Guidance

Elements and Uses of a Repository

IRBMED
Apr 9, 2019 9:45 pm

A research repository is defined as a collection of data/biospecimens that have been collected and stored with the intention of using the materials for future research, either by the investigator who collected them or by sharing the materials with other investigators.

Researchers interact with a repository in 3 different ways:

  1. Primary collection/aggregation of data/biospecimens
  2. Intake, storage, maintenance and distribution of repository data/biospecimens
  3. Secondary use/analysis of data/biospecimens obtained from a repository
  • 1. Primary collection/aggregation of information/biospecimens

    Collecting identifiable private information and/or identifiable biospecimens through interaction or intervention with living individuals is "human subjects research" per federal regulations 45 CFR 46.102

    It is sometimes useful to aggregate into a research repository information/biospecimens that are 

    • generated for non-research purposes and 
    • initially collected in databases such as medical records, pathology departments, census records, or other private or public sources.

    This aggregation usually does not involve interaction or intervention with individuals. When researchers obtain identifiable private information and/or identifiable biospecimens about living individuals, this is, however, also "human subjects research" per OHRP regulations 45 CFR 46.102. A human subjects research activity may collect information/biospecimens for future research use as a sub-study, or as its primary purpose.

    "Human subjects research" must be conducted in accordance with federal regulations and U-M Human Research Protection Program policies. U-M IRBs exercise oversight through the HUM project type in eResearch Regulatory Management (eRRM).

    Studies depositing data/biospecimens into a repository

    A human subjects research activity (approved through HUM) may collect data/biospecimens for future research use as a sub-study, or as its primary purpose. Studies depositing into an REP for long-term storage and/or other purposes should include "pointers" to the REP.  Initially, these should include:

    • HUM page 01, question 1.1.2 for "related projects": enter REP# and the Repository Title.
    • HUM page 11, question 11.6: check "Retain for future research use" (and others as applicable)
    • HUM page 11-4, question 11-4.2: check "Only at the University of MichiganOR "UM and Other Institutions" (as applicable)
    • HUM page 11-4, question 11-4.3: Refer to the REP. The REP application comprehensively addresses these questions. 
    • Informed Consent Documents (ICDs) uploaded in HUM page 10-1, question 10-1.1: Consent document should address explicitly plans for data/biospecimen use for future undefined research. U-M studies intending to collect biospecimens for unspecified future research use should consider using the Specialty Biorepository Informed Consent Template + informational sheet (in addition to or instead of another study-specific consent form, depending on the nature of the study). Note: UMMS Central Biorepository (CBR) requires studies depositing with them to use the biorepository template + informational sheet; however, no relationship with CBR is implied by the use of these documents in and of themselves.

    IRB staff create two-way hyperlinks between an REP and associated HUM(s). The links display in an REP space under “Related Projects” tab, and in an HUM space under “Document/Related Records” tab. Links are “live” (can be used to navigate from HUM to or from REP) for study team members listed on both applications, as well as for IRB staff and reviewers. (See also HUM-REP connections question at FAQ: Repository application.)

    HUM study teams and REP repository teams are responsible for presenting consistently their intended plans for working together in applications to the IRB.

  • 2. Intake, storage, maintenance and distribution of repository information/biospecimens

    A repository is a collection of information and/or biospecimens whose organizers 

    • May receive information/biospecimens from multiple sources
    • Maintain the information/biospecimens over time
    • Control access to and use of information/biospecimens by multiple individuals and/or for multiple purposes, which may evolve over time.

    A repository may receive information/biospecimens from research and/or non-research "primary collections." Multiple IRB-approved HUM studies may deposit information/biospecimens into a single repository registered via the REP. Among other responsibilities, the repository should have adequate procedures for recording and verifying any restrictions on future use, including but not limited to informed consent.

