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U.S. Department of Energy ORDER
Washington, D.C. DOE O 443.1A
Approved: 12-20-07
SUBJECT: PROTECTION OF HUMAN SUBJECTS
1. OBJECTIVE. To establish Department of Energy (DOE) procedures
and responsibilities for implementing the policy and
requirements set forth in 10 Code of Federal Regulations
(CFR) Part 745, Protection of Human Subjects; and in
DOE P 443.1A, Protection of Human Subjects, dated 12-20-07.
2. CANCELLATION. This Order cancels DOE Order 443.1, Protection of
Human Subjects, dated 5-15-00. Cancellation of an Order does
not by itself modify or otherwise affect any contractual
obligation to comply with the Order. Contractor Requirements
Documents (CRDs) containing directive requirements that have
been applied to a contract remain in effect until the
contract is modified to eliminate or replace requirements
from canceled directives.
3. APPLICABILITY.
a. DOE Elements. Except for exclusions in paragraph 3d,
this Order applies to all Departmental elements, including
those created after the Order is issued. (Go to
http://www.directives.doe.gov for the current listing
of Departmental elements.)
The National Nuclear Security Administration (NNSA)
Administrator will assure that NNSA employees and
contractors comply with their respective
responsibilities under this directive. Nothing in this
Order will be construed to interfere with the NNSA
Administrator’s authority under Section 3212(d) of
Public Law (P.L.) 106-65 to establish
Administration-specific policies, unless disapproved by
the Secretary.
b. DOE Contractors. Except for the exclusions in paragraph 3d, the
requirements of the Contractor Requirements Document
(CRD), Attachment 1, sets forth the requirements of
this Order that will apply to contracts that include
the CRD. The CRD must be included in contracts for the
management or operation of a DOE-owned or -leased
facility that involves human subjects research (HSR) as
defined in paragraph 6.e., and comprehensively
explained in DOE P 443.1A, irrespective of the party
conducting the HSR under the contract.
c. Other Contracts and Agreements. Refer to paragraph 5e(3).
d. Exclusions. Bonneville Power Administration.
4. REQUIREMENTS.
a. Approvals. No HSR conducted with DOE funding, at DOE
institutions, or by DOE personnel may be initiated
without both a Federalwide Assurance (FWA) and approval
by the cognizant Institutional Review Board (IRB) in
accordance with 10 CFR 745.103.
b. Solicitations. Any solicitation for research involving human
subjects must indicate the applicable requirements of
this Order, 10 CFR 745, and 45 CFR 46.
c. Contracts and Agreements. Any DOE contract, financial
assistance agreement, or other agreement involving HSR
must prescribe compliance with this Order, 10 CFR 745,
and 45 CFR 46. See also CRD (Attachment 1).
d. Notification. The HSR Program Manager (and when an
NNSA element is involved, the NNSA HSR Manager) must
be notified in writing and within a reasonable time of any new
solicitation or proposal involving HSR (including
personally identifiable information or materials) that
addresses:
(1) an institution without an established IRB;
(2) a foreign country;
(3) a potential for significant controversy (e.g., negative
press or reaction from stakeholder or oversight groups);
(4) research subjects in a protected class; or
(5) the generation or use of classified or unclassified
controlled information.
e. Reporting.
(1) HSR projects must be reported annually to the HSR Projects
Database in accordance with directions and schedules provided by
the HSR Program Manager.
(2) The HSR Program Manager will be notified in writing and
within a reasonable time of:
(a) significant adverse events, unanticipated risks, and
complaints about the research, with a description of
corrective actions taken and/or to be taken;
(b) suspension or termination of IRB approval of research; and
(c) known or potential incidents of noncompliance with
requirements of this Order, 10 CFR 745, 45 CFR 46, and any
approved plan for correcting a noncompliance.
f. Waivers. Requests for waivers from the requirements of
10 CFR 745 or this Order must be submitted to the HSR
Program Manager (and when an NNSA element is involved,
the NNSA HSR Manager) in writing. A waiver may be
recommended by the HSR Program Manager (or by the NNSA
HSR Manager when an NNSA element is involved) to the
Secretary or the Secretary’s designee. Waiver decisions
must set forth in writing the basis for granting or
denying the request.
g. Protected Classes. Research involving fetuses, pregnant women, and in
vitro fertilization; prisoners; or children must be
conducted in accordance with 45 CFR 46 Subparts B, C,
and D.
