SOP16: Standard Operating Procedure for Establishing Sites and Centres - Site Setup

SOP16: Standard Operating Procedure for Establishing Sites and Centres - Site Setup Authorship Team: Leanne Quinn for Joint SOP Group on Trial Processes (viz Ian Russell, Anne Seagrove, Jemma Hughes, Yvette Ellis) Approved by WWORTH JMG (Ian Russell in chair) Signature Date of Approval 0 Version Record Version Number Effective Date Reason for Change 0 20 Apr 2009 Derived from SOP approved by NWORTH 0.1 01 Apr 2009 Reviewed by JSOPG on 1 st May 2009 0.2 11 May 2009 Changes made by LQ following JSOPG meeting 0.3 06 Jul 2009 Changes made by LQ following review meeting 0.4 27 Aug 2009 Changes made by LQ following JMG meeting 0.5 06 Jul 2009 Approved in principle at JMG following reviewer s comments 1.0 06 Oct 2009 Changes made by LQ following review by Stefan Siebert 1.1 16 May 2010 Minor formatting amendments 1.2 04 Jul 2011 Egs in practice - RefraMED, SAFER 2, CONSTRUCT. Prepare SOP for JSOPG. MS 1.3 26 Jul 2011 Amendments following JSOPG meeting. MS & LQ. 1.4 16 Sept 2011 Amendments following JSOPG meeting LQ 2.0 16 Sept 2011 Approved for use by JMG 2.1 07 May 2014 Remove training log post JSOPG discussion - MS & CS WWORTH-SOP16SitesetupV2.1-140507 Page 1 of 12 Not guaranteed if printed

1 Table of Contents 0 Version record... 1 1 Table of Contents... 2 2 Glossary... 3 3 Introduction... 3 4 Purpose... 3 5 Roles and Responsibilities... 3 6 Procedure... 5 6.1 Procedure Flow Chart... 6 6.2 Site Selection... 7 6.3 Site Approvals... 7 6.4 Site Initiation... 8 6.4.1 Organising site visit... 8 6.4.2 Site Documentation... 9 6.4.3 Site Visit and Training... 9 6.4.4 Following the initiation visit... 10 6.5 Site Activation...11 7 Training plan...11 8 References...12 9 Related SOPs...12 WWORTH-SOP16SitesetupV2.1-140507 Page 2 of 12 Not guaranteed if printed

2 Glossary The full Glossary is in Swansea University H drive/documents/526- WWORTH/Development Group/Glossary. 3 Introduction Standard Operating Procedures (SOPs) are succinct formal documents designed to achieve consistency in specified trial functions by specifying standard practice in performing those functions (GCP 1.55 & 5.1.1(1). While SOPs should cite relevant legislation & regulations, and key references & evidence, they need not expound theory. WWORTH SOPs are written in compliance with regulatory requirements - The Research Governance Framework, EU Clinical Trial Directive, ICH Good Clinical Practice and Internal Guidelines NHS guidelines/policies/clinical governance. All SOPs will distinguish regulatory requirements between Clinical Trials Involving Medicinal Products (CTIMPs) and other research (non-ctimps). This document forms part of the set of SOPs of the West Wales Organisation for Rigorous Trials in Health - WWORTH. It describes the roles, responsibilities and actions of the individuals involved in site / centre identification, assessment, recruitment, set-up, initiation and activation.. For the purpose of this SOP, the term site will be taken to include centres too. Prior to a site being activated and starting participant recruitment, a site visit by the Trial Manager (TM) and other WWORTH team members may be required to prepare the site for participant recruitment. This should take place when all regulatory and ethics approvals for that specific site are obtained see WWORTH SOP14 Ethics RG approval and WWORTH SOP15 MHRA Approval. 4 Purpose To describe the process of study site identification, assessment, recruitment, set-up, initiation and activation, and who should perform those tasks. 5 Roles and Responsibilities An assessment of potential investigator(s) and institution(s) should be carried out to determine the suitability of that site to participate in the study. Accountable to the sponsor, it is the responsibility of the Chief Investigator (CI) or WWORTH to ensure appropriate sites are selected to participate in a study WWORTH-SOP16SitesetupV2.1-140507 Page 3 of 12 Not guaranteed if printed

