all its standing affiliates (see Appendix B) and Assurances or Agreements for all others, domestic or foreign, which may otherwise become affiliated on a limited basis in such research.
	E.	This institution is responsible for ensuring that no performance site cooperating in the conduct of federally sponsored research for which this Assurance applies does so without Federal department or agency approval of an appropriate assurance of compliance, in whatever appropriate form, and satisfaction of IRB certification requirements.
	F.	In accordance with the compositional requirements of Section 107, this institution has established the IRB(s) listed in the attached roster(s) (see Appendix C). Certain research supported by the U.S. Department of Education will be reviewed in accordance with the requirements of Title 34 CFR Parts 350 and 356 which require that the IRB(s) include at least one person who is primarily concerned with the welfare of handicapped children or mentally disabled persons.
	G.	This institution will provide both meeting space and sufficient staff to support the IRB's review and record-keeping duties.
	H.	This institution recognizes that involvement in research activities of any OPRR-recognized Cooperative Protocol Research Programs (CPRPs) will involve additional reporting and record-keeping requirements related to human subject protections.
	I.	This institution is responsible for ensuring that it and all its affiliates comply fully with all applicable Federal policies and guidelines, including those concerning notification of seropositivity, counseling, and safeguarding confidentiality where research activities directly or indirectly involve the study of human immunodeficiency virus (HIV).

