University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Policy and Procedure. PRMS Protocol Closure Policy

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1 University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Policy and Procedure PRMS Protocol Closure Policy PRMS Procedure for Closing Studies for Poor Accrual or Outdated Scientific Relevance Purpose Per CCSG Guidelines, it is particularly important for Centers involved in clinical research to establish a mechanism for assuring adequate internal oversight of the scientific aspects of all the cancer clinical trials in the institution or institutions that formally comprise the Center. The focus of the Protocol Review and Monitoring System (PRMS) is on scientific merit, priorities and progress of the clinical protocol research in the Center. The PRMS should have the authority to open protocols that meet the scientific merit and scientific priorities of the center and to terminate protocols that do not demonstrate scientific progress. The NCI requires that CCSG Competitive Renewal applications provide an account of how many protocols are monitored for progress and performance within a 12-month period and how many are closed. At UCSF, the Disease Site Committees are expected to review accrual and scientific merit regularly and to close trials that do not meet appropriate thresholds. In addition, the Protocol Review Committee (PRC) will independently review accrual and scientific merit of all open trials annually. The purpose of this policy is to document the process by which studies are reviewed and evaluated by both the Disease Site Committees and the PRC for possible closure for poor accrual or outdated scientific relevance. Procedures Disease Site Committee Initiated Review As specified in the PRMS Disease Site Committee Review Policy, Disease Site Committees are expected to review accrual. Trials which the Disease Site Committee decides to close will be recorded in the electronic database but will not undergo review by the PRC full committee once they are closed. Trials which the Disease Site Committee wishes to keep open to accrual will have a corrective action plan formulated by the Disease Site Committee to improve accrual. If after six months annual accrual does not meet the criteria in the table on page 3, the Disease Site Committee is expected to close the trial to further accrual (and terminate the study, if possible). It is not required that these corrective action plans be reported to the PRC. However, should the PRC conduct independent review as described below in and request a response to its concerns (including a corrective PRMS Closure Policy Page 1 of 5 Revision 5 06/19/2014

2 action plan), the Disease Site Committee can submit its existing corrective action plan in response to the PRC. Studies are monitored for progress and performance annually once they are approved by the institutional IRB (Committee on Human Research, CHR) and are open to enrollment. Prior to each Protocol Review Committee (PRC) meeting the PRC Administrator identifies all trials that are open to enrollment for at least one year, are not PRC exempt, and are due for annual review. Once identified, the following data is collected from the Cancer Center s electronic database for each identified study: Study Number PI Name Study Title Primary Objective Study Phase Sponsor Date Opened to Accrual Any temporary closure and re-opened dates PRC Annual Review (Continuing Review) expiration date Review Type (Initial, Annual, 6-Month Follow-Up) Waiver Information Protocol (Total) Target Accrual Figure Center s Anticipated Annual Accrual Rate Center s Actual Accrual Rate for the Last Year Center s Total Target Accrual Figure Center s Total Accrual Figure to Date PRMS Closure Policy Page 2 of 5 Revision 5 06/19/2014

3 At the meeting the full committee reviews accrual (see Table 1 below for minimum annual accrual requirements) and scientific relevance. Table 1 Required Minimum Annual Accrual Type of Trial Institutional Single Center Institutional Multi- Center (includes multi-center consortia led by other centers) Cooperative Group/ National Group Conventional Trial Orphan Disease Status, Molecularly Defined Subsets, Unique Correlative Science 5 3* 5 1* 3 1* Industry 5 1* * Waivers to this requirement can be granted by the PRC Chair at the time of PRC initial protocol review, or by the Chair, Vice Chair or full committee during the annual review process. The PRC Administrator ensures appropriate documentation of PRC approval of waivers granted at the time of annual review in the Clinical Trials Management System (CTMS). Waiver definitions can be found in the PRMS Protocol Review Committee (PRC) Review Policy. If the committee finds the accrual and scientific relevance acceptable, the study is approved for six months or one year from the date of initial review of this continuation review cycle (i.e., the date of the meeting), as determined by the committee. If the committee finds the accrual and/or scientific relevance unacceptable, the program PI and the relevant Disease Site Committee Chair (and, in the case of national group trials, the institutional PI) will be notified about this issue and requested to provide a response. Notification will cite a 30-day deadline for response, and will require the following information as applicable (will differ depending on whether the finding is low accrual or poor scientific relevance): Whether the annual target accrual goal was met Whether accrual figures in the Cancer Center s electronic database are accurate Whether there are patients on study treatment (and if yes, the plan for those patients) Whether the study is or will be closed to accrual Whether the study is or will be terminated (retired at the IRB) Whether there are extenuating circumstances that can be resolved with a revised recruitment action plan (which must be included with the response) and if relevant, whether the study still has scientific relevance The Cancer Center s electronic database will send notifications every 7 days reminding the PI and the Protocol Project Manager that a response has not been received. If no PRMS Closure Policy Page 3 of 5 Revision 5 06/19/2014