5. RESPONSIBILITIES.
a. Under Secretary for Science.
(1) Monitors implementation of 10 CFR 745 within the Department
in accordance with policy established by the Secretary and DOE P
443.1A in consultation with the NNSA, as appropriate.
(2) Determines what constitutes Departmental-related HSR, in
consultation with the NNSA.
(3) Ensures implementation of human research subject protection
measures in accordance with the requirements of this Order and 10
CFR 745 in consultation with the NNSA HSR, as appropriate.
(4) Designates the HSR Program Manager. For DOE, the HSR Program
Manager resides within the SC Office of Biological and
Environmental Research.
b. Under Secretary for Nuclear Security and Administrator of
the National Nuclear Security Administration designates the NNSA HSR Manager.
c. DOE HSR Program Manager.
(1) Develops procedures for the HSR program in consultation with
the NNSA HSR Manager, as appropriate.
(2) Prepares and updates guidance to be followed for obtaining
approval for HSR in consultation with the NNSA HSR Manager, as
appropriate.
(3) Reviews/approves (or when an NNSA element is involved,
reviews and may recommend approval of) local plans to correct any
noncompliance with applicable HSR requirements, or to mitigate
adverse study events.
(4) Provides advice and guidance on evolving Departmental and
national bioethics and regulatory issues regarding human research
subjects protection and helps identify and resolve
program/project concerns in consultation with the NNSA HSR
Manager, as appropriate.
(5) Develops and conducts educational programs on bioethics and
human research subjects protection requirements, practices, and
procedures relevant to DOE employees, DOE contractor personnel,
financial assistance recipients, and the public in consultation
with the NNSA HSR Manager, as appropriate.
(6) Regularly conducts institutional performance reviews to
assess compliance with human research subjects protection
requirements in consultation with the NNSA HSR Manager, as
appropriate.
(7) Serves as the Chair of the DOE Human Subjects Working Group
and as the official DOE representative to groups with bioethics
and HSR interests. The NNSA HSR Manager shall be invited to
attend all such meetings.
(8) Makes recommendations to the Secretary or the Secretary’s
designee regarding requests for waivers to requirements of 10 CFR
745.101 and satisfies the advance notice and publication
requirements of 10 CFR 745.101(i) prior to the granting of any
waiver (in consultation with the NNSA HSR Manager, as
appropriate).
(9) Concurs in HSR provisions in interagency agreements in
consultation with the NNSA HSR Manager, as appropriate.
(10) Maintains the HSR Projects Database for the Department.
d. NNSA HSR Manager.
(1) When an NNSA element is involved, reviews requests for
waivers to requirements of 10 CFR 745 and makes recommendations
to the Secretary through the NNSA Administrator. Ensures that the
advance notice and publication requirements of 10 CFR 745.101(i)
are met prior to the granting of any waiver.
(2) Works with the HSR Program Manager, as outlined in paragraph
5c of this Order.
e. Secretarial Officers or their Designees. Note: Per DOE M 251.1-1B and as
used throughout this Order, the term “Secretarial Officer” refers to the
Secretary, Deputy Secretary, the Under Secretaries, and
the Assistant Secretaries and Program Office Directors
reporting to the Secretary either directly or through
the Deputy Secretary or Under Secretaries. The NNSA
Administrator and Deputy Administrators are Secretarial
Officers.
(1) Ensure that all proposals for research, studies, tests,
surveys, surveillance, or other data collection are reviewed to
identify research involving human subjects.
