STANDARD OPERATING PROCEDURE SOP 720 RISK ASSESSMENT OF TRIALS SPONSORED. BY THE NNUH and UEA

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1 STANDARD OPERATING PROCEDURE SOP 720 RISK ASSESSMENT OF TRIALS SPONSORED BY THE NNUH and UEA Version 1.0 Version date Effective date Number of pages 11 pages Review date November 2018 Author NNUH UEA Joint Research Office Approved by Lisa Chalkley Role Research Services Manger Signature Lisa Chalkley Date Authorised by Prof Alastair Forbes Role Chief of Research and Innovation Signature Prof Alastair Forbes Date SOP 720 v1.0 Effective date: Page 1 of 11

2 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 Staff must ensure that they are adequately trained in the new procedure and must make sure that all copies of superseded versions are promptly withdrawn from use.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 DEFINITIONS 4 5 RESPONSIBILITY 5 6 PROCEDURE Risk Assessment Acceptable Limits Which Risk Assessment is required? Completing the Risk Assessment a) NNUH Sponsored CTIMPs Studies b) All other NNUH Sponsored Studies c) UEA Sponsored Studies Risk Assessment Review 8 7 REFERENCES 8 8 RELATED DOCUMENTS 9 9 LIST OF APPENDICES 9 Appendix 1: Flow chart of Responsibilities 10 Appendix 2: Change Control, Revision and Review Sheet 11 SOP 720 v1.0 Effective date: Page 2 of 11

3 1 ABBREVIATIONS AE CE CI CMD CTIMP CTM ecrf EDC EU GCP ICH-GCP IMP ISO MHRA MP MTD NHS NNUH PI R&D ReDA RF RGC RSM SDV SmPC SOP SUSAR TMF UK Adverse Event Conformité Européene Chief Investigator Clinical Investigation of Medical Device Clinical Trial of Investigational Medicinal Product Clinical Trial Monitor Electronic Case Report Form Electronic Data Capture European Union Good Clinical Practice International Conference on Harmonisation Guidelines for Good Clinical Practice Investigational Medicinal Product International Organization for Standardization Medicines and Healthcare products Regulatory Agency Monitoring Plan Maximum Tolerated Dose National Health Service Norfolk and Norwich University Hospitals Principal Investigator Research and Development Research Database Application Research Facilitator Research Governance Coordinator Research Services Manager Source Data Verification Summary of Product Characteristics Standard Operating Procedure Suspected Unexpected Serious Adverse Reaction Trial Master File United Kingdom 2 INTRODUCTION Sponsors are required to provide oversight of studies to ensure adequate protection of the participants, sponsor and data integrity; however conducting research carries inherent risks. The purpose of a risk assessment is to identify potential hazards and assess the likelihood of those hazards occurring and resulting in harm. Dependent on the risks of a study, alternative/proportionate monitoring may be considered when developing monitoring strategies. The Medicines for Human Use (Clinical Trials) Regulations 2004 allow for riskadapted approaches to the management of clinical trials of investigational SOP 720 v1.0 Effective date: Page 3 of 11

4 medicinal products (CTIMPs). Norfolk and Norwich University Hospitals NHS Trust (NNUH) has adopted the risk-adaptive approach for the management of all studies it sponsors, including CTIMPs, clinical investigations of medical devices and all other research. 3 SCOPE This SOP applies to all healthcare research sponsored by NNUH and 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. It is the responsibility of the local PI to ensure that studyspecific SOPs can be operated without conflicting with this SOP and in accordance with all organisational polices related to research. 4 DEFINITIONS CE Low Risk Likelihood Medium Risk Likelihood High Risk Likelihood "Conformité Européene" which literally means "European Conformity". The CE mark is required for all new products which are subject to one or more of the European product safety Directives. It is a visible sign that the manufacturer of the product is declaring conformity with all of the Directives relating to that product. Likely to be safe or without problem. Documentation and relevant experience / training in place. Concern of a possible effect on safety and/or possible problem arising, but evidence presented to address possible safety issues / problems. Majority of essential documentation and training in place with evidence of a plan to acquire missing documentation / training in place. Issues identified regarding safety and or problems arising, with no evidence presented to address safety issues / problems. Essential Documentation missing with no plan in place for acquiring documents. Evidence of relevant experience and/or training not demonstrated / documented, or with no plan in place to acquire necessary training / experience 5 RESPONSIBILITY Sponsor (fulfilled by the Research and Development (R&D) department on behalf of NNUH). Depending on the type of research being undertaken either the Research Facilitator (RF) or the Clinical Trial Monitor (CTM) will facilitate completion of the risk assessment and schedule attendees for the risk SOP 720 v1.0 Effective date: Page 4 of 11

