STANDARD OPERATING PROCEDURE SOP 410 Set up and Initiation of an Investigator Site Version 1.2 Version date 4.01.2017 Effective date 5.07.2017 Number of pages 13 Review date July 2019 Author Role NNUH UEA Joint Research Office Approved by Role Julie Dawson Acting Research Services Manager Signature Date 13.03.2017 Authorised for NNUH and UEA by Role Professor Alastair Forbes Chief of Research and Innovation Signature Date 5/7/17 SOP 410 v1.2 Effective date: 6.07.2017 Page 1 of 13
It is the responsibility of all users of this SOP to ensure that the correct version is being used. All staff should regularly check the NNUH R&D website for information relating to the implementation of new or revised versions of SOPs. Staff must ensure that they are adequately trained in the new procedure and must make sure that all copies of superseded versions are promptly withdrawn from use. The definitive versions of all Joint NNUH/UEA health care research SOPs appear online. If you are reading this in printed form please check that the version number and effective date is the most recent one as shown on the NNUH R&D website. TABLE OF CONTENTS 1 ABBREVIATIONS 3 2 INTRODUCTION 3 3 SCOPE 4 4 RESPONSIBILITY 4 5 PROCEDURE 4 5.1 Before initiation 4 5.2 Site initiation 5 5.3 After initiation 5 6 REFERENCES 6 7 RELATED DOCUMENTS 6 8 LIST OF APPENDICES 6 APPENDIX 1:Site Initiation Visit Checklist 7 APPENDIX 2: For Site Initiation Agenda 9 APPENDIX 3: Example Change Control, Revision and Review Sheet 12 SOP 410 v1.2 Effective date: 6.07.2017 Page 2 of 13
1 ABBREVIATIONS AHP Allied Health Professional CI Chief Investigator CRF Clinical Research Facility CTU Clinical Trials Unit CTIMP Clinical Trial of an Investigational Medicinal Product GCP Good Clinical Practice IMP Investigational Medicinal Products ICH International Conference for Harmonisation MP Medicinal Products NNUH Norfolk and Norwich University Hospital PI Principal Investigator R&D Research and Development Office REN Research and Enterprise Services UEA SIV Site Initiation Visit SmPC Summary of Product Characteristics SOP Standard Operating Procedure TMF Trial Master File UEA University of East Anglia 2 INTRODUCTION This SOP describes the processes required to set up an investigator site for a CTIMP, non-ctimp or device trial, as either a single site or one of multiple sites in a trial sponsored by NNUH or UEA. It provides information relating to planning for site initiation, the site initiation visit (SIV) and events following this. The site initiation visit can take place by either a physical visit to site or by teleconferencing. The CI/PI must be present at the site initiation visit/call. All staff who will be involved in the day-to-day operation of the trial should be invited to attend. Before a trial can be initiated at a site, all necessary regulatory and local approvals need to be in place. The site initiation process ensures that: all essential documentation is in place prior to the start of the trial each site has the essential documents to conduct the trial each site is aware of its roles and responsibilities each site is aware of the sponsor s requirements and the SOPs to be used site staff have evidence of current GCP training (updated every two years) a delegation log is completed prior to the start of trial activities. This log requires authorization by the CI/PI. site pharmacy arrangements (if appropriate) are in place to allow IMP ordering, receipt, dispensing and accountability. site arrangements are in place with the supplier of medical devices (if appropriate) to allow ordering, receipt, dispensing and accountability of the devices. SOP 410 v1.2 Effective date: 6.07.2017 Page 3 of 13
