Human Subjects Protection Program (HSPP) and Institutional Review Board (IRB)
The CHLA Human Subjects Protection Program (HSPP) administrative team, within the centralized department of Research Operations, is a vital resource for investigators conducting human research activities at CHLA. The HSPP team provides regulatory expertise and administrative support, and serves as the primary contact for investigators and research staff who are submitting research activities and clinical trials for IRB review.
How We Support
The HSPP team is responsible for managing the CHLA Human Research Program. The HSPP team provides administrative support for human research activities to be conducted at CHLA that are reviewed by the CHLA Institutional Review Board (IRB) and other external IRBs. In addition to working with IRBs, the HSPP team also works directly with CHLA investigators and research staff to facilitate submission of required information for IRB review.
The HSPP also has a Quality Assurance Program that provides education, training and quality improvement reviews to ensure compliance with federal and state regulations, and CHLA IRB policy and procedures. The program is responsible for evaluating, tracking and monitoring the effectiveness of the CHLA Human Research Program and for monitoring compliance with approved human research studies and clinical trials.
CHLA’s HSPP has full accreditation from the Association for the Accreditation of Human Research Protections Programs (AAHRPP). The program has been AAHRPP accredited since 2012, and was granted full re-accreditation on September 15, 2020 for five years.
- The CHLA Institutional Review Board (IRB)
- Reliance on an External IRB for Review and Oversight
- External Sites Relying on the CHLA IRB for Review and Oversight
The CHLA IRB is organized and operates in compliance with the Department of Health and Human Services (DHHS) regulations, as described in 45 CFR 46, for federally funded research and Food and Drug Administration (FDA) regulations, as described in 21 CFR Parts 50 and 56, International Conference on Harmonization (ICH) E6, and Good Clinical Practice (GCP), as applicable for FDA-regulated research. In addition, the IRB operates in compliance with portions of the HIPAA Privacy Rule that apply to research, as described in 45 CFR Parts 160 and 164.
Implementation of the Revised DHHS Common Rule (45 CFR 46):
- Studies initially approved before Jan. 21, 2019, are subject to the (pre-2018) Common Rule.
- Studies initially approved on or after Jan. 21, 2019, are subject to the 2018 Common Rule.
- FDA regulations (21 CFR Parts 50 and 56) have not been revised to coincide with the 2019 Common Rule. Research regulated by the FDA is subject to pre-2018 Common Rule regulations. Research regulated by both the FDA and the DHHS Common Rule will comply with the more stringent regulations.
CHLA holds a Federal Wide Assurance (FWA0001914). The CHLA IRB complies with the registration requirements for both OHRP and the FDA.
The membership of the CHLA IRB complies with all federal regulatory requirements. The CHLA IRB includes voting members, including a chair and vice chairs, in addition to a variable number of alternate members. Members are selected for their willingness to serve, their expertise and their familiarity with research design and procedures. Members include faculty from a wide variety of clinical disciplines and specialties to ensure adequate expertise. The IRB also includes nurses, pharmacists and others to provide needed expertise, and community members and non-scientists to represent the viewpoint of the general community and lay audience. Representatives unaffiliated with CHLA also serve on the IRB. The IRB also has a number of consultants to supplement existing expertise on the IRB. By maintaining a diverse membership, the CHLA IRB is able to review a wide variety of research studies conducted at CHLA.
To facilitate the conduct of human research, and to comply with the National Institutes of Health’s (NIH) grants policy and federal regulations requiring the use of a single IRB for review of collaborative (multisite) research and clinical trials, CHLA is willing to rely on an external IRB for multisite research between two or more institutions.
An IRB reliance agreement is necessary to allow for only one IRB review of multisite research. CHLA has established various IRB reliance agreements to allow an external IRB to serve as the Reviewing IRB for research that is conducted at more than one site. These agreements outline the responsibilities of each organization for IRB review, reporting and research oversight.
Reliance Agreement: A formal, written document that provides a mechanism for an institution engaged in research to delegate institutional review board (IRB) review to an independent IRB or an IRB of another institution. Institutions that are engaged in human subjects research, where one institution will rely on the other institution’s IRB, must agree to the terms of the Reliance Agreement before research can begin.
Single IRB (sIRB): An Institutional Review Board that oversees all sites participating in a multisite study. Single IRB and sIRB are terms used in DHHS regulations and NIH grant policy.
Multisite: Under the NIH Single IRB Review policy, “multisite” is defined as two or more sites.
Reviewing IRB: The IRB serving as the IRB of record for all participating sites in a multisite research study.
Relying IRB: The IRB that is relying on the review of another IRB that is serving as the IRB of record for a multisite research study.
