Chapter 2: Principal Investigators, Co- Investigators, and Other Research Personnel: Eligibility and Responsibilities

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Research Compliance and Tech Transfer

Chapter 2: Principal Investigators, Co- Investigators, and Other Research Personnel: Eligibility and Responsibilities

Every research study requires a Principal Investigator (PI). A PI is the individual who has the primary responsibility for ensuring the ethical conduct of the research study and assumes full responsibility for the conduct of the research. Sometimes projects may have more than one PI. Other study team members may include Co-PIs, Faculty Supervisors, and Research Assistants.

The PI is responsible for the overall conduct of the study for each human subject research protocol on which he or she is the named PI. This includes any modifications to the original submission. Investigators may not initiate or change research protocols until they have received IRB approval or exemption and may not continue ongoing programs without satisfying the federally-mandated periodic IRB continuing review requirement to assure that the research remains appropriate for human subjects and that the rights of these subjects remain fully protected.

Correspondence from the IRB is directed to the PI, who is then responsible for sharing any necessary information with study co-investigators or staff.

1. PI Eligibility

In accordance with 91��Ԫ policy, individuals who are eligible to serve as PIs on proposals for external funding may also serve as principal investigators on IRB protocols. In general, these are individuals who have faculty or other academic appointments or who are staff members at the 91��Ԫ. The groups listed below, which include students, adjunct faculty, faculty affiliates, and emeritus professors, are unique categories of investigators and may have different requirements than UM faculty and staff.

Students

Undergraduate students may not serve as the PI on any UM IRB study but may serve as Co-PI when the PI is a faculty supervisor. Graduate students may serve as PI on certain protocols but must also list a faculty supervisor.

Adjunct Faculty

UM adjunct faculty or researchers wishing to undertake research involving human subjects as part of their duties as an adjunct faculty member or researcher shall be subject to the same rules regarding IRB submission of their research proposal as regular UM faculty. If research continues at the 91��Ԫ beyond the adjunct faculty’s employment, then a modification shall be filed to transfer the project responsibilities to a new PI, who must be a current UM employee or student. If the adjunct faculty leaves the 91��Ԫ and wishes to continue the research at another institution, then a Closure report must be filed with the UM IRB office, and notification must be given to the IRB at the new institution and their procedures followed.

Faculty Affiliates

Faculty Affiliates are not University employees. Affiliates may:

Collaborate with full-time faculty, where a full-time faculty member serves as the Principal Investigator (PI) and the faculty affiliate serves as a co-PI. Full-time means full-time, not part-time or adjunct. The affiliate must report any Conflicts of Interest. If the affiliate represents an external business, a separate business contract may need to be established, intellectual property addressed, and liability clauses reviewed by legal counsel.
Request IRB review as an external researcher on a fee-based schedule.

Emeritus Professors

The IRB will conduct a review free of charge for emeritus professors. If the emeritus professor is conducting the research on his/her own as the PI, then he/she must provide evidence of their own liability insurance (that would clearly cover such activity). The university’s liability insurance does not extend to this. If the emeritus professor proposes research with student assistants, a full-time faculty member must serve as the PI. The PI is ultimately responsible for all aspects of conducting the research study. The emeritus professor may be designated as a co-PI.

2. Co-Investigators and Other Research Personnel

Any investigator engaged in human subjects research (other than the PI) must be designated as a Co-Investigator or Other Research Personnel in the IRB submission. Research personnel should be designated with the original submission or with an amendment if added or removed after original approval. An amendment must be submitted when personnel are added to or removed from the protocol. Only the named and approved research personnel may carry out procedures performed upon research subjects. Accordingly, anyone having direct contact with the subjects or their data (obtaining consent from subjects, recruiting of subjects, administering questionnaires and surveys, conducting clinical interventions, performing data analysis, etc.) must be listed on the protocol. The PI must take direct responsibility for the activities of all research personnel.

Listing Collaborators Outside of UM

UM researchers often collaborate with external partners on human subjects research projects. These collaborators are required to be listed on your IRB application if they are engaged in human subjects research. If your collaborators are affiliated with an institution that has its own IRB (ex., another university, a hospital, etc.), a reliance agreement may be needed if the protocol is Expedited or above. If your collaborators are not affiliated with an institution that has its own IRB, they will be required to complete an Individual Investigator Agreement.

3. Training

As federally mandated and required by the UM IRB, all key study personnel must complete a self-study course in human subject protection.