(see WWORTH SOP31 Sponsorship and Adoption), with the exception of commercial studies where it is the norm for the sponsor to have this responsibility. The CI is accountable to the sponsor for the participating sites. The CI can delegate the roles as indicated below: The Trial Manager (TM) / Trial Co-ordinator (TC) should: Ensure that all regulatory approvals for a site are obtained before a site visit and training takes place. Arrange a visit or if not practical video, audio or Skype can be used. Ensure all site team members (including pharmacy for CTIMPS) understand the study and its procedures. Ensure all site team members have received training in the principles of GCP. Obtain signatures; PI to trial protocol, all signatures on a delegation log and any SOPs (or modified procedures) used. A list of agreed SOPs should be sent to the site with a statement to say that WWORTH will work to these SOPs and request sign up by the site to the SOPs (MOPs). Confirmation via e-mail is acceptable. Ensure that all site team members that are to be involved in the study have signed the delegation log and provided their CV to demonstrate that they are qualified by training and experience to perform delegated study tasks. Ensure that the TSF contains all essential documentation and information that is particular to that site and may affect the running of the study (e.g. local laboratory reference ranges, accreditation certificates) and copy it to the TMF (see WWORTH SOP03 Master Site File). Ensure each site has sufficient copies of the study documentation (e.g. Trial Site File (TSF), Case Report Form (CRF), Investigator s Brochure (IB) (see WWORTH SOP03 Master Site File). Obtain the PI s signature to allow direct access to all trial-related source data or documents for the purpose of monitoring and auditing, WWORTH-SOP16SitesetupV2.1-140507 Page 4 of 12 Not guaranteed if printed

Activate the study site to begin participant recruitment. The PI s are responsible for a specific site and can delegate this role to the site trial co-ordinator. The Trial Data Manager s (TDM) role (with support from IT specialist) is to ensure training is received for all aspects of randomisation, data collection, CRF completion and/or input of electronic data. See WWORTH SOP24 Randomisation and WWORTH SOP22a Data Collection Management. The Trial Unit Manager has responsibility of ensuring study site set-up is in keeping with the principles of GCP. Site Staff need to understand their role and have an awareness of the duties of others in the team and read and understand applicable trial related documents as directed by the TM. 6 Procedure This section describes the responsibilities and procedures for identification, assessment, site recruitment, site setup, initiation and activation. WWORTH-SOP16SitesetupV2.1-140507 Page 5 of 12 Not guaranteed if printed

6.1 Procedure Flow Chart 6.2 Identification and assessment of potential investigator(s) and institution(s) is carried out by CI or delegated person. Confidentiality agreements may need to be in place before the release of any study documentation 6.3 Ethics approval, sponsorship, funding, research governance approvals are agreed for the trial as a whole. Site-specific ethics and regulatory approvals are obtained Sites may be added after full regulatory approvals are in place, although this would be a substantial amendment for CTIMPS only and site specific ethics and regulatory approvals would be required prior to the site being initiated. 6.4.1 A date for a site initiation visit is arranged if required. 6.4.2 Site documentation 6.4.3 TC and TM, TDM and IT specialist visit the site, 1) meet the PI and discuss clinical aspects, obtain his/her signature on the protocol 2) train staff on data collection and entry 3) for CTIMP, train pharmacy staff 4) train any other staff involved in trial-specific documentation (lab / imaging etc) 5) obtain signatures to a delegation log 6.4.4 TC and TM records any site-specific details or issues likely to affect the trial 6.4.4 A record of the visit, including answers to any questions raised, is filed and copy sent to the PI & CI 6.5 Site activated to begin participant recruitment 6.5 Following activation monitoring visits should be carried out as stated in the monitoring plan. If any problems are identified then a monitoring visit should be carried out as soon as possible WWORTH-SOP16SitesetupV2.1-140507 Page 6 of 12 Not guaranteed if printed