4 response is received within 30 days of the initial correspondence, the PRC will recommend closure. Responses received are reviewed at the next scheduled PRC meeting. Disease Site Committee Chair responses will be accepted in place of a PI response. If the study will not be closed or retired, the committee will assess the response as follows: If the committee agrees fully with the response, the study is approved for one year from the date of initial review of this continuation review cycle; if the committee agrees with conditions, the study is approved for six months from the date of initial review of this continuation review cycle. If the committee does not agree with the response, it will recommend closure. Correspondence detailing the PRC s recommendation for closure will be sent to the program PI and the relevant Disease Site Committee Chair (and, in the case of national group trials, the institutional PI). Appeals to PRC Recommendation for Closure If 30 days elapse from the time PRC issues its recommendation for closure with no appeal from the PI or Disease Site Committee Chair, then the PRC will close the study and inform the Director of Human Research Protection Program (HRPP) of the decision. If, after receiving the PRC s recommendation for closure, the PI or Disease Site Committee Chair appeals to the PRC within 30 days, then the trial will be referred to the PRC Chair for adjudication. If the PRC Chair cannot resolve the dispute, the PRC Chair will refer the trial to the Director of Investigational Trials Resource, who will convene an external grievance committee composed of three senior clinical leaders of NCIdesignated Cancer Centers, preferably from within the University of California (UC) system. The external grievance committee will decide via teleconference whether or not to uphold the PRC s determination. If the external grievance committee disagrees with PRC s determination, the study is approved for one year from the date of initial review of this continuation review cycle. If the external grievance committee recommends that PRC s determination be upheld, then the PRC will close the study and inform the Director of HRPP of the decision. Alternate Procedure Alternate procedure may be used for national group or consortium studies addressing rare malignancies such as pediatric malignancies. A program, PI or Disease Site Committee Chair may submit their own annual assessment of accrual for all studies if this method is previously approved by PRC; PRC reviews the annual assessment for accrual and scientific relevance, and will issue correspondence if the PRC disagrees with the program or PI or Disease Site Committee Chair assessment. PRMS Closure Policy Page 4 of 5 Revision 5 06/19/2014

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6 University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Policy Revision Summary of s Policy Title: Version Date: June 19, 2014 Version Number: 0BPRMS Protocol Closure Policy Revision 5 Notes: Page number corresponds to page number in updated version (Revision 3). New text in modified paragraphs is shown as bold italics and deleted text is shown as strikethrough. Page No.: All pages Revision 4 05/16/11 New Text Revision /169/20114 Section: Footer Updated text to reflect revised version number and date. Page No.: 1 Section: Purpose Per CCSG Guidelines, it is particularly important for Centers involved in clinical research to establish a mechanism for assuring adequate internal oversight of the conduct of all cancer clinical trials in the institution or institutions that formally comprise the Center. The focus of the Protocol Review and Monitoring System (PRMS) is on scientific merit, priorities and progress of the clinical research in the Center. The PRMS should have the authority to open protocols that meet the scientific merit and scientific priorities of the center and to close protocols that do not demonstrate adequate scientific progress. The NCI requires that CCSG Competitive Renewal applications provide an account of how many protocols are monitored for progress and performance within a 12-month period and how many are closed, along with the reason for closure. At UCSF, the Program Site Committees are expected to review accrual and scientific merit regularly and to close trials that do not meet appropriate thresholds. In addition, the Protocol Review Committee (PRC) will independently review accrual and scientific merit of all open trials annually. PRMS Protocol Closure Policy Page 1 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

