STANDARD OPERATING PROCEDURE Title Reference Number Site Initiation SOP-RES-010 Version Number 2 Issue Date 15 Apr 2016 Effective Date 26 May 2016 Review Date 26 May 2018 Author(s) Reviewer(s) Rachelle Ward, Research Project Manager Teresa O Leary, Head of Regulatory Compliance Authorisation (Original signatures are retained by Research & Innovation) Dr Stephen Ryder Director of Research & Innovation Dr Stephen Fowlie Medical Director 04 Apr 2016 11 Apr 2016 USERS OF THIS STANDARD OPERATING PROCEDURE MUST REFER TO WWW.NUHRISE.ORG TO ENSURE THE MOST CURRENT VERSION IS BEING USED
Page 2 of 8 1. Document History Version Issue Date Reason for Change Number 1 22 nd April 2014 Original SOP. It replaces SOP-45. 2 15 Apr 2016 Biennial review and inclusion of HRA approval
Page 3 of 8 2. Introduction The Research and Innovation (R&I) department, which acts on behalf of the sponsor for Nottingham University Hospitals NHS Trust (NUH), is responsible for putting in place the necessary procedures to secure the quality of every aspect of a clinical study including clinical study activities carried out by institutions and investigators participating in studies sponsored by NUH. Site initiation visits (SIVs) occur prior to site activation for a specific protocol. These visits have several goals: to orient and train staff on the protocol and study related processes; to confirm readiness for study implementation; and to identify additional requirements that must be satisfied prior to site activation and participant recruitment. 3. Purpose and Scope This standard operating procedure (SOP) outlines the SIV process for all clinical trials of investigational medicinal products (CTIMPs), clinical investigations of medical devices (CMDs) and gene therapy studies that are sponsored by NUH. Other studies (which are not a CTIMP or CMD) but also require an SIV (in accordance with the risk assessment outcome, SOP-RES-002 Risk Assessment) fall under the scope of this procedure. Studies can be single- or multi-site investigator-led and the SIV can be performed on-site or remotely. An SIV is required to prepare and set up a research site to conduct a study. The SIV will be scheduled according to the Monitoring Plan (MP) (TAFR00202) and must take place before the site can be given the green light (refer to SOP-RES-011 Site Green Light) to commence recruitment. 4. Responsibilities Sponsor (fulfilled by the Research and Innovation (R&I) department on behalf of NUH) The Head of Regulatory Compliance (HRC) and/or QA/GCP Auditor (QAA) will implement the Monitoring Plan (MP) based on the outcome of the risk assessment. The Research Project Manager (RPM) will undertake the SIV according to the MP. Chief Investigator (CI)
Page 4 of 8 Study specific elements of the SIV are delegated to the CI as outlined in the agreement and SIV agenda. 5. Definitions CA CI CMD CTIMP GCP Green Light HRA HRC IMP ISF MHRA NHS NUH PI QA QAA R&D R&I RPM SIV SOP SRM TMF Competent Authority, in the United Kingdom this is the MHRA Chief Investigator Clinical Investigation of a Medical Device Clinical Trial of an Investigational Medicinal Product Good Clinical Practice Sponsor authorisation for the site to commence recruitment; issued after the site has received all other approvals and HRA approval Health Research Authority Head of Regulatory Compliance Investigational Medicinal Product Investigator Site File Medicines and Healthcare products Regulatory Agency National Health Service Nottingham University Hospitals NHS Trust Principal Investigator Quality Assurance QA/GCP Auditor Research and Development Research and Innovation Research Project Manager Site Initiation Visit Standard Operating Procedure Senior Research Manager Trial Master File
Page 5 of 8 6. Procedure When HRA and all regulatory approvals are in place, and the host NHS organisation has confirmed their capacity to conduct the study, the RPM will arrange the SIV. The SIV should include a visit to the site pharmacy to discuss the Investigational Medicinal Product (IMP) management (for studies involving drugs). A study cannot commence in the NHS in England until HRA Approval has been issued Recruitment must not commence at the site until the sponsor has explicitly given authorisation ( green light ) for it to do so. A summary of the SIV process is provided in Appendix 1. 6.1 Preparation for the Site Initiation Visit The RPM will contact the CI/Principal Investigator (PI) and study Pharmacist (for studies involving drugs) to schedule the date, time and location of the SIV ensuring that it is as close to the HRA approval date as possible. It is essential that all relevant study team members identified by the CI/PI attend the SIV. Representatives from support departments should also attend if necessary (e.g. radiology and pathology). The RPM will send the PI the Site Initiation Confirmation Letter (TAFR01004) and Site Initiation Visit Agenda (TAFR01001) giving as much notice as possible. A copy of both will be sent to the CI. Prior to the SIV the RPM will ensure that the Trial Master File (TMF) has been set up according to regulatory and sponsor requirements (refer to SOP-RES-014 Maintaining Study Files). Any missing documents can be collected from- or provided to- the site during the SIV. 6.2 During the Site Initiation Visit The RPM will ask all members who attend the SIV to sign the Site Initiation Visit Attendance Log (TAFR01002). All aspects of the agenda must be covered in the SIV. The agenda may be restructured during the SIV to allow for research staff and facility availability. Any aspect of the agenda not covered in the SIV must be documented and may need to be covered at another date and time. The RPM will confirm this with the site as per 6.1.