6.2 Site Selection The CI is responsible for selecting appropriate investigator(s) and institution(s) for a study, in collaboration with WWORTH. Thorough site selection ensures that study resources are directed towards motivated, qualified staff, with the potential to recruit eligible participants and conduct the study within the context of relevant regulations and timelines. Potential investigator(s) and institutions(s) will be assessed to confirm their suitability to participate in the study. Confidentiality agreements may need to be signed by the potential investigator before protocols are issued to sites, especially in commercial research. Assessments may include; willingness to participate, approval turn around, the qualifications and training needs of site staff, potential to recruit participants and adequate facilities to conduct the study. Site suitability may be assessed in the form of a feasibility questionnaire or a feasibility site visit by the trial research team. Investigator specifications may include: Medical specialty Patient population Experience Facilities required (e.g. laboratories, treatment units, access to freezer and centrifuge Human Resources, either designated research nurse/ professional or other explicit arrangements like Network Staff) Staff Geographic location Recruitment If a site visit is carried out this should be documented in the form of a written pre-study report so feedback is provided to the site and sponsor. 6.3 Site Approvals Local approval procedures for potential sites should be discussed and clarified at the earliest possible stage. Favourable opinion must be sought by each site (where appropriate) from ethics, competent authorities, NHS Health Board and other relevant bodies, prior to the site initiation and activation for participant recruitment (see WWORTH SOP14 Ethics RG Approval and WWORTH SOP15 MHRA Approval). Copies of all approval documents should be sent to the CI or WWORTH for filing in the TMF (see WWORTH SOP03 Master Site File). Participating Site agreements must also be in place before site initiation, activation and recruitment. This is a written, dated and signed agreement between the WWORTH-SOP16SitesetupV2.1-140507 Page 7 of 12 Not guaranteed if printed

sponsor and site that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. A suite of Model agreements have been developed by the UKCRC to streamline the Research Governance Process and can be accessed at: http://www.ukcrc.org/regulationgovernance/modelagreements/mctaanddo wnloads.aspx 6.4 Site Initiation After regulatory and ethics approval has been secured and before a site opens to participant recruitment to the full or pilot study, the TM should organise a site visit or video-conference and if this is not possible, an audio conference to inform and train all site staff involved in the study, to ensure that they have a thorough understanding of the study procedures. The TM will develop a thorough understanding of each specific site s local practice which may affect participant recruitment. A site may be considered initiated once: All essential documents and approvals are in place. Site staff are familiar with study requirements and their role and responsibilities The site has been provided with documentation, equipments and or training to enable site staff to conduct the study. For a CTIMP, study drug is available to the site. Study drug can only be released to the site after all approvals are in place. During an initiation visit the study protocol, protocol procedures, important elements of the running of the study, inclusion/exclusion criteria, CRF completion and queries are clarified. The visit may also provide the opportunity to obtain essential documentation for the TMF (see WWORTH SOP03 Master Site File). The TM may provide the site with a TSF. 6.4.1 Organising site visit The TM will organise the site visit and training date. This should include all site team members where possible: Principal Investigator Co Investigator(s) Local Coordinator(s) Local collaborator(s) WWORTH-SOP16SitesetupV2.1-140507 Page 8 of 12 Not guaranteed if printed

Pharmacist (for CTIMPS only) and any others relevant to the success of recruitment e.g. clinicians, laboratory staff, data managers, network staff. Relevant team members from CI or WWORTH should attend: Trial Team If appropriate an IT specialist if the site selection processes have identified IT issues or if the study requires electronic data capture. 6.4.2 Site Documentation Ensure all sites are provided with or create their own TSF (see WWORTH SOP03 Master Site File) and receive the CRF, Investigator Brochure or SmPc (if appropriate) and pharmacy file (if appropriate). Check that all local forms and relevant approvals (Site Specific Assessment, research governance, finance) are in TSF. All documentation to be version controlled and dated (see WWORTH SOP01b Document Control). 6.4.3 Site Visit and Training Ideally arrange the visit and training to include training of the local coordinator and any other key staff. Training can also be organised at a central site. Presentation checklist should include the following: Trial procedure discussed Aims of trial Primary and secondary endpoints Inclusion/exclusion criteria Data collection, including CRFs or electronic data capture Inform when monitoring visits will take place GCP SOP or MOP training Pharmacovigilance If a CTIMP, discuss with PI and pharmacist the prescription of IMP, WWORTH-SOP16SitesetupV2.1-140507 Page 9 of 12 Not guaranteed if printed

