Policy Flowchart. Policy Title: Research Governance, Conduct and Management Policy. Reference and Version No: IG6 Version 5

Transcription

1 Policy Title: Research Governance, Conduct and Management Policy Reference and Version No: IG6 Version 5 Author and Job Title: J Greenaway Research and Development Manager Executive Lead Medical Director Validated By: Trust Research Awareness and Governance Committee (TRAG) Ratified By: Patient Safety and Quality Standards Committee Date Issued: 19 May 2016 Date for Review: 10 May 2019 Related Documents: IG14 Information Governance Policy IG9 Information Security Policy IG30 Data Breach Management Policy C49 Intellectual Property Policy HR24 Disciplinary Policy and Procedures RM14 Policy for reporting and dealing with Serious Incidents including Never Events RM15 Incident Reporting and Investigation Policy Policy Flowchart Patient Safety and Quality Standards Committee Medical Director Trust Research Advisory Committee (TRAC) Formulate strategy, promote R&D, contribute to strategy delivery Trust Research Awareness and Governance Committee (TRAG) Research and Development Director Research and Development Manager This Policy is Intended for: All Staff Groups involved in research The Trust is committed to the fair treatment of all, regardless of age, colour, disability, ethnicity, gender, gender reassignment, nationality, race, religion or belief, responsibility for dependants, sexual orientation, trade union membership or non membership, working patterns or any other personal characteristic. This policy and procedure will be implemented consistently regardless of any such factors and all will be treated with dignity and respect. To this end, an equality impact assessment has been completed on this policy. 1 of 21 (Date for review 10 May 2019)

2 CONTENTS 1. Introduction 2. Purpose 3. Scope 4. Definitions 5. Responsibility and Accountability 6. Legal and Professional Obligations 7. National and local approval processes 8 Research Sponsorship 9. Ethical Review 10. Research Funding and Finance 11 Clinical Trials of Investigational Medicinal Products 12. Use of Patient Data 13. Patient and Public Involvement 14. Study Agreements and Contracts 15. Risk Assessment 16. Monitoring, Audit and Reports 17. Indemnity 18. Research Misconduct 19. Research Dissemination 20. Intellectual Property 21. Staff Training and Development 22. Dissemination and Implementation 23. Document Control Including Archiving Arrangements 24. References Appendices Appendix A: Research, Clinical Audit or Service Evaluation Appendix B: Responsibilities for Conducting Research 2 of 21 (Date for review 10 May 2019)

3 1. Introduction 1.1 Health Research and Development (R&D) is core business for the NHS. It plays a vital role in improving health outcomes and the quality of care. It is therefore a core element of the NHS Operating Framework. Research studies enable clinicians and researchers to develop new treatments and resolve uncertainty about existing treatments and interventions; and for patients to benefit. NHS Organisations have to demonstrate their contribution to R&D in Quality Accounts. R&D in healthcare is highly regulated. Clinical trials, medical device studies, use of patient data, professional qualifications, access to and treatment of NHS patients and other aspects of R&D studies are regulated by EU directives, UK legislation and professional standards of good practice. The Research Governance Framework for Health and Social Care describes the overarching framework within which R&D studies are delivered within the NHS The Research Governance Framework for Health and Social Care was developed by the Department of Health to set out the broad principles of good research governance and to ensure the principles of the research governance framework are consistently applied. The framework ensures that high quality research is conducted in the NHS, focusing on scientific quality, ethical and financial standards, allocation of responsibilities and robust monitoring arrangements and is applied to all study types (treatment, intervention, qualitative). The framework consists of five core domains including: Ethics, Science, Information, Health and Safety and Finance. All NHS organisations involved in research with human participants, their organs, tissue or data are responsible for adhering to the five legislated domains outlined in the framework. In addition, for clinical trials of investigative medicinal products (CTIMPs), there is a strict legal framework within which clinical trials of Investigational Medicinal Products (CTIMPs) must be conducted. The EU Clinical Trials Directive and GCP Directive (transposed in UK law through the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 1031) and Amendment Regulations 2006 (SI 1928), state that clinical trials must be carried out to the principles of Good Clinical Practice (GCP) based on Article 2 to 5 of the GCP Directive. Approval by the Health Research Authority (HRA) is the new process for the NHS in England that comprises a review by a NHS Research Ethics Committee (REC) (where required) as well as an assessment of regulatory compliance and related matters undertaken by dedicated HRA staff. In England, it replaces the need for local checks of legal compliance and related matters by each participating NHS organisation. This allows these participating NHS organisations to focus their resources on assessing, arranging and confirming their capacity and capability to deliver the study. In addition to the above frameworks, approvals and laws, Trust R&D departments have a series of Standard Operating Procedures (SOPs) that provide guidance and frameworks for trust staff for the conduct of various elements of a research study from inception of the idea through to close down publication and archiving of the study materials. 3 of 21 (Date for review 10 May 2019)