contact details are up-to-date and clear lines of contact for enquiries are established between the sponsor/ci and the research team, and pharmacy (if appropriate). 3 SCOPE This SOP applies to all healthcare research sponsored by NNUH or UEA which falls within the scope of the Research Governance Framework (2nd edition 2005) or its successor. Where additional legislation applies, for example the Medicines for Human Use (Clinical Trials) Regulations 2004 (and amendments) or the Medical Devices Regulations 2002, required procedures will be indicated. External sponsors may require use of their own SOPs and this will be specified in site agreements. It is the responsibility of the local PI to ensure that study specific SOPs can be operated without conflict with this SOP and in accordance with all organisational polices related to research. 4 RESPONSIBILITY The Trial Manager/Co-coordinator (or equivalent) will usually act as the main line of communication between the site investigator and the Sponsor s representative and, in consultation with the CI/PI, will manage the process of site initiation. Where there is no Trial Manager/Co-coordinator, for example where the trial is of short duration and of low risk, the CI/PI will manage the process of site initiation. For CTIMPs it is expected that the Trial Manager /Co-coordinator, Trial Monitor, research study team and R&D representative will be involved in the process of site initiation. For non-ctimps where NNUH is a site, the R&D representative will be involved in the site initiation visit/call. For non-ctimps sponsored by UEA and where NNUH is not a site, the CI/PI will be responsible for the process of site initiation and for keeping the records and reports from the site initiation in the Trial Master File. The CI/PI must be present at the site initiation visit/call. All staff who will be involved in the day to day operation of the trial should be invited to attend. 5 PROCEDURE 5.1 Before the site initiation visit 5.1.1 The Trial Manager/Coordinator should check that all essential documentation, approvals and contracts are in place prior to the site initiation visit. The NNUH/UEA sponsor file/trial Master File will be held by the R&D/REN office and R&D/REN will be able to support in this process. 5.1.2 The Trial Manager/Co-coordinator in agreement with the trial pharmacist (as appropriate) should ensure that arrangements are in place for the sourcing and release of the IMP, checking this with the sponsor. SOP 410 v1.2 Effective date: 6.07.2017 Page 4 of 13
5.1.3 The Trial Manager/Co-coordinator should ensure that the site has the site initiation visit checklist (Appendix 1) to identify requirements at site and to set up the investigator site file (See SOP 305), pharmacy site file, if the study involves the supply of drugs or MPs, and any required study specific SOPs. The Trial Manager may set up the Pharmacy file in agreement with the Pharmacist and following Pharmacy SOPs. 5.1.4 If study specific SOPs are to be developed (in addition to local Trust SOPs) these must be available to the Research Team and the Sponsor prior to the site initiation visit. 5.1.5 The Trial Manager/Co-coordinator will need to confirm that the site has: local NHS permission / Confirmation of Capacity and Capability Completed Risk Assessment, a fully signed site agreement and agreements with 3 rd parties (if required). site investigator CVs and GCP certificates. staff delegation log. clear arrangements for monitoring, with a completed monitoring plan in place. pharmacy and/or medical device supply agreements (if appropriate) in place (including formal confirmation from pharmacy) Trial Master File and/or Investigator Site File. 5.1.6 An initiation visit/meeting should be arranged and set up at site by the Trial Manager/Co-coordinator, in consultation with the CI/PI. Staff who are involved in and/or responsible for this study at site must be invited to the meeting (CI/PI/Lead pharmacist) and should include the site Pharmacist, Trial Monitor, Trial Nurses/Allied Health Professionals and administrators who will be supporting the study at site. An agenda, detailing the requirements to be covered for the meeting should be circulated with the invitation. (See Appendix 2) 5.1.7 If the visit is taking place via teleconference then details of the location or dial in details should be circulated in advance. It may be helpful to develop and circulate a presentation or slide set based on the agenda items. (See Appendix 2) 5.2 Site initiation visit (SIV) 5.2.1 The meeting should be held according to the agenda, and a record of attendees at the meeting, and notes from the meeting should be kept in the Trial Master File and investigator site file(s). 5.2.2 Time should be allowed for the research team to raise any queries. If these cannot be resolved by the trial manager/coordinator at the meeting these should be followed up after the visit and resolved prior to the start of participant recruitment. 5.2.3 For CTIMPs and studies involving the supply of drugs, the pharmacy team should be familiar with the processes and documentation required. Arrangements for storage/transport /supply of IMP should be reviewed and approved by the Clinical Trial Pharmacist, the Trial Manager, Sponsor and the CI/PI. SOP 410 v1.2 Effective date: 6.07.2017 Page 5 of 13
