Chapter 8 - General Procedures for All IRB Submissions

Investigators involved in the conduct of human subject research that falls under the authority of the HRPO will be provided with instructions and guidelines for the submission of research studies and informed consent documents for IRB review and approval.  Specific instructions are found on the OSIRIS webpage ( http://www.hrpo.pitt.edu/OSIRIS) as well as in help text located throughout the OSIRIS system.  The following are general procedures for the IRB in processing all IRB submissions.

Assignment of IRB Number

New Protocols

All new protocols are required to be submitted through the OSIRIS system. IRB numbers are assigned by the system with the prefix “PRO.” The number assigned reflects the year and month of submission with consecutive numbers thereafter (e.g., PRO10060008 would mean the protocol was submitted in June 2010 and was the 8th protocol submitted in the month). Protocols that were originally approved in paper and converted into OSIRIS will begin with “IRB.”

Protocols that are utilizing an approved External IRB mechanism being registered with the HRPO will begin with the prefix “EXT.”

Emergency Use requests will begin with the prefix “EU.”

Renewals

Renewals that are currently being reviewed in a paper format will retain the number originally assigned with the addition of a four digit suffix to indicate the most recent date (i.e., year/month) of IRB continuation approval (e.g., 0603107-1003 for IRB continuation approval of this research granted in March 2010).

Renewals submitted through the OSIRIS system will be assigned a different IRB number with the prefix “REN.” The number assigned reflects the year and month of submission with consecutive numbers thereafter (e.g., REN10050003 would mean that the renewal was submitted in May 2010 and was the 3rd renewal of the month). The original number assigned will also remain with the submission and will be reflected on all correspondence generated for the renewal. Paper submissions will continue to utilize the previously assigned “IRB” number.
 

Modifications

Modifications that are currently being reviewed in a paper format will retain the number originally assigned to the study.

Modifications that are submitted through the OSIRIS system will be assigned the same IRB number as the original study but with the prefix “MOD.” This is because the modification is a copy of the original study. In addition, a suffix will be assigned to the modifications to indicate the sequential number of the modification (MOD0706008-01; MOD0706008-02, etc.) which would indicate that there have been two modifications submitted.

Required Ancillary Reviews

Required Ancillary Reviews

The OSIRIS system is constructed to automatically forward submissions to required ancillary reviews prior to submission to the IRB based on responses from the principal investigator to a series of "smart forms."

Scientific Review

All proposed human subject research are required to undergo scientific review prior to submission for IRB review, with the exception of (i) research qualifying for “exempt” review status; and; and (ii) research reviewed by a peer scientific review committee as a condition of research funding (e.g., NIH/NSF sponsored research).

Regardless of the exceptions cited above, the following types of human research studies MUST undergo unit-specific scientific review prior to the initiation of IRB review:

  • Research involving oncology patients or the use of University of Pittsburgh Cancer Institute (UPCI) resources must be approved by the UPCI Protocol Review Committee.
  • Research involving psychiatric patients or the use of Western Psychiatric Institute and Clinic (WPIC) resources must be approved by the WPIC Research Committee.
  • Research funded by, or using the resources of, the Magee Women’s Research Institute (MWRI) must be approved by the Clinical Research Use Committee of the MWH Clinical Translational Research Center.
  • Research funded by the Department of Defense.

Proposed modifications that substantially or materially impact the specific aims and/or design of an IRB-approved study must undergo scientific re-review prior to submission of the modifications for IRB approval.

If the proposed modifications to an IRB approved research study substantially change the design of the study, the IRB may require that the research be resubmitted for review as a new research study.

Radioactive Drug Research Committee/Human Use Subcommittee

All proposed human subject research involving the experimental use of procedures that include exposure to ionizing radiation must be reviewed and approved by the Human Use Subcommittee of the University of Pittsburgh Radiation Safety Committee (HUSC), and as applicable, by the University of Pittsburgh Radioactive Drug Research Committee (RDRC) prior to submission for IRB review.

  • Modifications to IRB and RDRC/HUSC approved research protocols must be submitted for RDRC/HUSC review and approval if the modification involves a change in the number of research subjects or a change that affects the radioactive drug, if applicable, or the subject’s exposure to ionizing radiation.

