University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Policy and Procedure

Transcription

1 Purpose Policy for Verbal Notification of New Risk This policy defines the process by which participants enrolled in therapeutic oncology clinical trials at the Helen Diller Family Comprehensive Cancer Center (HDFCCC) are notified of newly identified risks that have not been incorporated into the study specific informed consent form (ICF) approved by the UCSF Institutional Review Board (IRB) or outside IRBs, excluding the NCI CIRB. This policy specifies the period in which participants will be notified of newly identified risks. This policy applies to all therapeutic oncology trials regardless of the phase of the study. Background Informed consent and parental permission should be viewed as an ongoing process. The regulations do not explicitly describe all of the circumstances that might require repeating or supplementing the informed consent process. However, they do require that potential participants be provided, when appropriate, with a statement that significant new findings developed during the course of the research which may relate to the subject s willingness to continue participation will be provided to the subject (21 CFR (b) (5) and 45 CFR (b) (5). References HDFCCC Policy for Obtaining Informed Consent of Potential Patients for Therapeutic Oncology Clinical Trials (current version). 45 CFR CFR 50. UCSF Human Research Protection Program (HRPP) Policies and Procedures U.S. Department of Health and Human Services (HHS), Office for Human Research Protections (OHRP), Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Participants or Others and Adverse Events, 1/15/ Identifying New Risks and Procedures UCSF HDFCCC will rely on the Sponsor to make all determinations of whether there are new risks for a study. All new risk should be relayed explicitly by sponsors to UCSF HDFCCC investigators. New risk can include side effects from investigational agents and study procedures, animal studies, chemical manufacturing events, as well as from an internal adverse events (AEs). Some methods for the notification to investigators include: A Dear Investigator Letter informing the Principal Investigator (PI) that a new risk has been identified, and requiring notification of participants and an immediate modification of the ICF. An updated ICF that resulted from a change to the Investigator s Brochure (IB). A DSMB report, which includes new data or risk information that may affect the risk/benefit ratio of the study. Additional methods that the PI may identify a new risk: The PI may identify a new risk through the review of other safety information, such as external adverse event (AE) reports, FDA notifications, and IBs, whereby the sponsor or drug manufacturer did not relay new risk. The PI may identify a new risk through an adverse event experienced by a participant on a study at his or her institution (internal adverse event). These additional methods require the PI to first obtain sponsor approval to add the new risk to the ICF. The sponsor approval must occur before verbal notification occurs. The sponsor approval will need to be in written form and filed within the study binder. For all new risks, the sponsor must authorize the addition of the new risk to the ICF and thus the verbal notification and the PI s determination/acknowledgment of the new risk will be documented. (See Appendix B) 10.MAY.2018 v.2 1 of 9

