VA Requirements

• VA research is research that is conducted by researchers (serving on VA compensated, WOC, or IPA appointments) while on VA time or on VA property. The research may be funded by VA, by other sponsors, or be unfunded. VA research must have Research and Development (R&D) Committee approval before it is considered VA Research and before it can be initiated. All research activities approved by the R&D Committee are considered VA Research.
  • VA-affiliated nonprofit research and education corporations (NPC) are authorized by Congress under 38 U.S.C. 7361-7366 to provide flexible funding mechanisms for the conduct of research and education at one or more VA facilities. Research approved by a facility R&D Committee are considered to be a VA research project or a VA education activity respectively, regardless of the source of funding, the entity administering the funds, or the research or education site (see VHA Handbook 1200.17, Department of Veterans Affairs Nonprofit Research and Education Corporations Authorized by Title 38 U.S.C. Sections 7361 Through 7366, dated April 27, 2016 and revised May 9, 2017).
• VA research includes VA-approved research conducted at international sites not within the United States, its territories, or Commonwealths; and includes research where human tissues are sent outside the United States.
• The investigator must give first priority to the protection of research subjects, uphold professional and ethical standards and practices, and adhere to all applicable VA and other federal requirements, including the local VA facility’s policies and procedures, regarding the conduct of research and the protection of human subjects. The investigator must hold a current VA appointment to conduct VA research.
• Any study conducted by researchers while on VA time, including Without Compensation and Intergovernmental Personnel Act appointments, is subject to review and approval by the Madison Veterans Administration (VA) Research and Development Committee. The VA determines whether a particular study falls under VA purview.
• The responsibilities of the investigator may be defined in the protocol or IRB application. Specifically, the principal investigator’s and local site investigator’s responsibilities include, but are not limited to:
  • Qualifications to Conduct Human Subjects Research. VA investigators must have the appropriate training, education, expertise, and credentials to conduct the research according to the research protocol.
    • Students or trainees cannot serve as PI on VA human subjects research, but may participate as a study team member if enrolled at an institution with an educational affiliation agreement with the Madison VA or be directly appointed to a VA training program that has no external institutional sponsorship.
    • PIs must ensure that all research staff are qualified (e.g., including but not limited to appropriate training, education, expertise, and credentials) to perform procedures assigned to them during the course of the study.
    • Investigators and their staff conducting human subjects research must be credentialed and privileged as required by current local and VA requirements (see VHA Handbook 1100.19 and VHA Directive 2012-030, Credentialing of Health Care Professionals, or successor policy). Investigators and their research staff may only perform those activities in a research study for which they have the relevant credentials and privileges.
    • Investigators and co-investigators must be identified on the IRB application and must provide credentials, conflict of interest statements or other documentation required by VA and local facility policies.
    • All individuals involved in conducting VA human subjects research are required to complete training in ethical principles on which human subjects research is to be conducted. Specific requirements regarding the type and frequency of training are found on ORD’s Web site at: https://www.research.va.gov/programs/orppe/education/ord_training/default.cfm. All other applicable VA and VHA training requirements at the local and national level must be met (e.g., privacy and information security training).
    • Investigators must prospectively document their research with their supervisor in writing.
    • Investigators must submit exempt protocols that require limited IRB review to the IRB for limited IRB review/approval.
  • Research Protocol. The investigator must develop and submit a research protocol that is scientifically valid, describes the research objectives, background and methodology, provides for fair and equitable recruitment and selection of subjects, minimizes risks to subjects and others, and describes a data and safety monitoring plan consistent with the nature of the study. The research must be relevant to the health or welfare of the Veteran population. When relevant, the protocol must include the following safety measures:
    • The type of safety information to be collected including AEs;
    • Frequency of safety data collection;
    • Frequency or periodicity of review of cumulative safety data;
    • Statistical tests for analyzing the safety data to determine if harm is occurring; and
    • Conditions that trigger an immediate suspension of the research, if applicable.
  • Approvals. The investigator must submit the protocol for initial review and obtain written approvals from the IRB, other applicable committees, and from the R&D Committee. In addition, the investigator must receive written notice from the ACOS/R&D that the research may commence before initiating the research.
    • An investigator may not self-certify that a study is exempt.