Page 6 of 8 The RPM will use the Site Initiation Report (TAFR01003) template to document the SIV. 6.3 Post Site Initiation Visit The site initiation report and Site Initiation Follow-up Letter (TAFR01005) should be prepared by the RPM and reviewed by the Head of Regulatory Compliance (HRC) or Senior Research Manager (SRM) within 10 working days of the SIV. If any areas identified during the SIV require further clarification or any document anomalies need to be reconciled then these will be listed in the follow-up letter and the site may not be authorised to commence recruitment. A copy of the site initiation report and follow-up letter along with any supporting documents will be sent to the site PI and a copy sent to the CI. The original, signed site initiation report should be filed within the TMF and a copy filed in the Investigator Site File (ISF). The site will be authorised to commence recruitment once they receive the sponsor s green light. If the site has no outstanding actions following the SIV the RPM will issue the green light at the same time as the SIV follow-up letter. If the site had actions to address as identified in the SIV follow-up letter the sponsor s green light will only be issued once evidence has been provided to the RPM that all queries have been resolved. If the site fails to address outstanding actions from the SIV in a timely manner the RPM will escalate this to the Head of Regulatory Compliance or Senior Research Manager who will liaise with the site (and the CI) to complete the actions or to consider withdrawing the site from the study. Subsequent monitoring of the investigator site will occur at an agreed frequency according to the MP (refer to SOP-RES-013 Monitoring). 6.4 Remote Site Initiation Visit A site may be selected for a remote initiation as documented in the MP. The SIV will be confirmed as per 6.1. The RPM will provide an electronic copy of the Site Initiation Visit Attendance Log (TAFR01002) for the site to sign which should be returned to the RPM after the SIV. The SIV will be conducted either by teleconference or another remote communication method. The remote SIV will be followed up in the same manner as if it were conducted on-site (as per 6.2 and 6.3).
Page 7 of 8 7. References The Medicines for Human Use (Clinical Trials) Regulations 2004 and subsequent amendments International Conference on Harmonisation Guidelines for Good Clinical Practice E6 (R1) ISO 14155 Clinical Investigation of Medical Devices for Human Subjects TAFR00202 TAFR01001 TAFR01002 TAFR01003 TAFR01004 TAFR01005 TAFR01102 SOP-RES-002 SOP-RES-006 SOP-RES-011 SOP-RES-013 SOP-RES-014 Monitoring Plan Site Initiation Visit Agenda Site Initiation Visit Attendance Log Site Initiation Report Site Initiation Confirmation Letter Site Initiation Follow Up Letter Green Light Approval Letter Risk Assessment Local Assess, Arrange and Confirm Process Site Green Light Monitoring Maintaining Study Files 8. Appendices
Page 8 of 8 Appendix 1. Site Initiation Visit Process HRA Approval in place and site have confirmed capacity to conduct the study Arrange SIV Send SIV Confirmation Letter and SIV Agenda to site Site Initiation Visit SIV Report Outstanding actions SIV follow-up letter and SIV report sent to site along with supporting documentation No outstanding actions Green light approval letter sent to site Recruitment can commence at site