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All studies, regardless of review category, must be submitted through our electronic system, eRA. Any investigator intending to initiate a research study involving human subjects which is under IRB jurisdiction must submit an initial application for review and approval. No aspect of the study, including testing performed solely to determine eligibility for the study (e.g. "pre-screening"), may begin until the IRB has approved the initial application in writing. The IRB process is initiated by the submission of an initial application via .

If your study requires IRB review and you and the key personnel on the study have completed , your next step should be to create a new study package for IRB review. This is referred to as the Initial Application submission package in eRA. For step-by-step instructions for creating and submitting this submission refer to the .

The initial application submission should include, but is not limited to the following:

• HRP-211: FORM – Initial Application (only accessible via eRA)
• Recruitment material including copies of flyers or phone scripts
• Copies of CITI completion reports for each key personnel named on the study
• Any related grants applications
• Any other related study documents

If you have questions email irbadmin@colorado.edu or schedule time to meet with one of the .

Response Types

There are three types of Responses:

1. Response to Incomplete

A Response to Incomplete is generally submitted when a submission cannot be reviewed because it lacks a key requirement. Examples of when a submission has been marked incomplete includes, but are not limited, to:

• Incorrect or incomplete CITI training completion
• Vital supporting documents are missing – e.g. protocol, consent forms, etc.
• Faculty advisor review has not been obtained

2. Response to Modifications

A Response to Modifications is created when the review has determined that modifications to the study must be completed in order to obtain approval.�� These modifications may be determined by an individual reviewer via expedited review or by convened panel members at a full board meeting.

3. Response to Deferral

A Response to Deferral is created when the review determines that the submission should be deferred when substantial modification or clarification is required, or insufficient information is provided so the IRB is unable to judge the submission adequately,�� e.g., the risks and benefits cannot be assessed with the information provided. The Response to Deferral submission must be reviewed by the convened panel.��

Required Documentation

The required documentation will vary depending upon the provisions of the Response document. Although not a mandatory submission, it is useful when investigators create and include a response Word document with the Response submission. This document should address each of the itemized provisions that were outlined in the communication letter.

For step-by-step instructions for creating and submitting a Response submission refer to the��.��

An Amendment submission in eRA must be submitted by Investigators when any document or procedure within an IRB approved research protocol is revised. The review must be prospective. The change must not be implemented until after IRB approval has been given.

Amendments involving minor changes that pose no more than minimal risk to subjects can be reviewed on an expedited basis. When a proposed change in a research study is not minor or might adversely affect the willingness of current participants to remain in the study, then the IRB must review and approve changes at a convened meeting before changes can be implemented.

Investigators must submit the following documentation to inform the IRB about the proposed change:

• ��dz������ٱ����;
• Revised research protocol (if applicable);
• Revised or new consent/parental permission/assent documents (if applicable) or other documentation that would be provided to subjects when such information might relate to their willingness to continue to participate in the study;
• Any other relevant documents, revised or new.

Examples of amendments that may be reviewed using the expedited procedure include:

• The addition or deletion of key personnel;
• Changes to improve the clarity of statements or to correct typographical errors, provided that such a change does not alter the content or intent of the statement;
• Alterations in human research participant payment or liberalization of the payment schedule with proper justification;
• The addition of study sites (which may require a Federal Wide Assurance(FWA) and appropriate IRB approval) or the deletion of study sites.

Examples of amendments not eligible for review using the expedited procedure include:

• The addition of a description of serious unexpected adverse events or other risks;
• Substantial alteration to the research design or methodology;
• Personnel or site changes that affect the qualifications of the research team or facilities available to support the safe conduct of research.

The study expiration date is included in approval letters from the IRB. The IRB Office sends out reminders 60 and 30 days before the expiration date. It is the investigator's responsibility to submit a Continuing Review submission, allowing sufficient time for the review and re-approval process to be completed before the current approval expires.

If all study activities are complete, then a Final Review should be submitted. This should only be done once all uses of identifiable private information for research purposes have ceased, including data analysis, data transmission, preparation of a study publication, internal or external audit, and any other activity involving the use of identifiable private information for research purposes.