SMART IRB: The “SMART IRB” is not an IRB, but a master reliance agreement that was created in 2016 to harmonize and streamline the IRB review process for multisite studies. It enables reliance on a study-by-study basis, defines the roles and responsibilities of relying institutions and reviewing IRBs, and eliminates the need to sign reliance agreements for each study (e.g., a non-SMART IRB agreement). CHLA and another 500-plus institutions have already signed onto this agreement and are actively using it as the basis of reliance for multisite projects. See smartirb.org/participating-institutions/ for a listing of participating institutions.
SMART IRB Master Reliance Agreement: This is the master joinder agreement for becoming a member of SMART IRB.
Master Joiner Agreement: This is the SMART IRB agreement all institutions sign to become a member of the SMART IRB.
Flexibility Agreement: This is an additional agreement some institutions require to cover missing elements in the master joinder agreement.
Reliance Agreements in Place for CHLA
SMART IRB Agreement: CHLA is a signatory to the SMART IRB master reliance agreement. Many institutions use the SMART IRB agreement when single IRB review is required for multicenter research. In most instances, CHLA is willing to rely on another institution for IRB review using the SMART IRB agreement.
Master Agreements: CHLA has reliance agreements with independent IRBs and consortia groups.
- Advarra IRB
- Allows for IRB review of clinical trials by the Advarra IRB
- Applies to industry initiated and sponsored, multicenter clinical trials
- Allows for IRB review of clinical trials by the Advarra IRB that are authorized by the Therapeutics Development Network of the Cystic Fibrosis Foundation
- WIRB-Copernicus Group (WCG) IRB
- Allows for IRB review of clinical trials by the WCG IRB
- Applies to industry initiated and sponsored, multicenter clinical trials
- National Marrow Donor Program (NMDP) IRB - BMT-CTN, Be the Match, CIBMTR, Be the Match BioTherapies studies
- Allows for IRB review of research studies by NMDP IRB
- Applies to studies funded and/or supported by NMDP consortia
- University of Southern California (USC) IRB
- Allows for IRB review of research studies by CHLA IRB or USC IRB
- Applies to research conducted at both CHLA and USC
- National Cancer Institute (NCI) Central IRB (CIRB)
- Allows for IRB review of oncology group clinical trials (e.g., COG) by NCI CIRB
- Applies only to clinical trials that are reviewed by the NCI CIRB
New Reliance Agreements and Other Reliance Materials
In cases where an institution does not meet the eligibility criteria to sign on to the SMART IRB agreement, CHLA may use an IRB Authorization Agreement to establish a reliance relationship with an external institution. All requests for new reliance agreements with other commercial IRBs or institutions, or other reliance materials that require a signature must be reviewed by the HSPP Director. New reliance agreement requests are reviewed by the Director and signed by an authorized CHLA official . Fully executed reliance agreements are kept as IRB records for the CHLA HSPP.
To facilitate the conduct of human research, and to comply with NIH grants policy and federal regulations requiring the use of a single IRB for review of non-exempt collaborative (multisite) research and clinical trials, CHLA is willing to serve as the Reviewing IRB for one or more external Relying Sites. This process requires each institution to accept this arrangement. CHLA will serve as the Reviewing IRB when CHLA is the prime awardee of an NIH award. All requests to have CHLA serve as the IRB of Record must be approved by the Director.
Step 1: Initial Steps for Requesting CHLA to Serve as the IRB of Record
Contact the CHLA HSPP (firstname.lastname@example.org) to schedule a call to discuss your research and determine the best arrangements for IRB review. The HSPP office will need information about the funding, the research to be performed, and the institutions that will be conducting the research (Relying Sites). The HSPP office will determine the appropriate reliance agreement for each Relying Site. Some sites may be required to sign an IRB authorization agreement to rely on the CHLA IRB if there is no existing agreement in place. When the SMART IRB agreement is used a CHLA letter of indemnification must be in place with the Relying Site.
Contact the Relying Site Principal Investigators to discuss the submission and IRB review process when CHLA is the Reviewing IRB. Encourage them to speak to their local IRB about the requirements to rely upon an external IRB.
Step 2: Submit the Study for CHLA IRB Review and Approval
- Submit the study for review and approval to the CHLA IRB in iStar. The CHLA IRB will not approve any of the Relying Sites that will be conducting the research until the protocol, consent forms and other study materials are approved by the CHLA IRB.
- Note: All documents submitted for CHLA IRB review must include a Version Date for tracking purposes. The Version Date for each document approved will be reflected on the IRB approval letter.
- The initial iStar submission must include these documents:
- The master protocol that CHLA and the Relying Site(s) will follow.
