MSU HRPP Manual Section 2-2-E

U.S. Department of Energy

This policy applies to research involving human subjects conducted or supported by the U.S. Department of Energy (DOE). In addition to the Basic DOE policy for Protection of Human Subjects (10 CFR 745), additional requirements are provided in DOE 443.1C, Protection of Human Subjects (approved November 26, 2019). No human subject research conducted with DOE funding, at DOE institutions (regardless of funding source), or by DOE or DOE contractor personnel (regardless of funding source or location conducted), whether done domestically or in an international environment, including classified and proprietary research, may be initiated without both a Federalwide Assurance (FWA) or comparable assurance (e.g., Department of Defense assurance) of compliance and approval by the cognizant Institutional Review Board (IRB) in accordance with 10 CFR Part 745.103. (DOE443.1C (4)(a)(1)) Individuals engaged in human subject research subject to DOE requirements are responsible for complying with the DOE requirements as applicable, including exempt research.

Contractor Requirements

DOE 443.1C includes a “Contractor Requirements Document, Attachment 1,” (CRD), which sets forth the requirements of 443.1C that apply to contractors. The CRD will be included in contracts for the management or operation of a DOE-owned or leased facility that involves human subject research, irrespective of the party conducting the human subject research under the contract. For all other contracts that involve human subject research, the applicable requirements set forth in the CRD are included in the contract terms and conditions as appropriate.

When an IRB submission is received where DOE requirements may be applicable, an Michigan State University (MSU) Institutional Review Board (IRB) administrator is assigned to obtain information from the Principal Investigator (PI) of the study regarding the DOE requirements. Research involving human subjects, regardless of source of funding, must be conducted in accordance with applicable Federal, DOE-specific, sponsor-specific, and other applicable requirements, including relevant international requirements.(DOE 443.1C CRD#2) Relevant sections of the DOE 443.1C CRD are included below; however, see the DOE 443.1C for full requirements.

Definition of Generalizable

When determining whether an activity is research, DOE 443.1C defines generalizable as information/research findings that are intended to be applied to populations or situations beyond that studied/will have meaning and impact outside of the single immediate activity itself. (DOE 443.1C (8)(o))

Exemptions

All exempt human subject research determinations must be made by the appropriate IRB and/or IRB office. (DOE 443.1C CRD#5) Exempt human subjects research is human subject research that is minimal risk and meets one of the exempt categories outlined in 10 CFR Part 745. (DOE 443.1C (8)(m))

Multiple DOE Sites

Prior to initiation, human subject research involving multiple DOE sites must be reviewed and approved by one of the Central DOE IRBs or other appropriate IRB of record if authorized by the DOE and/or National Nuclear Security Administration (NNSA) DOE Human Subjects Protection (HSP) Program Manager. Examples of multiple DOE sites includes when members of the research team are from more than one DOE site and/or data or human subjects are from more than one DOE site. In all cases, an IRB Authorization Agreement (IAA) or Memorandum of Understanding (MOU) must be in place between the organization(s) conducting the human subject research and the organization responsible for IRB review. (DOE 443.1C CRD#7)

DOE Federal and/or Contractor Employees as Subjects

DOE 443.1C defines protected class of human subjects as populations who may be more vulnerable to coercion or undue influence when participating as research subjects, including children, prisoners, decisionally impaired individuals, economically or educationally disadvantaged persons, and other vulnerable populations, who are thus afforded additional protections by the Federal regulations (see additional subparts of 45 CFR Part 46) and/or the IRB.

