Institutional Review Board 3800 Spruce Street First Floor Suite 151 Philadelphia, PA 19104-6006 Phone: 215-573-2540 Continuing Review Application

FULL PROTOCOL TITLE:

PROTOCOL #:

PRINCIPAL INVESTIGATOR:

EXPIRATION DATE:

If IRB Approval Expired: No research related activities may occur after the protocol expiration date, unless the PI contacts the IRB in advance and it is determined that continuation during expiration is appropriate for subject safety. In the space below please indicate if any activity has occurred during the lapse in approval. If yes, please describe the activity in the space provided:

*IRB Reviewers should skip to page 3 where Continuing Review questions begin*

Continuing Review Submission Requirements Guidance: To assure timely IRB approval, continuing review submissions eligible for expedited review should be submitted at least 2 weeks prior to the expiration date. Submissions that require convened board review (greater than minimal risk research) should be submitted 6 weeks prior to the expiration date.

A. Documents: One Copy of each of the following documents may be required for continuing approval (for both biomedical and social/behavioral research): -Completed Continuing Review Form, (Paper submissions require PI signature) -Progress Report (See Section B for details) -The currently approved protocol document and protocol summary (if applicable) -Currently approved versions of Informed Consent Forms (unless enrollment is permanently closed or no informed consent forms are required or used in the research) -Applicable Supplemental Reports (See Section C for details)

For Biomedical Research Only: -Currently approved Investigators Brochures and/or Package Inserts for all study drugs/devices

B. Progress Report: Please include a cover letter or separate document that includes: 1. A narrative summary of the study activities that occurred during the approval year including notable comments on enrollment progress, subject experiences, any delays in study activities, and expected activities for the coming year.

Please Note: For studies that only analyze data, records, and specimens, please inform the IRB of your progress as it relates to data collection and analysis. UPENN IRB 2017.10 Page | 1 2. A summary of any planned/outstanding modifications that will be submitted to the IRB for review including the planned timeline for submission and the impact the modifications have for enrolled subjects, as applicable.

3. If applicable, additional information needed to clarify or elaborate on the details provided in response to other sections within this form.

C. Supplemental Reports: Please include the following documents if they are applicable to the study

1. Adverse Events: An adverse event is any untoward or unfavorable medical occurrence in a human subject (including both physical and psychological harms). Please submit a summary of the adverse events that were recorded during the past year. Please note the following when drafting the summary:  The document may be in the form of a narrative summary or an adverse event log,  The summary must include the following: 1) when the event(s) occurred, 2) a description of the event(s), 3) assessments as to whether the event(s) was expected/unexpected and related/unrelated, and 4) whether changes are planned in response to the event(s).  A sample adverse event log is shown below:

Date of Event Expected or Related or Are changes needed? Event Description Unexpected? unrelated? Assessment as to whether any changes The dates are planned based on the adverse a brief an assessment as to the events an assessment of events reported from the past description of the whether these events occurred. whether the events performance period [e.g. change in events that were related to the If ongoing were expected safety monitoring procedures, changes occurred study intervention specify to risk characterization in the consent form, etc].

2. Deviations: A deviation is an unintentional action or process that departs from the IRB approved study protocol that is identified retrospectively after the event occurred. Please submit a summary of all the deviations that that occurred over the past approval year. Please note the following when drafting the summary:  The document may be in the form of narrative summary or a deviation log,  The summary must include the following: 1) when the deviation(s) occurred, 2) a description of the deviation(s), 3) assessment as to whether the deviation(s) placed participates at increased risk of harm, could occur again, or could qualify as serious or continuing noncompliance, 4) if and when the deviation(s) were previously reported to the IRB, and 5) any corrective actions put in place in response to the deviation(s).  A sample deviations log is shown below:

Date of Deviation Subjects placed at increased Corrective action Previously Reported? Deviation Description risk? Plan an explanation as to whether any an indication of any A summary of any deviations placed participants at events that required a brief description of corrective action plans increased risk of harm, has the real time reporting to If ongoing the deviations that implemented to avoid potential to occur again, or the the IRB and the dates - specify occurred, similar deviations in has the potential to qualify as when they were the future. serious or continuing reported, noncompliance

UPENN IRB 2017.10 Page | 2 3. Other reportable events: If while preparing the continuing review submission you identify an event that meets the criteria for real time reporting to the IRB and was not previously reported, please submit a separate deviation or reportable event submission. For more guidance on events that require real time reporting to the IRB please refer to Section 404 of the IRB SOPs.