(2) Ensure that any questions or uncertainties regarding the
applicability of human research subjects protection requirements
to such proposals, and any other issues and concerns regarding
the requirements of this Order, are promptly referred to the HSR
Program Manager for resolution (or the NNSA HSR Manager when an
NNSA element is involved).
(3) Ensure that the contracting officer is advised when work
statements for proposed agreements include HSR. The requirements
of this Order will be applied to HSR conducted with DOE funding,
at DOE institutions, or by DOE personnel under agreements other
than site/facility management contracts, such as support services
contracts, grants, cooperative agreements, work-for-others
agreements, and interagency agreements.
(4) Ensure their staffs and subordinate field elements comply
with the requirements of this Order, including the notification
requirements in paragraph 4e.
(5) Actively participate in human research subjects protection
educational programs.
(6) Assure self-assessments are periodically conducted to verify
compliance with the requirements of this Order.
(7) At their discretion, conduct further review and approve or
disapprove research that has been approved by the IRB. (Note:
Secretarial Officers or their designees may not approve HSR that
has not been approved by an IRB. See 10 CFR 745.112.)
(8) Ensure appropriate oversight of the administration of
research subjects protection programs of contractors and
financial assistance recipients under their cognizance, and other
parties to DOE agreements, to ensure compliance with applicable
human research subjects protection requirements.
(9) Ensure that the HSR Program Manager and the NNSA HSR Manager
are involved in negotiating those portions of interagency
agreements that address HSR.
(10) Appoint a point of contact for interacting with the HSR
Program Manager (and/or NNSA HSR Manager, when an NNSA
element is involved) on program-related and/or Department-wide
issues.
6. DEFINITIONS.
a. Assurance. The written documentation, satisfactory to the
Secretary of Energy, required from the prospective
performing institution, that ensures institutional
compliance with and implementation of DOE and
Department of Health and Human Services (DHHS)
regulations for the protection of human research
subjects. The only documentation currently meeting this
requirement is a Federalwide Assurance (FWA). See
http://www.hhs.gov/ohrp/assurances/assurances_index.html.
b. Adverse Effect. A direct result of an administered research
protocol (e.g., negative or deleterious drug reaction,
collateral damage to the human subject).
c. Adverse Event. A result surrounding or indirectly related to the
entire research process (e.g., mishaps, mistakes,
incorrect dosage administered, reconsideration of human
subject involvement).
d. DOE HSR Projects Database. A compilation of summary
information, which is available on the website at:
http://hsrd.orau.gov/, updated annually, on every HSR
non-exempt project funded by DOE, conducted at DOE
institutions or facilities, or performed with DOE or contractor
personnel.
e. Human Subjects Research (HSR). Any systematic investigation
(including research development, testing, and evaluation) utilizing
living individuals or personally identifiable information or
materials, designed to develop or contribute to general
knowledge. See DOE P 443.1A for examples and
exclusions.
f. Human Subjects Research Program Manager (HSR Program
Manager). The DOE HSR Program Manager (SC23.2) designated
by the Under Secretary for Science.
g. NNSA Human Subjects Protection Designee (NNSA HSR Manager).
The NNSA HSR Manager designated by the NNSA
Administrator and Under Secretary for Nuclear Security.
h. Institution. Any public or private entity or agency (including
Federal, State, and other agencies). This term refers
to laboratories and other facilities managed by DOE,
DOE contractors, or DOE financial assistance
recipients.
i. Institutional Review Board (IRB). A committee or board established
by an institution that performs initial and continuing reviews of
research involving human subjects, and is registered
with the Office for Human Research Protections (OHRP)
and designated on an FWA.