Institutional Biosafety Committee

All proposed human subject research involving administration of recombinant or synthetic nucleic acid molecules or DNA or RNA-derived from this technology must be reviewed and approved by the Institutional Biosafety Committee (IBC) prior to IRB committee review.  

  • Modifications to IRB and IBC approved research protocols must be submitted for IBC review and approval if the modification involves a change in the materials or procedures that involve administration that were originally approved for intervention.

Office for Investigator Sponsored IND and IDE Support (O3IS)

All proposed human subject research involving investigator-sponsored FDA drug or device applications must be reviewed by the Office for Investigator-Sponsored IND and IDE Support prior to IRB review to ensure the following:

  • Those involved in the treatment and/or evaluation of study subjects under a FDA-accepted IND or IDE application have completed the required CITI Good Clinical Practice Training module;
  • FDA accepted the IND or IDE application without the issuance of a clinical hold;
  • Modifications indicated in the OSIRIS application, the FDA clinical protocol or investigational plan, and the informed consent document have been appropriately updated;
  • Modifications do not conflict with information provided in response to FDA comments from prior submissions, and;
  • Sponsor-investigators submit amendments/supplements prospectively to FDA when required

Conflict of Interest

The Conflict of Interest (COI) Office is required to review and approve through OSIRIS any study that is submitted for IRB review where the investigator indicates that any member of the study team who participates in the design, conduct, or reporting of the research protocol has a reportable conflict. COI management is also required if any researcher’s spouse, registered domestic partner, dependent, or other household members have a reportable conflict. If necessary, the standard Conflict of Interest Management Plan will be implemented to address the conflict (refer to Chapter 20 for more information).

Notifications to Other Offices

In addition to the requirements for approval by the Ancillary Review groups described above, the OSIRIS system will provide notifications to the following offices:

Investigational Drug Service (IDS)

The IDS of the UPMC Department of Pharmacy is notified of all proposed human subject research that involves the evaluation of an investigational or approved drug.

Office of Sponsored Programs and Research Support (OSPARS)

All proposed human subject research at UPMC facilities or with UPMC patients involving any of the following will be reviewed and approved by the UPMC Fiscal Review Committee consistent with their policy and procedures:

  • the performance of potentially billable procedures or tests;
  • the provision of services or hands on care;
  • the collection of biological specimens.

If required, OSPARS approval must be in place before research activities may commence within a UPMC facility. The IRB approval letter contains standard language indicating this requirement.

Clinical and Translational Research Center (CTRC)

For research studies where investigators indicate that CTRC resources will be utilized for research study procedures, the staff at the CTRC receives a notification from the OSIRIS system.

Human Stem Cell Research Oversight Commitee (hSCRO)

The University’s  Human Stem Cell Oversight (hSCRO)  Committee oversees all human embryonic stem (hES) cell research being conducted at the University, as well as limited categories of non-embryonic human stem cell research. There are two levels of hSCRO review, administrative review and review by the convened hSCRO Committee.  The hSCRO review/approval process is independent of IRB review and the submissions may be done in parallel. The OSIRIS system provides notification to the hSCRO Office when stem cells will be utilized in the research. The hSCRO Office determines if review is required; and if so, determines the appropriate review pathway per the hSCRO policies.

Data Security

The IRB will require a formal data security review, at a minimum, when sensitive identifiable information is being collected, transmitted, or stored on sites other than approved servers behind Pitt or UPMC firewalls, when mobile devices such as smartphones are used to collect and transmit data, when unapproved vendors host or have access to research data, and at the discretion of the HRPO staff or IRB committee members.  The purpose of the review is to consider whether adequate data security controls are in place when personally identifiable, sensitive information or protected health information is being recorded.

Ethical and Religious Directives

For research conducted at UPMC Mercy, a review to ensure compliance with the Ethical and Religious Directives will be conducted. Investigators will be notified to remove UPMC Mercy as a site if there are issues related to conduct of the study at that site.

Exceptions to Ancillary Review Approvals

Exceptions to the timing of ancillary review approvals/notifications may be granted by the IRB Chair or his/her designee. If an exception is permitted, final IRB approval will not be granted until approvals/notifications from all applicable committees are submitted.