4 2. Purpose 2.1 This policy provides a framework for the conduct and management of research within (NTHFT) in accordance with the standards and guidelines outlined in the Research Governance Framework, European Directives and Trust R&D SOPs by: Enhancing ethical and scientific standards and promoting good research practice Clearly defining accountability and responsibility for research governance Informing all staff of the appropriate procedures for conducting research within this Trust For the purposes of research governance, research means the attempt to derive generalisable new knowledge by addressing clearly defined questions with systematic and rigorous methods. Guidance on whether a project is research, audit or service evaluation can be found on the Health Research Authority (HRA) website using the HRA decision tool ( or by consulting the following guidance document 3. Scope 3.1. This policy and procedure applies to all staff and external researchers who wish to undertake research within the Trust. This policy does not apply to audit or service evaluations. For guidance on the differentiation between research, audit and service evaluations, please see Appendix A. 4. Definitions 4.1 A comprehensive list of definitions can be found on the R&D Intranet site Due to a significant amount of legislative documents, regulations and guidance for research being located online, it has been necessary to include website addresses in this policy to keep the policy relatively short. Readers are asked to consult the R&D office if any website addresses do not appear to work researchanddevelopment@nth.nhs.uk 5. Responsibility and accountability 5.1. All organisations conducting, sponsoring, funding or hosting health and social care research must have systems to ensure that they and their staff understand and follow the standards set out in the research governance framework The Chief Executive has overall responsibility for the strategic direction and operational management of NTHFT including ensuring that the Trust policies comply with all legal, statutory and good practice guidance requirements The Patient Safety and Quality Standards Committee (PSQSC) has responsibility for setting the strategic context in which organisational policies and procedures are developed, and for establishing a scheme of governance for the formal review and approval of these policies. 4 of 21 (Date for review 10 May 2019)

5 5.4. The Trust Research Advisory Committee (TRAC) responsibilities are: To develop and review R&D strategy To ensure that Trust research activities reflect national directives To develop the Trust s capacity through involvement with National Institute for Health Research (NIHR) Portfolio research projects. To promote effective liaison with other local, regional and national research bodies To ensure R&D training and development needs are addressed and establish collaborative training opportunities with local HEIs To plan and successfully develop academic research within the Trust leading to clinical academic partnerships. To ensure financial sustainability of the R&D Department and it s functions 5.5. The Trust Research Awareness and Governance Committee (TRAG) responsibilities are: To monitor Trust research activity at a directorate level and introduce a level of directorate awareness and accountability for research activity To encourage integration of research within directorates core business To ensure that Trust research activities reflect national directives and national governance frameworks To develop the Trust s research capacity through involvement with National Institute for Health Research (NIHR) Portfolio research projects and commercially sponsored studies. To promote effective liaison with other local, regional and national research bodies such as the Clinical Research Network for North East and N Cumbria (CRN:NENC) and their associated Specialty groups, local Higher Education Institutions (HEIs) and the local Research Design Service (RDS) To ensure R&D training and development needs are addressed and establish collaborative training opportunities with local HEIs To continually promote research activity within Trust Directorates and for members to be the contact point within Directorates for dissemination of relevant information. To ensure financial sustainability of the research within the Trust through encouragement of research grant applications and participation in commercially led research activity To provide a forum for Directorates to learn about local research initiatives and support through a guest speaker slot at each meeting The Trust Research Evaluation Board (TREB) responsibilities are: To support robust research activity that is both scientifically and ethically robust by ensuring all Trust sponsored research activity is scientifically peer reviewed To ensure that Trust sponsored research complies with the requirements of the Research Governance Framework and other regulatory requirements as appropriate. To provide advice and support to any Trust-based researchers who wish to submit an application for external research funding The R&D Director is responsible for: Oversight of Trust compliance with Research Governance Framework and EU Clinical Trials Directives for all studies 5 of 21 (Date for review 10 May 2019)

