Federal Regulations and Guidance
Office for Human Research Protections (OHRP)
Protection of Human Subjects: 45 CFR 46
Frequently Asked Questions about Human Research
Human Subject Regulations Decision Charts
OHRP Policy and Guidance
OHRP Compliance Oversight: Significant Findings & Concerns of Noncompliance
U.S. Food and Drug Administration
IRB Regulations: 21 CFR 56
Institutional Review Boards Frequently Asked Questions
Human Subject Protection (Informed Consent): 21 CFR Part 50
Information Sheets: Guidance for IRBs, Clinical Investigators, and Sponsors
Investigational New Drug Application: 21 CFR Part 312
Investigational Device Exemptions: 21 CFR Part 812
Good Clinical Practices
Good Clinical Practice in FDA-Regulated Clinical Trials
Good Clinical Practice Contacts
ICH E6: Good Clinical Practice: Consolidated Guidance
Medical Devices (Device Advice)
Principal Investigator Responsibilities and Qualifications
Principal Investigators (PIs) have the primary responsibility for protecting the rights and welfare of human research subjects as well as the overall conduct of research.
To be eligible to serve as a PI at Essentia Health, individuals must meet certain criteria.
Before agreeing to serve as a PI, consult Policy # EIRH 1001 Principal Investigator – Eligibility, Roles, and Responsibilities. Search EIRH 1001 on The Source to view this policy.
Determination of Research and Human Subjects
All projects at Essentia Health that meet the federal definition of “research” must submit a Preliminary Study Proposal Form to EIRH for approval.
All projects that meet the definition of “research” AND “human subject” must receive IRB review in addition to submitting a Preliminary Study Proposal Form to EIRH.
If you believe your project does NOT meet the definition of “human subjects research” or if you are unsure whether your project involves human subjects research, contact the HRPP office for official determination by submitting the Determination of Human Subjects Research Form.
See the Tools & Templates section for the Determination of Human Subjects Research Form.
Preliminary Study Proposal Form
The Preliminary Study Proposal Form is required for all research projects that will be conducted at or under the auspices of Essentia Health.
See the EIRH Website for the Preliminary Study Proposal Forms.
The proposal form is submitted to Proposals@eirh.org.
The Executive Director of the Essentia Institute of Rural Health must approve the proposal form before the project can move forward to IRB review.
Essentia Health requires CITI Training and Financial Conflict of Interest (FCOI) Training for all individuals involved in any of the following:
- The conduct of human subjects research
- Supporting human subjects research
- Reviewing human subjects research
- Oversight of human subjects research
For CITI Training information, see the CITI FAQ’s on the EIRH website for guidance and instructions.
FCOI Training will be assigned automatically upon CITI completion, you will receive instructions in your Essentia Health email, or you may initiate FCOI training before CITI completion by contacting Research Compliance.
Request an iRIS Account
Essentia Health uses iRIS (Integrated Research Information System) for all research.
All Essentia Health investigators and research staff conducting human subjects research must have an active iRIS account.
- To request an iRIS account, click “Request new account” on the log-in page at https://research.eirh.org/.
- CITI and FCOI training must be complete before you will receive an iRIS account.
- After Information Services has entered the new account, EIRH staff will notify the user to complete an initial log-in to finalize the iRIS account.
Resource & Department Reviews
In order to safeguard human subjects involved in research, researchers will ensure they have the necessary resources to conduct their proposed studies. This resource review includes, but is not limited to, areas such as staff, study costs, and/or other resources such as equipment, storage, etc.
For more information or assistance, contact EIRH Sponsored Programs Administration.
Research funding is generally obtained by applying to a funding source, describing in detail the kind of research or training that will occur and how much it will cost. There are several types of research funding, including federal, state, and internal (Essentia Health) foundation funding.
Funding is generally required for all projects conducted at Essentia Health. Sponsored Programs Administration at EIRH is available to provide guidance on potential funding opportunities for all Essentia Health investigators.
A Coverage Analysis is required for all clinical research studies for third party billing of costs associated with items and services related to patient care.
For more information or assistance, contact EIRH Sponsored Programs Administration.
Developing the Research Protocol
A protocol is required for all research at Essentia Health.
The protocol is a document that describes in detail the plan for conducting the study. The study protocol explains the purpose and function of the study as well as how to carry it out. There is no required format; different sections and formatting may be used, provided the necessary information is included.
Note that funding agencies may provide instructions that specify the form and content of the protocol. Careful attention to these instructions is essential because lack of conformity may cause the proposal to be returned without review.
See Tools & Templates for template protocols.
Developing Informed Consent Documents
Informed consent documents (standard consent form, short form, parental permission form, or assent form) or a request for a waiver of all or part of the consent process is required for all human subjects research projects at Essentia Health.
See Tools & Templates for template documents.
Creating the “Study Shell” in iRIS
The first step in using iRIS is to create the “study shell.” The study shell enables you to begin building your project in preparation for IRB submission as well as HRPP-facilitated scientific review.
The RCAP office has developed multiple iRIS Quick Guides that have step-by-step instructions for completing a variety of common tasks in iRIS. The iRIS Quick Guides are located in the Help section of iRIS.
See iRIS Quick Guide 2.1 for step-by-step instructions for creating the Study Shell.
Note: Only human subjects research projects must be entered into iRIS.
Evaluating Scientific Merit
Essentia Health requires scientific review for all research proposals that meet the following criteria:
- The proposals involve human subjects.