	A.	The ORA(s) will receive from investigators, through their supervisors, all research protocols which involve human subjects, keep investigators informed of decisions and administrative processing, and return all disapproved protocols to them.
	B.	The ORA(s) is responsible for reviewing the preliminary determinations of exemption by investigators and supervisors and for making the final determination based on Section 101 of the regulations. Notice of concurrence for all exempt research will be promptly conveyed in writing to the investigator. All nonexempt research will be forwarded to the appropriate IRB.
	C.	The ORA(s) will make the preliminary determination of eligibility for expedited review procedures (see Section 110). Expedited review of research activities will not be permitted where full board review is required.
	D.	The ORA(s) will review all research (whether exempt or not) and decide whether the institution will permit the research. If approved by the IRB, but not permitted by the ORA, the ORA will promptly convey notice to the investigator and the IRB Chair. Neither the ORA nor any other office of the institution may approve a research activity that has been disapproved by the appropriate IRB.
	E.	The ORA(s) will forward certification of IRB approval of proposed research to the appropriate Federal department or agency only after all IRB-required modifications have been incorporated to the satisfaction of the IRB.
	F.	The ORA(s) will designate procedures for the retention of signed consent documents for at least three years past completion of the research activity.
	G.	The ORA(s) will maintain and arrange access for inspection of IRB records as provided for in Section 115.
	H.	The ORA(s) is responsible for ensuring constructive communication among the research administrators, department heads, research investigators, clinical care staff, human subjects, and institutional officials as a means of maintaining a high level of awareness regarding the safeguarding of the rights and welfare of the subjects.
	I.	The ORA(s) will arrange for and document in its records that each individual who conducts or reviews human subject research has first been provided with a copy of this Assurance, as well as with ready access to copies of 45 CFR 46, regulations of other Federal departments or agencies as may apply, the Belmont Report, and all other pertinent Federal policies and guidelines related to the involvement of human subjects in research.
	J.	The ORA(s) will report promptly to the IRB(s), appropriate institutional officials, the Office for Protection from Research Risks (OPRR), and any other sponsoring Federal department or agency head:
		1. any unanticipated injuries or problems involving risks to subjects or others, 2. any serious or continuing noncompliance with the regulations or requirements of the IRB, and 3. any suspension or termination of IRB approval for research.
	K.	The ORA(s) will ensure (a) solicitation (or confirmation where applicable assurances to comply already exist), receipt, and management of all assurances of compliance (whatever the appropriate format), and (b) certifications of IRB review (where appropriate) for all performance sites to this institution (including those listed in Appendix B) and subsequent submission of new documents to the proper Federal department or agency authorities (e.g., OPRR for DHHS) as a condition for involvement of each site in human subject research activities sponsored by DHHS or any other Federal department or agency for which this Assurance applies.
	L.	The ORA will ensure that all affiliated performance sites that are not otherwise required to submit assurances of compliance with Federal regulations for the protection of research subjects at least document mechanisms to implement the equivalent of ethical principles to which this institution is committed (see Part 1, I).
	M.	When an IRB of this institution accepts responsibility for review of research which is subject to this Assurance and conducted by any independent investigator who is not otherwise subject to the provisions of this Assurance, the ORA will either: (a) obtain and retain an Noninstitutional Investigator Agreement (NIA) for CPRP activities (with copy to the investigator and the authorizing CPRP) or (b) obtain an Agreement for an Independent Investigator (AII) for review and approval by the appropriate Federal department or agency for non-CPRP activities to document the investigator's commitment to abide: (1) by the same requirements for the protection of human research subjects as does this institution(s) and (2) the determinations of the IRB(s).
	N.	The ORA(s) assumes responsibility for ensuring conformance with special reporting requirements for any OPRR-recognized CPRPs in which the signatory institution(s) participate(s).
	O.	The ORA(s) will be responsible for procedural and record-keeping audits not less than once every year for the purpose of detecting, correcting, and reporting (as required) administrative and/or material breaches in uniformly protecting the rights and welfare of human subjects as required at least by the regulations and as may otherwise be additionally required by this institution(s).
	P.	The ORA(s) will ensure compliance with the requirements set forth in this Assurance and Section 114 regarding cooperative research projects. In particular, where the IRB of another institution with a DHHS MPA is relied upon, the ORA(s) will ensure thatdocumentation of this reliance will be (a) in writing, (b) approved and signed by the ORA(s), (c) approved and signed by the correlative officials of each of the other cooperating institutions, and (d) retained by the ORA for at least three years past completion of the research project, if limited in scope to a specific research project or retained as a permanent addendum to the MPA if not restricted to a specific project. For all Cooperative Amendments (CAs), the ORA(s) will forward the original of the required signed understanding to OPRR for approval and inclusion in this Assurance as an addendum.
III.		Institutional Review Board (IRB)
	A.	The IRB(s) will review, and have the authority to approve, require modification in, or disapprove all research activities, including proposed changes in previously approved human subject research. For approved research, the IRB will determine which activities require continuing review more frequently than every twelve months or need verification that no changes have occurred if there was a previous IRB review and approval.
	B.	IRB decisions and requirements for modifications will be promptly conveyed to investigators and the ORA, in writing. Written notification of decisions to disapprove will be accompanied by reasons for the decision with provision of an opportunity for reply by the investigator, in person or in writing.
	C.	Initial and continuing convened IRB reviews and approvals will occur in compliance with 45 CFR 46 and provisions of this Assurance for each project unless properly found to be exempt (Section 101[b] or [i]) by the Office of Research Administration. Continuing reviews will be preceded by IRB receipt of appropriate progress reports from the investigator, including available study-wide findings.
	D.	The IRB(s) will observe the quorum requirements of Section 108(b). This institution's IRB(s) has effective knowledge of subject populations, institutional constraints, differing legal requirements, and other factors which can foreseeably contribute to a determination of risks and benefits to subjects and subjects' informed consent and can properly judge the adequacy of information to be presented to subjects in accordance with requirements of Sections 103(d), 107(a), 111, and 116.
	E.	The IRB(s) will determine, in accordance with the criteria found at 45 CFR 46.111 and Federal policies and guidelines for involvement of human subjects in HIV research, that protections for human research subjects are adequate.
	F.	The IRB(s) will ensure that legally effective informed consent will be obtained and documented in a manner that meets the requirements of Sections 116 and 117. The IRB will have the authority to observe or have a third party observe the consent process.
	G.	Where appropriate, the IRB(s) will determine that adequate additional protections are ensured for fetuses, pregnant women, prisoners, and children, as required by Subparts B, C, and D of 45 CFR 46. The IRB(s) will notify OPRR promptly when IRB membership(s) is modified to satisfy requirements of 45 CFR 46.304 and when the IRB fulfills its duties under 45 CFR 46.305(c).
	H.	Scheduled meetings of the IRB(s) for review of each research activity will occur not less than every 12 months and may be more frequent, if required by the IRB on the basis of degree of risk to subjects. The IRB may be called into an interim review session by the Chairperson at the request of any IRB member or institutional official to consider any matter concerned with the rights and welfare of any subject.
	I.	The IRB(s) will prepare and maintain adequate documentation of its activities in accordance with Section 46.115 and in conformance with Office of Research Administration requirements.
	J.	The IRB(s) will forward to the Office of Research Administration any significant or material finding or action, at least to include the following:
		1. any unanticipated injuries or problems involving risks to subjects or others, 2. any serious or continuing noncompliance with the regulations or requirements of the IRB, and 3. any suspension or termination of IRB approval.
	K.	In accordance with Section 113, the IRB(s) will have the authority to suspend or terminate previously approved research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects.
	L.	The IRB(s) for this institution will ensure effective input (consultants or voting or nonvoting members) for all initial and continuing reviews conducted on behalf of performance sites where there will be human research subjects. IRB minutes will document attendance of those other than regular voting members. The IRB list(s) in Appendix C includes those who are identified as knowledgeable about any affiliate institution having entered into an Inter-Institutional Amendment or other institutional performance site for which an Assurance is required when relying on one or more of the IRBs of this institution.
	M.	The IRB(s) will act with reasonable dispatch, upon request, to provide full board review of protocols of OPRR-recognized Cooperative Protocol Research Programs (CPRP). The IRB will not employ expedited review procedures for CPRP protocols when they are to be entered into for the purpose of research. Although emergency medical care based on such protocols is permitted without prior IRB approval, patients receiving emergency care under these conditions will not be counted as research subjects and resultant data will not be used for research purposes.
	N.	Certifications of IRB review and approval will be forwarded through the ORA to the appropriate Federal department or agency for research sponsored by such departments or agencies.
IV.		Research Investigator
	A.	Research investigators acknowledge and accept their responsibility for protecting the rights and welfare of human research subjects and for complying with all applicable provisions of this Assurance.
	B.	Research investigators who intend to involve human research subjects will not make the final determination of exemption from applicable Federal regulations or provisions of this Assurance.
	C.	Research investigators are responsible for providing a copy of the IRB-approved >informed consent document to each subject at the time of consent, unless the IRB has specifically waived this requirement. All signed consent documents are to be retained in a manner approved by the Office of Research Administration.
	D.	Research investigators will promptly report proposed changes in previously approved human subject research activities to the IRB. The proposed changes will not be initiated without IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subjects.
	E.	Research investigators are responsible for reporting progress of approved research to the Office of Research Administration, as often as and in the manner prescribed by the approving IRB on the basis of risks to subjects, but not less than once per year.
	F.	Research investigators will promptly report to the IRB any injuries or other unanticipated problems involving risks to subjects or others.
	G.	No research investigator who is obligated by the provisions of this Assurance, any associated Inter-Institutional Amendment, or Noninstitutional Investigator Agreement will seek to obtain research credit for, or use data from, patient interventions that constitute the provision of emergency medical care without prior IRB approval. A physician may provide emergency medical care to a patient without prior IRB review and approval, to the extent permitted by law (see Section 116[f]). However, such activities will not be counted as research nor the data used in support of research..
	H.	Research investigators will advise the IRB, Office of Research Administration and the appropriate officials of other institutions of the intent to admit human subjects *(e.g., into a hospital)* who are involved in research protocols for which this Assurance or any related Inter-Institutional Amendment or Noninstitutional Investigator Agreement applies. When such admissions are a planned part of DHHS-supported research, those institutions must possess an applicable OPRR-approved Assurance prior to involvement of such persons as human subjects in those research protocols at those institutions.
V.		Affiliated Institutions and Investigators (i.e., all performance sites, with or without IIAs)
	A.	Each performance site to this institution that is involved in federally sponsored research activities must provide to the Office of Research Administration an appropriate written assurance of compliance with the Belmont Report and the Federal Policy, to include Subparts B, C, and D or 45 CFR 46 where appropriate (or equivalent protections if a foreign site), for review and approval, as specified by the sponsoring Federal department or agency (e.g., by OPRR for DHHS), prior to involvement of human subjects or expenditure of funds or other support to do so.
	B.	Each institutional performance site must respond to a request by the Office of Research Administration of this institution for an Inter-Institutional Amendment, SPA, or CPA (as appropriate), whichever is most suited to the circumstances.
	C.	Each non-institutional performance site (e.g., a private practice physician not otherwise an employee of this institution or who otherwise would not ordinarily be bound by the provisions of this Assurance or any other applicable institutional Assurance) who is involved in human subject research of this institution must respond to a request by the Office of Research Administration of this institution for either an Agreement for an Independent Investigator or a Noninstitutional Investigator Agreement, as appropriate,depending on the nature of the research activity.
	D.	Performance sites that are legally separable from this institution (whether an institutional or non-institutional performance site) are not authorized to cite this Assurance.
Footnote ² Note to Preparers: This Part contains several administrative provisions that may be handled differently from one institution to another. Discretionary changes are expected. Please remember to highlight any changes to help speed review and approval.

