REG 10.10.03 – Human Subjects Research

Authority: Vice Chancellor for Research and Innovation

History: First Issued: October 22, 1987. Last Revised: July 30, 2019.

Additional References: 
Department of Health and Human Services, National Institutes of Health, Office for References: Protection from Research Risks, CFR 45, PART 46, Protection of Human Subjects, Revised November 13, 2001, Effective December 13, 2001
Institutional Review Board for the Protection of Human Subjects in Research 
University Requirement for the participation and administration of projects conducted with Human Subjects
Code of Federal Regulations Title 45 – Part 46 – Protection of Human Subjects
OHRP – Office of Human Research Protection
OHRP IRB Guidebook
5 U.S.C. 301; Sec. 474(a), 88 Stat. 352 (42 U.S.C. 2891-3(a))

Contact Info: Regulatory Compliance Administrator, Office of Sponsored Programs and Regulatory Compliance (919-515-4514)

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1. General

Federal law and NC State University regulations require that all research involving human subjects that is conducted by NC State researchers (including faculty, staff, and students) – regardless of funding source – must be reviewed and approved by the NC State Institutional Review Board (IRB) for the Use of Human Subjects in Research.

2.  SCOPE

2.1 Research projects that meet the definition of “research” and “human subjects” in section 3 of this regulation as well as the corresponding definitions in the Code of Federal Regulations, must undergo review by the IRB.

2.2  Some research projects may be subject to additional rules and regulations based on the sponsors, collaborations, and research designs.

3.  DEFINITIONS

For purposes of this regulation, the below terms have the following meanings:

3.1  “Adverse Events” means any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign, symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research. Adverse events encompass both physical and psychological harms.

3.2 “Clinical Trial” means a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.

3.3 “Human subject” means a living individual about whom an investigator (whether professional or student) conducting research:

3.3.1 Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or

3.3.2 Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

3.4  “Identifiable biospecimen” means a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen (see 45 CFR 46 (e)(1)).

3.5  “Identifiable private information” means private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information. This includes re-identification of the subject due to access, expertise, use of technology, and consideration of all data and information available.

3.6  “Interactions” includes communication or interpersonal contact between the investigator and subject.

3.7 “Intervention”  includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes.

3.8  “IRB Approval” means the determination by the IRB that the research has been reviewed and may be conducted within the constraints set forth by the IRB and by other institutional and federal requirements.

3.9  “Minimal risk”  means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (see 45 CFR 46.303(d)).

3.10 “Personally Identifiable Information (PII)” refers to information that can be used to distinguish or trace an individual’s identity, either alone or when combined with other personal or identifying information that is linked or linkable to a specific individual. Whether certain information is considered PII requires a case-by-case assessment of the specific risk that an individual can be identified. In performing this assessment, researchers should recognize that non-PII can become PII whenever additional information is made publicly available — in any medium and from any source — that, when combined with other available information, could be used to identify an individual.

3.11 “Private information” means information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place.  Private information also means information that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (e.g., a medical record, smartphone data, web browser history).

3.12 “Research” means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this regulation, whether or not they are conducted or supported under a program that is considered research for other purposes (see 45 CFR 46.102(l)).

3.13  “Unanticipated problems” means any incident, experience, or outcome that meets all of the following criteria (as determined by the IRB):

1. The problem is unexpected (in terms of nature, severity, or frequency) given the research procedures that are described in the protocol-related documents and the characteristics of the subject population being studied;
2. The problem is related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
3. The problem suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

4. GENERAL PRINCIPLES

4.1  Ethical Standards

All NC State researchers must adhere to ethical standards for the use of human subjects in their research. These principles and standards exist to protect the basic rights and welfare of humans participating in research. The Belmont Report establishes the principles of beneficence, justice, and respect for persons as core values in human subjects’ research. The ethical principles found in the Belmont Report are incorporated in 45 CFR 46.111 as criteria for IRB approval of research. Any research that departs from the spirit or practice of these principles and standards violates University policy and Federal law.

4.2  Student Projects

When student work is submitted for review, an NC State faculty or staff member will be the Point of Contact/Advisor, and the PI/Additional Personnel will be the student. The Point of Contact/Advisor will be responsible for the conduct of the research.

5. PROTOCOL SUBMISSIONS AND REVIEW

5.1  Submission

5.1.1 The online system is the electronic application system used by the NC State IRB office. This system allows researchers to submit an IRB application and study materials to the IRB for review and approval.  The online application is available to access via the NC State Human Subjects’ IRB Office Website.

5.1.2  All research study materials, including protocols, informed consent forms (if necessary), recruitment materials, and all data collection tools must be submitted with the application.

5.2 Review

5.2.1  Once the IRB application has been completed and all study materials have been uploaded into the electronic IRB application system, the IRB will review the application.

5.2.2  There are four or types of review for projects submitted to the IRB:  Administrative, Limited, Expedited, and Full Board. Determination of the type of review will be made by the IRB office (in conjunction with the IRB Chair as appropriate) upon consideration of the submitted application and study materials.  For more information on the types of review, see the NC State IRB Website.

6.  IRB APPROVAL

6.1  Approval Types

Upon review of the application, the IRB may issue the following types of approvals:

6.1.1  Approved – The study protocol was approved, and research with human subjects as described in the approved protocol may commence.

