Dana-Farber/Harvard Cancer Center Site Management Plan

Transcription

1 Dana-Farber/Harvard Cancer Center Site Management Plan 1.0 Oversight Responsibilities of the Overall Principal Investigator and Site Responsible Investigator A system using an Overall Principal Investigator (Overall PI) and Site Responsible Investigator, as described in the Dana-Farber/Harvard Cancer Center (DF/HCC) Policies, is utilized for the conduct of the clinical trial. The Overall PI has the responsibility for the conduct of the clinical trial. Each participating institution has a designated Site Responsible Investigator, who is responsible for the coordination of the trial at that participating institution. The Site Responsible Investigator is responsible for collaborating with the Overall PI to ensure appropriate clinical conduct. There will be one Form FDA 1572 signed by the Overall PI. This Form FDA 1572 covers all participating DF/HCC clinical sites. The Site Responsible Investigators are listed as sub-investigators on the Form FDA All essential regulatory documentation is maintained by the Overall PI in a master file at his or her respective site and is communicated to the Site Responsible Investigators and other research team members as required. This includes all regulatory documents submitted to the Institutional Review Board (IRB) responsible for review of the research (i.e. IRB of Record) and the Dana-Farber Cancer Institute (DFCI) Institutional Review Board (IRBOffice for Human Research Studies (OHRS). Each Non-Lead, Satellite and Network Affiliate site maintains a subset of regulatory files at their institution to demonstrate compliance with regulatory requirements. The DFCI IRB acceptsohrs requires electronic submissions for active clinical trials.the review of human subject research by the DFCI IRB; or when research is reviewed by another IRB of Record. The Overall PI is copied via on all submissions to OHRS for a given trial. This enables the Overall PI to be aware of any and all submissions to the IRBOHRS, including serious adverse events (SAEs) and protocol deviations/violations that are generated at the participating sites. This also serves as acknowledgement of the submissions. Copies of all submissions generated from Non-Lead, Satellite and Network Affiliate sites are maintained at the site of origin per applicable DF/HCC Policies. The Lead Site study contact is copied via on all submissions to ensure that copies are filed in the master regulatory file. Additional periodic communication between the Lead Site and Non-Lead, Satellite and Network Affiliate Sites are conducted including convened meetings, teleconferences or distributions in which other protocol/subject related issues can be reported. Documentation of the study communication is filed in all regulatory files. Participation includes all appropriate research team members, including investigators, research nurses and study coordinators. 2.0 Institutional Review Board The DFCI IRB is the IRB of record for cancer-related human subject research related to cancer forat the clinical institutions that comprise Dana-Farber/Harvard Cancer Center (Attachment 1). Cancer-related research conducted under the auspices of the DF/HCC may be reviewed by another external IRB under a Reliance Agreement. Reliance Agreements are maintained by the Office for Human Research Studies (OHRS). As previously noted, the Lead Site submits the majority of the regulatory documents. to the IRB of Record and OHRS. This includes continuing reviews, consent changes, protocol amendments, research team update forms, IDB amendment, etc. Some submissions, such as SAE reports and deviation/violation reports, are submitted to the IRB by the Non-Lead, Satellite or Network Affiliates Site at which the event occurred. The respective Site Responsible Investigator oversees the submission of these site- Page 1 of 9

2 specific reports and is responsible for communicating this information to the Overall PI. The participating sites are informed of all communications with the IRB. All communicationcommunication from the IRB of Record is sent to the Overall PI. This includes official approval documents. OriginalIf the DFCI IRB is the IRB of record, original stamped or signed copies of approval letters are not sent by the IRB.issued. This is not a requirement of the Food and Drug Administration (FDA), and is not the policy of the DFCI IRB. Other IRBs follow their own policies and procedures for issuing approval documents. The Overall PI is responsible for communicating external IRB of Record determinations to the OHRS. 3.0 Study Oversight/Dissemination of Study Safety Information Study Oversight The site of the Overall PI is designated as the Lead Site for the clinical trial. The Lead Site manages the overall coordination for the clinical trial. The Overall PI designates a study coordinator to aid in study logistics including coordination of study visits (e.g. pre-qualification and site initiation visits) and shipment of study supplies from sponsor to each site. The Lead Site is also responsible for overseeing subject recruitment at each participating DF/HCC institution to ensure the correct numbers of subjects are enrolled as agreed in the contract. Regular communications between Lead Site and Non-Lead, Satellite and Network Affiliate Sites ensures that contact information is up-to-date. There is frequent telephone and communication, as appropriate, between the Lead Site and all DF/HCC and Network Affiliate sites at which the trial is being conducted. The sites are aware that if there is a change in contact information the Lead Site must be notified in a timely manner. Dissemination of Study Safety Information IND Safety Reports The Overall PI reviews all IND Safety Reportsupdated safety information received from external sponsors per RCO- 204 and determines whether or not they meet the criteria set by the DFCI IRBis responsible for submission to the IRB. of Record, when applicable. The participating sites are informed by the Lead Site / Overall PI of all communications withsubmissions to the IRB of Record and/or OHRS. SAE Reports Each individual site generates its own SAE reports for the Overall PI, IRB of Record and sponsor, if applicable (in accordance with procedures described in the protocol). The IRB of Record notifies the Overall PI and Site Responsible Investigators when an SAE has been reviewed. following the IRB of Record s IRB Policies and Procedures. Study Supplies Sponsors must provide each DF/HCC participating site with its own supplies (e.g. Laboratory kits, ECG machines, Glucometers etc.). 4.0 Training of Site Study Staff Page 2 of 9

