Nebraska S Health Science Center Office of Regulatory Affairs (Ora)

______NEBRASKA’S HEALTH SCIENCE CENTER OFFICE OF REGULATORY AFFAIRS (ORA) Institutional Review Board (IRB)

FACILITATED CONTINUING REVIEW OF NCI PEDIATRIC CIRB APPROVED RESEARCH

SECTION I

1. IRB#: 2. TITLE OF PROTOCOL: 3. PRINCIPAL INVESTIGATOR NAME: A. Department: B. Address and/or campus ZIP: C. Phone: D. Email Address: 4. LEAD COORDINATOR NAME: A. Phone: B. Email:

5. STUDY STATUS: Mark the status of the study and complete sections as indicated: Complete Sections CATEGORY : : A. No subjects accrued. Continuation requested. 1, 2, 14-17

B. Subjects accrued. Accrual not complete. Continuation requested All

C. Subject accrual completed. Treatment and/or research related follow-up 1-17 tests ongoing. Continuation requested

D. Subject accrual completed. Treatment and/or research- related tests completed. Data analysis not completed or all data have not been submitted 1-11, 15-17 to the sponsor. Continuation requested. Note: This form is utilized only for ongoing studies where IRB re-approval is requested. If the study is now being reclassified as “completed” or “closed” at this site, please complete a Final Study Completion Report (found on the IRB website, www.unmc.edu/irb). Once a study is reclassified as completed or closed, all study interventions, data collection, and data analysis must cease.

Facilitated CIRB CR (09-10-10) Page 1 of 11 6. PRINCIPAL INVESTIGATOR'S ASSURANCE

The PI understands and accepts the following obligations to protect the rights and welfare of research subjects in this study:  I certify that I, and all listed research personnel, have the necessary qualifications, expertise, and hospital credentials, and will continue to conduct this study in a manner which fully protects the rights and welfare of research subjects.  As the PI, I will continue to fulfill my responsibility to ensure that this research and the actions of all research personnel involved in conducting the study conform to the: 1) IRB approved application, 2) detailed protocol, 3) HRPP policies, 4) HHS regulations for the protection of human subjects (45 CFR 46), 5) applicable FDA regulations, 6) other applicable federal regulations, and 7) state law.  As the PI, I will continue to fulfill my responsibility to ensure that valid informed consent/assent has been obtained from all research subjects or their legally authorized representatives (LARs). I will ensure that all research personnel involved in the process of consent/assent are trained properly and are fully aware of their responsibilities relative to the obtainment of informed consent/assent according to the HRPP policies, HHS regulations (45 CFR 46), applicable FDA regulations and state law.  I certify that the minimum amount of protected health information (PHI) necessary will be used and disclosed to conduct this research study. I have implemented reasonable safeguards to protect the PHI at all times.  I will promptly inform the IRB of any internal adverse events, as well as any other problems affecting subjects or others, in the time frame defined by HRPP policies.  I will promptly inform the IRB if I become aware of: 1) any complaints from research subjects, LARs, or others about research participation; 2) violations of HHS regulations at 45 CFR 46 and applicable FDA regulations; 3) violations of the HIPAA Rule; or 4) violations of HRPP policies.  I will promptly inform the IRB of the results of external audits performed by sponsors, Contract Review Organizations (CROs), cooperative groups, or FDA.  I will not initiate any change in protocol without IRB approval except when it is necessary to reduce or eliminate a risk to the subject, in which case the IRB will be notified as soon as possible.  I will maintain all required research records on file and I recognize that representatives from the IRB, OHRP, HHS, and FDA (as applicable) are authorized to inspect these records.  I certify that there continues to be adequate resources and facilities to safely carry out and complete this research. This includes sufficient staff, funding, space, record keeping capability, and resources necessary to address adverse events and any unanticipated problems involving risk to the subject or others. If the necessary resources become unavailable I will notify the IRB.  I will promptly inform the IRB of any significant negative change in the risk/benefit relationship of the research as originally presented in the protocol and approved by the IRB.  I understand that continuing review by the IRB is required at least annually in order to maintain approval status. I will maintain IRB approval as long as this study is active.  I certify that I and all other personnel listed in Section I of the IRB Application have disclosed all potential financial conflicts of interest as required and are in full compliance with the UNMC Conflict of Interest Policy. I further certify that all potential financial conflicts of interest are appropriately managed in order to ensure protection of the rights and welfare of patients.