4. DSMB/DSMC/Other Committee Reports: This section applies to any protocol that is overseen by a DSMB, DSMC, Scientific Advisory Board, Steering Committee or another entity that is required by its charter to issue reports that should be forwarded to the IRB for review. a) Please submit copy (ies) of the most recent report(s) and any reports received in the prior performance period that have not yet been submitted to the IRB for review. b) In addition, please include the following in the progress report:  A statement indicating the planned frequency of DSMB/DSMC review  A statement whether the DSMB/DSMC reports received to date have aligned with the plan (If not, why?)  If no reports have been made available to you indicate when the next report is expected.  If a change in the monitoring plan is pending, please specifically note this  If you have received any reports in the last review cycle that were not submitted to the IRB in real time, please provide a clear explanation for the delay in submission.

5. Monitoring Report Summary (Biomedical Research Only): See Section IV of the Continuing Review form below for requirements.

D. Directions for Concurrent Submission of Modifications: If a change to the procedures, protocol, personnel, or other study documents is required at the time of continuing review, please check the box in section II below, complete a separate Modification Submission Form and provide tracked change versions of all documents that are being submitted with edits. See IRB website guidance on modifications for further instructions on submitting changes.

E. Directions for Submitting a Closure Request: If your study is closing please do not complete this form. See the IRB website to download the appropriate form for Closures

Continuing Review Submission Questions:

I. Who should the IRB contact with questions? Name: Telephone: Penn Email:

II. Status of study: The risk level chosen should be based on the level of review indicated in your last Continuing Review approval letter. (Click grey button to select)

Risk Level of Research: Current Status: Choose Risk Level Choose Current Status

Is a modification being submitted at the same time as this continuing review? YES NO

UPENN IRB 2017.10 Page | 3 III. Subject Enrollment Reporting ENROLLMENT TYPE (Please check all that apply) This protocol involves research in which:

Subjects are enrolled via an IRB approved consent process Consent process requires documented consent Waiver of documentation of consent granted

No Consent Process: Subject data/records/specimens are collected and analyzed under a waiver or alteration of the process of informed consent and HIPAA authorization (if required).

Note: If your study does not include a consent process of any kind, do not complete the rest of section 3. See page 1 for instructions on reporting enrollment for this type of research in the progress report.

Enrollment Reporting (Items A – K) A. Target Enrollment at Penn: Note: Please list the maximum number of subjects approved by the IRB to be consented at Penn. If no maximum was set in the protocol, please enter “No Target Set.”

CONSENTED SUBJECTS BREAKDOWN: (Even if subjects do not sign their name to a form they are considered consented if an IRB approved process was completed to gain their permission to voluntarily participate) B. Number of subjects consented at Penn since the last Continuing Review: C. Number of subjects consented at Penn since the initiation of the study: Please be mindful that enrolling beyond the approved target is considered a deviation unless your protocol describes an enrollment plan that accounts for subjects who consent to participate and are later determined to be ineligible or were withdrawn for other purposes. If you have enrolled subjects beyond your target and plan to continue consenting subjects, please submit a modification to request an expansion of the target and provide rationale.

