Chapter 3: Submission and Review of Research Protocols

Aerial view of the 91��Ԫ campus and buildings around UM's Oval in Missoula, MT.

Research Compliance and Tech Transfer

Chapter 3: Submission and Review of Research Protocols

The 91��Ԫ requires that all research projects involving human subjects be approved by UM's IRB. Any employee, adjunct faculty member or student who, on behalf of the 91��Ԫ, conducts research using human subjects must receive IRB approval prior to recruitment and/or screening. The type of IRB review and the associated review process (e.g., full board, expedited, exempt, not human subjects research) are determined by the:

Level of risk to research participants
Type of research being conducted (e.g., an educational intervention, a survey, an ethnographic observation, etc.)
Sensitivity of the research questions or complexity of the research design
Involvement of vulnerable populations as research participants
Use of identifiable information or identifiable biospecimens
Applicability of one or more of the criteria for exempt or expedited review

After an application has successfully completed the pre-review process, it will be assigned a review type. In general, an application can be assigned to one of four review categories: Not Human Subjects Research (NHSR) (45 CFR 46.102(l)), Exempt Review (45 CFR 46.104), Expedited Review (45 CFR 46.109; OHRP Expedited Review Categories) and Full Board Review (45 CFR 46.109). In all cases IRB staff and members review protocols to ensure that:

Risks to the subjects are minimal, and are reasonable in relation to anticipated benefits
The subject selection is equitable
Privacy and confidentiality are protected
Informed consent processes meet federal, state, and UM regulatory requirements

All IRB applications should be submitted through the IRB’s online application system Cayuse Human Ethics (HE).

1. Deadlines and Review Times

New and continuing applications for review may be submitted at any time. Please allow up to three weeks for Exempt and Expedited review time. This timeline is an estimate; reviews may take longer if they are complex, require significant revisions, or require review by other reviewers or departments, such as Legal Counsel or the Institutional Biosafety Committee. Reviews may also take longer during high volume periods. All applications are processed in the order they are received.

If a proposal must be reviewed by the full committee, the application must be received at least four weeks before the next committee meeting in order to be considered at the next IRB meeting.

If this day falls on a weekend or holiday, applications may be submitted the following business day. Principal Investigators will be informed of the committee's decision by email within a week following the IRB meeting. As revisions are often required, please allow four to eight weeks for final approval to be obtained.

2. Determining “Research Involving Human Subjects”

Per 45 CFR 46.102(l), an activity is considered to be “research” if it involves a “systematic investigation designed to develop or contribute to generalizable knowledge.” Activities not systematic, not designed to contribute to general knowledge, or done only for personal use (i.e. not shared with anyone else, including other members of the department) do not meet this definition.

Per 45 CFR 46.102(e), research is considered to involve “human subjects” if it entails obtaining information about living individuals, either through intervention or interaction with the individuals, or if the research involves the use or receipt of individually identifiable information, including biospecimens, originally obtained in a context in which the individuals could reasonably expect privacy.

In order for research to be subject to FDA regulations, it must be a “clinical investigation,” which is defined as “any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit... The terms ‘research,’ ‘clinical research,’ ‘clinical study,’ ‘study,’ and ‘clinical investigation’ are deemed to be synonymous for purposes of this part” (21 CFR 56.102(c)). A “human subject” “means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient” (21 CFR 56.102(e)).

The IRB follows the regulatory definitions when considering whether a project is subject to IRB review as research involving human subjects.

If it is unclear as to whether an activity meets the regulatory definition of human subjects research, the IRB staff can assist in making this determination. If the IRB staff finds that the activity does not constitute human subjects research, the staff will, upon request, issue documentation stating that the activity does not require IRB review or approval. No further review of the project is required, unless aspects of the project change so that it then becomes research involving human subjects. Requests for this type of review should be submitted through the Cayuse Human Ethics platform via a “Human Subjects Research Determination Request”.

Note that federal, state, or local laws or regulations may apply to activities whether or not they meet the definition for research involving human subjects as outlined by 45 CFR 46 and 21 CFR 56.

Deceased Individuals

Federal human subjects research regulations only apply to living individuals. Work with deceased individuals does not need IRB approval. However, please note that the Health Insurance Portability and Accountability Act (HIPAA) Security and Privacy regulations [45 CFR 160, 164] apply to individuals both living and deceased. Thus, if any protected health information as defined by the HIPAA regulations is collected about deceased individuals, additional protections for subjects may be necessary before beginning a proposed activity (even if the activity does not otherwise qualify as human subjects research) to comply with HIPAA.