Facilitated CIRB CR (09-10-10) Page 2 of 11  I understand that I am responsible for appropriate research billing in accordance with UNMC Clinical Trial Professional and Technical Fee Billing Policy #8080.  I certify that I and all other responsible personnel listed in Section I of the IRB Application have disclosed all potential financial conflicts of interest as required and are in full compliance with the UNMC Conflict of Interest Policy 8010.  I understand that if there are any changes in the financial interests of responsible personnel during the course of the research, the IRB must be notified as soon as possible.  I understand that failure to comply with HHS regulations, applicable FDA regulations, HRPP policies and the provisions of the protocol as approved by the IRB may result in suspension or termination of my research project, and/or other administrative or legal actions.

______Printed Name of Principal Investigator

______Signature of Principal Investigator Date

Facilitated CIRB CR (09-10-10) Page 3 of 11 SECTION II

Instructions: Research is approved by the CIRB for a maximum period of one year. The PedsIRB must conduct a facilitated continuing review at the local level pursuant to its agreement with the CIRB and HHS regulations at 45 CFR 46/109(e) and FDA Regulations at 21 CFR 56.109(e). The Study Status category (see Section I) determines which subparts must be completed. Each subpart must be titled using boldface subheadings as described below and addressed independently. Please include sufficient information to facilitate an effective review by the IRB. All abbreviations and terms not part of common usage should be defined and simplified language should be used as much as possible. Pages should be numbered.

The IRB Application must provide sufficient information to facilitate an effective review by all members of the IRB including non-specialists. Information should be provided by site for all studies involving more than one site for which the PedsIRB has responsibility for oversight of local context. There is an educational guide to this application available on the IRB website titled “Educational Guide – CIRB Continuing Review”. Questions that have an educational note that explain the information requirements will be referred to the Guide with the statement “See Educational Guide – CIRB Continuing Review”. Applications that do not allow for an effective review may be returned to the investigator, without IRB review, for revision and resubmission.

Accrual & demographic information (1-4) 1. NUMBER OF SUBJECTS APPROVED BY PedsIRB A. How many subjects has the PedsIRB approved to be consented for participation in this study? See Educational Guide – CIRB Continuing Review

2. ACTUAL ACCRUAL A. Specify the total number of subjects who have signed the consent form at each study site approved by (i.e., under oversight of) the PedsIRB as follows: 1. Since initial activation of the study, what is the total number of subjects who have signed the consent form?

2. Since the last PedsIRB review, what is the total number of subjects who have signed the consent form?

B. Specify the total number of subjects who have completed the research at each study site and are evaluable as follows: 1. Since initial activation of the study, what is the total number of subjects who have completed the research and are evaluable?

2. Since the last PedsIRB review, what is the total number of subjects who have completed the research and are evaluable?

3. DISTRIBUTION OF SUBJECTS BY DEMOGRAPHIC CHARACTERISTICS A. Since activation of the study, indicate the number of subjects that have signed the

Facilitated CIRB CR (09-10-10) Page 4 of 11 consent form at each study site (e.g. UNMC, CHMC): 1. By gender and age: Number of Subjects Gender/Age Male <= 19 years of age Female <=19 years of age Male >19 years of age Female >19 years of age

2. By ethnic origin:

Ethnic Origin Number of Subjects Caucasian Black, not of Hispanic origin Hispanic Asian/Pacific Islander American Indian/Alaska Native Other

B. If the demographics of the subject population represent a disproportionate enrollment of one gender or ethnic group, please respond to the following: 1. Was this approved by the CIRB? Yes No

2. Does this reflect clinic or available patient/subject population? Yes No. Explain the disparity in recruitment.

3. Were there a disproportionate number of subjects from any gender or ethnic group who were offered but refused enrollment at the study site(s)? No Yes. Explain the disparity in recruitment.

4. SUBJECT WITHDRAWAL A. Since activation of the research, was any subject involuntarily removed from the study by the investigator because of a medical problem related to the study, or because the subject was determined to be ineligible (that is, failed screening after consent was obtained), or because of an adverse event or a protocol violation? No Yes. Describe the cause of the withdrawal for each subject. Mark withdrawals occurring since the last PedsIRB continuing review with an asterisk (*).

B. Since activation of the research, did any subject voluntarily choose to withdraw from the study for any reason? No Yes. Describe the reason for the withdrawal for each subject. Mark withdrawals occurring since last PedsIRB review with an asterisk (*).