3 All research team members receive site-specific training as provided by each institution. In addition, research team members are trained as appropriate for their protocol specific tasks. Training records are maintained at each institution. Per EDU-100, all research personnel listed on the delegation of authority log receive protocol-specific training as appropriate for their role and delegated responsibilities in research. The Overall PI is responsible for ensuring that initial training is completed prior to an individual performing any research activity, and ongoing training is completed as appropriate. Additionally, EDU-100 requires DF/HCC Policy training and ongoing Human Subject Protection and Good Clinical Practice Training for all applicable research personnel. Training documentation is required for all research staff and may be maintained individually or centrally. Investigators Meeting and/or Site Initiation Visit (SIV), if required by sponsor Research team members attend the Investigator s Meeting and/or Site Initiation Visit (SIV) where details of protocol eligibility, treatment schedule, toxicity management, etc. are discussed. Research team members who are unable to attend the Investigator s Meeting or SIV receive and review the materials and this is documented prior to performing their protocol specific tasks. In-Service(s), if required Infusion room nurses and pharmacists receive an in-service, where the specifics of the protocol such as drug administration are discussed, by the research nurse staff. Nurses and pharmacists who attend the in-service are required to sign an attendance sheet. This is coordinated by the research nurse and serves as documentation of training. Infusion nurses that are unable to attend the in-service will review the protocol and make an attestation in Healthstreamattest that they have reviewed the protocol per their institutional process, prior to caring for subjects enrolled on the protocol. Pharmacists not able to attend an in-service will also have the opportunity to learn about the protocol through staff communication and self-learning through the Online Protocol System (OncPro). Pharmacists must review key sections of the protocol each time prior to verifying a clinical trial patient s medication order. 5.0 Informed Consent Documents The most recent approved version of the informed consent document is available on the Oncology Protocol System (OncPro), and thus all informed consent documents must be printed from OncPro to ensure the correct version is used. The date and time that an informed consent document is printed is noted at the top of the informed consent document. The Overall PI and Site Responsible Investigators are informed by OHRS when a new or revised informed consent document is being posted tofor use on OncPro. DF/HCC requires that subjects in clinical trials be registered centrally in the OnCore Clinical Trial Management System. (CTMS). This registration is required in addition to any registration by the study sponsor. Documentation of informed consent and subject eligibility must be in place prior to registration. If a subject is not properly registered, s/he cannot receive protocol therapy. Ensuring that a subject is consented and/or has been re-consented is the responsibility of investigators at each site listed on the Form FDA At the time of informed consent document revisions, the Overall PI must inform the IRB of Record if the changes may affect the subject s willingness to continue participation in the study. If this is true, thea plan to notify subjects ismust be stated on the amendment form. If a plan to notify subjects is outlined on the Page 3 of 9