Key study personnel include the Principal Investigator and any other investigators and research personnel who are directly involved in conducting research with study participants or who are directly involved in using study participants’ identifiable private information during the research. Key personnel also include faculty supervisors/advisors who provide direct oversight to undergraduate and graduate students, as well as postdoctoral fellows. Members of the research team who have not completed human subject research protection training, or whose training is expired, may not take part in aspects of the research that involve human subjects or their private identifiable data.

The UM IRB uses the Collaborative Institutional Training Initiative (CITI) platform for all human subjects training. Researchers must take a CITI Basic course – either Social/Behavioral-Basic or Biomedical-Basic – in order to fulfill training course requirements. CITI training is valid for three years. Investigators and staff must renew their training certification before it expires by taking either a refresher course or retaking the full course. Certificates must be current throughout the duration of the research conducted under IRB oversight. More information about how to create a CITI account can be found on the IRB website.

Additional Trainings

Please note that researchers pursuing sponsored (funded) projects may need to complete additional training or other compliance requirements, such as a Responsible Conduct of Research (RCR) course. RCR courses are overseen by the Office of Sponsored Programs and are typically required by them for any sponsored projects. RCR courses do not fulfill the IRB human subjects protection training course requirement.

Investigators and staff funded by the National Institutes of Health (NIH) may be required to complete a Good Clinical Practice (GCP) course. GCP training demonstrates that individuals have attained the fundamental knowledge of clinical trial quality standards for designing, conducting, recording, and reporting trials that involve human research participants. GCP courses do not fulfill the IRB human subjects protection training course requirement.

UM also has additional CITI modules that researchers may be required to take, depending on the research project, including Conflict of Interest and FERPA modules.

Training for Community Research Collaborators

The UM IRB recognizes that in instances when university researchers are collaborating with community partners who are engaged in research, CITI training may not be the best or most accessible training option. In such cases, the UM IRB has the authority to approve alternative equivalent training options.

4. Responsibilities of Principal Investigators

The Principal Investigator is held responsible for ensuring that their protocols are conducted in accordance with the research plan and with all applicable regulations. Consequently, it is the responsibility of the PI to:

ensure that all procedures in approved protocols (including the consent process) are performed and/or supervised by the listed investigator or other authorized personnel (not unlisted investigators, students, technicians, etc.);
request approval from the IRB in the form of an amendment to change the investigator or other personnel;
provide the IRB with the appropriate information on the research protocol including initial information, notification of subsequent modifications, terminations, and unanticipated problems, and to use the appropriate IRB format and forms for supplying this information;
ensure that no research will be initiated until IRB approval is received;
carry out the protocol as approved, initiating modifications only after the IRB has approved the amendment;
obtain appropriate informed consent from subject(s);
ensure the timely completion and submission of the continuing review materials;
maintain confidentiality of all records;
report in writing to the IRB any unanticipated problems involving risks to subjects or others in accordance with the IRB policy;
keep appropriate records, including if applicable names and access information for all research subjects;
be aware of current IRB policies and procedures; and
complete all necessary training, including HIPAA compliance and human subjects protections training, and ensure that listed personnel have completed human subjects protections training as per UM IRB policy.

The IRB will direct original correspondence to the PIs, with exceptions on a case-by-case basis. It is the responsibility of the investigator to ensure that copies of IRB letters are distributed to appropriate individuals (e.g., grant and contract administrators, department administrators, granting agencies or pharmaceutical sponsors, other sites, etc.).

If the protocol is externally funded, the PI should receive a fully executed agreement before work on the research project can begin.

Termination of a Protocol

Investigators should terminate a protocol when human subjects are no longer being followed or studied. As long as subjects are still being followed at this site, even if the protocol is closed to subject accrual, or if data is still being analyzed, even if not being actively collected, a protocol is considered active and continuing review may be required. If no subjects are being followed and data analysis is complete, the study may be officially terminated. When research has been terminated, the responsible investigator must notify the IRB. This applies to certain Expedited protocols and all protocols that have been reviewed by the fully convened IRB.

When a faculty member leaves the University, they should either terminate their protocol(s) or submit an amendment form for each approved study indicating that the protocol(s) should be transferred to another investigator who will take responsibility for the research. See next section.

If the IRB discovers that an investigator has left the 91��Ԫ but that this PI’s studies have not been terminated through the IRB, the IRB staff may contact the PI’s former department chair to verify that studies are not currently active. IRB staff will also verify that the study or studies in question are not in the process of being transferred to another investigator through the amendment process. Depending on the department chair’s response, the IRB will then administratively terminate any remaining studies listed under the name of the departed PI.