7 New Text Per CCSG Guidelines, it is particularly important for Centers involved in clinical research to establish a mechanism for assuring adequate internal oversight of the conductscientific aspects of all the cancer clinical trials in the institution or institutions that formally comprise the Center. The focus of the Protocol Review and Monitoring System (PRMS) is on scientific merit, priorities and progress of the clinical protocol research in the Center. The PRMS should have the authority to open protocols that meet the scientific merit and scientific priorities of the center and to closeterminate protocols that do not demonstrate adequate scientific progress. The NCI requires that CCSG Competitive Renewal applications provide an account of how many protocols are monitored for progress and performance within a 12- month period and how many are closed, along with the reason for closure. At UCSF, the ProgramDisease Site Committees are expected to review accrual and scientific merit regularly and to close trials that do not meet appropriate thresholds. In addition, the Protocol Review Committee (PRC) will independently review accrual and scientific merit of all open trials annually. Updated text to better reflect the CCSG Guidelines revised May 6, 2013, and to reflect the new name for site committees. Page No.: 1 New Text Section: Purpose The purpose of this policy is to document the process by which studies are reviewed and evaluated by both the Program Site Committees and the PRC for possible closure for poor accrual or outdated scientific relevance. The purpose of this policy is to document the process by which studies are reviewed and evaluated by both the ProgramDisease Site Committees and the PRC for possible closure for poor accrual or outdated scientific relevance. Updated text to reflect the new name for site committees. Page No.: 1 New Text Disease Site Committee Initiated Review Program Site Committee Initiated Review ProgramDisease Site Committee Initiated Review Updated subheader text to reflect the new name for site committees. Page No.: 1 Disease Site Committee Initiated Review As specified in the PRMS Program Site Committee Review Policy, Program Site Committees are expected to review accrual. Trials which the Program Site Committee decides to close will be recorded in the electronic database but will not undergo review by the PRC full committee once they are closed. PRMS Protocol Closure Policy Page 2 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

8 New Text As specified in the PRMS ProgramDisease Site Committee Review Policy, ProgramDisease Site Committees are expected to review accrual. Trials which the ProgramDisease Site Committee decides to close will be recorded in the electronic database but will not undergo review by the PRC full committee once they are closed. Updated text to reflect the new name for site committees. Page No.: 1-2 New Text Disease Site Committee Initiated Review Trials which the Program Site Committee wishes to keep open to accrual will have a corrective action plan formulated by the Program Site Committee to improve accrual. If after six months annual accrual does not meet the criteria in the table on page 2, the Program Site Committee is expected to close the trial to further accrual (and terminate the study, if possible). It is not required that these corrective action plans be reported to the PRC. However, should the PRC conduct independent review as described below in and request a response to its concerns (including a corrective action plan), the Program Site Committee can submit its existing corrective action plan in response to the PRC. Trials which the ProgramDisease Site Committee wishes to keep open to accrual will have a corrective action plan formulated by the ProgramDisease Site Committee to improve accrual. If after six months annual accrual does not meet the criteria in the table on page 23, the ProgramDisease Site Committee is expected to close the trial to further accrual (and terminate the study, if possible). It is not required that these corrective action plans be reported to the PRC. However, should the PRC conduct independent review as described below in and request a response to its concerns (including a corrective action plan), the ProgramDisease Site Committee can submit its existing corrective action plan in response to the PRC. Updated text to reflect the new name for site committees, and to correct page number. PRMS Protocol Closure Policy Page 3 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