storage, and labelling of the medication and documentation of received, prescribed and destroyed IMP (see WWORTH- SOP04trialsupplieslabelling) Discuss any trial-specific lab procedures and check equipment is appropriate freezer temperatures, centrifuge speeds, calibration certificates etc. TSF maintenance Investigator and local co-ordinator responsibilities Informed Consent Randomisation Process Source Data Archiving Each PI. Co-Investigator, Local Collaborator must be qualified by education, training and experience and must have adequate resources to conduct the study properly [1]. For CTIMPs, it is a legal requirement for all site research staff with patient contact to be GCP trained and for non-ctimps it is best practice for all research staff to be GCP trained. GCP training would be repeated every 2 years or sooner if procedures, guidance or legislation change. Qualifications and training needs analysis would be one of the requirements of site selection. Evidence of qualifications and training of site research staff would be requested usually in the form of current curriculum vitae (CV) and would be requested by CI to store in the Trial Master File (TMF). Study-specific training may be required (eg questionnaire administration, CRF completion, specific intervention) but it is not the intention of this SOP to cover this type of training. This would be covered by study specific operating procedures and discussed at the site initiation visit if appropriate see WWORTH SOP02 Training. 6.4.4 Following the initiation visit The CI or trial team should submit a written report to the PI summarising what was discussed during the initiation visit, and should include action points and resolution of site queries. This should then be filed in the WWORTH-SOP16SitesetupV2.1-140507 Page 10 of 12 Not guaranteed if printed

TMF/TSF and any outstanding actions that arose from the initiation visit should be addressed promptly by the PI or a member of their team. 6.5 Site Activation Once the site has been initiated and all necessary documentation and training has been completed, an e-mail or fax is sent from the CI to formally inform the PI that they have been activated and that recruitment can commence at the site. Confirmation of the receipt of the notice of activation should be sent by the PI and this is filed in the TMF. Following activation, monitoring visits should be carried out as stipulated in the monitoring plan (see WWORTH SOP17 Monitoring). 7 Training plan All WWORTH staff involved with trials must undertake the appropriate generic and trial-specific training to ensure that they meet with the specific employers mandatory training requirements and the specific requirements of the trial. For example, for SU staff, all new employees must attend induction, fire and safety training (as well as role-specific training courses, e.g. laboratory safety). For new staff, additional training requirements should be identified alongside the specific role requirements and the WWORTH Unit Manager should make provision for the new staff member to attend the necessary courses as soon after appointment as is practicably possible. It is the responsibility of the WWORTH Unit Manager (alongside the CI or TM) to identify all the SOPs that are relevant to a specific trial and in which the new member of staff should be trained. The WWORTH UM or the SOP author will provide group training for trial staff and/or one-to-one training, as required for new staff in relation to the specific SOPs identified. Training records should be filed both by the main employer and the staff member, in accordance with the specific employer requirements. Trial specific training should be filed in TMF or TSF as appropriate and every individual involved in a trial should have an individual training record (see WWORTH SOP02 Training). Where the tasks specified in the individual SOPs are delegated to WWORTH staff, CIs/PIs or TMs, these delegated staff must ensure that they have attended a training course on GCP and keep up-to-date through attending refresher courses. It is the responsibility of the CI/PI to ensure that all staff allocated duties on the study delegation log template of responsibilities are suitably trained in the activities linked to those duties (see WWORTH SOP16 Site Setup, Appendix 9 and Appendix 10). Each trial should maintain a central training log and ensure that WWORTH WWORTH-SOP16SitesetupV2.1-140507 Page 11 of 12 Not guaranteed if printed

has access to that log, not least to integrate the logs of staff who work on more than one trial. Similarly trials should ensure that each site maintains a local training log, not least to integrate the logs of staff who work for more than one sponsor. This SOP will have a training plan and log to monitor training. In principle the trainer should be one of the authors. Training will be in two stages. First training in the principles of that SOP will take place during monthly meetings of JSOPGs. Second training in using that SOP in practice will take the form of regular supervision by an experienced trialist, culminating in approval of that SOP. WWORTH core staff should be involved in the training process. Both trainer and trainee will sign the log (see WWORTH SOP02 Training) to confirm that training is complete. To help individual staff record training for the purpose of their Continuing Professional Development, and help individual trials and WWORTH record training for quality assurance, WWORTH will aggregate training logs by individual within trial. 8 References 1. ICH Harmonised Tripartite Guideline for Good Clinical Practice (1996) 2.. 9 Related SOPs WWORTH SOP01b Document Control WWORTH SOP02 Training WWORTH SOP03 Master Site File WWORTH SOP04 Trial Supplies Labelling WWORTH SOP14 Ethics RG Approval WWORTH SOP17 Monitoring WWORTH SOP22a Data Collection Management WWORTH SOP24 Randomisation WWORTH-SOP16SitesetupV2.1-140507 Page 12 of 12 Not guaranteed if printed