    • Once approved by the IRB, the protocol must be implemented as approved. All modifications to the approved research protocol or consent form must be approved by the IRB prior to initiating the changes except when necessary to eliminate apparent immediate hazards to the subject.
    • The investigator must also obtain continuing review and approval at a frequency established by the IRB, but not less than once every year and is expected to submit all materials required for continuing review in sufficient time to assure approval prior to the expiration date. No research activities may be conducted at any time without a currently valid IRB approval.
  • Conflict of Interest. The investigator must disclose to the IRB any potential, actual, apparent, or perceived conflict of interest of a financial, professional, or personal nature that may affect any aspect of the research, and comply with all applicable VA and other federal requirements regarding conflict of interest.
  • Informed Consent for Research. The investigator must obtain and document legally effective informed consent of the subject or the subject’s LAR prospectively (i.e., no screening or other interaction or intervention involving a human subject can occur until after the IRB-approved informed consent requirements have been met) that is in alignment with ethical principles that govern informed consent for research. The only exceptions are if the IRB determines the research is exempt, or approves a waiver of the informed consent process, or approves a waiver of the signed informed consent document.
    • If the investigator does not personally obtain informed consent, the investigator must delegate this responsibility in writing (e.g., by use of a delegation letter) to research staff sufficiently knowledgeable about the protocol and related concerns to answer questions from prospective subjects, and about the ethical basis of the informed consent process and protocol.
      • If the investigator contracts with a firm, e.g., a survey research firm, to obtain consent from subjects, collect private individually identifiable information from human subjects, or are involved in activities that would institutionally engage the firm in human subjects research, the firm must have its own IRB oversight of the activity. In addition, the PO must determine that there is appropriate authority to allow the disclosure of individual names and other information to the contracted firm.
      • The investigator must ensure that all original signed and dated informed consent documents are maintained in the investigator’s research files, readily retrievable, and secure.
    • HIPAA Authorization. The investigator or designee must obtain HIPAA authorization for the use and disclosure of the subject’s PHI, or obtain an IRB-approved waiver of HIPAA authorization unless there is a limited data set and appropriate DUA. The written HIPAA authorization may either be a standalone document or combined with the research informed consent approved by the IRB, however, a combined form may only be used with prior permission from the RDC and VA Privacy Officer as the UW combined form template does not include required VA-specific language. If a standalone document is used as the written HIPAA authorization, VA Form 10-0493: Authorization for Use and Release of Individually Identifiable Health Information Collected for VHA Research, must be used to document the authorization.
  • Reporting. The investigator is responsible for reporting unanticipated problems involving risks to subjects or others, serious unanticipated problems involving risks to subjects or others, apparent serious or continuing noncompliance, any termination or suspension of research; and privacy or information security incidents related to VA research, including: any inappropriate access, loss, or theft of PHI; noncompliant storage, transmission, removal, or destruction of PHI; or theft, loss, or noncompliant destruction of equipment containing PHI, in accordance with local facility or IRB SOPs and VHA Handbook 1058.01.
    • VA personnel must ensure that the appropriate IRB of Record is notified, in writing, within five (5) business days after becoming aware of any apparent serious and/or continuing noncompliance with applicable laws, regulations, policies, and agreements pertaining to non-exempt human participants research. This includes, but is not limited to, serious or continuing noncompliance with the Common Rule, local VA medical facility policies and SOPs related to human participants research, if developed, IRB-approved protocols, and the requirements or determinations of the IRB.
    • In the event of a local research participant death, VA personnel must ensure that the appropriate IRB of Record is notified:
      • Immediately (i.e., within one hour) upon becoming aware of any local research death of a human participant that is believed to be both unexpected and related or possibly related to participating in a VA non-exempt human participant study. VA personnel must also provide follow-up written notification to the IRB within one (1) business day.
    • In the event of any apparent UPIRTSO, VA personnel must ensure that the appropriate IRB of Record is notified, in writing, within five (5) business days after becoming aware of any apparent UPIRTSO.
  • Research Records. All written information given to subjects must be in the investigator’s research file along with the consent form(s). All records regardless of format (paper, electronic, electronic systems) must be managed per NARA approved records schedules found in VHA RCS 10-1 and therefore must be retained until disposition instructions, as approved by NARA, are published in VHA RCS 10-1. NOTE: Once the disposition schedule is determined, records should be disposed in accordance with VHA RCS 10-1. If the investigator leaves VA, all research records must be retained by the VA facility where the research was conducted.