2 This policy assumes that the PI has carefully considered whether the new risk may require stopping treatment, and assumes that the new risk has been reviewed by the appropriate Site Committee and the following factors have been considered: Should treatment be stopped for the participant(s) that experienced the new risk? Should treatment of other participants enrolled on the study be stopped, or can treatment continue with careful monitoring? For Investigator-Initiated Trials, will a protocol amendment for be required in order to manage the new risk? Responsibilities of the Principal Investigator The Principal Investigator responsibilities for reviewing new risk to determine verbal notification begin at a study s IRB approval and continue until the following two accrual criteria are met for the study: Closed to accrual; and Zero active ( 30 days from last dose) or in follow-up (per protocol) participants. PIs can review risk and determine verbal notification of participants at any point in a trial, including after these criteria are met, but the HDFCCC Policy on Verbal Notification of New Risk only requires they do so during the above timeframe of a trial. Additionally, sponsors may require verbal notification of new risk that falls outside of this timeframe, as well. Refer to the HDFCCC Consent guidance for updating the Informed Consent Form (ICF) in these circumstances. Throughout this time, the PI has the following responsibilities: Report to the UCSF IRB Determine if the new risk meets the UCSF IRB reporting requirements. If reporting to the UCSF IRB is required, the safety information containing the new risk information will be submitted to the UCSF IRB. If there is no safety information that accompanies the new risk, reporting the new risk to the IRB is not required beyond the submission of modification. Report to other IRB If a study is using an outside IRB, defer to the IRB of record s policies for post-approval requirements. Modify the Informed Consent Document (ICF) The ICF will be updated to reflect the new risk and then will be submitted to the IRB of record. For sponsored studies, the modified ICF will be submitted to the IRB once the ICF has been approved by the sponsor. For IITs, the PI will provide final review of all ICF modifications prior to submission. Notify Enrolled Participants of New Risk Active participants ( 30 days from last dose) are required to be notified of new risk. The PI will determine when to notify active participants based on whether the PI believes the risk results in a more immediate notification (15 business days) or a more standard notification (30 business days) (Appendix A). Participants will be notified verbally by an authorized member of the study team. Until the modified ICF is approved, the verbal notification of new risk will be completed for all active participants. Notification of all risks for active participants will occur between 15 and 30 business days, as determined by the PI. New Risk from IBs and ICFs Since new risk arising from investigator brochures and ICF templates are not urgent, these risks can default to the 30 business days notification period, however, it is at the PI s discretion to notify participants earlier. Participants off treatment (> 30 days from last dose) and in follow-up (per protocol) are required to be notified of new risk, as well. The PI will determine when to notify off treatment participants and participants in follow-up (per protocol) based on whether the PI believes the risk results in a more immediate notification (30 business days) or a more standard notification (90 business days) (Appendix A). Participants will be notified verbally by an authorized member of the study team. Until the modified ICF is approved, the verbal notification of new risk will be completed for all active participants. When a PI notifies off treatment (> MAY.2018 v.2 2 of 9

3 days from last dose) and in follow-up (per protocol) participants, due to the time it takes to notify, 90 business days is the recommended notification period. Participants in survival follow-up and previous participants who are now off study are not required to be notified per this policy. Survival follow-up means the study team is only contacting the participant to see if they are still alive; no protocol activity is taking place during the contact. Generally, the following guide is used for notification period determination. When a PI notifies off-study and and/or in follow-up participants of a new risk, the 90 business days notification period can be used. Participant Status - Active ( 30 days from last dose) - Off treatment (> 30 days from last dose) - In follow-up (per protocol) Verbal Notification Period 15 Business If PI determines notification is urgent 30 Business Normal notification 30 Business If PI determines notification is urgent 90 Business Normal notification Notification not required - Off study* and Survival Followup** - Late effect risk*** 90 Business *When the PI notifies participants off treatment (> 30 days from last dose) and in follow-up participants of new risks, due to the time it takes to notify, 90 business days is the recommended notification period **Survival follow-up means the study team is only contacting the participant to see if they are still alive; no protocol activity is taking place during the contact. ***Sponsors are required to tell the HDFCCC PIs when a risk is a late effect risk. Active, off treatment, and in follow-up (per protocol) participants are required to be verbally notified of late effect risks. Off study and in survival follow-up participants are not required to be notified. A Note on Late Effect Risk o o o A late effect risk is an adverse event (i.e. secondary cancer) that can appear months or years after the initiation of a study treatment, such as chemotherapy, radiation therapy, and surgery. The UCSF HDFCCC and its PIs rely on study sponsors to determine whether a risk is a late effect risk, and to provide this notification in a timely manner. Active, off treatment, and in follow-up (per protocol) participants are required to be verbally notified of late effect risks within 90 business days. Participants will be re-consented after the modified ICF has been approved. This process will be documented in the medical record or study record. If participants cannot be reached or refuse re-consent, this will be documented in the medical record and study record showing the intent to re-consent the participant, including date(s) of contact and mailing of the modified ICF, as applicable. Off study and in survival follow-up participants are not required to be notified of late effect risk. Documentation of Verbal Notification When a participant is verbally notified of the new risk(s), the following will occur: 10.MAY.2018 v.2 3 of 9