7. REFERENCES.
a. DOE Human Subjects Protection Resource Book, Office of
Biological and Environmental Research, 2007.
b. DOE O 241.1A Chg 1, Scientific and Technical Information
Management, dated 10-14-03, which establishes Department of
Energy (DOE) requirements and responsibilities to ensure that
scientific and technical information (STI) is identified,
processed, disseminated, and preserved in a manner that (a)
enables the scientific community and the public to locate and use
the unclassified and unlimited STI resulting from DOE’s research
and related endeavors and (b) ensures access to classified and
unclassified controlled STI is protected according to legal or
Departmental requirements.
c. DOE O 412.1A, Work Authorization System, dated 4-21-05,
which provides the policy, responsibilities, and procedures for
authorizing and administering DOE-funded work performed under DOE
contracts.
d. DOE P 443.1A, Protection of Human Subjects, dated 12-20-07,
which defines DOE policy for the protection of human subjects in
research activities.
e. DOE O 481.1C, Work for Others (Non--Department of Energy
Funded Work), dated 1-24-05, which establishes the policy,
responsibilities, and procedures for authorizing and
administering work for non-DOE entities by DOE/National Nuclear
Security Administration (NNSA) and/or their respective contractor
personnel or the use of DOE/NNSA facilities that is not directly
funded by DOE appropriations.
f. DOE M 481.1-1A Chg 1, Reimbursable Work for Non-Federal
Sponsors Process Manual, dated 9-28-01, provides detailed
requirements to supplement DOE O 481.1C, Work For Others
(Non-Department of Energy Funded Work), dated 1-24-05, which
establishes requirements for the performance of work for
non-DOE/non-NNSA entities by DOE/NNSA/contractor personnel and/or
the use of DOE/NNSA facilities that is not directly funded by
DOE/NNSA appropriations.
g. DOE M 483.1-1, DOE Cooperative Research and Development
Agreements Manual, dated 1-12-01, which provides detailed
requirements to supplement DOE O 483.1, DOE Cooperative Research
and Development Agreements, dated 1-12-01, which establishes
requirements for the performance of technology transfer through
the use of Cooperative Research and Development Agreements
(CRADAs).
h. DOE O 484.1, Reimbursable Work for the Department of
Homeland Security, dated 8-17-06. The Order establishes DOE
policies and procedures for the acceptance, performance, and
administration of reimbursable work directly funded by the
Department of Homeland Security.
i. 10 CFR 600, DOE Financial Assistance Rules, which provides
the policies and procedures for administration and management of
all DOE financial assistance activities.
j. 10 CFR 602, Epidemiology and Other Health Studies Financial
Assistance Program, which sets forth the policies and procedures
applicable to the award and administration of financial
assistance agreements and cooperative agreements for
health--related research, education/training, conferences,
communication, and related activities.
k. 10 CFR 605, Office of Science Financial Assistance Program,
as explained at doe.gov/grants/605index.html, which provides
policies and procedures for the administration and management of
basic and applied research financial award agreements awarded by
the Office of Science.
l. 10 CFR 745, Protection of Human Subjects, which sets out
Federal requirements for DOE for the protection of human subjects
involved in research activities.
m. 10 CFR 1008, Records Maintained On Individuals (Privacy Act)
which establishes the procedures to implement the Privacy Act of
1974 (PL. 93-579, 5 U.S.C. 552a) within the Department of Energy.
n. 45 CFR 46, Protection of Human Subjects, Subparts B, C, and
D, which sets out DOE prescribed DHHS requirements for protected
classes of human research subjects.
o. The National Nuclear Security Administration Act, Title 32,
Pub. L No. 106-65, as amended.
p. 5 United States Code 552, The Freedom of Information Act
(Public Law 89-487 as amended), which establishes the right of
citizens to request information from Federal agencies and
establishes a framework of procedures to implement this right.
8. NECESSITY FINDINGS STATEMENT. In compliance with statutory requirements
in Sec. 3174, P.L. 104-201 (50 U.S.C. 2584 note), DOE hereby finds
that the subject Order is necessary for the protection of
human research subjects within the DOE community.