  • VHA Health Record. A VHA health record must be created or updated, and a progress note created, for all research subjects (Veterans or Non-Veterans) who receive research procedures or interventions as inpatients or outpatients at VA medical facilities that are either used in or may impact the medical care of the research subject at a VA medical facility or at facilities contracted by VA to provide services to Veterans (e.g., Community-Based Outpatient Clinics or nursing homes). Informed consent and HIPAA authorization documents are not required to be in the health record. The name and contact information of the researcher conducting the study should be included.
  • Investigational Drugs and Devices. The investigator must conduct VA human subjects research involving investigational drugs and devices in accordance with all applicable VA policies and other federal requirements including, but not limited to: VHA Directive 1200.05, VHA Handbook 1108.04, and applicable FDA regulations. The storage and security procedures for test articles used in research must be reviewed and approved by the IRB and follow all applicable federal rules.
    • The PI or Local Site Investigator (LSI) must provide the Pharmacy Service with the following:
      o Written approval letter signed by the ACOS for R&D that all relevant approvals have been obtained and that the study may be initiated at the site (VHA Directive 1200.01);
    • An IRB approval letter;
    • A copy of the approved study protocol;
    • A copy of VA Form 10-9012, when appropriate;
    • An IB, when appropriate;
    • Any sponsor-provided documents relating to the storage, preparation, dispensing, and accountability of the investigation products;
    • Protocol revisions, modifications, and updates after IRB approval and after the IRB approved the modification;
    • Updates and changes to authorized prescribers after IRB approval;
    • Documentation of IRB continuing review approval;
    • A copy of the consent document for each participating participant with all appropriate signatures;
    • Copies of all correspondence addressed to the Researcher from the FDA specific to the investigational drugs as appropriate;
    • Notice to the Chief, Pharmacy Service, the research pharmacy when applicable and the IRB in writing and the Research and Development Committee when a study involving investigational drugs has been suspended, terminated, or closed.
  • The PI or LSI must provide Pharmacy Service and/or the Research Service Investigational Pharmacy, investigational drug information on each patient receiving an investigational drug through the electronic medical record or other locally-approved means. This documentation is to include allergies, toxicities, or adverse drug events related to the investigational drug, or the potential for interaction with other drugs, foods, or dietary supplements (herbals, nutraceuticals).
  • The PI or LSI must place the completed VA Form 10-9012, or electronic equivalent, in the subject’s medical record.
  • The PI or LSI must comply with all dispensing requirements as well as all documentation requirements and make relevant records accessible to the investigational drug pharmacist when requested
• Initiation of Research Projects. IRB approval is for a specified time period based on the degree of risk of the study, not to exceed 1 year except for research subject to the 2018 Requirements where continuing review is not required. The IRB determines the expiration date based upon its date of review and communicates that date to the investigator in the written approval letter. The investigator must not initiate the IRB approved research protocol until all applicable requirements in VHA Directive 1200.01 have also been met including obtaining R&D Committee approval.
• Expiration of IRB Approval. There is no provision for any grace period to extend the conduct of research beyond the expiration date of IRB approval. Therefore, continuing review and re-approval of research must occur on or before the date when IRB approval expires. If approval expires, the investigator must:
  • Stop all research activities including, but not limited to, enrollment of new subjects, analyses of individually identifiable data, and research interventions or interactions with currently participating subjects, except where stopping such interventions or interactions could be harmful to those subjects; and
  • Immediately submit to the IRB Chair a list of research subjects who could be harmed by stopping specified study interventions or interactions. The IRB Chair must determine within 2 business days whether or not such interventions or interactions may continue.
• Documentation of Informed Consent
  • When documentation of informed consent is not waived by IRB, the investigator or designee must ensure that the informed consent document is signed and dated by the subject or the subject’s legally authorized representative,
  • If consent is obtained electronically, the following must be met:
    • Authentication controls on electronic consent provide reasonable assurance that such consent is rendered by the proper individual; and
    • The subject dates the consent as is typical or that the software provides the current date when signed.
• Other specific requirements of Veterans Administration (VA) research be found in HRP-318 – WORKSHEET – Additional Federal Agency Criteria.

