REQUEST FOR MODIFICATION APPROVAL FORM A pre-review process is MANDATORY for all modifications. Revisions need to be tracked from the currently approved protocol/application/ consent(s). Accept all previous changes and update the version date in the footer(s) of the document(s). ONLY current revisions should be present when documents are sent for pre-review. The revised IRB Application does NOT need to be signed, except at the time of a 5-year update or with a change in PI. The IRB Protocol vs. the IRB Application: o The IRB Application is used ONLY when you have a sponsor that has provided a stand-alone protocol. o The IRB protocol is used for investigator-initiated studies, and is the only protocol for these trials. If your study was approved prior to February 2011, your study was approved with an IRB protocol regardless of whether or not you have a sponsor’s protocol. Documents associated with your modification are to be sent irbhsr-mods@virginia.edu Pre-reviews are typically conducted within 10 business days. If you do not hear back from someone at the IRB within this timeframe, e-mail Medard Ng at htn3u@virginia.edu. Details regarding the modifications process can be found at the following website link: http://www.virginia.edu/vpr/irb/hsr/modifications_process.html Once the pre-review is complete, you will be instructed to submit hard copies. For specifics on submitting hard copies, refer to the “Modification Approval Instructions and Information” section at the end of this document. If multiple documents are submitted, they must be submitted with a Document Submission Form. You are encouraged to submit all large documents (e.g. sponsor’s protocols, investigators brochure(s), lab/study manuals) on a CD. This does not include IRB protocols/application or consents. These items are still submitted as hard copies. Documents on the CD must be in PDF format. The IRB # and Submission Date of the CD must be written directly on the CD. A Document Submission Form must be submitted with the CD. If you wish to modify this document or use the links, you must unprotect the document first. IRB-HSR #: PI Name: Sponsor: Amendment # (if applicable): Protocol Title: Check one: 1. Minor Changes/Minimal Risk Significant Changes/Greater than minimal risk (full board review required) Summarize and provide a rationale for the change(s) Website: http://www.virginia.edue/vpr/irb/hsr/index.html Phone: 434-924-2620 Fax: 434-924-2932 Box 800483 Version Date: 02/26/15 Page 1 of 6 If there is a sponsor’s summary of changes, you must still list the key revisions. Attach the sponsor’s summary when you submit your other documents for pre-review. 2. Does this modification include the addition of prisoners as research subjects? 3. Describe how this modification will affect the risk/benefit ratio for subjects. 4. Does this modification add new personnel who are not affiliated with UVa? Yes No Yes No If YES, submit a copy of their training in Human Subject Research Protection, a signed unaffiliated investigator agreement and modify the protocol to add or update the: Appendix: Non- Uva Personnel section. For additional guidance see # 18 below. 5. Do changes require revisions to the IRB-HSR protocol? Answer N/A if your study has an IRB N/A Application or if your HSR protocol is/will be retired. If YES, email a copy of the revised protocol with changes tracked. Once pre-review is complete, the protocol must be signed and dated by the PI. Dept. Chair Signature is NOT required unless a change in PI is part of the modification. 6. Do changes require revisions to the consent form(s)? Yes No N/A Yes No N/A 7. If YES, e-mail one copy of the consent(s) with changes tracked. Do changes require an additional consent form or a consent addendum? If now enrolling prisoners, respond YES and include a copy of the “ Consent AddendumPrisoner Subjects Population” If YES, email an original of the additional consent form OR consent addendum (to be used if the study is closed to enrollment). 8. Have subjects enrolled in this study? Yes No If YES, does the modification affect subjects currently enrolled, being treated, or in follow-up? Yes No If YES, describe how you will notify them of the changes(s): If NO, describe why subjects will not affect subjects previously enrolled. 9. Has the funding for the protocol changed? Yes No If YES, list new sponsor: If new funding is from a grant, list IRB-HSR grant #: If new funding is from a grant, do you certify that this protocol is consistent with the aims of the grant? Yes No 10. Do modifications require PRC approval? Answer N/A if this trial is not related to cancer research Yes No N/A If you are unsure if your study requires PRC approval, check your initial PRC approval form or contact the PRC Coordinator at 3-7064. If PRC approval is needed, it must be obtained PRIOR to submission to the IRB. Website: http://www.virginia.edu/vpr/irb/hsr/index.html Phone: 434-924-2620 Fax: 434-924-2932 Box 800483 Version Date: 02/26/15 Page 2 of 6 11. Yes No N/A Do modifications require Human Investigations Involving Radiology Exposure (HIRE) Committee approval? 12. Please complete all necessary forms per current HIRE procedure http://www.medicine.virginia.edu/clinical/departments/radiology/physics/hirecommittee.html If HIRE approval is needed, it must be obtained PRIOR to submission to the IRB. Was the title of the study revised? Yes No Yes No Yes No Yes No 13. If YES, make sure the protocol/consent headers were updated to reflect the new title. Are you requesting the sponsor’s protocol # field in IRB online be updated? 14. If YES, list new number: Were any modification changes requested following a Post Approval Monitoring (PAM) audit? 15. If YES, address any outstanding PAM issues with this modification. Are you changing the study status with this modification? If YES, check the new status: Open to Enrollment Closed to Enrollment, subjects being treated / Total # of subjects enrolled: Closed to Enrollment, subjects in follow-up / Total # of subjects enrolled: Closed to Enrollment, no subjects enrolled (do not check if anyone has signed a consent) Closed to Enrollment, performing Data Analysis / Total # of subjects enrolled: Temporarily Closed to Enrollment / Total # of subjects enrolled: Indicate reason: Temporarily closed by sponsor pending interim analysis Temporarily closed by study team because Other: 16. Are you adding an IND or IDE to a UVa investigator-initiated trial? Yes No Yes No Yes No 17. If yes, you need to obtain and submit a School of Medicine Clinical Trials Office (SOM CTO) review letter to the IRB. Are you becoming the overall PI of a multi-site study? 18. If yes, you need to obtain and submit a School of Medicine Clinical Trials Office (SOM CTO) review letter to the IRB. Are you revising the UVa enrollment figure? If yes, complete the Enrollment Change Form and submit this form along with the updated IRB protocol and/or consent (if applicable) Website: http://www.virginia.edu/vpr/irb/hsr/index.html Phone: 434-924-2620 Fax: 434-924-2932 Box 800483 Version Date: 02/26/15 Page 3 of 6 19. Yes No Do you need to add or significantly alter any of the following sections of the IRB protocol/IRB application/consent? Participation of Children Clinical Data Repository Cognitive Impairment Compensation and/or Reimbursement Drugs and Biologics Gadolinium-enhanced MRI Genetic Research Non- UVa Personnel or UVa Personnel not under the HIPAA Covered Entity Testing for HLA Status Research with Prisoners Specimen Banking Video/Audiotaping and/or Photography Waiver of Documentation of Consent (verbal consent) If yes, use IRB online and click on the “Modification Templates” tab to add the appropriate template sections(s) to your IRB protocol or application and/or consent. Link to IRB online: http://www.irb.virginia.edu/index.cfm?fuseaction=InvestigatorSearch.Search 20. Yes No Do you need to change/expand the recruitment methods or anything related to pre-screening? If Yes, 21. Yes No Yes No Yes No 22. 23. Go into IRB online and click on the “Modification Templates” tab. View the current Recruitment template for your study type against the Recruitment template in your approved IRB protocol or I application. If your study contains an outdated recruitment section, you will need to complete the current one UNLESS you are only making a very minor change. Recruitment and pre-screening revisions need to be submitted for pre-review along with any other revisions that may have been made. Do you need to add or significantly alter anything related to a study device? If Yes, Go into IRB online and click on the “Modification Templates” tab. Click on “Device Questions from Protocol Builder”, and answer the questions. E-mail the completed device questions document to Medard Ng. If you have an IRB protocol, also attach the currently approved protocol. In the subject line of the e-mail write “Device questions for review”. You will be provided with the template sections that need to be completed. If you are updating the consent, were non-medical terms used, and is the consent written at an 8th grade or lower reading level? Will this modification affect the content of an advertisement that has been previously approved? If Yes, revise the advertisement and submit it to the IRB (IRBHSRads@virginia.edu) for approval. Additional Comments: Submitted by: Date: Do you confirm that the PI approves these changes? Yes No Website: http://www.virginia.edu/vpr/irb/hsr/index.html Phone: 434-924-2620 Fax: 434-924-2932 Box 800483 Version Date: 02/26/15 Page 4 of 6 MODIFICATION APPROVAL INSTRUCTIONS & INFORMATION Once pre-review is complete, submit the following: Printed documentation: o Routing Form with Contact Information o One (1) MODIFICATION REQUEST FORM o One (1) original IRB-HSR protocol with tracked changes displayed, signed and dated by the PI (ONLY if revised with the modification) o One (1) original IRB-HSR Application with tracked changes displayed if revised with modification and if you utilize a sponsors protocol with an IRB Application. The signature of the PI is only required if this is a 5 year update or a change in PI. The signature of the Department Chair is only required if this is a change in PI. o One (1) tracked IRB-HSR consent (if revised with the modification) o Two (2) clean IRB-HSR consents (if consent revised w/ mod) Documentation in print OR as PDFs on a CD (NOTE: PDF documents included on the CD do not need to be printed. PDF on CD preferred for large document): o One (1) Sponsor summary of revisions AND revised sponsor’s protocol - both Tracked and Clean version (if applicable) o Any other documents pertinent to the modification request (e.g. sponsor's memo, protocol appendices) o One (1) copy of approval or letter from PRC/IBC/Radiation Safety Committee/School of Medicine Clinical Trials Office/Outside IRB (if applicable) o New Device Application Form (if applicable) o Document Submission form (if applicable) with CD (if applicable) NOTE: If you are utilizing the Investigational Pharmacy PLEASE REMEMBER to send them a copy of the revised protocol after it has been approved by the IRB. PO Box 800674. _____________________________________________________________________________ Background Information Per requirements of 45CFR46.103 (b)(4) and 21CFR56.108(a)(3)(4), changes in approved research cannot be initiated without IRB review and approval unless necessary to eliminate apparent immediate hazards to the subjects. Minor changes or amendments, that are not greater than minimal risk, may be reviewed by a designated member of the IRB-HSR staff, approved by the IRB-HSR Chair or Vice Chair, and then reported to the Full Board at a convened meeting. Major changes are changes that may increase the research population's risk or are of questionable risk. When the proposed change is major, the Full Board of the IRB must review and approve the proposed change at a convened meeting before the change may be implemented. If you anticipate that your request will require Full Board review and approval you should submit your modification in accordance with deadlines established for new submissions. Write “Full Board Modification” in the subject line of the pre-review e-mail sent to irbhsr-mods@virginia.edu If the overall risk(s) associated with the research as currently approved are either increased or decreased, an updated assessment of the risk(s) must also be provided. If the risk profile of the research is unchanged, this should be stated. Website: http://www.virginia.edu/vpr/irb/hsr/index.html Phone: 434-924-2620 Fax: 434-924-2932 Box 800483 Version Date: 02/26/15 Page 5 of 6 Examples of minor changes: Changes in research personnel that do not alter the competence of the research team to conduct the research ( submit the IRB-HSR Personnel Change Form) Scientific and/or therapeutic changes that leave the research population at the same or lower risk than risk(s) already approved (e.g. a minor increase or decrease in the number of participants (<25% change) Changes in research procedures that have a minor impact on risks of harm, such as changes in the amount and frequency of blood draws ( which remain within the expedited criteria), addition of a clinic visit that involves no new procedures, or addition of a questionnaire that does not introduce new subject matter. An increase in the number of study visits for the purpose of increased safety monitoring Minimal changes in remuneration Changes to improve the clarity of statements, enhance comprehension or to correct typographical errors, updating to current template, without altering the content or intent of the statement Clarification of discrepancies within the IRB review materials (protocol, consent) such as numbers of subjects, number and identity of research sites, timing, nature, and duration of research procedures. Examples of major changes that may increase risk: Knowledge of a new risk which might affect the risk/ benefit ratio (for example, a risk that is serious, lifethreatening, or could potentially result in permanent disability). The addition of these sorts of risk might affect the IRB’s view of the risk/benefit ratio and should therefore be reviewed by the full board. Increasing the length of time a study participant is exposed to experimental aspects of the study. Increasing the dose/strength of an investigational drug. Changing the originally targeted population to include a more at-risk population (example: previously excluded those with renal failure, and this population is now allowed to enroll, or adding children or pregnant women to the study. Adding additional procedures where the risk of the additional procedure is greater than minimal risk. Adding a blood draw such that the total amount of blood drawn or frequency of blood draws exceeds what is considered expeditable. Adding an element that may breech the confidentiality of the subject such as tissue banking or genetic testing. Requesting surrogate assent. Additional exposure to radiation as part of the study (i.e. additional x-rays, DEXA scans). Changes in study design and or inclusion/exclusion criteria. Substantial or extensive changes to the protocol Addition of Prisoners to the subject population If the level of risk is questionable or extensive changes are being made, it is left to the discretion of the IRB to determine whether the modification should be sent to the full board for review. Questions? Contact Medard Ng at 924-3278 Website: http://www.virginia.edu/vpr/irb/hsr/index.html Phone: 434-924-2620 Fax: 434-924-2932 Box 800483 Version Date: 02/26/15 Page 6 of 6