Step 3: Application Review Process

Federally funded studies seeking to answer a research question about health-related outcomes by prospectively assigning human participants to either a control group or one or more interventions in order to evaluate the effects of the intervention on biomedical or behavioral health-related outcomes are considered  “clinical trials” under federal regulation 45 CFR 46.102(b). All federally funded studies will be reviewed by the NC State IRB for intent and procedures that categorize the research as a “clinical trial.” This review occurs during the normal IRB review and approval process and it requires the researchers to take action after IRB approval is granted. 

If a study is deemed to be a clinical trial, the NC State IRB will provide the principal investigator with an additional clinical trial letter when the protocol is approval outlining the additional responsibilities of a clinical trial, including but not limited to registering the study with https://clinicaltrials.gov, publicly posting the study’s consent form(s), providing research progress updates at least annually, and sharing of finalized research results.

• NC State University IRB Clinical Trials Unit Standard

Cooperative research is when is when different people, groups, or organizations work together on a research project. Our website has an entire page dedicated to cooperative research that explains the different types of cooperative research and their associated application processes. For the purposes of this webpage, we’re only going to discuss the additional reviews that can occur with cooperative research studies.

• When the NC State IRB Office is the IRB of Record for a cooperative research study, the following additional reviews are required:
  • Research Site Context Review. The research site context review provides information to the NC State IRB office about the structure and operations of all research sites so that research risks can be properly identified and managed.
    • The NC State principal investigator works with their collaborators to complete a “Research Site Context Worksheet”
    • The worksheet is uploaded to the supporting documentation section of their protocol application for the NC State IRB to review.
    • The research site context review is concurrent with the IRB review and approval process.
  • Conflicts of Interest and Commitment Review. When the NC State IRB office serves as the IRB of Record for a cooperative research study, an assessment of every research team member’s actual and perceived conflicts of interest and commitment is made and, if necessary, a management plan is developed.
    • The NC State principal investigator ensures that each of their collaborators complete the Conflicts of Interest Attestation or Management Plan form/
    • The principal investigator uploads to the supporting documentation section of the protocol application for the NC State IRB to review.
    • The conflicts of interest and commitment review is concurrent with the IRB review and approval process.
• When another IRB serves at the IRB of Record for a cooperative research study, NC State researchers must file with the NC State IRB to request either a:
  • Letter of Acceptance of an Exemption Determination for cooperative research that was determined to be exempt by another IRB with an FWA number or
  • Reliance Agreement for non-exempt cooperative research reviewed by another IRB with an FWA number.

Depending on how the research is designed or a study’s source of funding can require additional review related to data management. These additional reviews can be a code review, ITPC review, or a data and access security plan review.

• Code Review: When a research study will use a commercially available but modified technology that is not licensed by the University or will use a purpose-built technology with human subjects or their data, a review of technology’s code is required to ensure that the data collection, storage, use, and sharing is both secure and compliant within applicable laws, standards, and participant consent.
  • The code review must be completed by someone who is not a member of the research team or otherwise has a conflict of interest.
  • The code review must be submitted with the protocol application for IRB review.
  • The NC State IRB cannot approve a study without a completed code review if a modified or purpose-built technology will be used.
• Data and Access Security Plan (DASP): When a research protocol will access or collect highly sensitive (red) data, ultra-sensitive (purple) data, identifiable data of minors, and/or are subject to data controls such as a data use agreement (DUA), material transfer agreement (MTA), Certificate of Confidentiality (CoC), NIH Data Management and Sharing Plan (NIH DMSP), a review is conducted by the NC State University Office of Information Technology (OIT)’s Security & Compliance (S&C) department who develops the protocol’s data and access security plan (DASP).
  • Researchers request a DASP for their protocol through OIT’s ServiceNow portal after all of their IRB materials and application has been drafted.
  • The DASP must be uploaded for the IRB to review and approve the study.
• ITPC Review: When a research team wishes to use an technology that is not licensed by NC State University – whether it’s commercially available, off-the-shelf in the United States of America or a technology that is modified or purpose-built for the research study – the study must undergo IT Purchase Compliance (ITPC) review by the NC State University Office of Information Technology’s Software Licensing Management team.
  • Researchers will contact the NC State Software Licensing Management team if an ITPC review is needed for their study.
  • ITPC review, if applicable, must be passed before the IRB can approve the study.