- CHLA site consent and assent forms (version dates should match those of the master forms)
- Any recruitment documents (if applicable)
- Any other study materials (e.g., data collection sheets, questionnaires, etc.)
- Upon approval, the CHLA IRB will issue the following documents:
- Approved master protocol that CHLA and all Relying Sites will follow
- Approved consent and assent forms to be used at CHLA
- Approved recruitment documents (if applicable)
- Approved study materials (as applicable)
- Master consent template documents and master recruitment documents (if applicable) for the Relying Sites to customize
Step 3: Communication with Relying Sites
Develop a plan for communicating with Relying Site Study Teams. Complete the CHLA Communication Plan document and submit it for CHLA IRB review and approval. Once approved, the Communication Plan should be shared with all Relying Site Study Teams.
Once the study is approved by the CHLA IRB, the master documents listed under Step 2 above must be shared with all Relying Sites that will be conducting the research. Many local IRBs will want to see the approved protocol and consent document(s) to determine if they will rely on the CHLA IRB.
Many local IRBs require that investigators submit a request to “cede” IRB oversight through their local IRB system. This submission is not usually an IRB review/approval (since the IRB review will be ceded to CHLA), but rather an administrative review to track research occurring at that site and to facilitate any required local ancillary reviews (safety committee reviews, clinical trials office reviews, etc.)
Please ensure that Relying Site investigators follow their local IRB’s process regarding these requests. The local IRB might require the investigator to customize some sections of the consent form(s) and other materials to meet institutional requirements before allowing reliance on the CHLA IRB. The master template consent form(s) should be used for this purpose.
Step 4: Adding Relying Sites to the Approved CHLA Protocol
The CHLA IRB requires submission of an amendment to the approved CHLA study to add all of the Relying Sites that will be conducting the research.
For each Relying Site, a “reliance packet” must be submitted with the amendment. All of the documents contained within the reliance packet should be submitted as a zip file in the iStar amendment for each Relying Site. Do not submit any Relying Site documents via amendment until all of the documents are available and complete for that site. The completed reliance packets for multiple sites may be grouped within a single amendment.
The reliance packet consists of the following:
- All consent forms and recruitment materials with Relying Site (local context) specific edits
- The Relying Site may make local context changes to the recruitment and consent forms, which are highlighted in yellow on the CHLA approved master consent and recruitment template forms.
- The CHLA study team must compare each of the Relying Site’s consent forms and recruitment materials against the CHLA master consent form templates, CHLA master recruitment templates, and the information included in the completed CHLA Institutional Profile form. This is necessary to ensure only local context specific edits were made by the Relying Site. Please assure that no required language in the forms have been changed by the Relying Site.
- Completed Institutional Profile Sheet.
- The institutional profile sheet provides CHLA with information about the Relying Site’s local context information and contains information about the Relying Site’s IRB and institutional processes and requirements. Note: the institutional profile sheet is required only for Relying Sites that are engaged in human subjects research.
- CVs of the site study team (PI and co-PIs)
- Conflict management plans for Relying Site study team personnel, if applicable
- Any other documentation from the local IRB (e.g., clearance letter)
As part of the amendment, the study team must identify under what IRB agreement the Relying Site is willing to use to rely on the CHLA IRB (e.g., SMART IRB).
If some or all of the Relying Site locations were not added with the initial iStar submission, the Relying Site locations should be added with the initial iStar amendment submission. Adding multiple Relying Site locations can be grouped within a single amendment. If there are plans to add more Relying Site locations after the initial amendment is approved, additional amendment(s) will need to be submitted in the future.
- When a Relying Site is approved, the CHLA IRB will issue the following documents to the CHLA investigator:
- CHLA IRB Approval Letter for the Relying Site
- Site-specific approved consent forms and recruitment materials (as applicable) for the Relying Site
The CHLA study team must forward these documents to the Relying Site.
Step 5: CHLA IRB Expectations for CHLA Study Teams
The CHLA study team is responsible for all submissions to the CHLA IRB regarding initial IRB review, continuing review of the research and the activities at each site, and protocol amendments.
The CHLA study team is responsible for sharing IRB approval documentation with the Relying Sites.
- The CHLA study team is responsible for communicating with Relying Sites about specific CHLA IRB/HSPP policies and procedures. Relying Sites investigators should be familiar with the CHLA HSPP website.
The CHLA study team must share the New Information That Requires Prompt Reporting guidance with Relying Sites. Any reportable events that occur at CHLA or one of the Relying Sites must be submitted to the CHLA IRB, by the CHLA study team, via the iStar system.
At the time of continuing review, the CHLA study team is responsible for collecting and combining information from each Relying Site’s progress report/continuing review application (e.g., number of subjects enrolled) and submitting it to the CHLA IRB as one submission for the entire study. Enrollment numbers across all sites (including CHLA) should be captured in the CHLA continuing review application.
Getting Started – Guidance for Investigators
The sections below are to support investigators, study coordinators and research staff in finding answers to questions related to the IRB approval process. It provides step-by-step explanations and important information related to conducting research. See the CHLA Investigator Manual for additional details.
- Principal Investigator Responsibilities
- Step 1: Determine if the Proposed Activity Requires IRB Review
- Step 2: Complete Required Training Courses
- Step 3: Conduct a Risk Assessment
- Step 4: Prepare the IRB Submission
- Step 5: Submit for IRB Review
- Step 6: CHLA IRB Review Process
- Step 7: IRB Approval Notices and Approval Periods
- Step 8: PI Responsibilities After Initial Approval
CHLA investigators assume important regulatory responsibilities when they serve as the Principal Investigator. By submitting an application to the CHLA HSPP for IRB review or clearance, and being named as the Principal Investigator (PI) of that study, the PI agrees to assume the overall responsibility for the study conduct. The Principal Investigator is responsible for knowing the research regulations and guidelines that apply to the study, and any additional requirements imposed by the funding agency and/or study sponsor.
The Principal Investigator has the following responsibilities:
Does not commence research until the Reviewing IRB approval letter is received and all other required department/division and ancillary approvals are obtained.
Complies with all requirements and determinations of the Reviewing IRB.
Ensures that there are adequate resources to carry out the research safely. This includes, but is not limited to, sufficient investigator time, appropriately qualified research team members, equipment and space.
Ensures that research staff are qualified (e.g., including but not limited to appropriate training, education, expertise, credentials, protocol requirements and, when relevant, privileges) to perform assigned procedures and duties during the study.
Personally conducts or supervises the research.
Conducts the research in accordance with the relevant current protocol approved by the Reviewing IRB.
Protects the rights, safety and welfare of subjects involved in the research.
Submits proposed modifications to the Reviewing IRB prior to their implementation.
Does not make modifications to the research without prior IRB review and approval unless necessary to eliminate apparent immediate hazards to subjects.
Submits continuing reviews when requested by the Reviewing IRB.
Submits a closure form to close research (end the IRB’s oversight) when:
- The protocol is permanently closed to enrollment
- All subjects have completed all protocol related interventions and interactions
- For research subject to federal oversight other than FDA:
- No additional identifiable private information about the subjects is being obtained
- Any analysis of private identifiable information is completed
If research approval expires, stops all research activities and immediately contacts the Reviewing IRB.
Promptly reports to the Reviewing IRB any new information that requires prompt reporting (refer to Reviewing IRB requirements).
Does not accept or provide payments to professionals in exchange for referrals of potential subjects (“finder’s fees.”)
Does not accept payments designed to accelerate recruitment that were tied to the rate or timing of enrollment (“bonus payments”) without prior IRB approval.
For studies regulated by a federal department or agency, follows any additional obligations, as applicable.
In general, any research that involves either the participation of human subjects or the use of human biological specimens, medical charts, or databases with identifying information about humans is considered to be human research and requires IRB review.
The CHLA IRB permits investigators to apply the definitions of “research” and “human subject” in order to determine whether their proposed activities meet the definition of human research. See HRP-001 SOP: Definitions for details. However, investigators frequently are unsure whether their proposed activities meet the definition of “research” or “human subject.” It is strongly recommended that investigators request a formal determination about whether an activity is human research. In addition, some funding agencies, sponsors, meetings, conferences and journals may require a formal determination from the CHLA IRB.
The most frequent questions about whether activities are human research concern the following:
- Receipt or use of deidentified or coded biospecimens or data
- Quality improvement/assurance activities
- Educational presentations
- Reports of notable or unique cases (case reports and case series).
CHLA faculty, employees and students are responsible to not conduct human research without prior IRB review and approval (or determination of exemption). Understanding the regulatory definitions of “research” and “human subject” can help distinguish between activities that require IRB review. Whenever there is uncertainty, the CHLA HSPP office should be consulted. See “Activities That Require IRB Review” for additional details.
All activities that constitute “human research,” which are performed by CHLA employees and students, must be reviewed and approved by the CHLA IRB or be certified exempt from IRB review prior to initiation.
An algorithm for determining whether an activity is human research can be found in the “WORKSHEET: Human Research (HRP-310)," Use this document for guidance as to whether an activity meets either the DHHS or FDA definition of human research, keeping in mind that the IRB makes the ultimate determination in questionable cases as to whether an activity constitutes human research subject to IRB oversight.
IMPORTANT NOTE: CHLA IRB review and approval, certification of exemption, and research and/or human subject determinations must be obtained prior to any contact with human subjects or any use of specimens, records or data. The CHLA IRB does not grant retroactive approvals, exemptions or determinations for activities that have already been performed.
Investigators and study team members may have additional training imposed by other federal, state or institutional policies.
Investigators and study team members conducting human research must complete the CHLA Collaborative Institutional Training Initiative (CITI) human subjects online training program.
- The CITI site can be accessed at about.citiprogram.org/en/homepage/.
- Instructions for creating a CITI account are found on the above website.
- All CITI training is valid for a three-year period, after which time refresher training must be repeated.
All members of the study team involved in the design, conduct or reporting of the research must complete training. Members of the study team who have not completed human research protections training may not take part in aspects of the research that involve human subjects.
Human Research Training
Biomedical training should be completed for researchers conducting:
- Retrospective chart reviews (related to medical conditions or injury)
- Biomedical repositories or data or specimens
- Clinical trials of drugs/devices/biologics
- Compassionate use (expanded access) of drugs/devices/biologics
Social/Behavioral training should be completed for researchers conducting:
- Retrospective chart reviews (related to behavioral health)
- Social/behavioral data repositories
- Research on behavioral interventions
- Survey research
- Research that includes quality-of-life instruments
If the planned research study is a combination of both types of research, all members of the study team must complete both trainings.
Good Clinical Practice (GCP) Training
In addition to Human Research Training, GCP training should be completed for researchers conducting:
- All human research that is more than minimal risk
- NIH funded biomedical and/or behavioral clinical trials, regardless of the level of risk
The NIH defines a clinical trial as "research in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health related biomedical or behavioral outcomes.”
Members of the study team who have not completed GCP training may not take part in aspects of the research that involve human subjects.
Through CHLA’s portal in citiprogram.org, you may access either the biomedical or social science/behavioral GCP courses. It is up to investigators to determine which GCP course is appropriate for the types of research they conduct. If you conduct research that includes both biomedical and social/behavioral research, consider taking both GCP courses.
Other CITI Training Certifications
Certifications from institutions other than USC are not accepted at CHLA, as the modules contained in those certifications may not meet the requirements specific to human subject research at CHLA. The CITI program automatically matches modules from an outside institution to those required for CHLA. It is possible that some of the CITI modules for certifications outside CHLA will match and the total number of required modules will be reduced.
Investigators must understand the concept of minimizing risk when designing research and conduct a risk-benefit assessment. In the protocol the Investigator should:
- Describe potential risks and discomforts associated with each intervention or research procedure
- Estimate the probability that a given harm may occur and its severity
- Explain measures that will be taken to prevent and minimize potential risks and discomforts
- Describe the benefits that may accrue directly to subjects
- Discuss the potential societal benefits that may be expected from the research
Risks to subjects who participate in research should be justified by the anticipated benefits to the subject or society. This requirement is found in all codes of research ethics and is a central requirement in the federal regulations (45 CFR 46.111 and 21 CFR 56.111). Two of the required criteria for granting IRB approval of the research are:
- Risks to subjects are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
- Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB Committee will consider only those risks and benefits that may result from the research, as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research.
Refer to Conducting Risk Assessments guidance for more information.
To prepare for a submission to the IRB, the investigator must develop a protocol, relevant consent and assent form(s) and recruitment materials (written or alternative media), and complete the IRB's online application in iStar. There are several protocol and consent templates and standard consent form language available on this Web site for developing a protocol and consent/assent forms.
Investigators developing a new research project should start by reviewing the information available on this page. Poorly written protocols and consent forms are the leading causes for delay in IRB approval.
A faculty advisor is required if the Principal Investigator is a trainee or is USC-affiliated (without a CHLA-affiliation). The faculty advisor is responsible for the oversight and conduct of the research at CHLA. As many trainees will not remain at CHLA for 6 years after the close of the research, the faculty advisor is responsible for retaining research records in accordance with HSPP policies.
CHLA uses a web-based submission and review platform called iStar. The application is a “smartform” that will branch to additional pages as needed depending on your responses to questions (e.g., special subject populations, drugs and devices). When you are ready to submit to the IRB, review these brief overview instructions to get started. First-time users may wish to review the iStar User Reference Guide for additional information.
The iStar system is shared between the IRBs at CHLA and both USC campuses. This means that you can add anyone with a CHLA OKTA ID or USC Shibboleth ID to your study application. However, the application is different depending on the site to which you are submitting. You can add people in certain roles (Principal Investigator, Co-Investigator, and Faculty advisor) to your study application. These people will need to log in to accept the role given to them before iStar will allow the application to be submitted.
Because iStar is shared and there is a collaborative agreement between CHLA and USC, it is possible, to only have one IRB conduct a complete review of your application. If this is your situation, please contact the HSPP office at (323) 361-2265 or email@example.com for guidance as to which IRB should conduct the complete IRB review of your application.
Log in to iStar
- Log in to iSTAR using your CHLA OKTA ID.
- Click here to obtain or activate your CHLA OKTA ID and password.
- If you are having trouble with your OKTA ID, you may review the following OKTA Enrollment Process Job Aid, email the CHLA Service Desk or call them at 323-361-4444.
Complete the iStar Application
- Select the type of submission you are making.
- For initial review of a new study by the CHLA IRB select, “Research Protocol or Study on Human Subjects.”
- For reliance on an External IRB select, “Rely on another IRB (Ceded).”
- Upload a protocol and refer to the protocol when information requested in the application can be found in the protocol document. Also, upload consent and assent forms, and other required documents, as applicable to the study.
- Be sure to Click the “Finish” button on the top or bottom of the application.
- Use the "Send Study Ready Notification" activity to send an email to the Principal Investigator (PI) and co-investigators with instructions for reviewing and submitting the application.
- All listed co-investigators (indicated in item 2.1.) must use the "Agree to Participate" activity and answer yes.
- Once all the co-investigators have agreed to participate, the Principal Investigator can submit the application by using the "Submit Application to the CHLA IRB.”
- The PI will have to check the PI endorsement box. The PI will also have to check the student endorsement box, if applicable.
- If the application is submitted successfully, the submission state will no longer display “Pre Submission.”
- The PI and Study Contact Person will receive an email confirming the application has been submitted.
After the application is submitted, it will be routed for various department/division and ancillary committee reviews before it comes to the IRB. Please see the CHLA Investigator Manual for more details.
CHLA HSPP Pre-Review:
HSPP staff will perform an administrative pre-review of submissions and may request additional information, changes and/or clarification to ensure the submission is complete. Additional information is often requested by the HSPP staff so the IRB can do the following:
- Determine level of review (not human research, exempt, expedited, full committee)
- Assess the regulatory criteria for approval (see Worksheet HRP-314)
- Make other required regulatory determinations (e.g., use of drugs and devices, children as research subjects, requests for waivers of consent and HIPAA)
Requests for additional information from the HSPP staff are submitted to the Investigator and study team contact(s) in iStar.
Submitted activities may fall under one of the following four regulatory classifications:
- Not “Human Research”: Activities must meet the institutional definition of “Human Research” to require IRB review. Activities that do not meet this definition are not subject to IRB review. Review the “WORKSHEET: Human Research (HRP-310)" for reference. Contact the Human Subjects Protection Program in cases where it is unclear whether an activity is Human Research, or if the investigator requires a formal determination from the IRB (e.g., for presentation or publication purposes).
- Exempt: Certain categories of Human Research are exempt from regulation but require HSPP or IRB review to confirm the exemption criteria are met. It is the responsibility of the institution, not the investigator, to determine whether Human Research is exempt from IRB review. Review the “WORKSHEET: Exemption (HRP-312)” for reference on the categories of research that may be exempt.
- Review Using the Expedited Procedure: Certain categories of non-exempt Human Research may qualify for review using the expedited procedure, meaning that the project may be approved by a single designated IRB reviewer, rather than the convened board. Review the “WORKSHEET: Eligibility for Review Using the Expedited Procedure (HRP-313)" for reference on the categories of research that may be reviewed using the expedited procedure.
- Review by the Convened IRB: Non-exempt human research that does not qualify for review using the expedited procedure must be reviewed by the convened IRB. The convened IRB meets weekly on Wednesdays.
- CHLA HSPP or IRB “not human research” determinations are provided for activities that have not started.
- The CHLA HSPP or IRB does not provide retroactive exemptions, or approvals for non-exempt research activities that already have been performed.
After IRB review, investigators will likely be asked to provide additional information or clarification about aspects of the research, add information to the protocol or application, and/or to review and accept changes made to consent and assent form(s) that are required for approval.
The IRB will provide the investigator with a written decision indicating that the IRB has approved the Human Research, requires modifications to secure approval, or has disapproved the study. HSPP staff will communicate the IRB’s decisions and requests to the investigator and study team contact(s) in iStar.
Investigators need to provide the requested information and materials and complete the requested revisions in order to complete the IRB review process.
- If the IRB has approved the human research: The Human Research may commence once all other institutional approvals have been met. IRB approval is usually good for a limited period of time which is noted in the approval letter. Exempt research has no expiration date.