4 amendment form, it submitted to the IRB of Record. It is the responsibility of the Lead Site to ensure that thisthe subject notification / re-consent plan is carried out as stated.approved by the IRB of Record. If no notification / reconsent plan is indicated onprovided in the Amendment form or if the DFCI IRB of Record determines that the plan submitted by the Overall PI should be modified, itthe IRB will notify the Overall PI in writing if they have determined that the subjects must be notified and whether re-consenting by signing the updated informed consent document is required.of their determination. The Lead Site / Overall PI is responsible for ensuring that all sites participating in the trial are aware of the need to notify / re-consent subjects. 6.0 Study Drug Storage/Transport/Dispensation Maintenance of Drug Accountability Records Drug inventoryat MGH, DFCI and BIDMC a standardized drug accountability form is utilized for maintaining drug accountability records for all DF/HCC clinical trials, except those which are maintainedsponsored by the research pharmacy at each of the sites utilizing the National Cancer Institute (NCI)). In those cases, the MGH, DFCI and BIDMC can print the electronic drug accountability forms in either standard NCI Drug Accountability Report (DAR). Record Format (DARF) or in the NCI oral DARF. Handling of Used Vials and Unused Drug The pharmacist or a pharmacy technician under the supervision of a pharmacist at each site will be responsible for handling the vials and drugs within the pharmacy. As per INV-100, all empty and partially used containers of investigational drugs are to be treated as hazardous substances with disposal occurring immediately after use into the hazardous drugs waste stream containers. The research pharmacies under no circumstances will store used product containers (vials, bottles, empty boxes, etc), unblinded/open label tear-off labels, or ancillary supplies for accountability purposes. Products will be prepared per standard pharmacy guidelines and used vials (or other products) will be destroyed as per institutional policy. Storage BIDMC: All investigational agents as well as drug accountability records are stored in a separate locked, limitedaccess pharmacy facility. The pharmacy is maintained at controlled room temperature in accordance with the United States Pharmacopoeia standard. The pharmacy along with its refrigerators and freezers are monitored with temperature recording devices. BIDMC does not retain used investigational vials or oral agents as per institute policy. Unused investigational agents are returned to the sponsor or destroyed onsite as per sponsors directive. Used investigational agents which are returned from the patients are destroyed onsite following reconciliation by pharmacy and research nursing personnel. DFCI: Investigational agents are stored in locked areas with restricted access. DFCI does not retain used investigational vials or oral agents as per institute policy. Unused investigational agents from within the pharmacy are returned to the sponsor or destroyed onsite as per sponsor s directive. Used investigational agents from within the pharmacy and used investigational agents which are returned from patients are destroyed according to DFCI guidelines for chemotherapy and hazardous waste. There are timeframes as per policy as to how long the pharmacy will retain investigational agents once a study is closed and the last participant completes treatment. The pharmacy investigational drug storage areas are monitored for room, refrigerator, and freezer temperatures. Page 4 of 9

5 MGH: All investigational products and supplies, as well as accountability records and patient information, is maintained within the pharmacy. The pharmacy has a limited access key card system. Only pharmacy personnel have access to dispensing and storage areas. If non-pharmacy personnel require entry into the area for maintenance or auditing purposes, they are supervised at all times. The pharmacy is maintained at controlled room temperature as required by United States Pharmacopoeia Standards. The pharmacy also has proper refrigeration and freezer facilities for storage of drugs that require special storage conditions. The pharmacy investigational drug storage areas are monitored for room, refrigerator, and freezer temperatures. All DF/HCC research pharmacies store investigational agents in locked areas under temperature control with restricted access. Drug Destruction Policy BIDMC: All unused bulk chemotherapy (antineoplastic/cytotoxic) waste, unless characterized as a non-hazardous pharmaceutical, cannot be destroyed by the current medical waste disposal company. This material will be returned to the study sponsor for destruction. Trace chemotherapy waste including sharps, syringes, IV tubing, BAS bottles, vials and other discarded contaminated items generated in the preparation and administration of cytotoxic antineoplastic drugs, will be accepted by the medical waste disposal company for destruction. Non-hazardous investigational agents will be either destroyed or will be returned to the sponsor for destruction depending on the sponsor s requirements. Please refer to the BIDMC Standard Operating Procedure for further detail. DFCI: The drug destruction DFCI Standard Operating Procedure is on file. A copy can be provided if required. MGH: All used investigational products are placed in a Chemotherapy Waste Container immediately after drug preparation and dispensation. Each container is then sealed and stored with other containers of chemotherapy waste. At the end of each day, Environmental Services removes the containers from the pharmacy to the building s loading dock for pickup by an outside vendor hired by MGH. All materials are then incinerated at an off-site facility. Please refer to the MGH Standard Operating Procedure for further details. Management of Drug Expiration Extension Upon notificationmedications that expire will be held for 30 days from the sponsordate of any pending expiration dates: BIDMC: Expired drug is quarantined and labeled as Do not use until it can be destroyed or sent back tofor sponsor disposition. At the company. Expiration extension information is recorded on inventory records and extension memos are placed inend of the pharmacy study file. DFCI: Any30 days, any remaining expired drug is sequestered from inventory and marked Do Not Use until it can be returned and/or destroyed or the expiration date is extended. The Research Pharmacy s contact information is on file for such extension notifications. There are timeframes as will be destroyed per Standard Operating Procedure as to how long the pharmacy will retain expired agents. MGH: Inventory is conducted on a monthly basis and at the time expiration dates and/or extension dates are recorded. Expired investigational product or supplies are removed from inventory and marked Do Not Use or Expired. Extension notifications are recorded on inventory records and are kept on file as a permanent record. Theeach Page 5 of 9