When performing research with human subjects that is funded by the Department of Defense (DoD) and/or uses any DoD resources or people (including those in ROTC), the project is subject to additional regulations. These requirements are detailed in the IRB unit standard for research associated with the DoD. Two of the key additional requirements for DoD affiliated studies is HRPO review (all studies, including exemptions, are required to undergo HRPO review) and a scientific merit review for all non-exempt DoD affiliated studies. 

• Scientific Merit Review: A scientific merit review is an independent review and approval that assesses the scientific merit of a study.
  • The NC State IRB office does not require a scientific merit review unless your study is affiliated with the DoD and reviewed at the expedited or convened full board level.
  • The NC State IRB office will not approve a non-exempt DoD affiliated study without a completed scientific merit review.
  • As the researcher, it is your responsibility to facilitate the scientific merit review process and to submit the completed review with your IRB application. The review cannot be done by you or anyone on your research team due to conflicts of interest.
  • The scientific merit review is done after all protocol materials are ready for final review as determined by IRB staff.

• HRPO Review: Research subject to the DoD regulations undergoes a second review after IRB approval is granted. This is called HRPO review and it is facilitated between the researcher and the DoD’s HRPO officer after IRB approval of the research protocol.

A local or participant context review evaluates the risks to participants in the proposed research. This review is completed by an expert in either the population being studied or the local culture and laws of the population being studied. This type of review is facilitated by the researcher and completed by a subject matter expert who is not an IRB full board member, a member of the research team, or someone with a conflict of interest. The local or context reviewer will provide insight and information about the culture, laws, or participants that the IRB may need to assess risk to participants in your research design.

Local and participant context reviews are conducted during the IRB review process, usually prior to the final review of the protocol. The researcher is expected to facilitate the local and participant context reviews, per the NC State IRB unit standard on local context and participant context reviews. For most expedited and convened full board studies using unique or international populations, an IRB application often cannot be approved without a context review. This type of review will always occur for international research reviewed at the expedited or convened full board level — and, on a case-by-case basis, may be required for studies deemed exempt.

Studies that involve the use of one or more medical device(s) that will be tested for efficacy, safety, a new indication or population, and/or are significant risk medical devices sometimes require review by the U.S. Food and Drug Administration for an Investigational Device Exemption (IDE), and IRB review by the WCG IRB with which NC State IRB has a standing agreement. Few studies completed at NC State require a full IDE and it is extremely rare that any study is referred out to the WCG IRB for IRB approval. 

Most medical device studies at NC State involve nonsignificant risk devices that will be tested for efficacy or safety and they seek abbreviated IDEs and IRB approval from the NC State IRB convened full board. Studies that are exempt from IDE requirements and involve nonsignificant risk medical devices used as research tools are reviewed by the NC State IRB often at the expedited (i.e., mid) level of IRB review if the study design fits within established expedited review categories.

Regardless of which IRB approves a medical device study or the medical device’s IDE requirements, the study will still be subject to clinical trial regulation if the research is studying a health-related outcome and prospectively assigning participants to an intervention.

All medical device studies submitted to the NC State IRB office will need to include a completed medical devices used in research form for each medical device that will be used in the study. The participant procedures template is required for BME studies but other departments can use the template if they find it helpful together with the instructions in Appendix B of the Mobile Software Applications and Wearables as Medical Devices guidance linked below. Modified and purpose-built medical devices may be required to be cleared by NC State’s Office of Information Technology (OIT) and/or Office of Research Commercialization (ORC) and/or undergo code review before the NC State IRB will approve the medical device study.

• NC State University IRB Medical Devices Unit Standard
• NC State University IRB Reviewing Research from the Joint BME Department Unit Standard
• Medical Devices Used in Research Form 
• BME Participant Procedures Template
• BME Study Submission or Update Checklist
• Mobile Software Applications and Wearables as Medical Devices