I.		Institutional Endorsement(s)
		The officials signing below assure that any research activity conducted, supported, or otherwise subject to DHHS or other Federal departments or agencies that are authorized to rely on this Assurance (Parts 1, 2, 3 and Appendices) or any other sources provided for in this Assurance, will be reviewed and approved by the appropriate IRB(s) in accordance with the requirements of all applicable Subparts of Part 46, Title 45 of the Code of Federal Regulations, with this Assurance, and the stipulations of the IRB(s).
A.	Primary Signatory Institution (if any)
	1.		AUTHORIZED INSTITUTIONAL OFFICAL
			Signature:	_____________________________Date: ________
			Name:	_____________________________
			Title:	_____________________________
			Institution and Address:	[This item must be completed for each additional signatory institution to this proposed DHHS MPA document in Part 3,I,B below.]
			Phone:	_________________
			Fax:	_________________
			E-Mail:	_________________
	2.		PRIMARY CONTACT (If same, write "SAME")
			Signature:	_____________________________Date: ________
			Name:	_____________________________
			Title:	_____________________________
			Institution and Address:	[This item must be completed for each additional signatory institution to this proposed DHHS MPA document in Part 3,I,B below.]
			Phone:	_________________
			Fax:	_________________
			E-Mail:	_________________
B.			Other Signatory Institutions [complete as many times as needed]
	1.		AUTHORIZED INSTITUTIONAL OFFICIAL
			Signature:	_____________________________Date: ________
			Name:	_____________________________
			Title:	_____________________________
			Institution and Address:	_____________________________
				_____________________________
				_____________________________
				_____________________________
				_____________________________
			Phone:	_________________
			Fax:	_________________
			E-Mail:	_________________
	2.		PRIMARY CONTACT (If same write "SAME")
			Signature:	_____________________________Date: ________
			Name:	_____________________________
			Title:	_____________________________
			Institution and Address:	_____________________________
				_____________________________
				_____________________________
				_____________________________
				_____________________________
			Phone:	_________________
			Fax:	_________________
			E-Mail:	_________________