5.2.4 Visits to local facilities such as laboratories and pharmacy should be arranged as necessary for the Trial manager/co-coordinator to discuss set-up arrangements either prior to or as part of the SIV. 5.3 After the site initiation visit 5.3.1 A report of the initiation meeting, along with any follow-up actions required/ undertaken should be prepared by the Trial Manager/Coordinator/Trial Monitor or Trial Facilitator and sent to the site. 5.3.2 A copy of the report should also be forwarded to the Sponsor, along with a copy of the signed delegation log. For CTIMPs the Sponsor will then issue a letter to the PI at site to allow release of IMP or medical devices at the site. 5.3.3 For NNUH sponsored or hosted studies, REN / R&D will record details of the site initiation and delegation in the sponsor/r&d file. For UEA sponsored studies not involving NNUH, the CI shall retain these records in the TMF. 5.3.4 For CTIMPs and Medical Devices studies a Green Light confirmation letter will be produced by the Sponsor to confirm that the site is ready to recruit participants. No study related activities can take place until Confirmation of Green Light from the Sponsor has been received by the CI/PI. (Please see Green Light Checklist in Appendix 2 as a guide.) 5.3.5 Following the site visit, representatives from the site should be invited by the trial manager/coordinator to attend any relevant steering group or data monitoring meetings. 6 REFERENCES Research Governance Framework (DH April 2005) or its successor. Medicines for Human Use (Clinical Trial) Regulations 2004 (SI 2004/1031) 7 RELATED DOCUMENTS SOP 305 Creating and Maintaining a Trial Master File and Investigator Site File SOP 330 Monitoring Clinical Trials SOP 335 Site Study Closedown SOP 505 Creating and Maintaining Training Records 8 LIST OF APPENDICES Appendix 1: Site Initiation Visit Checklist Appendix 2: Site Initiation Visit Agenda Appendix 3: Change Control, Revision and Review Sheet SOP 410 v1.2 Effective date: 6.07.2017 Page 6 of 13
Appendix 1: Site Initiation Visit Checklist Item Action Comments/Confirmation 1 Site initiation visit date: time, location, agenda issued 2 Roles and Responsibilities Delegation of responsibilities in place (sponsor and co-sponsor/staff delegation log) 3 Check all approvals are in place Ethics NHS Permission / Confirmation of Capacity and Capability (main site) NHS Permission / Confirmation of Capacity and Capability (local site) HRA Approval MHRA authorisations (if appropriate) Contract for funding (if appropriate) Drug supply Agreement (if appropriate) Laboratory Agreement (if appropriate) Technical Agreement (if appropriate) 4 Trial Master File / Investigator Site file contents and set up (See SOP 305 for guidance) 5 Training requirements: Study aims Time Frames Trial procedures Delegation log requirements Study outcomes Inclusion/Exclusion Recruitment Targets Data handling CRF/Electronic data capture systems Monitoring plan and visits (draft) (as agreed with Sponsor) including plans for close (see SOP 335) SOP 410 v1.2 Effective date: 6.07.2017 Page 7 of 13
Trial Specific SOPs or Working Practice Documents (if used) Safety reporting procedures Pharmacy procedures (for IMPs) Labelling Receipt Storage Prescriptions Product recall Destruction Laboratory procedures (if appropriate) Other departments (e.g. Radiology) Contact details for local site and study lead site Staff training log /Training records (See SOP 505) 6 Site initiation report completed. This checklist is for guidance purposes and should be adapted to the requirements of the study. SOP 410 v1.2 Effective date: 6.07.2017 Page 8 of 13
