Reliance on the IRB-HSR to serve as the Single IRB (sIRB) of record

Overview

The University of Virginia IRB-HSR may act as the single IRB of record, allowing other institutions to cede review to the UVA IRB.  UVA IRB-HSR may only engage in a Reliance Agreement for expedited and full board studies with no more than 10 relying sites. Reliance Agreements for sIRB review are ONLY used to cede the IRB review of projects. All institutionally required ancillary reviews must still be obtained locally, and it is up to the relying site(s) to identify these reviews (e.g., Conflict of Interest, Institutional Biosafety, IND/IDE Support, Radiation Safety, etc.) Oversight of these ancillary reviews still require local review and approval regardless of ceding IRB review. Local relying sites will be responsible to collect and provide the UVA IRB with any local ancillary reviews.

It is the responsibility of the UVA study team to evaluate the study to determine if the work to be done by personnel at an outside institution, meets the criteria for being engaged in Human Subject Research or a clinical investigation of a test article. The IRB-HSR staff is available to help make this determination if the answer is not clear.

The UVA PI takes on several additional responsibilities when serving as the overall PI of a multisite study.  It is important that you review UVA Study Team Responsibilities and Relying Site Responsibilities.    The UVA study team must ensure they have the resources to accomplish these responsibilities.  The UVA study team may take on these responsibilities or contract them out to a Data Coordinating Center (DCC).  The UVA SOM Clinical Trials Office may serve as the Data Coordinating Center. For more information on the UVA SOM serving as the DCC, call (434) 924-8530 or e-mail at uvaclinicaltrials@virginia.edu 

See also: UVA IRB-HSR TIP SHEET for RELYING SITES

Definitions

IRB of Record: A reviewing IRB (non-UVA IRB) that assumes IRB responsibilities for another institution/site.

IRB Reliance Agreement: A formal, written agreement in which the reviewing IRB agrees to serve as the IRB of Record for a Relying institution/site.  The signed agreement permits a single IRB to review human subject research activities for more than one site.

Multicenter/site research study: Human subject research conducted according to a single protocol but at more than one site, and therefore, carried out by more than one principal investigator.  Multisite research refers to research that is conducted at both UVA and non-UVA locations. Multisite studies do NOT include studies involving multiple UVA locations that fall under the purview of the UVA IRB-HSR. 

Relying Institution/Participating/Site: A relying institution/site is the site that has entered into an IRB Reliance Agreement with another site’s IRB to serve as the IRB of Record.

Lead Site/Study Team: site that (usually) receives the grant or contract from the funding source and then establishes sub-awards or subcontracts with the participating sites. The lead PI is the PI responsible for overall management and coordination of the study across all participating sites.

Engagement of Organization in Non-Exempt Human Subject Research: An organization is considered engaged in human subject research when its employees or agents, for the purposes the research project obtain:

1) Data about the subjects of the research through intervention or interaction with them;

2) Identifiable private information about the subjects of the research;

3) Informed consent of human subjects for the research; OR

4) A direct federal award to conduct human subject research, even when all activities involving human subjects are carried out by subcontractors (i.e. employees or agents of another organization). HHS Guidance: Engagement in Human Subjects Research.

 Engaged in Research: An institution becomes "engaged" in human subjects research when its employees or agents (all individuals performing institutionally designated activities or exercising institutionally delegated authority or responsibility) (i) intervene or interact with living individuals for research purposes; or (ii) obtain individually identifiable private information for research purposes [45 CFR 46.102( d), (f)]. Solicitation of consent by participating site staff would be considered engagement.

Federal-wide Assurance (FWA): A formal written, binding commitment that is submitted to a federal agency in which an institution promises to comply with applicable regulations governing research with human subjects and stipulates the procedures through which compliance will be achieved [45 CFR 46.103]. Since December 31, 2005, the Office for Human Research Protections (OHRP) only recognizes Federal-wide Assurances.

Investigator: A person responsible for the conduct of research at a site. If research is conducted by a team of individuals at a research site, the investigator is the responsible leader of the team and may be called the principal investigator [GCP E6 1.34]. 

Sponsor: The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization that takes responsibility for and initiates a clinical investigation. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator [21 CFR 312.3(b)].