II.		Office for Protection from Research Risks (DHHS) Approval
	A.	DHHS RECOMMENDING OFFICIAL
		Signature:	_____________________________Date: ________
		Title:	Assurance Coordinator
		Address:	Division of Assurances and Quality Improvement
			Office for Human Research Protections (OHRP )
			1101 Wootton Parkway, Suite 200
			Rockville, Maryland 20852
		Phone:	301-496-7005
		Fax:	301-402-0527
		EFFECTIVE DATE OF ASSURANCE: __________________
		EXPIRATION DATE OF ASSURANCE: ___________________
	B.	DHHS APPROVING OFFICIAL
		Signature:	_____________________________Date: ________
		Name:	________________________________
		Title:	Assurance Coordinator
		Address:	Division of Assurances and Quality Improvement
			Office for Human Research Protections (OHRP)
			1101 Wootton Parkway, Suite 200
			Rockville, Maryland 20852
		Phone:	301-496-7005
		Fax:	301-402-0527
		E-Mail:	_______________

MPA Signatory Institution #1(i.e., Primary):
	Components that Participate in Human Research
	Name:	City:	State:

MPA Signatory Institution #2:
	Components that Participate in Human Research
	Name:	City:	State:

MPA Signatory Institution #3:
	Components that Participate in Human Research
	Name:	City:	State:

MPA Signatory Institution #4:
	Components that Participate in Human Research
	Name:	City:	State:

MPA Signatory Institution #5:
	Components that Participate in Human Research
	Name:	City:	State:

MPA Signatory Institution #1 (Primary):
	Name:	City:	State:
Affiliate Institutions: