Research Involving Human Subjects

From Appalachian State University Policy Manual

University Policy 209

1. Purpose

This policy provides authority to the Appalachian State University Institutional Review Board (hereinafter “IRB”) to provide ethical and regulatory oversight for research involving human subjects conducted by Appalachian State University (“University”), its faculty, staff, students and visitors.

2. Scope

All research involving human subjects that is conducted by University researchers – regardless of funding or funding source – must be reviewed and approved by IRB for the use of human subjects in research. This policy applies to all Appalachian faculty, staff, students and any other individual engaged in cooperative research with University that involves human subjects.

3. General Principles

All University 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/or the federal regulation 45.CFR.46.

4. Definitions

4.1 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.

4.2 Anonymity

Means that the identity of a subject cannot be matched to their responses, either directly through identifiers or by "linked" or "coded" responses.

4.3 Clinical Trial

Means a research study in which one or more human subjects is prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the intervention on biomedical or behavioral health-related outcomes.

4.4 Confidentiality

Means not disclosing individually identifiable information received from a human subject to others in a manner inconsistent with the understanding of the original Informed Consent agreement.

4.5 Data Collection

Means any research procedure that is intended to elicit from or record the actions, reactions, attitudes, and/or behavioral manifestations of human subjects participating in a research project.

4.6 De-Identified Data

De-identified data refers to the dataset that an investigator has created when they initially generated identifiable data and then removed all direct and indirect identifiers from the data set. The investigator at one time had access to identifiable/indirectly identifiable data, but they have removed the ID/code from the dataset or destroyed the linkage file and thus, the data can no longer be linked back to any individual subject in the study.

4.7 Exempt Research

Means human subject research activities which are minimal risk in nature and fall into one or more of the federally defined exempt research categories.

4.8 Expedited Review

Means a review by the IRB Chair or designee of research proposals which involve minimal risk.

4.9 Full IRB Review

Means the review of proposals conducted during a convened IRB meeting at which a quorum has been established.

4.10 Human Subject

Means a living individual about whom a researcher conducting research that (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable bio-specimens.

4.11 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)).

4.12 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.

4.13 Interactions

Means communication or interpersonal contact between the investigator and subject.

4.14 Intervention

Means 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.

4.15 Informed Consent

Means the voluntary agreement by an individual or an individual's legally authorized representative to participate in a particular study without any element of force, fraud, deceit, duress, or any other form of constraint or coercion. Valid consent requires voluntary action, competence, informed decision, and comprehension of terminology.

4.16 IRB

Means the University’s institutional review board.

4.17 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.

4.18 Minimal Risk

Means that the probability and magnitude of harm(s) or discomfort(s) anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations.

4.19 Non-compliance

Failure of an investigator to follow the applicable laws, regulations, or institutional policies governing the protection of human subjects in research, or the requirements or determinations of the IRB, whether the failure is intentional or not.

4.20 Personally Identifiable Information (PII)

Means 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.

4.21 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).

4.22 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 policy, whether or not they are conducted or supported under a program that is considered research for other purposes. For example, some demonstration and service programs may include research activities.

4.23 Terms of Assurance

An assurance of compliance is a written document submitted by an institution (not an Institutional Review Board) that is engaged in non-exempt human subjects research conducted or supported by the Secretary of Health and Human Services (HHS). Through the assurance of compliance, an institution commits to HHS that it will comply with the requirements set forth in the regulations for the protection of human subjects at 45.CFR.46. The Federal wide Assurance (FWA) is the only type of assurance of compliance accepted and approved by the Office of Human Research Protections.

4.24 University

Means Appalachian State University.

4.25 Unanticipated problems:

Means any incident, experience, or outcome that meets all of the following criteria (as determined by the IRB):

4.25.1. 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;
4.25.2. 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
4.25.3. 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.

4.26 Vulnerable Populations

Means human subjects that are children, prisoners, pregnant persons, or any population that may be relatively or absolutely incapable of protecting their interests through the informed consent process. Other examples of vulnerable populations include people who are situationally vulnerable due to their status such as employee, student, student-athlete, or people who are marginalized due to their individual identity or demographics.