Verification of Training Requirements

All investigators and key personnel involved in Human Subject Research (including Faculty Mentors) are required to complete specific research ethic courses using the CITI training program. Only those individuals who have completed the required training are permitted to conduct human subject research or to access OSIRIS (IRB on-line application). At a minimum, all users must complete courses in Human Subjects Protections and Responsible Conduct of Research. The CITI program can be accessed through www.citi.pitt.edu. Questions related to training requirements should be sent to irb@pitt.edu.

Historic Review and Maintenance of IRB Database

Historical Review

For renewals and modifications submitted in paper format, the IRB file for research will be reviewed by an IRB member designated by the IRB Chair to ensure that the most current version of the research protocol with all modifications included and informed consent documents were submitted and that no outstanding issues or deficiencies exist.

For renewals and modifications submitted through the OSIRIS system, only the most current version is available and therefore a historical review will only be conducted on the consent documents uploaded into the system as a Word document.

Maintenance of IRB Database

For paper submissions, the HRPO staff maintains a database that includes, at a minimum the following fields: the IRB number assigned to the submission, principal investigator’s name, co-investigators names, title of the research, contact information, and IRB approval dates.

The OSIRIS system serves as a database and includes all information related to the individual projects submitted through the system.

Calculation of Approval and Expiration Dates

Calculation of Initial Approval Date

The IRB calculates the date of initial IRB approval in the following manner:

  • When a research study is approved at a convened meeting, the date of the convened meeting is the date of IRB approval.
  • When the research study is approved subject to modifications at a convened meeting, the date of IRB approval is the date that the requested changes are verified by the Chair, Vice Chair, or his/her designee.
  • When a research study is reviewed and approved through an expedited review process, the date that approval is extended by the Chair, Vice Chair, or his/her designee is the date of IRB approval.

Calculation of Expiration Date

Initial Approval

The IRB calculates the date of expiration in the following manner:

  • When a research study is fully approved at a convened meeting, the date of expiration is based on the date of the convened meeting (minus one day). For example, if the committee meeting date is 10/17/10, then the date of IRB expiration is 10/16/11 for an annual approval or 4/16/11 for a six month approval.
  • When a research study is approved subject to modifications, the date of expiration is one year from the date of the convened meeting (minus one day). It is not calculated from the date that the Chair, Vice Chair, or his/her designee verifies the requested changes and grants final approval. For example, if the committee approves a research study subject to modifications on 10/17/10 and the response is verified by the Chair, Vice Chair, or his/her designee on 10/20/10, then the date of IRB approval is 10/20/10 and the expiration is 10/16/11 for an annual approval or 4/16/11 for a six month approval.
  • When a research study is reviewed and approved by expedited review, the date of expiration is based on the date that the Chair, Vice Chair, or his/her designee verifies any requested changes and grants final approval (minus one day).

The approval period expires at 11:59 p.m. on the date set forth in the IRB approval letter.

Modification Dates

The IRB calculates the date of modification approval in the following manner:

  • When a modification is approved through an expedited review mechanism, the modification approval date is the date that the Chair, Vice Chair or his/her designee reviews and approves the modification.
  • When a modification is reviewed at a full board meeting and is approved at the meeting, the modification approval date is the date of the IRB meeting.
  • When a modification is reviewed at a full board meeting and is approved subject to modifications, the modification approval date is the date that the response is verified by the Chair, Vice Chair, or his/her designee.

Expiration dates are maintained as the date assigned upon initial or continuing review unless the IRB determines that there has been a significant change to the risk/benefit ratio which would require a more frequent continuing review. If this change occurs, the IRB will notify the principal investigator of the study of the new expiration date. The new date must never exceed the original expiration date.

Maintenance of Anniversary Date (Expedited Submissions Only)

OHRP recognizes the logistical advantages of keeping the IRB approval period constant from year to year throughout the life of each project. When continuing review occurs annually and the IRB performs continuing review within 30 days before the IRB approval period expires, the IRB may retain the anniversary date as the date by which the continuing review must occur.

