How to submit a research protocol for IRB review

How to submit a research protocol for IRB review

IRB approval must be prospectively obtained prior to the implementation of any proposed research activity involving human subjects.

Human Use Protocol Submission Process:

  1. Obtain approval or the recommendation for IRB review from the Office of Research. This requires a fully signed USU Form 3208 for Investigators or a signed USU form 3202 for student research projects.
  2. The HRPP Office will accept the submission documents via the new eIRB system- iRIS. To access the system, please go to:  https://dmrncac.dhhq.health.mil (link is external)  (for new accounts, contact the HRPP office (301) 295-3303 for instructions on how to request an eIRB account)
  3. The protocol application is a fillable eIRB form. In addition to the protocol, the following required documents may be uploaded, as applicable :
    1. For all research: Current Curriculum Vitae (CV), CITI human subjects protections training certifications, HIPAA training certification, Signed Researcher Responsibility Form, - These forms may be uploaded only once into the researcher’s eIRB profile to avoid being asked for these documents with each new IRB submission.
    2. For sponsored/ funded research: Financial Disclosure/Conflict of Interest Form
    3. For non-exempt studies: Proposed informed consent document (ICD) or information sheet unless a waiver of consent or a waiver of documentation of consent is being sought.
    4. For studies involving protected health information (PH): a separate HIPAA Research Subject Authorization (RSA) or a compound ICD that includes the required HIPAA elements ,
    5. For exempt studies involving PHI: Request for a HIPAA Waiver of RSA, Request for Limited Data Set(LDS)/Data Use Agreement(DUA), information sheet to accompany a survey/questionnaire,
    6. For research activities taking place outside of USU: Site permission letters or permission requests, Data Sharing Agreement
    7. For subject recruitment: Recruitment materials including advertisements, flyers, telephone or verbal scripts, letters or other communication directed at potential participants,
    8. For Data collection: Case Report Forms, Case History Forms, Data Collection Instruments, forms for testing tools, surveys, questionnaires,
    9. For studies involving external collaborators: copies of the signed or final draft or the of the Data Sharing Agreement, Material Transfer Agreement, approved Statement of Work (SOW) for studies with contracts or funded grants , Memorandum of Understanding,
    10. For studies involving School of Medicine (SOM) or Graduate School of Nursing (GSN) students: Use of SOM Students Approval Form, Use of GSN Students Approval Form.
    11. For FDA regulated research: FDA Form 1572 (for investigational new drug studies), FDA IND or IDE related correspondence, GCP certificates, current health care provider licenses, investigator's brochure (IB) or product inserts.

USU Human Subject Protection Review Process

Summary: Document processing time for the USU Human Subject Protection Office decreased from November 2016 to January 2017 through implementation of new processes and is now at an efficiency equal to or better than published national norms. However, the total time from first submission to outcome determination for research project related documents continues to be delayed by passbacks from the analysts to the study team to address inconsistencies, deficiencies, or errors in the documents. The Office of the Vice President of Research (VPR) developed a plan to reduce passbacks and thereby eliminate avoidable delays.

Background

USUHS has a research compliance program with four components- Human Subject Protection Review, Research Animal Protection Review, Human Anatomic Material Use Review, and Biosafety. All are staffed by trained professionals whose responsibility is to review the quality of submissions prior to the formal peer review process that makes a determination on if and how a research project may proceed.

For Human Subject Protection, if a project is classified as research and if living identifiable people voluntarily provide facts, opinions, or biological material, there are three possible outcomes.

  1. The project is exempt from Institutional Review Board review and oversight. The determination of whether a project is exempt is made by a certified Exemption Determination Official (EDO) based on specific criteria published in the relevant regulations. USUHS currently has three EDOs to cover the portfolio.
  2. The project is non-exempt and the material in the submission is limited in scope and considered minimal risk. Such a submission will receive an expedited review meaning that the Institutional Review Board (IRB) Chair or delegate will review the material and make a determination with the time for review relative to the complexity of the material.
  3. The project is non-exempt and the submission is either for a new study or contains material that merits discussion by the full IRB at the next scheduled meeting. This type of submission is often referred to as requiring full board review.