SUBJECT STATUS BREAKDOWN: When responding to these items please only account for subjects enrolled at Penn and do not account for subjects in multiple categories D. Number of subjects actively participating in study procedures: E. Number of subjects participating only in follow up procedures: F. Number of subjects completed since enrollment began (no further study activities or contact required):

G. Are there any subjects who provided consent that are no longer participating for reasons other than completion? YES NO

If Yes: Please provide a summarized list below of subjects that have ended participation since the last IRB approval (Initial or Continuing Review). Include the reasons other than completion and the number of inactive subjects in each category. (Categories to consider: determined ineligible after consent, lost to follow up, voluntary withdrawal, withdrawal by the PI, disease progression, adverse event, ETC…)

MULTI SITE ENROLLMENT: Do not report any Penn enrollment in this section UPENN IRB 2017.10 Page | 4 H. Are subjects enrolled at external sites not overseen by a Penn PI? YES NO

IF YES: Target Enrollment for other sites combined:

Current Enrollment for other sites combined:

EQUITABLE SUBJECT SELECTION: This section should include all subjects since enrollment began:

NOTE: Many funded studies require collecting and reporting this information. If your study is funded by an entity that requires tracking/reporting of this information, please complete the following sections. I. Is information from/about subjects’ gender and/or sex being YES NO collected?

If yes, please provide a tally for the information you have collected. If no, please leave sections blank or place N/A in the associated box.

 Sex assigned at birth:

Males: Females: Intersex:  Gender identity provided by the subjects:

Men: Women: Transgender: Another Identity:

J. Is information from /about subjects’ race/ethnicity collected? YES NO

If yes, please provide a tally for the information you have collected. If no, please leave sections blank or place N/A in the associated box.

American Indian or Alaskan Native: Asian: Black or African American: Native Hawaiian or Pacific Islander: White: Hispanic or Latino: Other: Unknown or Not Reported: UPENN IRB 2017.10 Page | 5 K. VULNERABLE POPULATIONS THAT REQUIRE SPECIAL CONSIDERATIONS: Has your study enrolled: Pregnant Women? YES NO Prisoners? YES NO Children (aged 17 or younger)? YES NO Please Note: If your study has enrolled any of the above populations and the inclusion of these populations was not previously approved by the IRB, a separate deviation report must be submitted to the IRB for review/consideration. In that deviation report please provide a description of all study activities that have occurred with the vulnerable population(s) to date.

IV. Monitoring Report Summary (Greater than Minimal Risk Biomedical Research Only) Please note: If your study is minimal risk, has not enrolled any subjects to date, or you are closed to enrollment and had no active subjects during the year you are reporting for, please skip this section.

As part of the continuing approval request process, the Principal Investigator and their team are required to conduct a self-assessment of monitoring/auditing activity. To meet this requirement; please create and attach a summary report that includes the following information from the past year:  The methods used to develop the summary (PICA only? Site visit reports? Combination?)  If site monitoring/auditing visits are included in your monitoring plan, please describe the planned frequency, whether it was followed, and account for any deviations from the existing plan  An overall determination about study conduct derived from the monitoring/auditing activities  For examples and additional guidance on drafting a monitoring summary please see the IRB website

Please see clarifications below to determine what steps to take in drafting your monitoring summary based on your study’s approved monitoring plan: A. For studies that either: 1) do not undergo external monitoring/auditing by a Sponsor, Funding Agency, Office of Clinical Research, Abramson Cancer Center Department of Compliance and Monitoring, or other external monitor; or 2) have not had a monitoring/auditing visit within the past approval year  Please complete the Principal Investigator Compliance Assessment and then create a separate summary document that highlights the findings of that assessment activity.  Please do not upload the Principal Investigator Compliance Assessment form to the continuing review, but maintain a copy for your records. B. For studies that have had at least one monitoring /auditing visit within the past approval year from a Sponsor, Funding Agency, Office of Clinical Research, Abramson Cancer Center Department of Compliance and Monitoring, or other external monitor:  Please provide a separate summary of the monitor(s) findings and potential impact on the conduct of the research and/or protections for the human participants.  Please do not upload any monitoring reports, but maintain a copy for your records.

V. Records Retention 1. If written informed consent is obtained from subjects for this YES NO NA project are the signed forms on file for each subject?