    A repository maintains the information/biospecimens over time. Among other responsibilities, the repository should have adequate procedures for 

    • Data security 
    • Physical storage
    • Sustaining the repository over time, including managing financial and physical resources

    Many existing repositories at U-M already have approval through an HUM application. New repositories should be registered through the REP application in eRRM. (See also "Previously approved repository" and "New repository" questions at FAQ: Repository application). Repositories maintaining identifiable private information and/or identifiable biospecimens require IRB approval. Repositories maintaining strictly de-identified or anonymous data/specimens may receive a "Not Regulated" determination upon registration. Depending on the amount and complexity of data/biospecimens stored, a governance or oversight committee may be appropriate for the repository, for example to review applications for use of materials, make decisions about the allocation of rare resources (primarily biospecimens), and/or resolve disputes. 

    Medical School Governing UMMS Research Biorepositories Policy” (available through PolicyStat) Section II, D requires an oversight committee for every biorepository "established with the express intent of sharing biospecimens or samples outside the department or beyond collaboration with its creator/s." This requirement applies whenever the repository is funded by a UMMS Department, it operates in UMMS space, or the creator of the repository holds even a partial appointment in the Medical School Faculty. (See also "UMMS policy" questions at FAQ: Repository application).

    A repository distributes information/biospecimens for multiple research uses over time. Some repositories are intended only for use by a select few investigators. Some repositories intend limited purposes for their information/biospecimens. Others are available for general use to any qualified investigators and for a wide variety of scientific investigations. Among other responsibilities, the repository should have adequate policies/procedures for

    • verifying that a proposed use is consistent with restrictions imposed at collection of information/biospecimens.
    • ensuring security and confidentiality of data/biospecimens during transfer/release
    • identifying and managing proposed research uses that present especially high risk to subjects or groups of which they are members
  • 3. Secondary use/analysis of information/biospecimens obtained from a repository

    Primary uses are defined as those specific research uses for which information/biospecimens were initially acquired. A secondary use investigates a new research question, whether conducted by the investigator who initially acquired the information/biospecimens or by any other investigator. 

    Some repositories, such as the UMMS Central BioRepository, will distribute information/biospecimens for primary uses, if the repository provides biospecimen processing and/or storage services as a component of a particular study. More commonly, repositories store information/biospecimens long-term which are intended for secondary use.

    A repository likely will have an application process for requesting secondary use of data/biospecimens, which may be more or less restrictive depending on the scope and resources of the repository, in addition to any requirements for IRB approval.Secondary uses that meet the definition of "human subjects research" must be conducted in accordance with federal regulations and U-M Human Research Protection Program policies. U-M IRBs exercise oversight through the HUM project type in eResearch Regulatory Management (eRRM).

     

    Studies obtaining data/biospecimens from a repository

    Secondary use analysis of data and/or biospecimens (including distributions from data repositories and biorepositories) require IRB oversight if the analysis meets the regulatory definition for "human subjects research." See IRBMED FAQ questions "What kind of research and other activities require IRB review?" and "Do I need to submit an IRB application?" Secondary use analysis "involves human subjects" when the investigator conducting the research "obtains identifiable private data."

    eResearch HUM application "Secondary research uses of private information and/or biospecimens" application type is designed to route through the correct IRB review and determination path (i.e., not regulated, exempt, or comprehensive IRB approval) all secondary use studies where U-M study team performs data analysis.

    Not Regulated may apply if the researchers doing the analysis do not at any point have access to "re-identify" the data.

    • U–M people receiving data/specimens without identifiable data through an 'honest broker', either internal (e.g. DataDirect, Central Biorepository, Tissue Procurement Service) or external (e.g. dbGaP, BioLINCC or CMS-ResDAC). In this case, choose either "Secondary research uses..." or  "Activities not regulated..." in application type 01-1.
    • U-M people PREPARE "coded" or "de-identified" dataset/specimens for analysis by EXTERNAL investigators (U-M role is limited to data PROVIDER). In this case, choose "Activities not regulated..." in application type 01-1.

    Exemption 4 is available for retrospective and/or prospective data/biospecimens and is expected to apply to most IRBMED secondary use research without federal funding

    • public data sources such as phone book;
    • non-public data/biospecimens sources if study team may view but will not record any direct or indirect identifiers.
    • "HIPAA exemption" - all data are covered by HIPAA
      • data sources are regulated as PHI;
      • ALL study team members are members of a HIPAA "covered entity (CE)";
      • ALL institutions involved with the study are "covered entities";
      • The data either NEVER leaves a CE, or is covered by HIPAA-specific data use agreements throughout any and every transfer.
      • Where biospecimen analysis is involved, original specimen/data collection must include informed consent and HIPAA authorization for secondary use (U-M implementation).