3. Protocol Submission Process

The 91��Ԫ IRB uses the web-based system Cayuse Human Ethics for managing human subject research studies. Cayuse Human Ethics is an electronic protocol management platform that is cloud-based, user-friendly, and secure. Cayuse Human Ethics should be used to prepare and submit all initial human subjects research studies, as well as make modifications, request renewals, and report incidents. Investigators can find information on using Cayuse Human Ethics on the IRB website.

The IRB website is also regularly updated to include revised or new policies and procedures. When preparing a protocol, it is advisable to consult the IRB website and/or contact the IRB staff for assistance to ensure an acceptable submission. Review of a protocol may be delayed if further information is required.

Developing the Study Protocol

Project information entered into the IRB application should be thorough and complete. Incomplete or inaccurate information is one of the most common reasons IRB applications get returned to PIs for revisions. Sources should always be cited within the application when relevant.

Information requested by the IRB application includes, but is not limited to:

The purpose of the research and why human subjects must be involved, including any relevant hypotheses, study design, and study location information.
Project funding, especially if federal funding sources are involved. A note on subcontracted research: when a UM researcher is engaged in a subcontracted portion of a non-exempt human subjects research study, regardless of whether that portion considered by itself would meet an exemption, the subcontracted researcher must obtain IRB review and approval for that activity.
Identification of the participants, including inclusion/exclusion criteria, the number of people enrolled, their ages (or an age range), whether minors are involved, and/or whether participants are members of a physically, psychologically, or socially vulnerable population. You will also be asked to describe how the subject's personal privacy will be protected, and the confidentiality of information maintained.
The informed consent process, including copies of any informed consent forms being used. The IRB highly recommends that researchers use our informed consent templates to customize their own forms.
Recruitment/selection procedures, including copies of all flyers, advertisements, and other recruitment materials that may be used.
A precise and explicit description of the activities the subjects will perform, including the instrumentation and procedures to be used and kinds of data or information to be gathered. Provide enough detail so the IRB will be able to evaluate the intrusion from the subject's perspective.
The benefits of the research, if any, to the human subjects and to scientific knowledge. If the subjects will not benefit from their participation, so state.
The risks and discomforts to which the subjects will be exposed. Such deleterious effects may be physical, psychological, professional, financial, legal, spiritual, or cultural. Some research involves violations of normal expectations, rather than risks or discomforts; such violations, if any, should be specified. It is highly unusual to state there are no risks or discomforts. Also include a description of how each deleterious effect or violation will be minimized.

Additional application sections will be required if study teams are: conducting international research; conducting research on an Indian reservation and/or specifically recruiting a Native American population; and/or are collaborating with external researchers outside of UM.

Be prepared to attach several files to the submission. These may include informed consent forms, recruitment materials, survey instruments, interview questions, site permission letters, and more. All participant-facing materials require prior IRB review and approval.

Ensure All Necessary Reviews, Approvals, and Site Permissions are in Place

Depending on the particulars of your research study, you may need to secure additional reviews, approvals, or notifications from other units or organizations prior to initiating your research. Studies that involve external funding must have appropriate contracts and agreements in place with the Office for Sponsored Programs.

Please note that any researchers working with human blood, body fluids, genetic material, and/or tissue are required to submit a UM Institutional Biosafety Committee (IBC) application.

It is the Principal Investigator’s responsibility prior to conducting research to determine what, if any, permissions are required. Certain UM departments, campus buildings, schools, external organizations, and other sites may require researchers to obtain site permission before conducting research. Some examples include, but are not limited to:

UM Athletics – researchers are required to obtain permission from the UM Athletics director prior to conducting any research that specifically recruits UM student athletes, as per NCAA regulations.
Other UM auxiliary sites, such as the University Center, clinics, and the ASUM Daycare Center.
K-12 schools, preschools, and daycare centers – permission must be given by either a principal or the superintendent.
Corporate and privately-owned businesses, as well as non-profit agencies such as the YMCA, YWCA, or food banks. Hospitals, clinics, and other healthcare organizations are included as well.
Public locations where there is an expectation of privacy, such as bathrooms.
Trailheads on Federal Land (A National Park Service (NPS) research permit is required for all types of research).
Indian reservations.

Site permission can be submitted to the IRB via the IRB application or, in certain cases, via email.

4. IRB Review Process

Application Pre-Review

When an IRB application is submitted, it is first sent to the UM IRB office staff for pre-review. During this process, the application is reviewed for completeness, thoroughness, and accuracy. IRB staff check to make sure that all questions were answered and that the investigator has provided enough information for the application to move to the next step in the workflow process. IRB staff will also review the application for mistakes, such as spelling and grammatical errors (particularly in the informed consent form and any other participant-facing documents, such as flyers) or missed questions. Applications may be returned to investigators at this stage for revisions before it is sent on to the next step in the review process.