Facilitated CIRB CR (09-10-10) Page 5 of 11 C. Were there a disproportionate number of subjects from any gender or ethnic group who voluntarily withdrew from the research? No Yes. Explain the disparity in voluntary withdrawal.

STUDY RESULTS (5) 5. STUDY RESULTS A. What is the current health status of subjects enrolled at each site under the jurisdiction of the PedsIRB?

ADVERSE EVENTS (6) 6. INTERNAL ADVERSE EVENTS A. Since initial approval of the research have there been any internal adverse events (AEs)(unexpected, related or possibly related) reported to the PedsIRB? No Yes. Provide a brief summary of the number and clinical nature of the internal adverse events. Mark events reported since the last PedsIRB review with an asterisk (*)

B. Since initial approval of the research, has the frequency of serious and expected, internal adverse events been greater than predicted? No Yes. Please provide a brief summary of the serious and expected, internal adverse events. See Educational Guide – CIRB Continuing Review

PROTOCOL DEVIATIONS AND PROTOCOL VIOLATIONS ( 7-8) 7. SINGLE SUBJECT PROTOCOL DEVIATIONS Since initial approval of the research have there been any single subject protocol deviations approved by the PedsIRB? See Educational Guide – CIRB Continuing Review No Yes. Describe each deviation. Mark deviations reported since the last PedsIRB review with an asterisk (*).

8. PROTOCOL VIOLATIONS Since initial approval of the research have there been any protocol violations reported to the IRB? See Educational Guide – CIRB Continuing Review No Yes. Provide a brief description of each violation. Mark reported violations occurring since the last PedsIRB review with an asterisk (*).

Facilitated CIRB CR (09-10-10) Page 6 of 11 PROBLEMS AND COMPLAINTS (9-10) 9. PROBLEMS INVOLVING SUBJECTS OR OTHERS Since initial approval of the research have there been any other unanticipated problems involving subjects or others reported to the PedsIRB? See Educational Guide – CIRB Continuing Review No Yes. Provide a brief description of each problem. Mark problems occurring since the last PedsIRB review with an asterisk (*).

10. COMPLAINTS Since initial approval of the research have there been any complaints about the research? See Educational Guide – CIRB Continuing Review No Yes. Provide a brief description of each complaint. Mark complaints occurring since the last PedsIRB review with an asterisk (*) and indicate the date the complaint was submitted to the IRB.

INFORMED CONSENT EVALUATION (11-14) 11. OBTAINMENT AND DOCUMENTATION Since initial approval of the research have there been any problems in the obtainment and documentation of informed consent? No Yes. Provide a brief summary of the problems. Mark problems occurring since last PedsIRB review with an asterisk (*).

12. CURRENT ADDENDUM CONSENT FORM ASSESSMENT Are the local study site Addendum consent forms still acceptable? See Educational Guide – CIRB Continuing Review Yes No. Attach a Request for Change Form describing the required modifications in the addendum consent forms.

13. RECONSENT/SUBJECT NOTIFICATION Since the last PedsIRB review, have any subjects been re-consented or notified about new information? No Yes. If so, respond below. A. Is the reconsent process complete or ongoing? Complete Ongoing

14. TYPES OF CIRB CONSENT FORMS AND INFORMATION SHEETS, PedsIRB ADDENDUM CONSENT FORMS Check all types of consent and information sheets which are being used in the protocol: PedsIRB Approved Adult/Parental addendum consent form(s) List types if more than one:

Facilitated CIRB CR (09-10-10) Page 7 of 11 CIRB approved Cooperative Group Consent form(s) List types if more than one:

CIRB approved youth information sheet(s) List types if more than one:

CIRB approved child information sheet(s) List types if more than one:

ADDITIONAL INFORMATION (15-17) 15. PROJECT PERSONNEL A. List all personnel to be involved in the study according to the classifications below. See Educational Guide – CIRB Continuing Review 1. Principal Investigator:

2. Secondary Investigator:

3. Participating Personnel:

4. Lead Coordinator:

5. Coordinator:

6. Administrative/data management:

B. List all personnel who are authorized to document the obtainment of consent (that is, sign the consent form). See Educational Guide – CIRB Continuing Review

C. List personnel to be added or deleted. See Educational Guide – CIRB Continuing Review Typed Full Name Document Financial Added or PLEASE DO NOT USE Classification informed Interest in the Deleted? NICKNAMES. consent? research? Principal Investigator No No Added Secondary Investigator Yes Yes Deleted Participating Personnel *See Educational Lead Coordinator Guide