Transferring a Protocol to Another Investigator

When an investigator chooses to transfer their status as PI on an approved protocol to another investigator, the IRB must be notified. The new investigator must be eligible to serve as Principal Investigator. To note this transfer, an amendment should be submitted to the IRB. The new principal investigator should provide adequate documentation to acknowledge that he/she is now responsible for the study. Appropriate changes to consent forms, advertisements, and other relevant study documents must also be submitted to the IRB when transferring a protocol. The amendment should specify whether the original investigator will remain on the study as a co-investigator or other research personnel.

The new PI will be notified if and when the amendment is approved.

Unanticipated Problem Reporting

Investigators are required to promptly report to the IRB all unanticipated problems involving risks to human subjects or others under Title 21 of the Code of Federal Regulations (21 CFR) part 56 (Institutional Review Boards), part 312 (Investigational New Drug Application), and part 812 (Investigational Device Exemptions) as well as under 45 CFR 46.108(a)(4). Sponsors and investigators should differentiate those unanticipated problems that must be reported to the IRB and those that do not, under this policy. The 91��Ԫ IRB policy is consistent with guidance set forth by OHRP (“Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events, presented January 15, 2007) and the FDA (Guidance for Clinical Investigators, Sponsors, and IRBs: Adverse Event Reporting to IRBs — Improving Human Subject Protection, dated January 2009) when determining what related events require review by the Institutional Review Board.

Unanticipated problems involving risks to subjects or others refer to a problem, event or information item that is not expected, given the nature of the research procedures and the subject population being studied; and which suggests that the research places subjects or others at a greater risk of harm or discomfort related to the research than was previously known. The IRB considers unanticipated problems, in general, to include any incident, experience, or outcome that meets ALL the following criteria:

unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol, investigator’s brochure, drug or device product information, informed consent document, or other research materials; and (b) the characteristics of the subject population being studied, including underlying diseases, behaviors, or traits;
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
suggests that the research places subjects or others at a risk of unknown harm or addition/increased frequency of harms (including physical, psychological, economic, legal, or social harm) than was previously known or recognized.

Unanticipated problems may be adverse events, protocol deviations, noncompliance or other types of problems, but MUST meet all the criteria listed above. It is the expectation of the IRB that all approved protocol procedures are being followed without alteration unless the IRB has been informed of a protocol change or deviation.

When reviewing a particular incident, experience, or outcome reported as an unanticipated problem by the investigator, the IRB may determine that the incident, experience, or outcome does not meet the criteria for an unanticipated problem.

Unanticipated problems occurring in research that is federally funded may or may not require further reporting to appropriate institutional officials, the department or agency head (or designee), and OHRP. The IRB has the authority, under HHS regulations at 45 CFR 46.109 and 21 CFR 56.109, to require, as a condition of continued approval by the IRB, submission of more detailed information by the investigator(s), the sponsor, the coordinating center, or the Data Safety Monitoring Board/Committee about any unanticipated problem occurring in a research protocol.

It is the responsibility of the investigator to ensure that written notification of unanticipated problems and adverse events is submitted to the IRB. The investigator should complete an Incident Report in Cayuse HE and attach any additional information necessary in evaluating the report (such as laboratory or autopsy reports). All other events or adverse events that do not meet reporting criteria can be submitted as a summary at the time of continuing review.

In reviewing the unanticipated problem, to ensure adequate protection of the welfare of subjects, the IRB will consider whether the event impacts the risk/benefit ratio and may need to reconsider approval of the study, require modifications to the study, or revise the continuing review timetable. Furthermore, the IRB may suspend or request further changes to an individual study due to safety concerns.

The IRB retains submitted unanticipated problem reports. Notification of review of these reports is sent to the PI.

All internal and external Unanticipated Problems must be reported to the IRB in a timely manner following the investigator’s knowledge of the event. For internal events that are fatal or life-threatening Unanticipated Problems, the PI should notify the IRB Manager by phone immediately and consider voluntarily halting subject enrollment.

For device studies, investigators are required to submit a report of an unanticipated device effect to the sponsor and the reviewing IRB as soon as possible, but in no event later than 10 working days after the investigator first learns of the event. Unanticipated device effects are defined as “any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects” (21 CFR 812.3(s)).

Reporting Unanticipated Changes to the Protocol

The federal regulations require the IRB to review and approve proposed changes to research studies prior to initiation of these changes, except when changes are “necessary to eliminate apparent immediate hazards to the subject” [45 CFR 46.108(a)(3)(iii)/21 CFR 56.108(a)(4)]. Most proposed changes are reviewed through submission of amendments. Any changes that are made to eliminate apparent immediate hazards to a subject should be reported as an Unanticipated Problem to the IRB and an amendment should be submitted as soon as possible to change the protocol to eliminate future hazards of this type, as appropriate.