Investigators are encouraged to consult with the UM IRB office on complex protocols prior to submission. Clearing up questions and issues beforehand reduces the chances that an application will be returned to the study team for revisions, thus saving time and effort for all involved.

Assigning a Review Type

After an application has successfully completed the pre-review process, it will be assigned a review type. In general, an application can be assigned to one of four review categories: Not Human Subjects Research (NHSR), Exempt Review, Expedited Review, and Full Board Review. In all cases, but most especially for Expedited and Full Board reviewed studies, IRB staff and members are reviewing protocols to ensure that:

Risks to the subjects are minimal and are reasonable in relation to anticipated benefits.
The subject selection is equitable.
Privacy and confidentiality are protected.
Informed consent processes meet federal, state, and UM regulatory requirements.

5. IRB Review Categories and Decisions

Research that is Not Human Subjects Research (NHSR)

Not all research-related activities that involve people, their data, or their biospecimens are covered by the regulations governing human research (see above section). Submission to the IRB is not required for the following activities:

Case studies
Class activities (with some exceptions; does not include theses and dissertations)
Journalism/documentary activities
Oral history
Quality assurance and quality improvement activities unless they meet the federal definition of human subjects research
Research using deidentified data or biospecimens
Research using publicly available data sets

Exempt Review

Per UM IRB policy, investigators must submit an IRB application for determination of exemption before research begins. It is important to note that an Exempt determination is different than a Not Human Subjects Research determination. Exempt research still meets the federal definition of “human subjects research” and must fit within one of six very specific Exempt review categories as defined in 45 CFR 46.

While the use of a formal informed consent form containing all the elements of consent is not required for Exempt research, the UM IRB still requires researchers to provide information, in written form, to potential participants prior to their enrollment in the research. At minimum, this information should include:

A statement that participants must be 18 years or older to participate;
An explanation of the research, including the expected time commitment;
Any potential risks or discomforts related to participation, such as discomfort responding to personal/sensitive questions, privacy concerns, disclosure risks;
A statement that the research is voluntary and that they may withdraw at any time;
How privacy and confidentiality will be protected;
Contact information for the PI and the UM IRB;
And any other key elements of the study that participants should know before agreeing to take part.

Projects receiving an exempt determination are not subject to the Continuing Review process. Amendments are required only if the changes to the project would alter the exemption criteria or if new study personnel are added to the project. An Exempt determination does not lessen the researcher's ethical obligations to participants as articulated in the Belmont Report or to the codes of conduct for specific disciplines.

Research involving prisoners or certain types of research with children (e.g. surveys, interviews, observations of public behavior where the investigator interacts with the children) does not qualify for exemption.

Expedited Review

Federal regulations (45 CFR 46.110) authorize the use of an expedited review process for:

Minimal risk human research that meets one or more of the OHRP Expedited Review Categories.
Minor changes to research previously approved by the full board.

Applications qualifying for Expedited review are reviewed by the IRB Manager, the IRB Chair, and potentially to one or more experienced IRB members. These reviewers may request additional clarifications or changes from a PI before the application is approved. During an Expedited review process, a submission may be referred to the full board for review instead (for reasons of clarification, expertise, etc.), including in cases of disapproval. Only the full board has the authority to disapprove a study.

Most studies that qualify for the expedited review process do not require annual Continuing Review.

Expedited studies must meet all of the federal requirements for the elements of informed consent (45 CFR 46.117). These elements may only be waived if the investigator formally applies for such a waiver and the IRB formally grants it. Investigators must have a compelling argument for why a certain element of informed consent, such as a written signature, should be waived.

All signed Informed Consent forms must be retained by the PI for at least 3 years after completion of the research, per federal regulation [45 CFR 46.115(b)]. The forms must be stored in a secure, locked location separate from the de-identified data. If the study involves HIPAA, consent forms must be kept for at least 6 years.

Full Board/Committee Review

Federal regulations and institutional policy require a review by the IRB Full Board for applications where the research involves more than minimal risk to human subjects, does not meet the criteria for one of the categories of expedited review, and/or has been referred to the committee by an Expedited reviewer or the Chair/Manager. Regardless of risk level, the UM IRB may require full board review when the research involves:

Vulnerable populations, particularly prisoners.
Sensitive topics, including illegal behaviors which may require an NIH Certificate of Confidentiality (CoC) to protect subject data from compelled disclosure.
Research involving genetic/genomic analyses.
A complex research design requiring the expertise of multiple board members to evaluate

If an application is “committee ready”, meaning that it contains all the information and materials necessary for the full board to conduct its review, the application will be assigned to the next IRB meeting date, except where the agenda is already full or a reviewer with the necessary expertise is not available for that meeting. Investigators may be invited to attend the meeting to answer questions from the board. At the conclusion of the meeting, the board votes and issues a determination for the submission.