Facilitated CIRB CR (09-10-10) Page 8 of 11 Other Coordinator Data/Administrative Secondary Investigator No No Added Participating Personnel Yes Yes Deleted Lead Coordinator *See Educational Other Coordinator Guide Data/Administrative Secondary Investigator No No Added Participating Personnel Yes Yes Deleted Lead Coordinator *See Educational Other Coordinator Guide Data/Administrative Secondary Investigator No No Added Participating Personnel Yes Yes Deleted Lead Coordinator *See Educational Other Coordinator Guide Data/Administrative 1. Is an Appendix - Personnel Change Form** attached? No Yes. Please specify # of forms attached ** If additional space is needed for personnel changes, fill out the “Appendix - Personnel Change Form” located in the Miscellaneous section of the Forms sections on the IRB website and answer questions above.

16. Are there any changes in the financial interests of investigators or other key personnel? No Yes. Submit an updated UNMC Disclosure of Potential Conflict of Interest form to the ORA.

17. STUDY PERFORMANCE SITES A. List all PedsIRB approved study performance sites at which this research is conducted. See Educational Guide – CIRB Continuing Review Primary Site(s): UNMC and/or CHMC Secondary Sites:

Facilitated CIRB CR (09-10-10) Page 9 of 11 FACILITATED CONTINUING REVIEW OF NCI PEDIATRIC CIRB APPROVED RESEARCH

GENERAL INFORMATION  In order to facilitate PedsIRB re-review of the research in the local context and to avoid unnecessary delays, please ensure that each applicable section of the Facilitated Continuing Review application has been completed according to the instructions.  Information must be provided insufficient detail to allow the PedsIRB to perform the required review. Failure to provide all necessary information may delay IRB continuation of the protocol and could result in an expiration of IRB approval if there is not sufficient time for the IRB to complete its review prior to the current approval expiration date. HHS and FDA regulation prohibit the PedsIRB from granting extensions or temporary approval.  Should expiration of PedsIRB approval occur, all subject accrual must cease as of the date of expiration and research related procedures can no longer be performed on human subjects who are currently enrolled in the study. If stopping research related procedures would represent a health hazard to subjects, the investigator must contact the IRB immediately.  Per institutional policy, all new investigators and participating personnel must have successfully completed the CITI training before IRB approval for continuation of the study can be granted. Alternatively, any individual who has not completed the CITI training must be removed as listed study personnel.  If the study is classified as completed or closed, submit the Final Study Completion Report.

SUBMISSION DEADLINE The IRB strongly recommends your application be submitted as soon as CIRB approval is available. Unless your project is re-reviewed and re-approved by the PedsIRB within twelve (12) months from the date the protocol was last reviewed by the CIRB (or within any shorter approval period specified by the CIRB), federal regulations require immediate expiration of IRB approval.

SUBMISSION CHECKLIST  Submit one (1) original copy (printed single-sided) and one (1) double-sided copy of the following items the Office of Regulatory Affairs (UNMC – 7830): This Continuing Review form

The consent form(s) used to enroll the last subject in this study. Note: The parent/guardian or subject’s name and signature must be obliterated to protect confidentiality. (Categories A-D only) The current PedsIRB approved Facilitated Review Application. (Categories A & B only) Email the FINAL Word files (saved on the appropriate departmental stationery as applicable) of each CIRB consent form, PedsIRB Addendum consent form, CIRB youth/child information sheet(s) intended for use during the next IRB approval period to [email protected]. Each file must be marked with the PedsIRB# of the study. From the Cooperative Group Website: The most recent CIRB Continuing Review Application

Facilitated CIRB CR (09-10-10) Page 10 of 11 The most recent group wide progress report The most recent DSMB report The CIRB approved consent form(s) and Information sheets All notification letter(s) The final approval letter Include the following as applicable: Request for Change form and all supporting documents relating to all modifications in the local protocol and/or Addendum consent forms

 Email the following documents to the IRB email address: [email protected]: All consent forms, addendum consent forms and youth/child information sheets [Word (DOC) format] PedsIRB facilitated continuing review form [Word (DOC) format]

ADDITIONAL REVIEW REQUIREMENTS UNMC Eppley Cancer Center Scientific Review Committee (SRC) Continuing review by the SRC is required for all protocols involving cancer patients.

Institutional Biosafety Committee (IBC) Continuing review by the IBC is required for all protocols involving the use of gene transfer and vaccines.

Facilitated CIRB CR (09-10-10) Page 11 of 11