9 Page No.: 2 Original Text Once identified, the following data is collected from the Cancer Center s electronic database for each identified study: New Text Reason for Study Number PI Name Study Title Primary Objective Study Phase Research Type Date Opened to Accrual Anticipated Annual Accrual Rate Actual Accrual Rate for the Last Year Total Target Accrual Figure Total Accrual Figure to Date Once identified, the following data is collected from the Cancer Center s electronic database for each identified study: Study Number PI Name Study Title Primary Objective Study Phase Research TypeSponsor Date Opened to Accrual Any temporary closure and re-opened dates PRC Annual Review (Continuing Review) expiration date Review Type (Initial, Annual, 6-Month Follow-Up) Waiver Information Protocol (Total) Target Accrual Figure Center s Anticipated Annual Accrual Rate Center s Actual Accrual Rate for the Last Year Center s Total Target Accrual Figure Center s Total Accrual Figure to Date Updated text to reflect current practice. Page No.: 3 Original Text New Text At the meeting the full committee reviews accrual (see table below for accrual requirements) and scientific relevance. At the meeting the full committee reviews accrual (see tabletable 1 below for minimum annual accrual requirements) and scientific relevance. PRMS Protocol Closure Policy Page 4 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

10 Reason for Renamed table and clarified that the table is displaying the minimum required levels for annual accrual. Page No.: 3 Original Text Type of Trial (UCSF) Investigator Initiated, Single Center (UCSF) Investigator Initiated, Multi- Center Non-UCSF Investigator Initiated, Consortium or Coop Group (UCSF not lead) At least 5 patients UCSF required? Accrual completion within 3 years required? No Orphan disease accrual criteria (IF waiver granted) 3 patients accrued per year, AND accrual completion within 5 years 1 patient per year UCSF, or 3 patients per year accrued nationally, AND accrual completion within 5 years 1 patient per year UCSF >50% of yearly targeted UCSF required? Yes Yes >50 % of yearly national accrual required? Industry Yes No N/A Yes No Yes N/A Yes No PRMS Protocol Closure Policy Page 5 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

11 New Text Table 1 Required Minimum Annual Accrual Type of Trial (UCSF) Investigator Initiated, Single Center (UCSF) Investigator Initiated, Multi- Center Non-UCSF Investigator Initiated, Consortium or Coop Group (UCSF not lead) At least 5 patients UCSF required? Accrual completion within 3 years required? No Orphan disease accrual criteria (IF waiver granted) 3 patients accrued per year, AND accrual completion within 5 years 1 patient per year UCSF, or 3 patients per year accrued nationally, AND accrual completion within 5 years 1 patient per year UCSF >50% of yearly targeted UCSF required? Yes Yes Yes >50 % of yearly national accrual required? Industry Yes No N/A Yes No Type of Trial Conventional Trial Orphan Disease Status, Molecularly Defined Subsets, Unique Correlative Science Institutional Single Center Institutional Multi- Center (includes multi-center consortia led by other centers) Cooperative Group/ National Group 5 3* 5 1* 3 1* N/A Yes No Industry 5 1* PRMS Protocol Closure Policy Page 6 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

12 Reason for Added table name. Replaced table with the new table approved by ITR Steering Committee: removed 50% minimum accrual requirements; deleted study completion target of 3 years for institutional trials; reduced non-waiver minimum for cooperative group trials; added waiver option for Industry trials; expanded waiver definitions to include molecularly defined subsets; definitions can be found in the PRMS Protocol Review Committee (PRC) Review Policy. Page No.: 3 Original Text New Text Reason for * Waivers to this requirement can be granted by the PRC chair, at the time of PRC initial protocol review only. * Waivers to this requirement can be granted by the PRC chairchair, at the time of PRC initial protocol review, or by the Chair, Vice Chair or full committee during the annual review process only. The PRC Administrator ensures appropriate documentation of PRC approval of waivers granted at the time of annual review in the Clinical Trials Management System (CTMS). Waiver definitions can be found in the PRMS Protocol Review Committee (PRC) Review Policy. Clarified language to indicate that waivers can also be approved at full committee during an annual review. Page No.: 3 If the committee finds the accrual and/or scientific relevance acceptable, the study is approved for six months or one year from the date of the meeting, as determined by the committee. If the committee finds the accrual and/or scientific relevance unacceptable, the program PI and the relevant Program Site Committee Chair (and, in the case of cooperative group trials, the institutional PI) will be notified about this issue and requested to provide a response. Notification will cite a 30-day deadline for response, and will require the following information as applicable (will differ depending on whether the finding is low accrual or poor scientific relevance): Whether accrual figures in the Cancer Center s electronic database are accurate Whether there are patients on study treatment (and if yes, the plan for those patients) Whether the study will be closed to accrual Whether the study will be terminated (retired at the IRB) Whether there are extenuating circumstances that can be resolved with a revised recruitment action plan (which must be included with the response) and if so, whether the study still has scientific relevance PRMS Protocol Closure Policy Page 7 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