A review of IRB submissions over the past year identifies one factor as the major cause for delay in processing- the need to passback the submission to the study team. Although there are multiple reasons for passbacks, the most common are summarized in the following table.  No matter the document type, some examples are:

  • Records without documents attached
  • Missing documents
  • Missing information within documents
  • Inconsistencies between documents

 

Table-1 Common Reasons for USUHS IRB Submission Document Passbacks

Document TypeSpecific DeficiencyComment
Submission Software SpecificFailure to attach uploaded documents to a submission.
Initial Submission for a new protocolIncomplete submission: missing entire documents
Initial Submission for a new protocolDocuments not completedfor example unanswered questions on protocol application
Initial Submission for a new protocolInformation inconsistency: a). within document b). between documentsfor example protocol and consent differ
Initial Submission for a new protocolPersonnel training documentation incomplete, outdated, or has errors
Continuing ReviewContinuing Review form incompletefor example unanswered questions
Continuing ReviewInvestigators fail to provide current study results and progress, fail to provide cited abstracts or articles, or cut and paste results from prior year
Continuing ReviewProvide literature search but do not provide summary of the current literature or indicate whether the risk/benefit of the study has changed
Continuing ReviewInconsistent reporting periods resulting in enrollment number errors between continuing review periods
ModificationsLack of identification of all requested revisions
ModificationsLack of justification for requested revisions
ModificationsIncomplete submission: missing documents (personnel or other)
ModificationsInformation inconsistency: a). within document b). between documentsfor example protocol details and consent details differ

General information for submission of EIRB documents

A major operational goal of the human subject protection program at the USU is to minimize, if not eliminate, the need for passbacks by establishing processes, including training and advice, that result in the submission of high quality documents.

To achieve that goal, the Office of the Vice President for Research (VPR) designed a multistep program.

  1. Flagging submissions that are candidates for exemption determination with a prefix code of EXM before the protocol title.
  2. Preparation of instructional material to provide a high quality submission for various use cases. The instructional material will be available on the upcoming revised USU VPR website
  3. In person teaching sessions for the USU community to be held quarterly.
  4. Identification, training, and support for IRB submission enablers distributed across the programs and departments to function as the first line for preparation of submissions, to respond to questions, and to provide initial support.
  5. Shifting the USU IRB Analysts to function as second level support for IRB submission preparation so that they will devote most of their time to processing submissions, teaching, and quality improvement.

On an operational basis, the general problem is mapping information from often multiple sources into a structured document. The mapping is neither simple nor straightforward. The process has a learning curve and USU VPR encourages limiting the number of people in a given program, department, or center who perform the mapping and data entry to increase the proportion of people with sufficient experience and expertise by fostering a system where fewer people do more submissions.

The IRB submission process begins with a study team entering data into the EIRB system.

A more comprehensive checklist for the study team to follow in preparing a new submission follows in Table 2 entitled "Detailed Generic Checklist for study team initial submission of EIRB documents". This list was adapted from initial work from John Morais of the Infectious Disease Clinical Research Program and Crystal Kelly, USU IRB Analyst.

Table 2

CategoryDocumentCommentsReason
AdministrativeUSUHS Form 3208 (for faculty) and Form 3202 (for students)Linkage with USUHS VPR research project tracking system
AdministrativeSummary of Grant ApplicationIf applicableIs protocol aligned with goals of funded project?
AdministrativeVerification of Scientific ReviewDocumentation of who, when, where, outcome, if applicable. Members of study team cannot participate in scientific reviewIRB will only review protocols that have undergone competent scientific review
AdministrativeDocumentation of local command pre-IRB reviewIf applicableAssure local command at Department of Defense study sites is aware and accepts protocol participation
Study TeamConflict of Interest StatementUse version from March 2016Assure quality and integrity of study team
Study TeamResearcher Responsibility StatementUse version from October 2015Assure quality and integrity of study team
Study TeamVerification of relevant CITI Training for all members of Study TeamAssure quality and integrity of study team
Study TeamCurriculum Vitae for all members of Study Team, relevant licensesAssure quality and integrity of study team
ProtocolProtocol documentIf requesting or anticipating that the project will be exempt from IRB review and oversight, include the letters “EXM” as the first letters of the titlePrimary review document
ProtocolSample Informed Consent FormPrimary review document
ProtocolData Collection Forms (Case Report Forms), survey instruments, questionnairesPrimary review document
ProtocolAdvertising materialPrimary Review Document
ProtocolHIPAA Waiver of AuthorizationIf applicableData custody and privacy
AgreementsCopy of MOUs and Partnership AgreementsIf applicableData custody and privacy
AgreementsData Sharing AgreementsIf applicableData custody and privacy
AgreementsLetters of SupportIf applicableSupporting document
Product SafetyInvestigator’s BrochureIf applicableSupporting document
Product SafetyApproved Product Package InsertIf applicableSupporting document
Product SafetyFood and Drug Administration IND or IDE number. If study under IND, Principal Investigator must be an MD.If applicableSupporting document