6 Growth of research activity within the required governance regulations and guidelines Development of academic partnerships and promoting the initiation of Trust sponsored NIHR research funding applications Working with the R&D Manager to ensure the Trust meets Care Quality Commission requirements and NIHR performance metrics which relate to research governance and performance 5.8. The R&D Manager is responsible for : Ensuring efficient systems are in place within the Trust for the review, management and audit / monitoring of research studies Implementing and evaluating streamlined research review procedures in line with evolving national processes Raising the profile of research within the Trust and encouraging increased participation in research in all directorates Supporting novice and experienced researchers in developing Trust sponsored research grant applications Oversight of staff training and development to ensure competent and skilled workforce with suitable skills to safely and effectively deliver research in line with national and international requirements Strategic management of R&D finances to allow for sustainability of workforce and growth Review of performance in relation to NIHR High Level Objectives (HLOs) for research studies (commercial and non-commercial) and identification of strategies where performance is sub-optimal 5.9. The R&D Team Leader is responsible for: Day to day management of the research nurse team and ensure continuity of service through appropriate staff recruitment and retention measures Contributes to the R&D team meetings to evaluate effective research delivery staff cover for new studies Assesses and identifies training needs of research delivery staff and work with R&D Manager to provide training where appropriate. Acts as a co-ordinator for external grant submissions for trust researchers Raises the profile of opportunities for grant submissions and support the identification and mentoring of potential Chief Investigators The R&D Facilitator is responsible for Review of feasibility of new studies in order to perform Assess, Arrange, Confirm activities in support of HRA approval process. Monitoring and auditing of research studies in line with relevant R&D SOPs Identification of any possible barriers to supporting new studies or issues that affect recruitment to existing studies Reporting of performance in relation to NIHR High Level Objectives (HLOs) for research studies (commercial and non-commercial) via quarterly Performance in Initiation and Delivery of research (PID) submissions to the Department of Health The R&D Administrator is responsible for Collation of all relevant documentation relevant to each new and existing study Processing of amendment submissions 6 of 21 (Date for review 10 May 2019)

7 Maintaining accurate and up to date records of GCP training for all Trust staff and monitoring renewal requirements. Processing of all requests for Honorary contracts / Letters of Access Administration for all R&D committees First point of contact for governance queries 6. Legal and professional obligations 6.1 The R&D department s ability to Assess, Arrange and Confirm participation in new research studies is informed by approvals and advisory guidance granted from relevant bodies according to study type. These include: UK Clinical Trial Regulations and related statutory Instruments and amendments Research Governance Framework for Health and Social Care Healthcare Commission Core Standards (Section C12) International Conference on Harmonisation Good Clinical Practice (ICH GCP) Medicines and Healthcare products Regulatory Agency (MHRA) Health Research Authority (HRA) 6.2 Implementation of the Research Governance Policy in this Trust must also comply with the following Trust policies: Information Governance Policy (IG14 v 5) Information Security Policy (IG9, v8) Intellectual Property Rights (C49 v3) 7. National and local approval processes Before commencement of any research activity research projects taking place within the NHS must obtain HRA approval. It is against the law to start or conduct clinical research or to recruit participants to a Clinical trial of investigative medicinal product (CTIMP) until there is favourable HRA approval (which includes ethics committee approval and authorisation from the competent authority where relevant). At a local level, participating Trusts are required to assess, arrange and confirm their ability to participate prior to the study commencing at participating sites. The new HRA approval process places increased responsibility on sponsors of research to prepare a comprehensive information pack as part of the HRA application process with the aim of reducing subsequent detailed reviews by individual participating trusts. Every proposal/protocol must be subjected to review by experts in the relevant fields able to offer independent advice on its quality. It is the research sponsor s responsibility to ensure adequate peer review is in place which is proportional to the scale of the research Responsibilities Trust-sponsored research studies: All Trust sponsored studies will have a Chief Investigator (CI) who has overall responsibility for the study. Following review of sponsorship requirements by the Trust and confirmation of the trusts ability to sponsor a study, the CI is required to obtain HRA approval ( which combines NHS ethics and other regulatory approval) as well as approval from participating sites (where applicable). 7 of 21 (Date for review 10 May 2019)