13 New Text If the committee finds the accrual and/or scientific relevance acceptable, the study is approved for six months or one year from the date of initial review of this continuation review cycle (i.e., the date of the meeting)the date of the meeting, as determined by the committee. If the committee finds the accrual and/or scientific relevance unacceptable, the program PI and the relevant ProgramDisease Site Committee Chair (and, in the case of cooperativenational group trials, the institutional PI) will be notified about this issue and requested to provide a response. Notification will cite a 30- day deadline for response, and will require the following information as applicable (will differ depending on whether the finding is low accrual or poor scientific relevance): Page No.: 4 New Text Whether the annual target accrual goal was met Whether accrual figures in the Cancer Center s electronic database are accurate Whether there are patients on study treatment (and if yes, the plan for those patients) Whether the study is or will be closed to accrual Whether the study is or will be terminated (retired at the IRB) Whether there are extenuating circumstances that can be resolved with a revised recruitment action plan (which must be included with the response) and if sorelevant, whether the study still has scientific relevance Added clarification concerning the timing of six-month and one-year approvals, updated the name of cooperative groups, updated text to reflect the new name for site committees, and updated bullet points to match revisions made to the PRC Annual Review Outcome and Response memo. Responses received are reviewed at the next scheduled PRC meeting. Program Site Committee Chair responses will be accepted in place of a PI response. If the study will not be closed or retired, the committee will assess the response as follows: Responses received are reviewed at the next scheduled PRC meeting. ProgramDisease Site Committee Chair responses will be accepted in place of a PI response. If the study will not be closed or retired, the committee will assess the response as follows: Updated text to reflect the new name for site committees. Page No.: 4 If the committee agrees fully with the response, the study is approved for one year from the date of initial review; if the committee agrees with conditions, the study is approved for six months from the date of initial review. PRMS Protocol Closure Policy Page 8 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

14 New Text If the committee agrees fully with the response, the study is approved for one year from the date of initial review of this continuation review cycle; if the committee agrees with conditions, the study is approved for six months from the date of initial review of this continuation review cycle. Added clarification concerning the timing of six-month and one-year approvals. Page No.: 4 If the committee does not agree with the response, it will recommend closure. Correspondence detailing the PRC s recommendation for closure will be sent to the program PI and the relevant Program Site Committee Chair (and, in the case of cooperative group trials, the institutional PI). New Text If the committee does not agree with the response, it will recommend closure. Correspondence detailing the PRC s recommendation for closure will be sent to the program PI and the relevant ProgramDisease Site Committee Chair (and, in the case of cooperativenational group trials, the institutional PI). Updated text to reflect the new name for site committees, and updated the name of cooperative groups. Page No.: 4 New Text Section: Appeals to PRC Recommendation for Closure If 30 days elapse from the time PRC issues its recommendation for closure with no appeal from the PI or Program Site Committee Chair, then the PRC will close the study and inform the Director of Human Research Protection Program (HRPP) of the decision. If 30 days elapse from the time PRC issues its recommendation for closure with no appeal from the PI or ProgramDisease Site Committee Chair, then the PRC will close the study and inform the Director of Human Research Protection Program (HRPP) of the decision. Updated text to reflect the new name for site committees. Page No.: 4 Section: Appeals to PRC Recommendation for Closure PRMS Protocol Closure Policy Page 9 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