Possible decisions that can be made by the fully convened IRB include:

• Approved: the application is approved as submitted.
• Conditional Approval: the application is approved, contingent on submission of specified changes to the protocol, informed consent document(s) and/or other supporting materials. Final approval status is granted when either the IRB or the IRB Chair (if so authorized by the board) has reviewed and approved all requested changes.
• Resubmission: the IRB needs additional information from the investigator before the IRB can make all of the determinations found at 45 CFR 46.111 necessary to approve the study. The principal investigator must submit the requested additional information before the IRB will consider the application for further review.
• Disapproved: the protocol does not provide adequate protection to human participants, and it is unlikely that it can be modified to provide such protection. The IRB notifies the principal investigator of the disapproval in writing, including a statement of the reasons for its decision, and provides the opportunity for the investigator to respond to the IRB in person or in writing.

All full board reviewed research is required to be issued an expiration date of no more than one year from the original date of approval. Applications must be renewed every year. Projects that are expired must cease all work immediately until the project is brought back into compliance.

If you think that your research may require a full board review, please consult with the UM IRB office. The submission deadline for full-board reviewed proposals is the first business day of each month.

6. Appeal of IRB Decisions

If an investigator wishes to make an appeal of any IRB decision regarding a protocol proposal or a previously approved protocol, the investigator must submit a formal request in writing to the IRB Committee. The appeal must include details as to the exact nature of the investigator’s disagreement with the Committee decision and the basis for making a claim to overturn that decision, including supporting evidence. The thorough review of and discussion on every submission to the IRB by the Committee ensures that the Committee feels confident in decisions they have made; consequently, an investigator wishing to make an appeal must present sufficient evidence to persuade the Committee to reconsider their decision. Assessments regarding whether or not to bring a protocol back to the Committee for further review upon the appeal of the investigator will be made by IRB Manager and the Chair, in consultation with Vice-Chair(s), Associate Vice President for Research and/or the Vice-President for Research.

If an appeal is insufficient for review by the full Committee, the investigator will be notified in writing. If the Committee does consider an appeal, the Committee’s decision regarding the merits of the appeal will be conveyed in writing to the investigator following the meeting.

External institutions or authorities cannot override IRB decisions; only the IRB Committee itself can overturn its decisions.

7. Continuing Review and Study Closure

Continuing Review

When a study is nearing its expiration date, the PI must submit a renewal request, also known as a continuation, in order to continue with the research. The renewal will need to be approved before the PI can continue with the study. A study renewal may be required for certain studies and under certain circumstances. All Full Board-approved studies are required to be renewed not less than once a year and are issued an expiration date. Most Expedited and Exempt studies are not required to be renewed and are not issued an expiration date unless the IRB decides there is a reason to monitor a study.

All Expedited and Full Board studies approved before January 1st, 2019 will have been issued an expiration date and must be annually renewed or formally closed. All studies approved before January 1, 2024 that have been issued an expiration date will continue to use the previous paper/email submission system.

Projects for which approval has expired are in non-compliance with federal regulation and UM IRB policy and all work must cease.

Studies submitted through Cayuse HE will automatically receive a 90-, 60-, and 30-day notification prior to their study expiration date. Principal Investigators are responsible for keeping track of their study expiration date.

Principal Investigators who are submitting continuations for studies that were approved prior to the Cayuse HE system will receive a notification from the IRB office at least 30 days prior to the expiration of their approval. This notification is simply a courtesy; PIs are responsible for keeping track of their own study expiration date. To submit a continuation/renewal using this method, download, complete, and submit the Continuation / Closure Report (form RA-109), located on the IRB website.

Study Closure

If a study was issued an expiration date, then it must be formally closed when at least one of the following situations occurs: the research is completed; when analysis is limited to de-identified data only; or if the project has been abandoned or significantly postponed.

A research project no longer involves human subjects once the investigators have finished obtaining data through interaction or intervention with subjects or obtaining identifiable private information about the subjects, which includes the using, studying, or analyzing identifiable private information. Once all such activities described in the IRB-approved protocol are finished, the research project no longer needs to undergo continuing review and may be closed. For example, when the only remaining activity of a research project involves the analysis of aggregate data sets without individual subject identifiers, no further continuing review is necessary. At that point, the IRB can formally close the IRB file for the project and advise the investigator of that action.