5. Policy and Procedure Statements

5.1 Roles and Responsibilities

5.1.1 Research Investigators

The primary responsibility for the ethical and compliant conduct of research shall reside with the investigators who are conducting the research. This includes but is not limited to responsible and compliant research design, implementation, and the seeking of appropriate research protocol approvals. When student work is submitted to the IRB for review and approval, a University faculty member must serve as the primary investigator and as the student’s advisor, and must assume responsibility for the conduct of the student’s research under their direction.

5.1.2 Institutional Official

The Institutional Official (IO) is the individual who is legally authorized to act for the institution and, on behalf of the institution, obligates the institution to the Terms of the Assurance. The IO is responsible for ensuring that the Human Research Protection Program (HRPP) functions effectively and that the institution provides the resources and support necessary to comply with all requirements applicable to research involving human subjects. The IO represents the institution named in the FWA. The IO is a Chancellor appointed individual of sufficient rank who has the authority to ensure that all obligations of the HRPP are carried out effectively and efficiently.

5.1.3 The IRB Chair

The IRB Chair promotes a culture consistent with the objectives of University’s HRPP, with special emphasis on the respect for and protection of individuals participating in research at the University. The IRB Chair presides over meetings of the fully convened IRB and ensures that the IRB carries out its duly authorized responsibilities as required by federal regulations, ethical principles, state laws, and University policy. The IRB Chair works closely with the IRB Office Staff and the IO to ensure that policies and procedures are current, research with human subjects, regardless of level of review, meet all necessary standards or criteria for approval.

5.1.4 The IRB Full Board

The IRB Full Board is made up of a diverse group of people proposed by the IRB Chair and the IO. The IRB Full Board must be composed of people who are scientists, non-scientists, unaffiliated with the University in any other way, and experts in research areas commonly employing human subjects at University, and those with expertise with unique or vulnerable populations. The IRB Full Board is responsible for reviewing and approving research with human subjects to ensure compliance and ethical treatment of participants. A convened IRB Full Board is the only authority that can “disapprove” a study.

5.1.5 Office of Research Protections

The Office of Research Protections provides administrative support and leadership to the IRB Office.

5.1.6 The IRB Office Staff

The IRB office is made up of administrative staff who are tasked with managing the daily operations for facilitating the review and approval for research with human subjects completed by Appalachian State University faculty, staff, and students. The IRB office, in conjunction with the IRB Full Board, is responsible for the interpretation and implementation of this Policy and all subsequent unit standards and operating procedures.

5.2 IRB Oversight

5.2.1 Any research involving human subjects, regardless of funding or funding source, where University faculty, staff or students are engaged in the project as research personnel, must be reviewed and approved by the IRB prior to implementation of any research procedures including recruitment and consent, implementation of intervention, interaction with participants, manipulation of participant’s environment, or access to private identifiable data.

5.3 Protocol Submission, Review, and Approval

5.3.1 Protocol Submission

5.3.1.1. University researchers are expected to complete thorough and internally consistent IRB applications adhering to all applicable laws, policies, regulations, and unit standards.

5.3.1.2. The IRB accepts IRB applications via an online electronic application system. This system allows researchers to submit an IRB application and related study materials to the IRB for review and approval. The online application system is accessible via University’s IRB Website.

5.3.1.3. A student may complete the IRB application and provide related materials. However the application itself must be formally submitted to the IRB by the student’s faculty advisor (FA), designated as the primary investigator (PI) in the application and all supporting documents. After ensuring all aspects of the application are complete, the FA may then certify the application and supporting documents for review by the IRB.

5.3.2 Protocol Review

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. There are four types of review for projects submitted to the IRB. 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.

5.3.2.1. Administrative review leading to an Exemption Determination

The federal regulations governing research with human subjects (45.CFR.46.104) detail categories of research involving human subjects that are deemed “exempt from the requirements of the regulation.” At University, the IRB office makes this determination, the researcher does not. This means that when a researcher submits an application to the IRB for review, that the IRB office will review the protocol and determine its eligibility for exemption. These studies are beholden to ethical standards and applicable federal, state, and local laws.