15 New Text If, after receiving the PRC s recommendation for closure, the PI or Program Site Committee Chair appeals to the PRC within 30 days, then the trial will be referred to the PRC Chair for adjudication. If the PRC Chair cannot resolve the dispute, the PRC Chair will refer the trial to the Director of Investigational Trials Resource, who will convene an external grievance committee composed of three senior clinical leaders of NCI-designated Cancer Centers, preferably from within the University of California (UC) system. If, after receiving the PRC s recommendation for closure, the PI or ProgramDisease Site Committee Chair appeals to the PRC within 30 days, then the trial will be referred to the PRC Chair for adjudication. If the PRC Chair cannot resolve the dispute, the PRC Chair will refer the trial to the Director of Investigational Trials Resource, who will convene an external grievance committee composed of three senior clinical leaders of NCIdesignated Cancer Centers, preferably from within the University of California (UC) system. Updated text to reflect the new name for site committees. Page No.: 4 New Text Page No.: 4 Section: Appeals to PRC Recommendation for Closure The external grievance committee will decide via teleconference whether or not to uphold the PRC s determination. If the external grievance committee disagrees with PRC s determination, the study is approved for one year from the date of initial review. If the external grievance committee recommends that PRC s determination be upheld, then the PRC will close the study and inform the Director of HRPP of the decision. The external grievance committee will decide via teleconference whether or not to uphold the PRC s determination. If the external grievance committee disagrees with PRC s determination, the study is approved for one year from the date of initial review of this continuation review cycle. If the external grievance committee recommends that PRC s determination be upheld, then the PRC will close the study and inform the Director of HRPP of the decision. Added clarification concerning the timing of six-month and one-year approvals. Section: Alternate Procedure Alternate procedure may be used for cooperative group or consortium studies addressing rare malignancies such as pediatric malignancies. A program, PI or Program Site Committee Chair may submit their own annual assessment of accrual for all studies if this method is previously approved by PRC; PRC reviews the annual assessment for accrual and scientific relevance, and will issue correspondence if the PRC disagrees with the program or PI or Program Site Committee Chair assessment. PRMS Protocol Closure Policy Page 10 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5

16 New Text Alternate procedure may be used for cooperativenational group or consortium studies addressing rare malignancies such as pediatric malignancies. A program, PI or ProgramDisease Site Committee Chair may submit their own annual assessment of accrual for all studies if this method is previously approved by PRC; PRC reviews the annual assessment for accrual and scientific relevance, and will issue correspondence if the PRC disagrees with the program or PI or ProgramDisease Site Committee Chair assessment. Updated text to reflect the new name for site committees. Page No.: 5 Section: Policy Approval Susan Desmond-Hellmann, MD, MPH Date Chancellor, University of California, San Francisco New Text Susan Desmond-HellmannJeffrey A. Bluestone, MD, MPHPhD Date Chancellor, University of California, San FranciscoExecutive Vice Chancellor and Provost Deletion of Executive Vice Chancellor and Provost signatory. (Please note: upon signing of Revision 4 the signatory was changed to the EVCP on paper only; the electronic version of the document still reflected the Chancellor as signatory. Hence, in this Revision 5, the signatory was to be updated to the EVCP, but it was then decided to delete the signatory altogether.) Page No.: 5 Section: Policy Approval Judith Luce, MD Date Chair, Protocol Review Committee New Text Judith LuceAndrew Ko, MD Date Chair, Protocol Review Committee in leadership. Page No.: 5 Section: Policy Approval John Heldens, CIP Date Director, Human Research Protection Program New Text Lisa Denney, MPH, CIP, CCRPJohn Heldens, CIP Date Interim Director, Human Research Protection Program in leadership. PRMS Protocol Closure Policy Page 11 of 11 Version Date: 06/19/2014 Summary of s Version Number: Revision 5