    Comprehensive (non-exempt) IRB review and approval is required when "not regulated" and "exempt" are not available. For instance,

    • Research dataset for analysis comprises/includes identifiable private information not covered under HIPAA
    • Biospecimen analysis where associated identifiable data are kept, which will require waiver of informed consent and/or HIPAA authorization (U-M implementation of "HIPAA exemption")
    • Requirement from data/biospecimen provider for full or expedited IRB review (e.g. some dbGaP datasets, based on Data Use Certification)
    • Data are intended for IDE (Investigational Device Exemption) or In Vitro Diagnostic (IVD) device application to FDA
    • Secondary use is paired with interaction/intervention. In this case, choose "Human Subjects research involving interaction or intervention..." in application type 01-1.

    NOTE: Exemption 4 eligibility is expanded under Revised Common Rule, active as of January 2019. U-M applied the expanded Exemption 4 as a Flexibility Initiative June 2018 - January 2019. Pre-2018 Exemption 4 covered only analyses where both (1) all data already existed at time of IRB application and (2) one of the following applied:

    • public data/biospecimen sources such as phone book;
    • non-public data/biospecimens sources such as medical records only if study team may view but will not record any direct or indirect identifiers.

    Informed Consent & HIPAA authorization for secondary use

    An application for "secondary use" research may ask about consent and/or HIPAA authorization for the data/biospecimens received. Consent process or waiver and HIPAA authorization process or waiver MUST be compatible with each other.

    Informed Consent

    The IRB regulations regarding informed consent apply only to secondary use research requiring comprehensive (non-exempt) IRB review and approval. It is common for these to operate under a waiver of consent and waiver of HIPAA authorization. Waivers are not necessary for "secondary use" research if the initial consent collecting data/biospecimens already addresses broad permission for future use: this constitutes "pre-existing consent." In some cases, a "secondary use" researcher may need to recontact original subject-donors of data/biospecimens to request a new consent.

    Situation  Expected answers

    Full waiver of consent
    or                

    Use of data from prior research study for purpose not contemplated in original consent

    10.3: Request for waiver of informed consent/parental permission/legally authorized representative consent                 

    10-3.1: Waiver – General - ALL of the project

    Use of data from prior research study for purpose consistent with original consent 10.3: Pre-existing consent covers this activity                 

    10.3.1: Refer to REP

    Re-consent 10.3: Re-consent/assent subjects for use of existing data/records/specimens for a new research purpose.                 

    10-1 filled out

    Is waiver for PART of the project ALSO required for pre-screening? This depends on whether original consent mentioned possible re-contact. If so ...

    10.3: Request for waiver of informed consent and Re-consent

    10-3.1: Waiver - General - PART of the project

     

    HIPAA Authorization

    Situation  Expected answers
    Full waiver of consent
    or                 

    Use of data from prior research study for purpose not contemplated in original consent

    25-1.3: Authorization "... will not be obtained from any subjects”

    25-1.3.2: "Request for full or partial waiver ...”

    25-2.1: “Entire project”

    Use of data from prior research study for purpose consistent with original consent

    25-1.3: Authorization “...was/will be obtained from all subjects”

    25-1.3.1: “integrated with” or "separate from" informed consent document, as applicable to original authorization

    Re-consent

    25-1.3: Authorization “...was/will be obtained from all subjects”

    25-1.3.1: “integrated with” or "separate from" informed consent document

    Is PARTIAL authorization waiver ALSO required for pre-screening? This depends on whether original authorization mentioned possible re-contact. If so...

    25-1.3: "... will not be obtained from some subjects before...."

    25-1.3.1: “integrated with” or "separate from" informed consent document

    25-1.3.2: "Request for full or partial waiver ...”

    25-2.1: “Recruitment portion only"

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Edited By: larkspur@umich.edu
Last Updated: April 9, 2019 9:45 PM