Appendix 2: Agenda for Site Initiation: To be adapted to the requirements of the study Initiation Visit Agenda <Insert protocol title> Protocol Number/Eudract reference: <Insert protocol reference> Principal Investigator: <Insert PI name> <Insert site location> Meeting Date/Start Time: <Insert date and time> Attendees: Representing Name Role or Title Topic 1 Welcome and Opening Comments 1.1 Statement of visit objectives 1.2 Review of agenda 2 Introductions/Roles and Responsibilities {Consider using the Delegation of Responsibilities Log to guide some of the introductions.} Presenter Duration/Start time 3 Investigator Responsibilities 3.1 Good Clinical Practice (GCP) 3.2 Records Retention SOP 410 v1.2 Effective date: 6.07.2017 Page 9 of 13
Topic 4 Protocol Overview 4.1 Type of study 4.2 Study objectives 4.3 Enrolment 4.3.1 Recruitment Screening/Consort targets 4.3.2 Plans for reporting recruitment 4.4 Informed Consent Discussion 4.5 Key inclusion/exclusion criteria 4.6 Study visit schedule/schedule of events 5 SOPs and Study Procedures 5.1 Review/Patient pathway 5.2 Discussion of procedure for handling updates to study specific SOPs; Working Practice Documents and other study specific information 6 Safety: Definitions, Collection, and Reporting 6.1 Adverse Events (AEs) 6.2 Serious AEs (SAEs) 6.3 Unanticipated Problems: Urgent safety measures and protocol violations 6.4 Queries resulting from the above 7 Data Collection/Source Documentation 7.1 Paper or Electronic Data Capture (edc) CRF discussion 7.2 Source Documents 6.4.1 Definitions of 6.4.2 Retention of 7.3 Query process 7.3.1 Data query form (template) Presenter Duration/Start time SOP 410 v1.2 Effective date: 6.07.2017 Page 10 of 13
Topic 8 Investigational Product (if applicable) 8.1 Description of Product 8.2 Review of Investigator Brochure (IB) or SmPC (if applicable) 8.3 Storage 8.4 Dosing Instructions 8.5 Dispensing 8.6 Accountability 8.7 Return/Destruction Considerations 8.8 Authorisation of release 9 Specimen Processing (if appropriate) 9.1 Collection 9.2 Storage 9.3 Transport 10 Clinical Monitoring 10.1 Contacts 10.2 Responsibilities of 10.3 Frequency (to be discussed and confirmed after site visit) 10.4 Close out procedures (see SOP 335) 11 Investigator Site File Review 11.1 Structure of the File as well as Essential Documents to include: Ethics approval, NHS permission, MHRA authorizations (See SOP 305) 12 Tour of Facilities (if appropriate) 13 Closing/Review of Action Items. Presenter Duration/Start time SOP 410 v1.2 Effective date: 6.07.2017 Page 11 of 13
Appendix 3. Sponsor Confirmation of Green Light checklist Sponsor Confirmation of Green Light checklist (for CTIMs and Medical Devices studies) Study title: RD number: N/A Completed Date completed Risk assessment completed MHRA approval received REC favorable opinion letter received HRA approval received Trust R&D Confirmation of Capacity and Capability in place Confirmation of Insurance in place: Finance Approval received Site Pharmacy Agreement in place Fully signed site agreement in place Monitoring Plan completed SIV completed Trial Master File / Investigator Site File set up Other: Sponsor Confirmation of Green Light letter sent on (date): SOP 410 v1.2 Effective date: 6.07.2017 Page 12 of 13
Appendix 3: Change Control, Revision and Review sheet CHANGE CONTROL, REVISION and REVIEW SHEET: SOP 410 Version No Change Date Reason for Change V1.1 02/12/2013 General update and typing corrections throughout, amendments to roles to be involved at planning, visit and post visit, additional agreements added to Site Initial Visit Checklist (Appendix 1) and data query form and authorisation of drug/imp release added to Initial Visit Agenda (Appendix 2). Combining of SOP control and revision sheets. Reviewer : Andrew A Walker 1.2 Reviewer : Laura Harper Reviewer : Basia Brown Designation : Clinical Trials Manager Designation : Research study and Recruitment Facilitator Designation : Research Governance Cocoordinator Signature and Date A A Walker 20 th December 2013 General grammar changes, addition of items to the list of abbreviations. Clarification in the introduction of the policy that trials SOP refers to trials sponsored By NNUH or UEA. Signature and Date General formatting and updating SOP following staff changes. Sponsor filed referred to as Trial Master File in line with SOP 305 (p.4) Addition of reference to Green Light confirmation letter and Green Light checklist. Signature and Date: 4.01.2017 SOP 410 v1.2 Effective date: 6.07.2017 Page 13 of 13