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Use of Preparatory to Research

VA investigators may use individually-identifiable health information to prepare a research protocol prior to submission of the protocol to the IRB for approval without obtaining a HIPAA authorization or waiver of authorization.

• VA investigators must not arbitrarily review PHI based on their employee access to PHI until the investigator documents the following required information as “Preparatory to Research” in a designated file that is readily accessible for those required to audit such information (e.g., Health Information Manager or PO):
  • Access to PHI is only to prepare a protocol;
  • No PHI will be removed from the covered entity (i.e., VHA); and
  • Access to PHI is necessary for preparation of the research protocol.
• Non-VA researchers may not obtain VA information for preparatory to research activities without appropriate VA approvals (see VHA Directive 1605.01).
• During the preparatory to research activities the VA investigator:
  • Must only record aggregate data. The aggregate data may only be used for background information to justify the research or to show that there are adequate numbers of potential subjects to allow the investigator to meet enrollment requirements for the research study;
  • Must not record any individually identifiable health information; and
  • Must not use any individually identifiable information to recruit research subjects.
  • Preparatory activities can include reviewing database output (computer file or printout) containing identifiable health information generated by the database owner, if the investigator returns the database output to the database owner when finished aggregating the information.
• Contacting potential research subjects and conducting pilot or feasibility studies are not considered activities preparatory to research.
• Activities preparatory to research only encompass the time to prepare the protocol and ends when the protocol is submitted to the IRB.

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Recruiting Veterans

During the recruitment process, members of the research team must make initial contact with potential subjects in person or by letter prior to initiating any telephone contact, unless there is written documentation that the subject is willing to be contacted by telephone about the study in question or a specific kind of research as outlined in the study. (NOTE: This does not apply to situations where a Veteran calls in response to an advertisement. If existing information from sources such as a medical record or database, research or non-research, are used to identify human subjects, there must be an IRB approved HIPAA waiver for this activity in the new protocol.)

• Any initial contact by letter or telephone must provide a telephone number or other means that the potential subject can use to verify that the study constitutes VA research.
• If a contractor makes the initial contact by letter, the VA investigator must sign the letter.

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Special Populations in VA Research

The following populations are considered categorically vulnerable and have specific VA requirements for their inclusion in research:

• Pregnant Persons, Human Fetuses, and Neonates
• Prisoners
• Children
• Subjects who Lack Decision-making Capacity

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Certificates of Confidentiality in VA Research

If information about the subject’s participation will be included as part of the VHA medical record that information must be given to the prospective subject as part of the informed consent process that information regarding study participation will be included in the medical record.

In instances where a written informed consent form is used, inclusion of a statement that the study has been issued a CoC is required.

Investigators should work with the research office in their facility to assure that when Veterans are enrolled in a study protected by a Certificate of Confidentiality, they are not simultaneously enrolled in other interventional studies unless it is absolutely clear that this enrollment does not raise safety issues.

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Collaborative VA Research

This section addresses collaborations between VA and non-VA investigators. Collaboration is encouraged when VA investigators have a substantive role in the design, conduct, and/or analysis of the research. VA may also serve as a Coordinating Center for collaborative studies. NOTE: Collaborative studies do not include studies conducted under a CRADA with pharmaceutical companies or other for-profit entities.

IRB of Record Approval

Each institution is responsible for safeguarding the rights and welfare of human subjects and providing oversight of the research activities conducted at that institution.

• Each collaborating institution engaged in human subjects research must obtain approval from its IRB of Record and hold a FWA or another assurance acceptable to VA, e.g., DoD assurance.
• VA investigators must submit a protocol or other documentation to their VA IRB of Record that delineates which research activities will be conducted by VA.
• Each institution engaged in the collaborative research must use the informed consent document and HIPAA authorization required by their respective institutional policies for subjects recruited from that institution, or procedures requiring participation of the subject at that institution. The informed consent document may contain information on the project as a whole as long as the document clearly describes which procedures will be performed at VA and which will be performed at other institutions.
  • The VA informed consent document must clearly state when procedures mentioned at other institutions are part of the VA’s portion of the study.
  • The informed consent document and HIPAA authorization must be consistent and include information describing the following:
    • PHI to be collected and/or used by the VA research team;
    • PHI to be disclosed to the other institutions; and
    • Purpose for which the PHI may be used.

Waivers

PHI obtained in research for which the IRB of Record has waived the requirements to obtain a HIPAA authorization and a signed informed consent document may not be disclosed outside VA unless the VA facility Privacy Officer ensures and documents VA’s authority to disclose the PHI to another institution. A waiver of HIPAA authorization is not sufficient to fulfill the requirements of other applicable privacy regulations such as the Privacy Act of 1974 (5 U.S.C. 552a).