Generic checklist for IRB analyst initial administrative pre-review of EIRB submissions

What follows is referred to as a pre-review by an IRB analyst so that when either an Exemption Determinations Official, the IRB Chair, or the full IRB review a document they have all the essential information organized in a consistent manner.

The pre-review has two stages- an initial administrative review to determine if all the required documentation and related information is present and then a content review to determine if the submitted information is complete and consistent. If during the administrative review documents or information are missing, the IRB analyst will contact the study team to provide what is missing. If during the content review the IRB analyst finds inconsistent or missing or ambiguous information, he or she will contact the study team for clarification.

A schematic of the process is:

IRB Process Schematic

 

 

The internal checklist for initial administrative pre-review follows in Table 3.

If any of the documents or information, listed in Table 3, are considered necessary to perform a content review by the Analyst in preparation for the formal review by the IRB and are missing from the application, then the submission is returned so that the study team can provide the appropriate documentation to the EIRB system to complete the submission. An incomplete submission cannot be properly reviewed by the IRB analyst nor by the subsequent peer review.

Table 3

The internal checklist for initial administrative pre-review follows.
CategoryDocumentCommentsReason
AdministrativeUSUHS Form 3208 (for faculty) and Form 3202 (for students)Linkage with USUHS VPR tracking system
AdministrativeSummary of Grant ApplicationIf applicableIs protocol aligned with goals of funded project?
AdministrativeVerification of Scientific ReviewDocumentation of who, when, where, outcome, if applicable. No member of the study team can be a member of the scientific review board or processIRB will only review protocols that have undergone competent scientific review
AdministrativeCommand AuthorizationsIf applicable. Local site Human Subject Protection Administrators have done a pre-review and sent an acknowledgment letterAssure that authorization is prospective
Study TeamConflict of Interest StatementAssure quality and integrity of study team
Study TeamResearcher Responsibility StatementAssure quality and integrity of study team
Study TeamVerification of relevant CITI Training for all members of Study TeamAssure quality and integrity of study team
Study TeamCurriculum Vitae current within the past two years for members of Study Team, relevant licenses that are currentInclude state of each individual’s role on the study, location, contact information, and responsibilities. Research medical monitors require conflict of interest statement, medical license, researcher responsibility form, documentation of human subject research training and a Curriculum VitaeAssure quality and integrity of study team
ProtocolProtocolPrimary review document
ProtocolSample Informed Consent FormPrimary review document
ProtocolData Collection Forms, survey instruments, questionnairesPrimary review document
ProtocolRecruitment and Advertising materialPrimary Review Document
ProtocolHIPAA Waiver of AuthorizationIf applicableData custody and privacy
AgreementsCopy of MOUs and Partnership AgreementsIf applicableData custody and privacy
AgreementsData Sharing AgreementsIf applicableData custody and privacy
AgreementsMaterial Transfer AgreementsIf applicable. Agreements are usually in draft form and not executed until the study has IRB approvalReagent, resources, and sample custody and responsibilities
AgreementsStatement of WorkIf applicable
AgreementsMemoranda of UnderstandingIf applicableSupporting document
AgreementsIndividual Investigator AgreementIf applicableSupporting document
AgreementsLetters of SupportIf applicableSupporting document
Product SafetyInvestigator’s BrochureIf applicableSupporting document
Product SafetyApproved Product Package InsertIf applicableSupporting document
Product SafetyFood and Drug Administration IND or IDE numberIf applicableSupporting document