5 assessment meeting, as required. Refer to flow chart in Appendix 1 for responsibility. The final decision to Sponsor a Trial will be made once the final signed Risk Assessment has been reviewed by the Research Services Manager (RSM). The CTM and/or RF or Research Governance Co-ordinator (RGC) or Research Services Manager (RSM) will implement the monitoring plan (MP) based on the outcome of the risk assessment. Chief Investigator (CI) To meet with RF and/or CTM for an initial Sponsored Risk Assessment meeting and complete any required follow-up actions. 6 PROCEDURES 6.1 Risk Assessment The risk assessment is based on identifying the potential hazards associated with the trial and assessing the likelihood of those hazards occurring and resulting in harm. Appropriate management/mitigation strategies should then be identified and implemented to bring any harm within an acceptable limit. The risk assessment should be undertaken prior to Sponsorship approval for studies the Trust will potentially be sponsoring. For UEA Sponsored studies where the Norwich Clinical Trials Unit (NCTU) has been designated to have a level of involvement where it is necessary for a risk assessment to be conducted, the NCTU will use its own risk assessment tool and follow its own processes. However NNUH will still carry out a risk assessment in accordance with this SOP Acceptable Limits If any section is rated high risk, after mitigating factors have been taken into account, the study will not be accepted for sponsorship. Sponsorship will be reconsidered by the RSM and/or RGC once it has been demonstrated by the CI that appropriate mitigating factors have been implemented to reduce the likelihood of risk to at least a medium risk level. If any section is rated medium risk, after mitigating factors have been taken into account this will trigger a monitoring plan reflective of the level of risk; the monitoring plan will be reviewed and updated if the level of risk is reduced by subsequent mitigating actions. If the overall outcome of the risk assessment is low the monitoring plan will be reflective of this level of risk; the monitoring plan will be reviewed and updated if the level of risk alters during the study. Refer to SOP 330 Monitoring for further details Which Risk Assessment is required? If it is unclear whether NNUH is the potential study Sponsor or Host, the RF or CTM should discuss with the RSM prior to conducting the risk assessment. SOP 720 v1.0 Effective date: Page 5 of 11

6 If NNUH is the potential host for a study please refer to R&D SOP_725 Capacity Capability and Risk Assessment of Trials Hosted by NNUH. If it is unclear what type of research is being undertaken (i.e. is it a clinical trial?) the RF or CTM or CI should seek to clarify this - if necessary by contacting the Medicines and Healthcare products Regulatory Agency (MHRA). The RF or CTM will co-ordinate the risk assessment depending on the type of research being conducted (see 6.1.4) and Appendix 1 for guidance. If, during the risk assessment meeting, risks are identified which are not appropriately managed/mitigated by the CI and study team, the RF or CTM will liaise with the RSM or RGC as soon as possible, the RSM and/or RGC will decide appropriate action. If risks are not satisfactorily managed/mitigated this may affect study set-up activity and the study could be put on hold Completing the Risk Assessment a) NNUH Sponsored CTIMP Studies Prior to Sponsorship approval, the RF will contact the CI and arrange a meeting with them and the study team. It may be possible for the RF to complete parts of the NNUH Sponsored Risk Assessment Tool prior to the meeting based on the study information available to them already (e.g. Protocol). The RF will meet with the CI and study team and conduct the NNUH Sponsored risk assessment. The RF should then complete any section that could not be done prior to the meeting. Where an NNUH Sponsored study has significant UEA involvement the RF should notify the relevant REN Project Officer of the risk assessment meeting. In some instances where it is felt that the risk assessment meeting would benefit from UEA REN involvement, the relevant UEA REN project officer will also attend the risk assessment meeting. Once finalised the Risk Assessment Tool should be sent by the RF to the CI to review, sign and return. The RF should then countersign the Risk Assessment Tool. In all instances where an NNUH Sponsored study has significant UEA involvement a copy of the final Risk Assessment Tool should be sent to the UEA REN project officer who was notified of the risk assessment meeting. The summary table of risk at the end of the tool should only be completed with the level of risk recorded for each section and sub-section. Any actions resulting from the risk assessment meeting should be entered into the table at the end of the tool; completion of the actions can take place after the NNUH Sponsored Risk Assessment Tool has been finalised. The RSM and/or RGC will be notified by the RF once the NNUH Sponsored Risk Assessment has been completed and a copy of the fully executed Risk Assessment Tool sent to them and to the CI. SOP 720 v1.0 Effective date: Page 6 of 11