Extended Approval Periods (approved 8.15.2014)

Certain types of non-exempt research may be granted a three year approval. In order to be eligible for the extended approval period, the research must present no more than minimal risk to human subjects as determined by the convened IRB or through an expedited review mechanism, and must not include any of the following:

  • Federal funding, including federal training and program project grants and federal no-cost extensions
  • Subawards issued to University of Pittsburgh where the prime award is federal
  • FDA regulated
  • Prisoners as subjects

Expiration dates are maintained as the date assigned upon initial or continuing review (not at the time of a modification). If during the course of the three year approval period, changes occur that affect the eligibility of the study to continue with an extended approval, the study will immediately become subject to annual review.

The IRB reserves the right to make exceptions to this policy, and inclusion/exclusion of any research project under this procedure will be at the IRB’s discretion.

During the extended approval period, principal investigators retain responsibility for all regulatory requirements including submission of modifications, reportable events, suspension and/or terminations.

Members of the Regulatory Affairs Division will periodically monitor a random sample of studies to confirm continued eligibility for the three year approval period. Studies found to not meet the criteria will be subject to annual review.

New Information

Throughout the life span of a research protocol, the IRB may determine that currently enrolled subjects need to be notified of new information or significant new findings that alter the risk benefit ratio and may affect their willingness to continue study participation. New information may be presented to research participants via an addendum consent form or a modified consent form (See Chapter 13).

Verification from Other Sources

Protecting the rights and welfare of participants sometimes requires that the IRB verify independently, utilizing sources other than the investigator, that no material changes occur during the IRB designated approval period. Additional sources may include: audit by the Education and Compliance Office for Human Subject Research, investigational pharmacy records, incident reports, radiation safety or source documents, as well as information from staff, research participants, families, sponsors or others.

Criteria for determining if verification is required includes, but is not limited to:

  • Complex protocols involving unusual levels or types of risks to subjects;
  • Protocols conducted by PIs who previously have failed to comply with Federal regulations or the requirements or determinations of the IRB;
  • Protocols where concern about possible material changes occurring without IRB approval have been raised based on information provided in continuing review reports or from other sources.

Investigator Communications

Initial Comments from the IRB – General Information

The principal investigator will be notified, in writing, of the IRB’s decision to approve, reconsider, or disapprove the proposed research, or of the modifications required to secure IRB approval of the research study. Comments will be issued to investigators once either the minutes from the full board meeting have been accepted by the IRB Vice Chair, or the comments have been finalized for expedited or exempt submissions. Correspondence will contain, at a minimum:

  • the name of the principal investigator;
  • the title of the project;
  • the IRB number assigned to the submission;
  • the decision of the IRB.

Full Board Decisions

The IRB full board decisions will be outlined in the investigator communications as follows:

  • Full Approval - If a convened IRB determines that the study can be approved as submitted, the investigator will be issued a full approval letter.
  • Approved subject to minor modifications (comments must be directive)- If the IRB decides to approve a research study subject to modifications, the written notification will include the specific revisions stipulated by the IRB in order to obtain full approval to conduct the research.
    • The written notification provides instruction to the investigators to revise the research and informed consent document(s) in accordance with the specific revisions stipulated by the IRB and to resubmit for final IRB approval.
  • Reconsideration - If a convened IRB decides to reconsider a research activity, the written notification to the investigator will include:
    • a statement of the primary reason(s) for the IRB’s decision to reconsider the research;
    • a listing of additional problems and/or deficiencies identified by the IRB;
    • instructions relating to resubmission of the research for full-board IRB review, including statements that the principal investigator should address in writing the comments and concerns of the first IRB review and that s/he may appear in person to address additional questions or concerns related to full-board IRB review of the resubmitted protocol.
  • Disapproval – If a convened IRB decides to disapprove a research activity, the written notification to the investigator will include:
    • a statement of the primary reason(s) for the IRB’s decision to reconsider the research;
    • a listing of additional problems and/or deficiencies identified by the IRB;
    • instructions relating to resubmission of the research for full-board IRB review, including statements that the principal investigator should address in writing the comments and concerns of the first IRB review and that s/he may appear in person to address additional questions or concerns related to full-board IRB review of the resubmitted protocol.