5.3.2.2. Limited review leading to an Exemption Determination

The federal regulations governing research with human subjects (45.CFR.46.104) detail categories of research involving human subjects that are deemed “exempt from the requirements of the regulation.” When a human subjects research protocol is minimal risk, fits into the regulatorily defined exemption categories, and the IRB completes a “Limited Review,” studies that may have required an Expedited review due to privacy and confidentiality concerns, may instead be eligible for exemption. A Limited review is completed by the IRB and ensures that there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of their data.

5.3.2.3. Expedited Review

Expedited review consists of a review of a research protocol involving human subjects by the IRB chairperson or by an experienced reviewer designated by the chairperson from among members of the IRB in accordance with the requirements set forth in 45 CFR 46.110. A study is eligible for Expedited review when the proposed research poses no more than minimal risk to participants and study procedures involve only one (or several) of the categories of research outlined by 45.CFR.46 and supplemental guidance. These categories will be maintained by HHS, updated as appropriate, and posted as a notice in the Federal Register. Studies undergoing Expedited review are subject to all aspects of 45.CFR.46.111.

5.3.2.4. Full Board Review

Studies requiring Full Board review and approval are studies that are considered “more than minimal risk,” testing a medical device for safety or efficacy, investigating a drug or biologic, or a study that is “minimal risk” but it does not fit into any eligible Expedited review categories. Studies requiring Full Board review are subject to all regulations set forth in 45.CFR.46 and the study may only be approved at a convened Full Board meeting with quorum.

5.3.2.5. Amendment Requests

Any changes to the research procedures or study documents in an IRB approved protocol - regardless of level or review - an Amendment Request must be submitted to the IRB office via the electronic IRB application system before any changes are implemented. No changes to the approved study protocol may be implemented until the Amendment Request is processed and approved by the IRB.

5.3.2.6. Annual Approval Renewal

All studies reviewed via the Full Board, some studies reviewed via Expedited procedures, or studies contractually obligated to do so, must undergo Annual Approval Review.

5.3.3 Protocol Approval

5.3.3.1. Approved

The study protocol was approved by the IRB, and research with human subjects as described in the approved protocol may commence.

5.3.3.1.a. For all non-exempt studies, in order for a study to be considered approved, the IRB must find that the study has met the criteria for approval as defined in the federal regulation 45.CFR.46.111.

5.3.3.1.b. For all studies resulting in an Exemption Determination from the IRB, the IRB must find that the study is minimal risk, applicable laws are accounted for, and participants are appropriately treated throughout the research. When a “Limited Review” is required for an Exemption Determination, the IRB must find that the study has met the criteria for approval as defined in the federal regulation 45.CFR.46.111.a.8.

5.3.3.2. Approved with Stipulations

If the study is approved with stipulations, the IRB staff will work with the PI to complete the necessary changes and finalize approval. Research procedures may not commence until final approval is granted.

5.3.3.3. Deferred

If the convened IRB Full Board is unable to document that the criteria of approval detailed in 45 CFR 46.111 have been satisfied, 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.

5.3.3.4. 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 convened IRB Full Board with quorum. This decision may only be appealed/overturned by a convened IRB Full Board with quorum. Any appeal shall be in writing to the IRB Full Board and, upon request, the PI may present arguments and evidence to the IRB Full Board at a duly convened meeting of the IRB Full Board. While the PI may request notification of the appeal to the Provost or other academic administrator, the final decision of any appeal rests with the IRB Full Board and no further appeal shall be available to the PI.

5.3.3.5. 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. This includes recruitment of participants, consenting participants, collecting data from participants, implementing an intervention with participants, manipulating participants’ environment, and analyzing identifiable or re-identifiable private information. Under special circumstances, the IRB may require approval renewal for studies at increments shorter than one year. An approval period is applicable to all full board studies, and in some cases, studies receiving expedited approval or studies eligible for exemption.

5.3.4 Ancillary Reviews

Research proposals approved by the IRB may be subject to ancillary reviews by University officials as appropriate.