7 The Sponsorship Review letter, containing the official decision regarding sponsorship will be sent to the CI by the RSM, following completion of the risk assessment. Risk assessment documentation should be saved electronically in the projects shared folder, documented in ReDA, and filed in the sponsor trial master file (TMF). For NNUH Sponsored CTIMP Studies where NNUH has retained monitoring responsibilities the RF and NNUH Clinical Trial Monitor should work together to complete all steps mentioned in a, with the Clinical Trial Monitor taking overall responsibility for the completion of the risk assessment b) All other NNUH Sponsored Studies Prior to Sponsorship approval the RF will contact the CI and arrange a meeting with them, and the study team. It may be possible for the RF to complete parts of the NNUH Sponsored Risk Assessment Tool prior to the meeting based on the study information available to them already (e.g. Protocol). The RF will meet with the CI and study team and conduct the NNUH Sponsored risk assessment. The RF should then complete any section that could not be done prior to the meeting. Where an NNUH Sponsored study has significant UEA involvement the RF should notify the relevant REN Project Officer of the risk assessment meeting. In some instances where it is felt that the risk assessment meeting would benefit from UEA REN involvement the relevant UEA REN project officer will also attend the risk assessment meeting. Once finalised the Risk Assessment Tool should be sent by the RF to the CI to review, sign and return. The RF should then countersign the Risk Assessment Tool. In all instances where an NNUH Sponsored study has significant UEA involvement a copy of the final Risk Assessment Tool should be sent to the UEA REN project officer who was notified of the risk assessment meeting. The summary table of risk at the end of the tool should only be completed with the level of risk recorded for each section and sub-section. Any actions resulting from the risk assessment meeting should be entered into the table at the end of the tool; completion of the actions can take place after the NNUH Sponsored Risk Assessment Tool has been finalised. The RSM or RGC will be notified by the RF once the NNUH Sponsored Risk Assessment has been completed, and a copy of the fully executed Risk Assessment Tool has been sent to the CI. The Sponsorship Review letter, containing the official decision regarding sponsorship will be sent to the CI by the RSM, following completion of the risk assessment. SOP 720 v1.0 Effective date: Page 7 of 11

8 Risk assessment documentation should be saved electronically in the projects shared folder, documented in ReDA, and filed in the sponsor trial master file (TMF) c) UEA Sponsored Studies Sponsorship approval at both the application and award stages includes risk assessment following the REN Processes and Guidance Notes. Where the studies are adopted by the NCTU, additional risk assessments are undertaken as per NCTU processes and risk assessment tool. 6.2 Risk Assessment Review The risk assessment may be reviewed at any time during the study, taking into account new knowledge and experience, and may include reconsiderations of the acceptable limit of risks (refer to 6.1.2). This may occur as a result of any of the following (this list is not exhaustive): i. Monitoring findings; ii. Audit or inspection outcome; iii. Safety review; iv. Serious breach or non-compliance; v. Change to protocol, resources, personnel, facilities or external service providers. The risk assessment review will be completed as per It may not be necessary to revise all sections of the NNUH Sponsored Risk Assessment Tool, or to convene a meeting of all original members of the sponsor panel. The RF or CTM, RSM or RGC and CI will agree which sections will be revised and who should attend the review meeting. The RF or CTM will update the study Monitoring Plan accordingly, following the risk assessment review and will notify the CI. 7 REFERENCES ICH Harmonised Tripartite Guideline Quality Risk Management Q9: Current Step 4 version, 9 November 2005 MRC/DH/MHRA Joint Project Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products: version 10 October 2011 The Medicines for Human Use (Clinical Trials) Regulations 2004 Medical Devices Regulations 2002 The MHRA Good Clinical Practice Guide 2012 Research Governance Framework (2nd edition 2005). Nottingham University Hospitals SOP-RES-002 Risk Assessment SOP 720 v1.0 Effective date: Page 8 of 11

9 8 RELATED DOCUMENTS Joint Arrangements for Research NNUH Sponsored Risk Assessment Tool R&D SOP_725 Capacity Capability and Risk Assessment of Trials Hosted by NNUH R&D SOP_330 Monitoring Clinical Trials Sponsorship Review Letter REN Processes & Guidance Notes. B: Applications. C. Awards 9 LIST OF APPENDICES Appendix 1: Flow chart of Responsibilities Appendix 2: Change Control, Revision and Review Sheet SOP 720 v1.0 Effective date: Page 9 of 11

10 Appendix 1: Flow chart of Responsibilities Is this study a CTIMP? YES NNUH Sponsored Study Is the Study Sponsored by NNUH or UEA? NNUH UEA Clinincal Trial Monitor will work with Research Facilitator and CI to complete risk assessment. Research Facilitator will work wiith CI to complete risk assessment. Refer to REN Processes and Guidance Notes. B: Applicationa C. Awards - "Risk Assessment of Trials Sponosred by the NNUH and UEA" SOP to be followed - Sponsored Risk Assessment Tool to be completed - Research Service Manager or Research Governance Co-ordinator will be informed by Research Facilitiator or Clinical Trial Monitor when risk assessment has been completed What is the outcome of risk assessment? High Low Medium Study will not be accepted for Sponosrship. Sponsorship will be formally confirmed - Sponsorship will be reviewed by the Research Service Manager or Research Governance Coordinator once it has been demonstrated by the CI that appropriate actions have been implemented to reduce the likelihood of risk to at least a medium risk level. Once the risk has been reduced - Monitoring plan will be reflective of the risk for the study. - Risk assessment can be reviewed at any point of the study - Risk assessment documentation should be saved electronically in the projects shared folder, and documented in ReDA, and filed in the sponsor trial master file SOP 720 v1.0 Effective date: Page 10 of 11

11 Appendix 2: Change Control, Revision and Review Sheet CHANGE CONTROL, REVISION AND REVIEW SHEET: SOP 001 Version No Change Date Reason for Change Reviewer : Designation : Signature and Date: Reviewer : Designation : Signature and Date: SOP 720 v1.0 Effective date: Page 11 of 11