Similarly, simply maintaining individually identifiable private information without using, studying, or analyzing such information is not human subjects research and thus does not require continuing review. If a study is in data analysis only AND the PI has destroyed all private information about the subjects, the IRB can be notified and they will close the study.

If you need to close your study, you can do so by completing a Study Closure submission. A closure submission within Cayuse HE indicates that the research is complete and will not be continuing. Closed studies are marked as finalized and can no longer be modified.

Studies approved prior to January 1, 2024 (and prior to the Cayuse HE system implementation) will need to submit a closure report using our paper-based system. To submit a closure report using this method, download, complete, and submit the Continuation / Closure Report (form RA-109), located on the IRB website.

8. Student Research and Courses Involving Students’

Investigations Using Human Subjects UM students wishing to conduct research involving human subjects for any course, including thesis, dissertation, research methods or independent study courses shall be subject to the same rules regarding IRB submission of their research proposal as UM faculty. Student projects involving human subjects must be supervised by a UM faculty member who has been approved by his/her department to supervise this type of student research. The faculty member cannot be a supervisor in name only but must provide actual supervision.

Independent research projects that include human subjects and employ systematic data collection with the intent of contributing to generalizable knowledge will require IRB review. Theses, dissertations, and honors research projects involving human subjects that are considered research as defined by 45 CFR 46 (i.e., “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge”) always require review by the IRB.

Research projects for which the overriding and primary purpose is a learning experience in the methods and procedures of research do not meet the federal definition of research and are therefore generally not subject to (i.e., is excluded from) IRB review/approval. Curriculum projects in which students conduct research involving human subjects need not be reviewed by the IRB if the following conditions are satisfied: the research is minimal risk and does not include any vulnerable populations, as defined by the federal regulations (e.g., children, prisoners, pregnant women, fetuses, or neonates); the project does not involve sensitive topics or confidential information like medical or education records data; participation is voluntary; and the results are never distributed outside the classroom (i.e., published or presented at a conference).

9. Subcontracted Research

When a UM researcher is engaged in a subcontracted portion of a non-exempt (i.e., Expedited or Full Board Review) human subjects research study, regardless of whether that portion considered by itself would meet an exemption, the subcontracted researcher must obtain IRB review and approval for that activity. The researcher may take either of the following actions:

1. Submit an application to the UM IRB for review of the subcontracted portion of the study. The complete, approved application from the parent organization’s IRB may be submitted to the UM IRB if it contains sufficient detail of the subcontracted work. Otherwise, a separate UM application needs to be submitted along with the determination letter from the parent organization’s IRB.
Contact the UM IRB to inquire whether a reliance agreement can be entered into with the parent organization, it which case the researcher would need to comply with their application and review procedures.

10. External Reviews

The 91��Ԫ IRB will conduct reviews of appropriate, external, human subjects research proposals on a fee-based schedule.

When an investigator is not engaged with the 91��Ԫ as an employee or student for the purpose of conducting a research project involving human subjects, that project will be considered external and charged a fee regardless of the for-profit or non-profit nature of the project, investigator, or investigator’s company or agency.

The UM IRB will only conduct external reviews of proposals for which it is qualified in terms of adequate experience and subject expertise. Specifically, the IRB reserves the right to accept or decline a request for review on a case-by-case basis. In most cases, the IRB authorizes the IRB Manager to make this decision, but accepting or declining review will in some cases be determined by the board. The UM IRB will review proposals at the Full Board, Expedited, and Exempt levels of review as is appropriate to the complexity and risk level of the proposal.

Fee Schedule upon acceptance:

• $1,000 initial review
• $400 amendments
• $200 continued review
• $50 closure report

The fees are assessments of costs associated with study reviews conducted by the IRB and are charges for services rendered. The initial review fee also includes access to UM’s CITI account for any human subjects training that the investigating team may need. Fees are due and payable upon submission to the IRB for initial, continued, amendment or closure review. Checks are payable to the 91��Ԫ.

Fees are non-negotiable and non-refundable. Because the IRB office commits its resources appropriate to each level of review, fees are due in full from the applicant regardless of subsequent conduct of the study, including disapproval by the IRB or early termination by the investigator or sponsor.

Intellectual Property and Technology Transfer

Externally reviewed projects are not subject to the 91��Ԫ’s intellectual property rights and, therefore, are not subject to its licensing policies. Any intellectual property that results from externally-conducted research is subsequently owned by the external investigator(s), company, or agency.