6 research pharmacy returns or destroys investigational products once the appropriately party provides the proper disposition procedurespharmacy s institutional policy. Processes for Prevention of Errors in Drug Dispensation All investigational drugs are marked with the DFCI IRB protocol number. Each subject is registered in the OnCore Clinical Trials Management System before they can receive study drug. This registration is verified prior to dispensing. Study Drug/Supply Shipment for BIDMC, DFCI, MGH main institutions: Drug and other pharmacy study supplies are shipped from the sponsor to the research pharmacy of each site. Study Drug/Supply Shipment for Satellites and Network Affiliates sites (see definitions): Satellites generally receive study drug and pharmacy supplies from the main institution s research pharmacy. However, a sponsor must ship study drug directly to each Satellite location in some instances. These include, but are not limited to, the following: Cooperative group studies and other studies where drug is supplied by the NCI Pharmaceutical Management Branch (PMB) Studies using an Interactive Web & Voice Response system (IWRS or IVRS system) to assign study drug to individual subjects. DF/PCC Network Affiliates will receive all pharmacy study supplies directly from the sponsor and NCI. 7.0 Source Documents Electronic medical records and/or paper charts are maintained by each site according to the respective institutional policy. Access to source documentation will be provided according to institutional policy. 8.0 Case Report Forms (CRFs) The study coordinator responsible for the study at each site completes CRFs. Monitoring occurs at each individual site. Query resolution should be directed to the study coordinator at the site maintaining the CRF that generated the query. The Overall PI or delegated research team member at each institution is responsible for signing the CRF signature pages, if applicable, for that site. The Overall PI has ultimate responsibility for all aspects of trial performance including CRF completion. Data Submission and Entry Requirements Data submission and entry requirements for DF/HCC investigator-sponsored trials are defined in DATA- 100 and DATA-103. For externally-sponsored trials, DF/HCC will follow the sponsor s timeline for electronic CRF data management provided that those timelines minimally allow 10 days from a subject visit for data entry and 5 days for query resolution. When requested by the sponsor, investigator sign off of the CRFs will occur for formal database locks and prior to study completion. Page 6 of 9

7 9.0 Maintenance/Record Retention of Regulatory Files The master regulatory file is maintained at the Lead Site. Each Non-Lead, Satellite and Network Affiliate site maintains a subset of regulatory files at their institution. These files are maintained according to DF/HCC Policies. Study drug logs are maintained independently by the research pharmacy at each site and will be monitored individually. The completion of study is defined as when the sponsor verifies that all data is up-to-date and correct (e.g. there are no outstanding data requests or queries, the final report has been approved by the IRB of Record and no further research may occur under the protocol, and a formal study close out visit has been completed). At that point, the documents may be shipped to a long-term storage facility where they are kept for the period required per 21 CFR (c). Documents can be retrieved from the long-term storage facility upon request. Page 7 of 9

8 Attachment 1 Definitions: Lead Site: The site at the same physical location as the Overall PI. Non-Lead Site: The site at the same physical location of the Site Responsible Investigator(s). This does not include Satellite or Network Affiliate Sites. Satellite Site: A site licensed and accredited under one of the DF/HCC institutions that functions under the wider umbrella of the parent institution. Network Affiliate: Select New England area community hospitals that have a contractual agreement with Dana-Farber/Partners Cancer Care (DF/PCC) and access to selected Phase II and Phase III trials. BIDMC: Denotes Beth Israel Deaconess Medical Center and its satellite facilities. DFCI: Denotes Dana-Farber Cancer Institute, Dana-Farber/Brigham and Women s Cancer Center, Dana-Farber/ Boston Children s Cancer and Blood Disorders Center, and satellite facilities of the Dana- Farber Cancer Institute. MGH: Denotes Massachusetts General Hospital and its satellite facilities. BCH: Denotes Boston Children s Hospital when participating separately from DFCI. BWH: Denotes Brigham and Women s Hospital when participating separately from DFCI. Page 8 of 9

9 Attachment 2 DF/HCC Satellite Locations: DFCI: Dana-Farber/New Hampshire Oncology-Hematology (DF/NHOH) 40 Buttrick Road, Suite B Londonderry, NH Dana-Farber/Brigham and Women s Cancer Center at Milford Regional Medical Center 20 Prospect Street Milford, MA Dana-Farber/Brigham and Women s Cancer Center in Clinical Affiliation with South Shore Hospital 101 Columbian Street Weymouth, MA Dana-Farber Cancer Institute at St. Elizabeth s Medical Center 736 Cambridge Street, Cushing Pavilion, 5 th Floor Brighton, MA MGH: Massachusetts General Hospital Cancer Center at Emerson Hospital Bethke 131 Old Road to Nine Acre Corner Concord, MA Massachusetts General / North Shore Cancer Center (MG/NSCC) 102 Endicott Street Danvers, MA Massachusetts General Hospital Cancer Center at Newton-Wellesley Hospital 2014 Washington Street Newton, MA BIDMC: Beth Israel Deaconess Cancer Center and Surgical Pavilion (BIDMC-Needham) 148 Chestnut Street Needham, MA Page 9 of 9