Data Coordinating Center (DCC): a site that is responsible for the collection, verification and storage of data collected from all sites involved in a multi-site trial.

Sponsor-Investigator: An individual (usually the study Principal Investigator) who both initiates and conducts a clinical investigation, and under whose immediate direction the investigational product is administered or dispensed. The term does not include any person other than an individual investigator. The requirements applicable to a sponsor-investigator under FDA subpart [21 CFR 312 Subpart D] mean that sponsor investigators must follow the regulations for both an investigator and a sponsor [21 CFR 312.3(b)]. 

Local Research Context: Information provided to the IRB of record by a local context reviewer, consultant, or a participating site's IRB regarding the participating site's local community, geographical area, institution, and/or other factors that may influence the conduct of the proposed research, including local laws, regulations, customs, and practices.

Grant Proposal Instructions:

As of March 2017, the National Institutes of Health (NIH) requires the use of a single Institutional Review Board for non-exempt human subjects research protocols funded by the NIH that are carried out at more than one site in the United States.  Additional information regarding this policy may be found HERE.

For NIH-funded research, you may obtain a Letter of Support from the UVA IRB-HSR to include in the NIH grant submission. This should be requested by email to SIRB@virginia.edu: Subject heading: Letter of Support Request for NIH Grant Submission.

Your request should include the following information. The IRB-HSR cannot write the letter without this information.

  • Name of the funding organization
  • Name of the UVA PI (lead PI)
  • Name of the organization that will serve as the Data Coordinating Center (DCC)
  • Title of the study/grant
  • A brief description of the study (can attach a protocol or draft portions of the grant proposal)
  • Grant deadline
  • What role(s) UVA will play in the research (can attach a scope of work)
  • Whether this grant is for multiple studies and/or a network that will design and conduct studies
  • The names of the proposed participating/relying sites, and how many are domestic vs. foreign

For additional information: See Section D “NIH Grant Application/Contract Proposal Preparation” of the NIH FAQ Single IRB Policy and Multi-site Research and (for specific details) Section 3.2 of the PHS Human Subjects and Clinical Trials Information Form Application Guide.

NIH expects the following NEW information in grant applications for multi-site research:

  • A Single IRB plan describing the use of a Single IRB, unless otherwise stated in the RFP or solicitation for contracts.
  • The content of the sIRB plan must include:
  • Description of how you will comply with the NIH Single IRB (sIRB) policy. If you are requesting an exception for some or all participating sites, follow the NIH Guidance Requesting an Exception.
  • The name of the IRB that will serve as the Reviewing IRB.
  • An indication that all identified participating sites have agreed to rely on the proposed Reviewing Single IRB and that any sites added after receipt of award will rely on the Reviewing IRB.
  • Description of how communication between sites and the Reviewing Single IRB will be handled.
  • Indication that all relying sites will, prior to initiating the study, sign a reliance agreement that will clarify the roles of the Reviewing IRB and the Relying site(s).
  • Indicate which institution or entity will maintain records of the reliance agreement and the communication plan.
  • An estimate of the direct costs (if any) for IRB review, in the grant budget
  • The administrative cost of covering IRB oversight for external sites. Create a grant budget that reflects the additional costs associated with UVA acting as sIRB of Record.
  • Large scale, complex projects should budget to hire a Research Coordinator and/or create an arrangement with a Data Coordinating Center (DCC).

STUDY TEAM SUBMISSION INSTRUCTIONS:

  1. If a UVA study team is creating a NEW multisite study, if not already considered, the study team will need to write the protocol using a template designed to work for all participating sites. Include a reference to a Data Coordinating Center if one is being utilized for the study. A protocol template will NOT be provided through Protocol Builder.  Possible templates may be found HERE.    
  2. If this is an active multisite study for which the IRB of Record is being transferred from a non- UVA IRB to the UVA IRB-HSR take the following steps:
    1. Re-create the study in Protocol Builder. Do not enter CRConnect. Keep the same UVA Study Tracking #.  Create the IRB application and consent forms using templates provided by Protocol Builder. You may submit the data security plan reviewed when UVA was relying on the non-UVA IRB, however, as the lead site, you may need to revise the plan accordingly
    2. The UVA study team will submit the study documents to the UVA IRB-HSR for review and approval per usual practice. See Protocol Submission Process. Because you are not managing the study via CR Connect, you will need to directly email the IRB staff member responsible for either expedited or full board review.   
      1. Notify the IRB-HSR staff during pre-review that this is an ongoing/active study at UVA for which the IRB of Record is transferring to the IRB-HSR.
      2. If contact information (local PI/ IRB of Record) in the consent has changed and previously enrolled subjects continue in the study, submit a consent addendum to be used to re-consent subjects so they are aware of new information.
      3. Notify the IRB-HSR if the grant is moving to UVA.
    3. After the study is approved by the IRB-HSR, submit a modification to add additional sites relying on the IRB-HSR. -Resume #4 below

 

  1. For either a full board or expedited study where the UVA PI will be the overall PI for the multisite study, the protocol must be submitted to the School of Medicine Clinical Trials Office for review.  This letter of review must accompany your submission to the IRB-HSR either at the time of initial review by the UVA IRB, or at the time of a modification to add a relying site.   In addition, the SOM CTO will review and provide approval to the protocol EACH time a relying site is added via a protocol modification. For more information on how to submit to the SOM CTO, please call (434) 924-8530 or e-mail at uvaclinicaltrials@virginia.edu
  2. Once the protocol is approved by the UVA IRB-HSR, the UVA study team or the UVA Data Coordinating Center (DCC) is ready to send the required documents to the Relying site(s) and can confirm the Relying site’s agreement to rely on the UVA IRB-HSR as the sIRB of record. 

              Submit the following documents to the Relying site:

Note: The sections of the consent that Relying Sites are permitted to edit are as follows:

  • Institutional letterhead (if applicable)
  • Local study staff & contact information
  • Local compensation for injury language (if the procedures have the potential to cause physical harm)
  • Local data storage and/or retention requirements
  • Local compensation (if applicable)

The following completed documents will be submitted via IRB PRO-Modifications.

  • Completed IRB Reliance Agreement Request Form: UVA IRB-HSR to serve as the IRB of Record: one request form per site
  • Modification Request form
  • SOM CTO Letter of review for UVA PI to serve as the overall PI of a multisite study  
  • Consent/assent documents incorporating the Relying site local context information tracked.
  • If revisions are required to the Reliance Agreement Request form or consent/assent documents, a draft of the document(s) will be emailed to the UVA study team or DCC with a request for revisions.
  1. Following final review by the IRB-HSR, the UVA study team or the DCC will receive the following documents via IRB PRO.
    • IRB-HSR Letter of Agreement (signatures from both the UVA IRB and the Relying site IRB)
    • Assurance indicating a modification to add the Relying site
    • Approved site-specific consent/assents for the Relying site.  

NOTE: It is the responsibility of the DCC or the UVA study team to send the consent/assent documents back to the Relying site.

HIPAA Privacy Board

When the UVA IRB will serve as the Privacy Board for the relying sites that are covered entities, the protected health information (PHI) will not be shared among relying institutions unless there is:

  1. appropriate authorization to use and disclose such information for the purpose of the research [as outlined in the informed consent], or
  2. 2) an appropriate waiver of HIPAA authorization has been granted by the UVA IRB in accordance with the HIPAA Privacy rule, or
  3. 3) the information constitutes a limited data set pursuant to a Data Use Agreement as those terms are defined in HIPAA.

HIPPA Authorization Language

The relying sites must use the UVA HIPAA consent language (with the exception of adding Local site Contact information).  The UVA IRB will ensure the appropriate authorization language is incorporated into the informed consent document for use at the relying site. Relying sites also have the opportunity to have their local IRB/institution serve as the HIPAA Privacy Board.  This must be identified in the Reliance Agreement Request form. If the Relying site serves as the HIPPA privacy board, the following will apply:  1) The Relying Institution HIPAA Privacy Board will grant all HIPAA waivers/partial HIPAA Waivers; 2) The Relying Institution will use their own institutional HIPAA Privacy Authorization Form.  The Relying site’s institution’s language will not be included in the IRB approved consent form.