- If the IRB approves with contingencies: The investigator must make or accept the requested modifications and submit them to the IRB. If all requested modifications are made or accepted, the IRB will issue a final approval. Research cannot commence until this final approval is received. If an investigator does not make or accept the modifications, a written response must be submitted to the IRB.
- If the IRB defers the human research: The IRB will provide a statement of the reasons for deferral and offer suggestions to make the study approvable. The investigator is given an opportunity to respond the review in writing. In most cases, if the IRB’s reasons for the deferral are addressed by providing the requested information, the Human Research can be approved.
- If the IRB disapproves the Human Research: The IRB will provide a statement of the reasons for disapproval and give the investigator an opportunity to respond in writing.
See the investigator guidance CHLA IRB Review Outcomes for Non-Exempt Research for a detailed explanation of the possible IRB review outcomes.
Below are details and information about CHLA IRB approval letters and approval periods:
- Exempt human research, once approved, does not have an expiration date.
- Expedited research approved under the Revised Common Rule does not have an expiration date unless the research is FDA regulated or otherwise requires continuing review.
- A study that is approved with contingencies does not mean the research has been approved. No research activities may begin until the IRB issues an approval letter.
- Unless otherwise indicated, the approval period for research requiring a convened IRB review will end one year from the date of the meeting, and the approval period for research reviewed under expedited review procedures will end one year from the date of the IRB Chair/designee’s review.
- The IRB approval notice will state the requirements for consent, parental permission, assent, and the requirements for an Experimental Subject’s Bill of Rights (ESBOR), and HIPAA Research Authorization.
- IRB approvals are valid until 11:59 p.m. on the expiration date listed on the IRB approval notice. If the study expires before the continuing review is approved, all study activities must stop until the study is reapproved.
- Approval of amendments to previously approved research will not change the previously assigned expiration date unless the amendment is submitted with a continuing review application.
- The IRB can approve a protocol for a shorter period if warranted by the risks presented to participants.
- Written IRB correspondence and IRB approval notices are issued electronically via iStar.
- Notification of IRB correspondence and IRB approval are provided to the Principal Investigator, faculty advisor, if applicable, and persons designated as study contact personnel in iStar.
Below are details and information about CHLA clearance letters and CHLA stamping of consent documents approved by an external IRB:
- Ceded clearance letters for reliance on an external IRB other than NCI CIRB (e.g., WIRB, USC) do not include an expiration date. Refer to the external IRB approval letter for the study expiration date.
- Consent and assent forms approved by an external IRB are not stamped with a CHLA clearance or expiration date, and do not contain the CHLA watermark.
- Consent and assent forms approved by an external IRB are cleared by CHLA (via ceded review application amendment) and are found in the “Approved Documents” tab of the ceded review submission in iStar.
Investigators have these additional responsibilities for communicating with the IRB after study approval is granted:
Comply with all Investigator Obligations in the Investigator Manual.
Obtain prospective IRB approval for any changes or amendments to previously approved research, unless changes are made to avoid immediate, apparent hazards to subjects.
Obtain IRB continuing review at least annually (when required). Do not let IRB approval for a study expire.
Submit reportable new information that may adversely affect the safety of participants or the conduct of the research, and any noncompliance with the approved protocol or determinations of the IRB.
Maintain records of all approved-IRB documents and correspondence which must include at minimum the IRB application, sponsor protocol (if applicable), screening, recruitment and consent documents, data collection materials and instruments, documentation of subject eligibility and participation and a copy of all signed consent/assent forms unless waived by the IRB.
Submit a closure report when the research is complete.
Investigator Guidance Documents
Below are guidance documents for CHLA investigators who are conducting human research.
- Submitting for IRB Review
- Recruitment, Consent and Assent
- Reporting Events and New Information to the IRB
- Drugs and Devices
- Amendments to CHLA IRB Approved Research
- Continuing Review Requirements and Submission of Closure Reports
- Identification and Recruitment of Research Participants
- Research Involving Children
- Obtaining and Documenting Consent and Assent
- Remote Consent for Research: Obtaining Consent and Documenting Consent (Electronic Consent)
- Consenting Participants with Limited English Proficiency
- CHLA Requirements for Certified Translations and Use of Interpreters
- Consent from Adults that Require a Legally Authorized Representative
- Waivers of Consent and Documentation of Consent
IRB Templates and Forms
All research studies submitted for IRB review should include a protocol. There are protocol templates below for describing research studies that do not have a sponsor written protocol. These templates include the required information needed to make regulatory determinations for IRB approval.