Exempt/Expedited Submissions

Submissions that are reviewed by the Exempt/Expedited Team can either receive full approval or approval subject to minor modifications. In the event that directive comments cannot be provided or if the study does not meet a regulatory category which would permit an expedited review, the investigator will be notified that the study will be reviewed by the convened IRB.

Investigator Responses

Responses of the principal investigator are returned to the IRB reviewer who conducted the initial review (i.e., or to another IRB reviewer if the initial reviewer will be unavailable for an extended period) for final approval.

In the event of a failure to resolve problems or concerns related to the investigator’s response(s), the IRB submission (to include prior correspondence between the IRB reviewer and investigator) will be reviewed at a convened meeting of an IRB committee (i.e., full-board IRB review).

Response Deadline

The communication to the principal investigator specifies that s/he must respond to the comments or concerns of the IRB reviewer within 6 weeks of the date of the communication, and that failure to respond within this 6-week period may result in withdrawal of the project by the IRB.

Content of IRB Concurrence/Approval

The principal investigator is notified of IRB concurrence/approval through written correspondence prepared and discharged by the HRPO staff. All correspondence contains:

  • the name of the principal investigator;
  • the title of the project;
  • the IRB number assigned to the submission;
  • the date of IRB approval/concurrence;
  • the date of IRB expiration (for expedited and full board studies only) the date of IRB modifications (for modification requests only);
  • a statement that modifications to the IRB approved research study will require either notification to the IRB (for no human subjects research or exempt determinations) or approval by the IRB (for expedited or full board studies).

For studies that are designated as “not human subject research” the correspondence will indicate a concurrence that the project does not meet either the definition of "research" at 45 CFR 46.102(d) or "clinical investigation" at 21 CFR 56.102(c), or the definition of "human subject" at 45 CFR 46.102(f) or 21 CFR 56.102(e).

For activities determined by the IRB Reviewer to meet either the DHHS or FDA definition of “human subject research,” the principal investigator will be advised to resubmit the project for exempt, expedited or full-board IRB review as appropriate.

For studies that are designated as "exempt" the correspondence includes the basis for granting exempt status (i.e., 45 CFR 46.101(b)(1-6) and/or 21 CFR 56.104(d)). For research activities that involve human subjects but are determined to not qualify for exempt status, the principal investigator will be advised to resubmit the research for expedited or full-board IRB review as appropriate.

For studies that are approved as "expedited" the correspondence includes the basis for granting expedited approval of the research. This would not only include the minimal risk status of the research, but the applicable category or categories of research activities listed in the OHRP and FDA document, "Categories of Research That May Be Reviewed by the Institutional Review Board through an Expedited Review Procedure". That information is documented, with justification, within the IRB Research Protocol and/or review materials. For research activities that are determined to not qualify for expedited review status, the principal investigator will be advised to resubmit the research for full-board IRB review.

Renewal Reminder Notices

For renewals that have been approved in a paper format, the IRB Office will send a reminder notice to the principal investigator and, if applicable, the study coordinator, 60 days and 30 days in advance of the expiration date of IRB approved research studies.

For renewals that have been approved in the OSIRIS system, the system automatically generates an e-mail notification to the principal investigator and, if applicable, the study coordinator, 90, 60 and 30 days in advance of the expiration date of the IRB.

Study Expiration

If the study is not reviewed and approved by the IRB prior to the expiration date of the previous IRB approval, the principal investigator will be required to cease all research activities described in the IRB protocol (including data analysis) until notification of final IRB approval for continuation of the research has been issued. The approval period expires at 11:59 p.m. on the date set forth in the IRB approval letter. The notification sent to the investigator will indicate that: 1) enrollment of new participants must stop; 2) all research activities must stop; and 3) any continuation of research activity is a violation of Federal regulations. The letter also indicates that the investigator may petition the IRB Chair for permission to continue certain research activities if there is an overriding safety concern or ethical issue.  However, under no circumstances can new subjects be enrolled into a research study after expiration of IRB approval. In order to preserve the historical integrity of a research study, investigators who want to continue research activities must submit a renewal to the IRB. Research activities may not resume until a new IRB approval has been issued.

version 12.10.2015