The UVA IRB will review requests for waiver or alteration of authorization to the extent it is compliant with the local UVA HIPAA policies and procedures. The UVA IRB will notify all affected relying sites of the rationale for the waiver so that the relying sites can accomplish accounting of disclosures.

Breach Notifications

Relying sites are responsibility for investigating and reporting to appropriate authorities, including privacy officers, breaches of PHI in accordance with institutional policies.  Relying sites must promptly notify the UVA IRB of any PHI breaches that occur as well as to any individuals or offices required by local institutional policy (e.g. their local privacy officer).  The UVA IRB will evaluate the breach as a potential unanticipated problem.  Reporting will occur according to the UVA reporting procedures for unanticipated problems.  

Any data breach will be reported per the UVA Information Security Incident Reporting Policy.  The data breach will be reported to the study team or DCC if the report meets the criteria of an Unanticipated Problem. 

Continuations  

  1. Continuation reviews will be completed by the UVA IRB as per usual practice
  2. Either the UVA study team or the DCC responsible for obtaining information from each Relying site will submit ONE comprehensive Protocol Status Report to the IRB-HSR. The UVA site is responsible for obtaining the information from each relying site so the IRB-HSR can review a comprehensive report regarding study progress, enrollment numbers, reportable events, new information, and any problems that have occurred.
  3. If a relying site does not provide the UVA study team with the required information before the continuing review is submitted to the UVA IRB, the UVA study team should report this absence of this information as part of the continuing review and notify the relying site study team of lapse in approval for their site and any applicable corrective active plans.
  4. The UVA IRB-HSR will conduct continuing reviews in accordance with applicable federal regulations, the local context provided by each of the relying sites and the UVA IRB SOP’s.
  5. In the event any continuing review information is submitted to the UVA site from a relying site after UVA IRB-HSR approval for the study expires or the study expires before the UVA IRB-HSR can reapprove the study, the UVA IRB-HSR will notify the relying sites of the expiration.
  6. The UVA IRB is responsible for reviewing all relevant information on the Protocol Status Report until the research is closed.
  7. Upon approval, the UVA site or DCC is responsible for providing all currently approved documents along with the assurance to the relying sites. If the UVA IRB-HSR determines that it cannot reapprove the study, the IRB-HSR will notify the UVA site and relevant relying sites of its determination and the reasons for the determination.

Modifications/Personnel Changes:   

  1. Modification review will be completed by the UVA IRB as per usual practice. 
  2. Modifications are submitted to the UVA IRB-HSR by either the UVA study team or the DCC. 
  3. The UVA IRB-HSR will review the study modification in accordance with applicable federal regulations and the local context provided by the relying sites and the UVA SOP’s.
  4. The UVA site will report changes in UVA personnel and potential conflicts of interest as they change/occur to the DCC for submission to the UVA IRB or to the UVA IRB directly.
  5. Relying sites are responsible for documenting their own personnel changes, with the exception of a PI change at a relying site, which requires a modification approval from the UVA IRB.
  6. If a study is closed to enrollment, the UVA IRB will notify the study team or DCC whether a revised consent form or an addendum is to be used.
  7. If a Consent Short Form is required for a potential subject that speaks a language other than English or Spanish, see the information located on Consent Short forms for non-English Speaking Subjects.

Recruitment: 

  • The UVA study team will submit recruitment material on behalf of all or some of the relying participating sites. These materials must include the local investigator-specific contact information of the relying site. 
  • All questions and requests for modifications to the submitted materials will be directed toward the local UVA contact for the study.  The UVA IRB may directly contact the relying site study team to discuss site specific brand issues if necessary. 
  • The UVA IRB will review and approve the recruitment material and will correspond with the local UVA study team contact(s) identified in the recruitment email request for the UVA study team to disseminate the approved recruitment material.

 

 

Subjects Enrolled as Minors who Reach the Age of Majority

If a subject is enrolled while a minor, and they have now or will reach the age of majority, you may use the following two forms as a template to obtain consent of the subject. Age of Majority: Cover Letter Template and Age of Majority Consent.

 

 

Reportable Information for Relying Sites

Unanticipated Problems

Protocol Deviations, Non-compliance and Protocol Exceptions

Serious Adverse Events

Resources