4 Documentation of the new risk in the medical record with a note stating that the participant has been informed of the new risk(s) and whether the participant will continue on study treatment. The New Risk Notification Form will be used to further document the discussion of new risks and the participant s decision to remain on study. This form will be signed and dated by a member of the study team authorized to consent, after discussion of the new risk(s) with the participant. (Appendix B) Note - if a translator is required during the initial consent process, then a translator is required during the verbal notification process. If the verbal notification is via phone call, then the translator will provide their translator identification number to the member of the study team authorized to consent and this ID number will be documented on the signature line at the bottom of the form. The verbal notification and documentation procedure will not be used after the modified ICF is approved by the IRB. (Refer to the current HDFCCC Consent Policy for re-consenting procedures). If a participant is verbally notified of new risk(s) and subsequently goes off study prior to the IRB approval of the updated ICF, the participant does not need to resign the new consent form. The verbal notification, as a continuation of the consent process, will satisfy the requirement to notify the participant. Documentation of the Withdrawal of Verbal Notification In the event that the ICF is not updated with the new risk(s) (e.g. new information is received) after participants have been verbally notified of a new risk, participants will be notified of this and it will be documented in the medical record with a note stating that the participant has been informed. The Withdrawal of New Risk Form will be used to document this notification process and whether the participant decided to remain on study. This form will be signed and dated by the investigator after discussion of the withdrawal of the new risk(s) with the participant. (Appendix C) Alternate Procedures There are no alternate procedures to this policy. For IRB policies always check the UCSF HRPP website for forms and guidance ( Policy Review Review and revision to this policy is to be completed every two years. Summary of Changes Section Number and/or Name N/A Revisions from Version 1 dated February 13, 2012 to Version 2, dated March 13, 2018 Revisions to Text Changed subject to participant, except in quotations from federal guidance Brief Rationale for Change N/A References Identifying New Risks Changed CHR to UCSF IRB Updated titles and website addresses 1. Added and procedures 2. Added language to reflect UCSF HDFCCC reliance on sponsors to provide new risks 1. To merge the two sections, Identifying New Risks and Procedures 10.MAY.2018 v.2 4 of 9

5 Responsibilities of the Principal Investigator Documentation of Verbal Notification 3. Updated examples of sponsor notifications of new risk and ways a PI may identify new risk 4. Added that PIs will have to request approval from sponsors to add new risk and that sponsors must authorize the addition of new risk 1. Deleted the requirement for new risk notification when a study s accrual status has participants only in long-term follow-up or off treatment. 2. Added other IRB 3. Added clarification for IIT ICF review by PI before IRB submission 4. Added language Active participants ( 30 days from last dose) are required to be notified of new risk.. 5. Added language that the PI will determine notification timelines (15/30 business days) 6. Added Active, off treatment, and in follow-up (per protocol) participants are required to be verbally notified of late effect risks within 90 business days. 7. Added that previous participants now off study are not required to be verbally notified 8. Provided a general reference for verbal notification by participant type and notification timeline 9. Clarified actions for off study participants if they cannot be located or refuse to sign updated ICF 1. Added language to account for verbal notification occurrence and participant subsequently going off study Summary of Changes Added to version 2, dated March 13, 2018 Appendices 1. Updated to include a PI Review of New Risk Documentation Form 2. Updated New Risk Form 3. Added Withdrawal of New Risk Form 2. To fall in line with the External AE SOP drafted and released in August Clarity 4. This is due to prior experiences where PIs have wanted to add new risk and sponsors have told them no after participants have been notified and central resources have worked on updating the ICF and preparing for IRB submission 1. New risk is primarily for participants taking the study drug 1. In review of studies, this has occurred and, without policy, it was unclear on how to proceed. 2. Updated to reflect the updates throughout the policy 3. There were a few studies whereby participants were verbally notified of a new risk, yet the sponsor subsequently denied the addition of the new risk to the ICF. This form is for these future events. 10.MAY.2018 v.2 5 of 9

6 Policy Approval This policy document was approved by the following personnel on the following dates: Kate Shumate Chief of Staff Director, Administration and Planning 5/11/2018 Thierry M. Jahan, MD Professor of Medicine Chair, Data and Safety Monitoring Committee 5/11/2018 5/11/2018 Eric Small, MD Professor and Chief, Division of Hematology and Oncology Deputy Director, UCSF 10.MAY.2018 v.2 6 of 9