5.4 Required Reporting Post-Approval Monitoring

5.4.1. Required Reporting

5.4.1.1. Non-compliance

University researchers conducting research with human subjects must comply with the provisions of the IRB-approved study as well as all related federal laws and regulations, university policies, and state and local laws. The failure (regardless of intention) to comply with any applicable federal laws and regulations, university policies, and state and local laws governing human research constitutes non-compliance. If a researcher becomes aware of any non-compliance, the researcher must report this to the IRB Office immediately. A non-compliance investigation will commence in accordance with the IRB unit standard for issues of non-compliance.

5.4.1.2. 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.

5.4.1.3. Participant Concerns and Complaints

All participant complaints and concerns regarding the conduct of human subject research completed by University researchers should be brought to the attention of the IRB office. Complaints and concerns may be raised by past, present, and potential research participants, family members, designated spokespersons, or anyone else associated with the research project. Should a researcher receive a complaint or concern directly from a participant, the researcher must notify the IRB office of the issue as soon as possible. If the IRB office receives the complaint or concern, an IRB office representative will review the issue and take appropriate steps for resolution.

5.4.2. Post-Approval Monitoring

The IRB may conduct “for cause” and random audits of IRB approved research protocols in accordance with the IRB’s Standard for Post-Approval Monitoring.

5.5 Suspension or Termination of a Human Subjects’ Research Protocol

5.5.1. The IRB may suspend or terminate some or all research activities on a specific research protocol if events are identified that represent serious or continuing noncompliance or unanticipated problems involving additional or increased risk to subjects or others.

5.5.2. The IRB may suspend some or all of the research conducted by a principal investigator as a result of serious or continuing noncompliance or if there are unanticipated problems involving additional or increased risk to subjects or others.

5.5.3. Suspension or termination of a protocol or multiple protocols from one PI, is most often determined by the convened IRB Full Board with quorum. However, the IRB Chairperson in conjunction with the Director for Research Protections or Institutional Official has the authority to suspend some or all research activities if exceptional human subject safety issues are identified.

6. Cooperative Research

Cooperative research projects are those projects that involve University and at least one other researcher not associated with University. When conducting cooperative research projects, each investigator is responsible for safeguarding the rights and welfare of human subjects, for complying with 45.CFR.46, and their affiliated IRB is responsible for oversight.

6.1. Any IRB that has a researcher engaged in a federally funded non-exempt cooperative research project, must rely upon the review and approval of a single IRB via a formal agreement.

6.2. Any IRB that has a researcher engaged in an unfunded non-exempt cooperative research project, may rely upon the review and approval of a single IRB for research via a formal agreement.

6.3. Any IRB that has a researcher engaged in cooperative research eligible for an exemption determination, may rely upon the review and approval of a single IRB for research via a formal agreement.

6.4. Any investigator that is unaffiliated with an IRB, but engaging in cooperative human subjects research with a University researcher, must engage in a formal agreement with the IRB indicating that the unaffiliated investigator will abide by all University policies, standards, and requirements stated in the associated IRB approved protocol.

7. Data Management and Security

Data must be managed as described in the approved IRB protocol and in accordance with all federal laws, state laws, local laws, and University data management standards.

8. IRB Office Standards

All researchers conducting research with human subjects must adhere to all unit standards established by the IRB.

Additional Resources

Forms

Statutes

Code of Federal Regulations, Title 42, Chapter 6(a) Public Health Service, Subchapter III Part H

Code of Federal Regulations, Title 45, Part 46 (Protection of Human Subjects)

U.S. Food and Drug Administration Regulations, Title 21, Parts 50, 56, 312, 812

North Carolina Statute on Practice of Medicine

Appalachian State University's Federal-wide Assurance

Appalachian State University's Standard Operating Procedures for Human Subjects Research

Policies and Standards

Appalachian State University’s Human Subject Research Recruitment Policy

Data Management Standard

UNC System Office Records Retention and Disposition Schedule (2021)

Administrative Unit Contact

Director of Research Protections Division
Web Link
(828) 262-2901

History

Issued: April 29, 2019

Revised:
December 1, 2021
March 8, 2024
January 27, 2025