Research Data

The protocol, addendum, and/or IRB of Record application must describe the data to be disclosed to collaborators, the entity(ies) to which the data are to be disclosed, and how the data are to be transmitted. This includes data from individual subjects as well as other data developed during the research such as the analytic data and the aggregate data.

• Each VA facility must retain a complete record of all data obtained during the VA portion of the research in accordance with privacy requirements, the Federal Records Act, and VHA Records Control Schedule (RCS) 10-1.
• All disclosures and data transmission must meet privacy and security requirements per VA Directive 6500, VHA Handbook 6500, and VHA Handbook 1605.1.

Written Agreements

Collaborative research involving non-VA institutions may not be undertaken without a signed written agreement (e.g., a CRADA or a Data Use Agreement (DUA)) that addresses such issues as the responsibilities of each party, the ownership of the data and the reuse of the data for other research.

NOTE: Any reuse must be consistent with the protocol, the informed consent document, and the HIPAA authorization.

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Photography, Video and/or Audio Recording for VA Research

The informed consent for research must include information describing any photographs, video, and/or audio recordings to be taken or obtained for research purposes, how the photographs, video, and/or audio will be used for the research, and whether the photographs, video, and/or audio will be disclosed outside the VA.

• An informed consent to take a photograph, video, and/or audio recording cannot be waived by the IRB.
• The consent for research does not give legal authority to disclose the photographs, video, and/or audio recordings outside the VA. A HIPAA authorization is needed to make such disclosures.

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VA International Research

VA international research is defined as any VA-approved research conducted at international sites (i.e., not within the United States (U.S.), its territories, or Commonwealths), any VA-approved research using either identifiable or de-identified human biological specimens or identifiable or de-identified human data originating from international sites, or any VA-approved research that entails sending such specimens or data out of the U.S. This definition applies regardless of the funding source (funded or unfunded) and to research conducted through any mechanism of support including MOUs, CRADAs, grants, contracts, or other agreements. NOTE: Research conducted at U.S. military bases, ships, or embassies is not considered international research.

• Sending specimens or data to individuals with VA appointments at international sites (e.g., a WOC appointment, a VA investigator on sabbatical at an international site) is considered international research. Remote use of data that is maintained on VA computers within the U.S. or Puerto Rico and accessed via a secure connection is not considered international research.
• International research includes multi-site trials involving non-U.S. sites where VA is the study sponsor, a VA investigator is the overall study-wide PI, VA holds the Investigational New Drug (IND), or the VA manages the data collection and the data analyses.
• International research does not include studies in which VA is only one of multiple participating sites where the overall study-wide PI is not a VA investigator (i.e., the PI for the study as a whole is not a VA investigator).

Before approving international research involving human subjects research, the IRB must ensure that human subjects outside of the U.S. who participate in research projects in which VA is a collaborator receive equivalent protections as research participants inside the U.S. (see OHRP guidance at http://www.hhs.gov/ohrp/international/index.html). NOTE: The VA medical facility Director must approve participation in the proposed international research.

All international research must also be approved explicitly in a document signed by the VA medical facility Director, except for Cooperative Studies Program activities which must be approved by the CRADO.

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Posting VA Clinical Trial Consent Forms

For studies subject to the 2018 Requirements, if a VA research study is a clinical trial, one IRB-approved informed consent form used to enroll subjects, unless the IRB waived documentation of informed consent, must be posted by either the investigator or the Federal department or agency conducting or supporting the study. The informed consent form must be posted after the clinical trial is closed to recruitment and no later than 60 days after the last study visit by any subject as described in the IRB-approved protocol. For multi-site studies, it applies when the entire study has closed to subject recruitment. Any proprietary or personal information (such as names and phone numbers) must be redacted prior to posting the informed consent form.

• For any ORD-funded clinical trial, the applicable ORD funding service will be responsible for posting the informed consent form.
• For a clinical trial funded or supported by a Federal agency or department other than VA, the awardee is responsible for posting the informed consent form.
• For a clinical trial funded or supported by a non-Federal agency or department (e.g., university, industry, nonprofit organization) or not funded, the VA Investigator conducting the clinical trial is responsible for ensuring that the informed consent form is posted. If the clinical trial includes multiple sites engaged in the clinical trial, an agreement must exist specifying who is responsible for posting the informed consent form.

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