There are consent form templates and standards below for writing new consent and assent forms, or to customize consent document(s) so they include CHLA required consent language. While there is no requirement to use a CHLA consent template, there is a requirement to include specific language in all consents that will be used to enroll CHLA participants.
- IRB Protocol Templates
- IRB Consent Form Templates and Consent Form Standards
- Other Consent Resources
- CHLA Consent Form Standards and Sample Language
- CHLA Template Informed Consent/Parental Permission/Assent Form
- CHLA Template Simplified Assent Form for Children and Adults Unable to Consent
- CHLA Template Research Information Sheet (minimal risk – no signature blocks)
- CHLA Template Addendum Consent for New Information
- CHLA Template Addendum Consent for Subjects Turning 18
- CHLA Template Informed Consent Parental Permission Assent Form for Single Patient Treatment IND or IDE (expanded access)
- CHLA Template Simplified Assent Form for Single Patient Treatment IND or IDE (expanded access)
- PRISM Readability Toolkit – A resource to help health care researchers develop print materials that study participants can easily read and understand.
- Side Effect Tables for Common Oncology Drugs – A resource for adding drug risks to oncology consent forms
- Side Effect Tables of Common Oncology Drug Regimens – A resource for adding drug regimen risks to oncology consent forms
- Instructions for Activating ClinCard Debit Cards
- Sample NIH GWAS Statements for Consent Documents
Short Form Consents, HIPAA Research Authorizations, CA Subject’s Bill of Rights, Other IRB Forms
CHLA short form consents, HIPAA research authorization forms, CA Subject’s Bill of Rights, and other IRB forms are below.
- Translated Short Form Consents
- CHLA HIPAA Authorization Forms for Research
- CHLA California Experimental Subject's Bill of Rights
- Other Forms
- Short Form – English (for additional translations only)
- Short Form – Spanish
- Short Form – Arabic
- Short Form – Armenian
- Short Form – Chinese (Simplified)
- Short Form – Chinese (Traditional)
- Short Form – Farsi
- Short Form – French
- Short Form – Indonesian
- Short Form – Japanese
- Short Form – Korean
- Short Form – Portuguese
- Short Form – Punjabi
- Short Form – Russian
- Short Form – Tagalog
- Short Form – Thai
- Short Form – Vietnamese
Other Short Forms
When the IRB requires investigators to obtain written HIPAA authorization from participants, one of these forms must be used.
These forms have been approved by CHLA Legal Counsel and the Privacy Officer, and the template content of these forms must not be altered. Investigators do not need to submit HIPAA Research Authorization forms to the IRB before use as long as they one of these templates is used. Any changes to the approved template language, such as those requested by study sponsors, must be approved by the CHLA Legal Counsel and the Privacy Officer, and by the CHLA IRB prior to use.
Written Authorizations for Research
- HIPAA Authorization Form – English
- HIPAA Authorization Form – Spanish
- HIPAA Authorization Form – Arabic
Written HIPAA Authorizations - Short Forms
- HIPAA Short Form – English (for additional translations only)
- HIPAA Short Form – Spanish
- HIPAA Short Form – Arabic
- HIPAA Short Form – Armenian
- HIPAA Short Form – Chinese (Simplified)
- HIPAA Short Form – Farsi
- HIPAA Short Form – French
- HIPAA Short Form – Indonesian
- HIPAA Short Form – Japanese
- HIPAA Short Form – Korean
- HIPAA Short Form – Portuguese
- HIPAA Short Form – Punjabi
- HIPAA Short Form – Russian
- HIPAA Short Form – Tagalog
- HIPAA Short Form – Thai
- HIPAA Short Form – Vietnamese
Written Authorizations for Case Reports
When the IRB requires the CHLA California Experimental Subject’s Bill of Rights, one of these forms must be used.
- ESBOR – English
- ESBOR – Spanish
- ESBOR – Arabic
- ESBOR – Armenian
- ESBOR – Chinese (Simplified)
- ESBOR – Chinese (Traditional)
- ESBOR – Farsi
- ESBOR – French
- ESBOR – Indonesian
- ESBOR – Japanese
- ESBOR – Korean
- ESBOR – Portuguese
- ESBOR – Punjabi
- ESBOR – Russian
- ESBOR – Tagalog
- ESBOR – Thai
- ESBOR – Vietnamese
- Nonsignificant Risk Device Form
- Research Monitoring Plan
- Clinical Radiation Safety Committee Application (Instructions)
- Research Repository Worksheet
- CoC Instructions for FDA
- CoC: FDA Application Template
- CoC: FDA Assurance Template
- CoC: FDA Contacts
- CoC Instructions for NIH
- CoC: NIH Assurance Template