Investigators must submit the following documentation to request continuing review:

• Completed Continuing Review E-Form.
• A copy of the most recent monitoring report, if the study is overseen by an independent monitoring body (e.g., Data Safety Monitoring Board report, Data Monitoring Committee report)
• Any relevant recent literature If applicable, any relevant multi-center trial reports
• If lead site, IRB approvals from other sites
• If applicable, HIPAA Authorization forms

A study will usually undergo the same level of review for initial and continuing review. For example, a study that was originally reviewed using the expedited review procedure will usually undergo its continuing review on an expedited basis. The most common exception to this rule is a study that was originally reviewed by the full board but that had no accrual during the previous period, or that remains open only to data analysis. This class of study may be reviewed using an expedited review. Studies certified as exempt are not required to undergo Continuing Review.

Continuing review provides an opportunity to reassess the totality of the study and assure that, among other things, risks to subjects are being minimized and are still reasonable in relation to anticipated benefits. Reviewers will evaluate whether the research meets the criteria for IRB approval.

Research activities can continue while the IRB reviews the Continuing Review submission, as long as the expiration date has not passed. However, the Continuing Review submission must be approved by the IRB by the end of the expiration date. For example, if the expiration date is 01-Jan-2011, the Continuing Review must be approved by 11:59 pm 01-Jan-2011. If it is not approved, the study would be expired at 12:00 am 02-Jan-2011.

There is no grace period extending the conduct of the research past the expiration date. Extensions will not be granted. The continuation of research after the expiration date is a violation of the regulations. Therefore, if approval of the Continuing Review submission is not obtained before expiration, all research activities pertinent to the study must stop. Approval must be given by the IRB before the research activities can resume.

If a study is expired for more than 90 days, the study will be closed permanently. A new application may be submitted for the continuation of the project, which will go through IRB review.

In rare cases, the IRB may find that failure to continue research activities after the expiration would seriously jeopardize the safety or well-being of an individual. The IRB will consider these situations on a case-by-case basis. Please�� with any questions about this process.

Closure of a study means that no further research,��follow-up, or data analysis will be performed.��If any subjects are continuing in a study, the study may not be closed.��A study is not closed simply because no additional subjects will be enrolled.�� ��

If your study is ready to be closed, complete a Final Review submission, including the Continuing Review E-Form, in eRA.��Note that the information requested is the same for a Continuing Review as for a Final Review.��Your responses in the Study Details - Current Protocol Status section will determine whether the study meets the criteria for closure.

����������to report information that fall into one or more of the categories below. Information that does not fall under any of the categories does not require reporting to the IRB.��Reportable information items must be reported to the IRB��within 5 business days��of the date the Principal Investigator became aware of the information.��

If changes to the protocol or consent are required based on the information being reported, an Amendment must be submitted as a separate submission in eRA.��

Categories:

1. Information that indicates a new or increased risk, or a new safety issue, for example:
   1. New information (e.g., an interim analysis, safety monitoring report, publication in the literature, sponsor report, or investigator finding) indicates an increase in the frequency or magnitude of a previously known risk, or uncovers a new risk.
   2. Protocol violation that harmed subjects or others or that indicates subjects or others might be at increased risk of harm
   3. Complaint of a subject that indicates subjects or others might be at increased risk of harm or at risk of a new harm
   4. An investigator brochure, package insert, or device labeling is revised to indicate an increase in the frequency or magnitude of a previously known risk, or describe a new risk
   5. Withdrawal, restriction, or modification of a marketed approval of a drug, device, or biologic used in a research protocol
   6. Changes significantly affecting the conduct of the clinical trial or increasing the risk to participants
2. Harm experienced by a subject or other individual (e.g. adverse event), which in the opinion of the investigator are unexpected�����Ի���probably��related to the research procedures.
   1. A harm is����вԱ���𳦳ٱ��”��when its specificity or severity are inconsistent with risk information previously reviewed and approved by the IRB in terms of nature, severity, frequency, and characteristics of the study population.
   2. A harm is��“probably related”��to the research procedures if in the opinion of the investigator, the research procedures more likely than not caused the harm.
3. Non-compliance with the federal regulations governing human research or with the requirements or determinations of the IRB, or an allegation of such non-compliance
4. Failure to follow the protocol due to the action or inaction of the investigator or research staff
5. Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a subject.
6. Breach of confidentiality
7. Complaint of a subject that cannot be resolved by the research team
8. Premature suspension or termination by the sponsor, investigator, or institution
9. Incarceration of a subject in a study not approved by the IRB to involve prisoners
10. Audit, inspection, or inquiry by a federal agency and any resulting reports (e.g., FDA Form 483)
11. Written reports of study monitors
12. Unanticipated adverse device effect (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)