IRBs have been advised that they should place special emphasis on 10 CFR 745.111 (b) if employees are research subjects. Section 10 CFR Part 745.111(b) states: “When some or all of the subjects are likely to be vulnerable to coercion or undue influence ... additional safeguards have been included in the study to protect the rights and welfare of these subjects.” (DOE Institutional Official Memo dated May 22, 2015) DOE and DOE site employees are considered vulnerable subjects when participating in research and additional care must be taken to ensure their participation is truly voluntary (e.g., by ensuring they do not report to members of the research team), and that data collected about them is kept confidential. (DOE 443.1C (8)(z))

Human subject research that involves DOE Federal and/or contractor employees as subjects must first be reviewed and approved by the appropriate DOE IRB (the DOE site IRB or one of the Central DOE IRBs), or if deemed more fitting, by the Federally assured DOE site or Headquarters or other appropriate IRB of record. in accordance with an IAA or MOU negotiated between the DOE site or Headquarters and the organization responsible for IRB review. (DOE 443.1C CRD#8)

Human Terrain Mapping

Human Terrain Mapping (HTM) work is managed as human subject research and must comply with the DOE requirements. (DOE 443.1C CRD#10)

Human Terrain Mapping is defined as research and data gathering activities primarily conducted for military or intelligence purposes to understand the “human terrain,”—the social, ethnographic, cultural, and political elements of the people among whom the U.S. Armed Forces are operating and/or in countries prone to political instability. This work includes observations, questionnaires, and interviews of groups of individuals, as well as modeling and analysis of collected data, and may become the basis for U.S. military actions in such locations. In addition to Human Terrain Mapping (HTM), such activities are often referred to as human social culture behavior (HSCB) studies. It is DOE policy that HTM activities will be managed as human subject research. HTM Data is defined as data collected or used as part of HTM efforts, as described above, as well as any auxiliary data on the same group(s) of individuals. (DOE 443.1C (8)(r), (s))

HTM projects, conducted with DOE funding, at DOE sites/institutions (regardless of funding source), or by DOE or DOE contractor personnel (regardless of funding source or location conducted), whether done domestically or in an international environment, including classified and proprietary research, must be strictly limited to only those projects involving the analysis and modeling of de-identified data. (DOE 443.1C CRD#10(a))

Statements of work for HTM projects must be submitted to the DOE HSP Program Manager (and when an NNSA element is involved, the NNSA HSP Program Manager), for DOE Headquarters review and approval prior to initiation. See 443.1C for full requirements. (DOE 443.1C CRD#10(b))

Social Media Data

Research that uses social media data must be submitted to the appropriate IRB for human subject research review and determination. (DOE 443.1C CRD#12)

Study of Humans in a Systematically Modified Environment

Research involving the study of humans in a systematically modified environment must be submitted to an appropriate IRB for human subject review and determination. (DOE 443.1C CRD#13)

Modification of the human environment research is defined as research (1) in which people have their environment intentionally changed or manipulated for the purposes of the research, with or without their knowledge; and/or (2) that cannot be validly conducted without people present (other than those conducting the research), regardless of whether identifiable private information is collected about them. Before such research begins, the potential risks to those individuals must be considered by the appropriate DOE IRB. (DOE 443.1C (8)(w))

Protection of Personally Identifiable Information

In accordance with the Privacy Act, the DOE has established requirements for the protection of Personally Identifiable Information (PII) with the DOE Privacy Program (DOE Order 206.1). Investigators are required to follow applicable DOE requirements for the protection of personally identifiable information. Researchers must ensure that personally identifiable information collected and/or used during human subject research projects is protected in accordance with the requirements of DOE Order 206.1. (DOE 443.1C CRD#15)

Personally Identifiable Information is defined as any information collected or maintained about an individual, including but not limited to, education, financial transactions, medical history and criminal or employment history, and information that can be used to distinguish or trace an individual’s identity, such as his/her name, Social Security number, date and place of birth, mother’s maiden name, biometric data, and any other personal information that is linked or linkable to a specific individual. (DOE 443.1C (8)(y))

Notification and Reporting Requirements

Prior to initiation of any new human subject research, the DOE Human Subject Protection (HSP) Program Manager (and when an NNSA element is involved, the NNSA HSP Program Manager) must be notified when the study involves:

  1. An institution without an established Institutional Review Board (IRB);

  2. A foreign country;

  3. Potential for significant controversy (e.g., negative press or reaction from stakeholder or oversight groups);

  4. Research subjects in a protected class (prisoners, children, individuals with impaired decision making capability, or DOE/NNSA federal or DOE/NNSA contractor employees as human subjects, who may be more vulnerable to coercion and undue influence to participate) that is outside of the reviewing IRB’s typical range/scope; or

  5. Generation or use of classified information.

The MSU HRPP manager or designee will work with the PI to assure this notification occurs when necessary.

