Protocol Requirements

Investigators must submit an online Initial Query (a shortened, partial application that may be used to determine if a research study is considered human subjects research or not, if it qualifies as exempt research, or if additional information is required) or a Full Application, including Informed Consent (IC) documents. All IRB applications must be submitted using the IRB Protocol Application System (PAS), which can be found under the Research Services section at access.caltech.edu for qualified Caltech investigators.

Please refer to the PAS User Guide that will assist you in creating and submitting your online protocol applications.

Protocol applications must be submitted prior to the submission deadline in order to be considered at an upcoming IRB meeting. The IRB requests submission at least 6 weeks before the scheduled meeting. Any deviations to deadlines will be posted on the IRB website.

Any questions or concerns regarding access to the application and the online submission process should be directed to the IRB Administrator ([email protected]). Investigators are encouraged to read pertinent background information also available on the IRB website, and to contact the IRB Administrator with questions, prior to submitting a protocol application.

IRB review is required when an activity meets the federal definition of both research and human subjects. Investigators should submit an Initial Query through the IRB Protocol Application System (PAS) and obtain the IRB decision that a study is or is not considered human subjects research.

OHRP 45 CFR 46.102(1) and the Health Insurance Portability and Accountability Act (HIPAA) definitions:

Research: A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge

Human Subject: A living individual about whom an investigator (whether professional or a student) conducting research: (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

Intervention: Includes 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.

Interaction: Includes communication or interpersonal contact between investigator and subject.

Private Information: Includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for scientific purposes by an individual and that the individual can reasonably expect will not be made public (e.g., a medical record).

Identifiable Private Information: Private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information.

Identifiable Biospecimen: A biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen.

FDA 21 CFR 56.102(c), (e) definitions:

Clinical Investigation: Any research experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to teh FDA or 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.

Human Subject: 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.

Activities that May Not Require IRB Review:

Classroom Projects: The purpose of these projects is to provide education in research and are not intended to contribute to the generalizable knowledge; however, if the scope of the project widens to contribute to the scholarly knowledge, the intention has changed and meets the definition of research.

Quality Improvement/Quality Assurance: The purpose of these projects is to measure the effectiveness of programs and are not intended to contribute to the generalizable knowledge. If the data is shared outside of Caltech or compared with other projects, the intention has changed and meets the definition of research.

Repository Research, Tissue Banking, and Databases: If the provider and recipient investigators cannot readily ascertain the identity of the participant from whom the data or biospecimens (cells, tissues, fluids) originated (i.e., the data is stripped of identifying information, or coded and the investigator does not have access to the key), these activities may not require IRB review.

In accordance with federal regulations, certain research involving human subjects is exempt from IRB review. Categories of exempt research are stipulated in the Common Rule, Subpart A of 45 CFR 46. While such research is exempt from federal regulations, the research must meet Caltech ethical standards governing the conduct of research.

PIs must submit an Initial Query through the IRB Protocol Application System (PAS) system. The Query is a shortened, partial application that may be used to determine if a research study qualifies as exempt research, or if additional information is required. All researchers participating in human subjects research, including exempt studies, must complete the appropriate training in human subject protections, available through CITI.

If research qualifies as exempt, it will be reviewed by the IRB Chair in consultation with other IRB members, as needed. Upon this determination, the PI will receive notice of exemption and that continuing IRB review is not required, but that an appropriate notice and/or Informed Consent document may still be required to fulfill obligations outside of the purview of the IRB. As noted, exempt protocols do not require annual review, but PIs are obligated to inform the IRB if they would like to amend the approved exempt protocol. If the criteria for the exemption are altered with the update, the protocol may need to be converted to a Full Application and undergo additional review. PIs must contact the IRB Administrator if changes to an exempt protocol are necessary .

Expedited review typically applies to protocols that involve no more than minimal risk and to protocols that involve well established and approved procedures. Expedited review cannot be used if the identification of the human subjects would reasonably place them at risk of criminal or civil liability or be damaging to the subjects in any way, or if the research is classified. Categories of expedited research are stipulated in in Subpart A of 45 CFR 46.

If research qualifies for expedited review, it will be reviewed by the IRB Chair in consultation with other IRB members, as needed. The reviewer(s) act on behalf of the IRB and have the authority to approve, require modifications to secure approval, or request full committee review (FCR).

Protocols that require FCR include studies that are greater than minimal risk and those that do not qualify for exempt or expedited review. Any IRB member may request that a protocol submission be reviewed by FCR, even if it qualifies for exempt or expedited review.

Modifications to an existing approved protocol must be submitted and approved by the IRB before any deviations from the approved protocol are implemented.

Amendment applications must be submitted using the online IRB Protocol Application System (PAS). Amendment applications may be eligible for expedited review.

After review by the IRB, the PI will receive notice that the amendment to the protocol has been approved, disapproved or requires modification.

All IRB protocols are reviewed at least annually, and can be renewed up to four times. The PI must submit an Annual Renewal application, an updated Informed Consent document, and any other relevant documents, (e.g., updated recruitment materials, new questionnaires, current copies of partner institution's IRB approvals or reliance agreements), using the online IRB Protocol Application System (PAS). After four renewals, the PI must submit a de novo application. The IRB may waive this requirement in exceptional circumstances.

After review of the application, Informed Consent and other documents by the IRB, the PI will receive notice that the protocol has been renewed, disapproved, deferred or requires modification. Continuing review typically occurs on an annual basis, but the IRB may decide a more frequent basis is necessary.

A Data Analysis Only application may be created when your study is no longer recruiting participants and collecting data. You may only continue analysis of previously collected data prior to this application. Up to four Data Analysis Only renewals may be submitted for a protocol.

The IRB Chair may determine whether a protocol qualifies as not human subjects research, in which case, no IRB involvement is needed. The IRB Chair, sometimes in consultation with other IRB members, will determine whether the research described in the protocol qualifies as exempt, or for expedited or full committee review. The IRB Chair, in consultation with the Institutional Official or members of the IRB, will determine if the protocol describes FDA-regulated research, and if so, it will be reviewed accordingly. The IRB Chair, in consultation with the Institutional Official, will also determine whether a protocol can be approved on the basis of review by another Institution's IRB.

After the IRB has made a decision on whether to approve, disapprove, require modification of the protocol in order to secure approval, or defer the application, it will notify the PI. If the IRB decides to disapprove a protocol application, the IRB will provide the investigator with a statement of the reasons for its decision and an opportunity to respond. If approved, the PI will also be told whether future Continuing Review will be on an annual or more frequent basis.