If such a change is implemented to eliminate immediate hazards to a subject, enrollment of new subjects should be halted until the IRB has had an opportunity to consider such changes. The reviewer may also recommend that the subjects on the study be provided specific information about the change and the cause of the change.

Reporting Deviations

An IRB is asked to ensure prompt reporting of serious or continuing noncompliance with regulations or noncompliance with the IRB’s own requirements/determinations [45 CFR 46.108(a)(4)(i) and 21 CFR 56.108(b)]. Deviations from the approved protocol may fall into this category of noncompliance. A protocol deviation occurs when the study departs from the IRB-approved protocol in any way without the investigator first obtaining IRB approval.

Deviations range in seriousness according to how the changes may impact subject safety, the degree of noncompliance with federal and state regulations, and the degree of foreknowledge of the event. Anticipated changes to a protocol should always be reported prior to the event occurrence unless an immediate change is necessary to protect subject safety. Repeated deviations of the same type may be an indication that an amendment is needed to permanently change study criteria.

A major deviation is one that may impact subject safety or alter the risk/benefit ratio, compromise the integrity of the study data, and/or affect subjects’ willingness to participate in the study. Major deviations should be reported as Unanticipated Problems. A description of the effect of the deviation on subject safety and a description of how similar events will be avoided in the future should be provided.

Reporting Noncompliance

Noncompliance is a failure to comply with the requirements of an applicable law, regulation, or institutional policy pertaining to the protection of human subjects, and/or with the requirements or determinations of an IRB that results in harm to subject’s rights, safety or welfare, or on the integrity of the data. Non-compliance results from the action or inaction of anyone conducting protocol procedures. See Chapter 10 for more information on noncompliance.

Protocol deviations and noncompliance should be reported to the IRB as soon as possible. An initial report should be made to the IRB Office by email within one (1) week (7 calendar days) of when the investigator became aware of the adverse event. Any adverse event involving serious injury or danger to the subject must be reported immediately. The initial report must be followed by a formal Adverse Event submission in Cayuse Human Ethics within no more than two (2) weeks (fourteen (14) calendar days) of when the investigator became aware of the event. Reports of possible noncompliance should include a complete description of the event and include sufficient detail to allow the IRB to make an assessment.

Whenever possible, reports should be submitted via the investigator. However, if the reporting party deems it necessary and/or wishes to remain anonymous to the investigator, they may contact the IRB office directly. The IRB office will do its best to protect the confidentiality of informants. Protocol deviations and/or noncompliance incidents may be discovered by IRB office staff as part of continuing review of nonexempt protocols, or audit activity, or an incidental awareness (e.g., due to a news article, errant email or incidental finding of recruitment material).

Reporting Conflict of Interest

If there is a known or potential conflict of interest at the time of IRB submission, investigators are asked to detail the nature of the conflict with the initial submission. Any subsequent change to this status as related to a protocol should also be brought to the attention of the IRB. In addition, any new conflicts of interest which arise from the PI or any co-investigator(s) should be brought to the attention of the IRB as soon as possible. The IRB will coordinate with the Institutional Official or designee as to the appropriate measures or protections to be implemented or that may have already been implemented to manage the conflict of interest.

Research Records

It is required that all research records (including a copy of all materials submitted to the IRB) be maintained by the investigator. The permanent record of research done on each subject consists of signed consent forms together with the names and access information for all subjects, other research data, budget and accounting records, and the subjects’ medical records, as applicable.

Records should be kept confidential to the extent required by the protocol and, as applicable, the consent form. Records that are subject to HIPAA must be stored in a HIPAA-compliant manner. If the investigator leaves the 91��Ԫ, the records must be kept at the University in the hands of the designated investigator taking over the study, and the IRB should be notified of the transfer prior to the investigator's departure. The records shall be accessible for inspection and copying by authorized representatives of the Department of Health and Human Services, the Food and Drug Administration, and/or the sponsor at reasonable times and in a reasonable manner.

Record retention requirements will vary depending upon the type of research, sponsor requirements, relationship to intellectual property protection, and federal requirements. It is typical to retain records for three years after the completion of the research (as defined by the last publication related to the study). HIPAA regulations require that authorizations (e.g., the consent form) be kept for at least six years. For FDA-regulated studies, materials must be maintained for two years following the date of marketing application approval for the device or drug for the indication for which it was being investigated.