After the human subject research has been initiated, the PI must immediately report any of the following to the IRB:

  1. Any significant adverse events, unanticipated problems, and complaints about the research;

  2. Any significant non-compliance with DOE HSP Program procedures or other requirements

  3. Upon finding of a suspected or confirmed data breach involving PII in printed or electronic form

  4. Any suspension or termination of IRB approval of research

  5. Serious adverse event.

The MSU HRPP manager or designee will work with the PI to assure that the DOE Human Subject Protection (HSP) Program Manager (and when an NNSA element is involved, the NNSA HSP Program Manager) are notified within the required timeframes below. The notification must include a description of the corrective actions taken and consultation with the DOE HRP Program Manager(s) is needed regarding additional corrective action to be taken.

Immediately:

  1. Upon finding of a suspected or confirmed data breach involving PII in printed or electronic form

  2. Upon learning of a serious adverse event

Within 48 hours of:

  1. Any significant adverse events, unanticipated problems, and complaints about the research

  2. Any suspension or termination of IRB approval of research

  3. Any significant non-compliance with DOE HSP Program procedures or other requirements

Additionally, the PI must immediately notify the DOE-Cyber Incident Response Capability, in accordance with the requirements of the CRD associated with DOE O 206.1.

An adverse event is defined as any unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research (Unanticipated Problems Involving Risk and Adverse Events Guidance, OHRP, 2007). (DOE 443.1C (8)(a))

A significant adverse event is an adverse event that is unexpected and substantively impacts the human subjects. (DOE 443.1C (8)(a))

A serious adverse event (Unanticipated Problems Involving Risk Adverse Events Guidance, OHRP, 2007) is any adverse event temporally associated with the subject’s participation in research that meets any of the following criteria:

a) results in death;

b) is life-threatening;

c) requires inpatient hospitalization or prolongation of existing hospitalization;

d) results in a persistent or significant disability/incapacity;

e) results in a congenital anomaly/birth defect, or

f) based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. (DOE 443.1C (8)(a))

In general, to be classified as an unanticipated problem, any incident, experience, or outcome should meet all three of the following criteria:

  1. Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied

  2. Related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research)

  3. Likely to place subjects or others at greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. (DOE 443.1C (8)(ee))

See the following sections of the HRPP Manual for specific requirements (e.g., timeframes): 4-8 “Reporting,” 9-1 “Unanticipated Problems Involving Risks to Subjects or Others,” 9-2 “Noncompliance,” and 9-3 “Termination or Suspension of Research.”

Classified Research

Classified Human Subjects Research is research involving human subjects that is classified, in whole or in part, in accordance with the Federal sponsor and/or DOE criteria. (DOE 443.1C (8)(e)) Classified research must comply with additional requirements. See 443.1C for requirements. MSU does not accept classified projects. See MSU Manual Business Procedures Section 315: Sponsored Projects, Fee-for-Service, and Gifts.

Informal Internal Review

The MSU Human Research Protection Program must perform informal internal review(s) of its program, or portions of the program, at least annually, consulting with the site office as appropriate. (DOE 443.1C CRD#18)

This policy and procedure supersedes those previously drafted.

Approved By: Vice President of Research and Graduate Studies, 7-19-2011. Revision 1 approved by VP Research & Graduate Studies on 12-9-2015. Revision 2 approved by Assistant VP Regulatory Affairs on 11-8-2021. Revision 3 approved by Associate VP Research Regulatory Support on 7-23-2022.

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