UPENN IRB 2017.10 Page | 6 2. If written HIPAA authorization is required from subjects for YES NO NA this project are the signed forms on file for each subject?

Please answer both questions 1 & 2 if a combined consent and HIPAA authorization form is used.

3. Are IRB Communications (e.g. IRB approval letters) YES NO maintained on file and available?

4. Are all IRB-approved version of the study protocol maintained YES NO on file and available? 5. All IRB submissions for Greater Than Minimal Risk research must include a complete list of documents being submitted for review as they should appear in your determination letter (document name, version #, date). Please list your documents in the space below or in a separate attachment:

6. Is each document you have listed currently approved by the YES NO IRB? If any of the above documentation compliance questions are answered “NO”, please provide an explanation in the attached progress report for consideration by the IRB, with any associated corrective action plan.

VI. Financial Conflict of Interest Reporting : Investigators (persons responsible for the design, conduct or reporting of this research protocol) must disclose any of the following financial interests / relationships with any entity that sponsors, provides support, or otherwise has a financial interest in the conduct or outcome of this research protocol (Outside Organization):  Payments received for the past 12 months from a publicly traded Outside Organization for personal services (e.g., consulting, lecturing / speaking, service on the Scientific Advisory Board) plus the value of any current equity that when aggregated exceeds $5,000  Payments received for the past 12 months from a non-publicly traded Outside Organization for personal services that in total exceed $5,000, or having any equity interest  Membership on the governing board of any Outside Organization, including service on its board of directors, or having a position of authority or responsibility to act in its best interests, including being an officer, manager, partner, or limited liability company member with management responsibility

Investigators must also disclose any financial interest in a drug, device or other product or a competing product (IP rights), regardless of whether the IP has been patented, licensed, or assigned to Penn, if such IP is being tested, evaluated, or developed in, or if its commercial value could be affected by, this protocol.

Investigators are not required to disclose equity in mutual funds and retirement accounts, as long as the Investigator does not directly control the investment decisions made in these vehicles.

UPENN IRB 2017.10 Page | 7 a) Does any person who is responsible for the design, conduct, or reporting of this research protocol have a SIGNIFICANT FINANCIAL INTEREST, as defined above, including: • You and your spouse, parents and any children; • The spouses, parents and any children of any person responsible for the design, conduct, or reporting of this research; and • Any corporation, foundation, trust or other entity controlled or directed by any of the above individuals? Yes No

b) If the answer to Question A is “YES”-For this protocol, was this SIGNIFICANT FINANCIAL INTEREST previously reported to the Office of the Vice Provost for Research? Yes No *If No is selected, please report at this time.

c) If the answer to Question B is “YES”- For this protocol, has there been a change regarding any SIGNIFICANT FINANCIAL INTEREST(S) from what was previously reported to the Office of the Vice Provost for Research? Yes No *If yes is selected, please report at this time.

d) Certification I have reviewed the University of Pennsylvania Policy on Conflict of Interest Related to Research, effective August 24, 2012, and to the best of my knowledge, all Investigators with a SIGNIFICANT FINANCIAL INTEREST have been identified above.

VII. CR Form Completion- This section not required if submitting via HSERA By signing this form, the principal investigator and the person completing the form (if other than the investigator) certify that he/she has disclosed to the IRB all relevant information that might affect re- approval of this study. (Click to review PI responsibilities)

Principal Investigator Name:

Principal Investigator Signature:

Date:

Name of Person Completing this Form:

Signature of Person Completing This Form:

Date:

*Reminder: Before submitting, please revisit the requirements section on Pgs. 1 -3 to assure all necessary elements have been addressed. *

UPENN IRB 2017.10 Page | 8 THIS SECTION FOR EXPEDITED AND ADMINISTRATIVE IRB USE ONLY

APPROVED VIA EXPEDITED IRB REVIEW:

Issues Identified – Referred to IRB staff with instructions

Signature of Expedited Approver: DATE:

UPENN IRB 2017.10 Page | 9