- The proposals involve greater than minimal risk.
- Essentia Health employees have initiated the proposed research and the project has not undergone scientific review by an external source. (Documentation of review is required if an external review occurred, with the exception of industry sponsored clinical trials and projects sponsored by federal agencies.)
Departments within Essentia Health may have additional requirements for scientific review.
Industry-sponsored clinical trials and studies sponsored by federal agencies such as NIH, NCI, SAMHSA, NSF, CDC, and AHRQ do not require additional scientific assessment at Essentia Health.
Note: If a project requires Scientific Review, the review must be complete before the project is submitted for IRB review.
Refer to Policy #: EIRH 1002 Scientific Review of Proposed Research: Authority, Purpose, Reviewers, and Scope for information concerning the scientific review process. Search EIRH 1002 on The Source to view this policy.
Conducting Learner (Student) Projects
A student cannot be a Principal Investigator (PI) on a research project at Essentia Health. Students may participate in research only if an Essentia Health approved PI is functioning as the Lead PI for the research project.
Note: Per policy #EIRH 2001 Student projects can involve research ONLY when required as part of their academic program.
All Learner Projects must first be reviewed and approved by the EIRH Director of Education. Contact the EIRH Director of Education for more information.
See Policy # EIRH 2001 Clinical Learner Projects for detailed information. Search EIRH 2001 on The Source to view this policy.
Submitting to the IRB
The IRB application process starts with your submission of the IRB Application and the Initial Review Submission Form in iRIS.
To submit to the IRB in iRIS, complete the following steps:
- Complete the application (Quick Guide 2.2)
- Complete the Initial Review Submission Form (Quick Guide 2.3)
- Obtain department sign-off (Quick Guide 2.5)
- Complete the Financial Conflict of Interest (FCOI) Survey (as applicable)
The iRIS Quick Guides are located in the Help section of iRIS.
See Tools & Templates for sample iRIS applications.
FCOI Surveys: Department sign-off automatically triggers iRIS notification to the Essentia Health Organizational Integrity and Compliance Office (OIC). Compliance and/or IRB staff will determine if your project requires additional information, depending on the funding source. If a conflict is identified, compliance staff will work with the individual to address the conflict.
Once the IRB office has determined that your submission is complete and any FCOIs have been addressed, the submission will move to IRB review.
Investigators may not solicit subject participation or begin data collection until they have received approval from the appropriate IRB or notification that the research has been determined to be exempt.
To approve research, the IRBs must determine that the research meets the regulatory criteria for approval. Initial reviews must be conducted by the IRBs at convened meetings except for studies that fall into one of the expedited review categories.
You will be notified via iRIS when your submission has been assigned for review by the convened board. The Investigator or study staff will also receive notification at that time if their attendance at the IRB meeting is required.
Research Administration Sign-off
Once the project has received IRB approval, the submission is reviewed by EIRH research administration. This review may include the following: a final contract and finance check by the EIRH Grants and Finance departments, contract signatures obtained as needed, and HRPP check to ensure that all applicable departments have completed review and that the consent form and contract are consistent with each other.
Once the project has been reviewed and approved by EIRH administration, the project is made active in the iRIS system, and the research can be initiated.
Continuing review refers to the regularly scheduled reevaluation of the project that occurs at least annually for non-exempt research projects.
The electronic system sends reminders to the principal investigator and study contacts before the continuing review is due. The Continuing Review Form should be completed in iRIS before the suggested completion date in the notification.
See Tools & Templates for sample Continuing Review submission forms.
Once the IRB has approved a project, the researchers must conduct the study as approved. The IRB must approve any changes in subject population, recruitment plans, research procedures, study instruments, study sites, or research personnel before the researchers may initiate or implement them. Changes enacted without prior approval may constitute protocol violations.
- The changes described above must be submitted to the IRB using the Amendment Form in iRIS.
- Personnel changes must be submitted using the Add/Remove/Change Study Personnel Form in iRIS.
Federal regulations (45 CFR 46.103[b] and 21CFR 56.108[b]) require the IRB to ensure that investigators promptly report “any unanticipated problems involving risk to subjects or others” (UPIRTSO).
The IRB defines a UPIRTSO as any problem or event which in the opinion of the local investigator was unanticipated, reflects new or increased risk to the subjects, and was possibly related to the research procedures.
To notify the IRB of an event, use the Event Report Form in iRIS.
Researchers should maintain a file of all documents concerning the use of human subjects in research for at least three years from the completion of IRB-related work and six years for research subject to HIPAA requirements, including original consent forms and HIPAA authorizations as well as copies of other regulatory documents. The principal investigator's records should be a mirror image of the IRB's records: where the IRB holds an original, the principal investigator should hold a copy, and vice versa.
IRB records are subject to inspection by federal authorities. Sanctions for incomplete or nonexistent records include suspension of funding, fines, exclusion from future funding, and suspension of research privileges.
See Manage your Project for additional guidance on record keeping.
When the study is completed, researchers must complete a Permanent Study Closure Form in iRIS as a final report on the project.
If a Permanent Study Closure Form or a Continuing Review Form is not submitted and the researcher does not respond to IRB requests, the investigator cannot participate in any new projects until the lapse is properly addressed.
The Essentia Health Research Compliance and Assistance Program (RCAP) conducts quality assurance reviews to ensure compliance with applicable regulations and policies as well as to evaluate study conduct, organization, record-keeping, and documentation.
See Quality Assurance for more information.