7 Appendix A This form completed for all new risk for all studies. It is designed to be used per the UCSF HDFCCC Verbal Notification of New Risk Policy. The form can be modified to accommodate extraordinary circumstances (i.e. sponsor requirement to verbally notify participants off study; PI wanting to notify off-treatment participants within 15 days. PI Review of New Risk Documentation Form This form completed for all new risk for all studies, per the UCSF HDFCCC Verbal Notification of New Risk Policy. Sections in red are completed by PI. All other information completed by CRC. CC#: Study Title: Study specific circumstances (e.g. study drug only used in one arm or cohort): New Safety Information Type* - Select all that apply Investigator s Brochure* External AE Report DSMB/DSMC Report Dear Investigator Letter Internal AE Other *Risks from IBs and ICF templates from sponsors can default to 30 business days notification period New risk(s) and Drug/Agent Name 1 (Example: Tinnitus (ringing in the ears)/ Atezolizumab) Participants to Notify (check all that apply) Active ( 30 days from last dose) Off treatment (> 30 days from last dose) and In follow-up (per protocol) 3 Off study and Survival Follow-up 4 Notification Time Period (Choose 1 for each Participant type selected) 15 Business 30 Business 30 Business 90 Business No Notification Required Late Effect Risk? Yes (90 Business Notification List late effect risks 2 PI to complete only if there is no need to add new risk/verbally notify participants (e.g. study closing Do Not Add Risk Do Not Reason: Verbally Notify Principal Investigator Attach documents 1 Provide lay term and technical term, if available. If no lay term available (including online, in lay language dictionary: request lay language from the PI. If one risk is 30 business days and another 15 business days, notification of all risks default to the soonest, 15 business days. 2 Sponsors are required to tell the HDFCCC PIs when a risk is a late effect risk. Active, off treatment, and in follow-up (per protocol) participants are required to be verbally notified of late effect risks. Off study and in survival follow-up participants are not required to be notified. 3 If PI decides to notify off treatment (> 30 days from last dose) or in follow-up (per protocol) participants, due to the time it takes to notify those off study, 90 business days is the recommended notification period 4 Survival follow-up means the study team is only contacting the participant to see if they are still alive; no protocol activity is taking place during the contact. 10.MAY.2018 v.2 7 of 9

8 Appendix B New Risk Notification Form This form completed for all new risk for all studies, per the UCSF HDFCCC Verbal Notification of New Risk Policy. Sections in red are to be completed by PI. All other information to be completed by CRC. of Notification: Participant s Name/MRN: CC# & Study Title: Participant Status: New Participant (use form until IRB approves ICF; notification period below does not apply) Active ( 30 days from last dose) Off Treatment (>30 days from last dose) In Follow-up Risk(s) and notification time period: Business 30 Business 90 Business 15 Business 30 Business 90 Business 15 Business 30 Business 90 Business I have explained the above information to this participant and encouraged him/her to ask any questions he/she may have. I have also explained that the risk(s) will be added to the ICF and as soon as we receive IRB approval, he/she will have to sign the revised ICF at a future study visit (unless he/she goes off study before the ICF is IRB approved). I have reminded him/her that study participation is voluntary and may be discontinued at any time. The participant chooses to: Continue study participation and sign the revised ICF at a future study visit. Discontinue study participation. N/A (participant off study) Principal Investigator Was a translator required at the time of original consent? Yes No 10.MAY.2018 v.2 8 of 9

9 Appendix C Withdrawal of New Risk Form (File with New Risk Notification Form) This form is completed for when a participant is verbally notified of a new risk, that is ultimately determined to not be a new risk by either the sponsor, the PI, or both. Sections in red are to be completed by PI. All other information to be completed by CRC. of Notification: CC#: Participant s Name/MRN: Study Title: Participant Status: New Participant Active ( 30 days from last dose) Off Treatment (>30 days from last dose) In Follow-up Reason for withdrawal: Risk(s): I have explained the above information to this participant and encouraged him/her to ask any questions he/she may have. I have also explained that the risk(s) will not, as previously discussed, be added to the ICF and he/she will not sign a revised ICF with the risk(s) at a future study visit. I have reminded him/her that study participation is voluntary and may be discontinued at any time. The participant chooses to: Continue study participation and sign the revised ICF at a future study visit. Discontinue study participation. N/A (participant off study) Principal Investigator Was a translator required at the time of original consent? Yes No 10.MAY.2018 v.2 9 of 9