6.1.2  Approved with Stipulations – If the study is marked as approved with modifications, the IRB staff will work with the PI to complete the necessary changes and finalize approval.

6.1.3  Deferred – If the convened IRB is unable to document that the criteria provided in 45 CFR 46.111, Criteria for IRB Approval of Research,  have been satisfied without additional information, then the IRB may defer the study. If the study is deferred, the IRB staff will work with the PI to prepare the study for review again.

6.1.4  Not Approved – The study as submitted to the IRB for review, is not approvable and no research with human subjects may take place. This decision may only be made by a fully convened IRB Full Board. This decision may only be appealed/overturned by a fully convened IRB Full Board.

6.2  Approval Period

When an application is approved, the research approval period is issued.  Any research done before or after this approval period is subject to an investigation of non-compliance (see section 10 below).  This includes recruitment of participants, consenting participants, collecting data from participants, and analyzing identifiable or re-identifiable private information.

6.3 Amendment Requests

If any changes must be made to the procedures or study documents in IRB approved research – including protocols undergoing Administrative Review, Limited Review, Expedited Review, and Full Board Review –an Amendment Request must be submitted to the IRB office via the electronic IRB application system. No changes to the approved study protocol may be implemented until the Amendment Request is processed and approved.

6.4  Annual Approval Renewal

All studies reviewed via the Full Board and some studies reviewed via Expedited procedures, must undergo Annual Review.

7.  COOPERATIVE RESEARCH

7.1  Cooperative Research with Other Institutions

Cooperative research projects are those projects that involve NC State University and at least one other institution or unaffiliated investigator. When conducting cooperative research projects, each institution or unaffiliated investigator is responsible for safeguarding the rights and welfare of human subjects and for complying with 45 CFR 46 (Protection of Human Subjects Research). Any institution or unaffiliated investigator that is engaged in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted. Details about Cooperative research can be found at 45 CFR 46.114, Cooperative Research.

7.2 Determination by Another Institution

7.2.1 For cooperative research where a study has been reviewed and approved by another IRB (not NC State’s IRB), and that study was deemed Exempt, the NC State IRB may provide the researcher with a letter “accepting the exemption determination” from the other IRB provided that the NC State researcher is implementing procedures approved by the other IRB.

7.2.2 For cooperative research where a study has been reviewed and approved by another IRB (not NC State’s IRB), and that study was deemed non-exempt, the NC State IRB and the other IRB, provided that the NC State researcher is implementing procedures approved by the other IRB, will enter into a Reliance Agreement. This agreement allows one IRB to rely on the review and approval of another IRB.

7.3 Unaffiliated Investigators

For cooperative research where a study will be reviewed and approved by NC State’s IRB and an unaffiliated investigator is involved, the NC State IRB will enter into an Individual Investigator Agreement. This agreement allows the NC State IRB to serve as the IRB of record for the unaffiliated investigator.

8.  DOCUMENT RETENTION

8.1. Researchers

Researcher(s) are responsible for retaining copies of all research records relating to the research project (original submitted protocol, changes to protocols, signed consent forms, correspondence with the IRB, etc.) for no less than three (3) years after the completion of the research.

8.2. IRB Office

The IRB Office is responsible for retaining copies of all approval information and considerations regarding the research with human subjects and all information regarding participant complaints, unanticipated problems, adverse events, and non-compliance. This documentation is retained for three (3) years after completion of the research.

9.  DATA MANAGEMENT

Data must managed as described in the approved IRB protocol and in accordance with all federal laws, state laws, local laws, and NC State regulations and data security standards.

10.  MANDATORY REPORTING

10.1  Unanticipated Problems and Adverse Events

All Unanticipated Problems and Adverse Events must be reported by the researchers to the IRB office as soon as possible with all appropriate information for the IRB to make relevant determinations.

10.2  Non-compliance

NC State researchers conducting research with human subjects must comply with the provisions of the IRB-approved study as well as all related federal regulations, university policies, and state and local laws. The failure (regardless of intention) to comply with any federal, state, or local regulation governing human research including university policies on human research constitutes “non-compliance”.  Non-compliance includes any deviation from the protocol approved by the IRB, or deviations from stipulations imposed by the IRB, as a condition of approval. If a researcher becomes aware of any non-compliance, the researcher must report this to the NC State IRB Office immediately.

11. SUSPENSION OR TERMINATION OF STUDIES

The NC State University IRB may suspend or terminate some or all research activities on a protocol if events are identified that represent serious or continuing noncompliance or unanticipated problems involving risk to subjects or others. The NC State IRB may also suspend some or all of the research conducted by a principal investigator as a result of serious or continuing noncompliance with the research or if there are unanticipated problems involving risk to subjects or others.  This action is most often determined by a convened board. However, the IRB Chair in conjunction with the IRB Director and Director for Regulatory Compliance has the authority to suspend some or all research activities if exceptional human subject safety issues are identified.

12.  IRB POLICIES AND GUIDELINES

All researchers conducting research with human subjects must adhere to all policies established by the NC State IRB. Policies may be found on the NC State Human Subjects’ IRB Website.