9. CONTACT. Questions regarding this Order should be addressed to
the DOE Program Manager, HSR Program, at the Office of
Science (SC23.2), telephone 301-903-3213, or the NNSA human
subjects protection designee, as appropriate. Information
about the DOE HSR protection program may be found at
http://humansubjects.energy.gov/.
BY ORDER OF THE SECRETARY OF ENERGY:
CLAY SELL
Deputy Secretary
CONTRACTOR REQUIREMENTS DOCUMENT
DOE O 443.1A, PROTECTION OF HUMAN SUBJECTS
Regardless of the performer of the work, the contractor is
responsible for compliance with the requirements of this CRD. The
contractor is responsible for flowing down the requirements of
this CRD to subcontracts at any tier to the extent necessary to
ensure the contractor’s compliance with the requirements.
As directed by the contracting officer, the contractor must—
Note: Throughout this CRD, the term “Human Subjects Research
Manager (HSR Manager)” refers either to the DOE HSR Manager
(SC23.2) or to the NNSA human subjects protection designee except
where otherwise noted.
1. Ensure that the HSR Program Manager (and, when an NNSA
element is involved, the NNSA HSR Manager) is notified of any new
HSR project involving:
a. an institution without an established Institutional Review
Board (IRB);
b. a foreign country;
c. the potential for significant controversy (e.g., negative
press or reaction from stakeholder or oversight groups);
d. research subjects in a protected class; or
e. the generation or use of classified or unclassified
controlled information.
2. Ensure that research involving human subjects conducted at
the contractor-operated institution, with the contractor's
DOE-contract funding, or by contractor personnel is
conducted in accordance with applicable requirements. (See
10 CFR 745 and 45 CFR 46.)
3. Ensure that contractor-issued solicitations or proposals for
research, studies, tests, surveys, surveillance, or other
data collection are reviewed to identify research involving
human subjects and that any resulting agreements include the
substance of the requirements in this CRD.
4. Ensure that no research involving human subjects conducted
at the contractor-operated institution, with the
contractor's DOE-contract funding, or by contractor
personnel is initiated without prior IRB approval under the
terms of an approved assurance covering the research.
5. Submit an application for a Federalwide Assurance (FWA) to
the Office of Human Research Protections with the Department
of Health and Human Services (DHHS) and, once approved,
maintain this FWA covering proposed and ongoing HSR. The FWA
has been accepted by the Secretary of Energy as appropriate
written documentation from the prospective performing
institution that ensures institutional compliance with and
implementation of DOE and DHHS regulations for the
protection of human research subjects. See
http://www.hhs.gov/ohrp/assurances/assurances_index.html
and/or contact the DOE HSR Protection Program, SC-23.2,
telephone 301-903-3213, or the NNSA human subjects
protection designee, as appropriate.
6. Ensure that research is reviewed at intervals appropriate to
the degree of risk, but not less than once per year, to
assess the risk to test subjects and to assure the risk is
reasonable in relation to anticipated benefits.
7. Periodically conduct self-assessments to ensure compliance
with the HSR Program procedures and other requirements.
8. Prepare and submit an annual report for the HSR Projects
Database in accordance with directions and schedules
provided by the HSR Program Manager and the contracting
officer.
9. Report the following to the HSR Program Manager (and, when
an NNSA element is involved, the NNSA HSR Manager):
a. any significant adverse events, unanticipated risks; and
complaints about the research, with a description of any
corrective actions taken and/or to be taken;
b. any suspension or termination of IRB approval of research;
c. any significant non-compliance with HSR Program procedures
or other requirements.
NOTE: The adverse effects of any study are to be reported
to the IRB for evaluation for further action with HSR
Program Manager, (and, when an NNSA element is
involved, the NNSA HSR Manager)
10. Submit requests for waivers from these requirements in
writing through the contracting officer to the HSR Program
Manager (and, when an NNSA element is involved, the NNSA HSR
Manager) with appropriate justification.
11. Actively participate in HSR educational programs.