8 When an application is being submitted, it may be necessary for the researcher to gain authorisation from other key personnel or departments within the Trust prior to submission, to ensure adequate resources are available to support their study. The R&D department will be able to assist with this process at request; however, it is the overall responsibility of the CI to produce adequate evidence of authorisation from these personnel and departments to support their application. Trust-based academic research: For studies conducted in pursuit of an academic qualification, it is expected that the applicant s Host University will act as the sponsor of the research and co-ordinate submissions for HRA approval. The Trust will be approached to be a participating site and will not be required to undertake independent scientific review of the study. The academic supervisor (non-doctoral studies) or applicant (post-doctoral studies) will co-ordinate the HRA approval application and liaise with potential participating trusts to enable them to assess, arrange and confirm their ability to participate. Multi-centre (Trust-hosted) research studies: Multi-centre studies will have a sponsor and/or a Chief Investigator (CI) who has overall responsibility for the study and its approval through HRA. The Principal Investigator (PI), at each local site along with the R&D department is required to confirm ability to participate. When an application is being reviewed, it may be necessary for the PI to gain authorisation from other key personnel or departments within the Trust, to ensure adequate resources are available to support their study. The R&D department will assist with this process however; it is the overall responsibility of the PI to produce adequate evidence of authorisation from these personnel and departments to support their application. Where a research nurse is employed in a particular clinical specialty she may be able to assist in this process. Once PI and R&D have confirmed their ability to support the study, and HRA approval is confirmed, research can begin. Clinical Support Services all studies Before the trust can confirm their ability to participate, the PI is responsible for ensuring that the relevant designated individuals (DIs) in Radiology (the Clinical Director and Radiology Service Managers), Pharmacy (the Clinical Trials Technician, Head of Service), and Pathology (the: Deputy Clinical Director, Service Managers) are informed from the outset of any potential clinical trials which involve their services. The R&D department will liaise with the relevant DI to ensure the full implications of the trial are understood and all issues discussed and costings approved prior to R&D confirmation of ability to participate. In addition, for CTIMPs, recruitment not be started until the Pharmacy Green Light has been formally issued. The detailed process for each scenario above is contained with R&D SOP 04 obtaining Research Approval and is available on the trust intranet. 8. Research sponsorship All research that takes place in the context of the NHS must have an identified research sponsor who takes overall responsibility for the proper initiation, financing, management and monitoring of the study. The sponsor could be the Chief Investigator s employing 8 of 21 (Date for review 10 May 2019)

9 organisation, the lead organisation providing care, a commercial company or a university. If the sponsor is outside the UK, it must have a legal representative in the UK. Evidence of research sponsorship will be required for HRA approval. The decision for NTHFT to sponsor a project will be based on Trust priority, capability, risk and impact on the organisation and will be processed according to local R&D SOP Decision on sponsoring SOP 2. The Trust s Operational Capability Statement for R&D on the R&D section of the Trust s internet site outlines the scope of studies normally considered for sponsorship. This will be reviewed frequently. 9. Ethical review 9.1 The dignity, rights, safety and wellbeing of participants must be the primary consideration in any research study. The Department of Health requires that research involving patients, service users, care professionals or volunteers, or their organs, tissue or data is reviewed independently to ensure it meets ethical standards. The NHS Research Ethics Committee (REC) is not accountable in any way to NHS Trusts, and in particular is separate from Trust Research Departments in respect of the accountability for their operational processes and decision-making. 9.2 Research applications for all REC approvals must be made to the Health Research Authority (HRA) using the Integrated Research Applications Service (IRAS) REC approval is no longer a stand-alone approvals process, as of April 2016 it is granted as part of overall HRA approval. 9.3 Any Trust sponsored studies reviewed through the Trust Research Evaluation and Review Board (TREB) will receive approval to progress to ethics approval (where applicable). Once we are informed of successful REC approval for these studies, we will confirm ability to proceed to opening of the study and commencement of recruitment. REC approval will be granted as part of overall HRA approval. 9.4 Amendments to research proposals, such as change in protocol, change in Principal Investigator (PI), must be communicated to the HRA. The Trust R&D Manager ( or delegated individual for studies where sponsor oversight duties may be delegated to a CTU) will review all research amendments, liaise with the Chief Investigator to ensure that all HRA processes are followed and that amendments are communicated to all participating sites (where relevant). 10. Research funding and finance 10.1 Funding for commercially contracted research (funded and sponsored by a commercial company) should cover the full costs incurred including appropriate Trust overheads and capacity building income. For all commercial research at NTHFT there will be a non-refundable R&D set up fee and Departmental Set-up fee for all relevant departments. For NIHR portfolio research, the Industry Costing Template will be used to calculate and negotiate costs All research income will be managed by the R&D Manager. All R&D income is coded to the appropriate research cost code at invoicing stage to ensure the specialty specific cost code is reimbursed for their work. The NIHR Industry Distribution Model Guidance Tool is used to assign the appropriate per patient costs, overheads and capacity building costs to the appropriate departmental cost codes. The Trust 9 of 21 (Date for review 10 May 2019)

10 Management Accounts Department will monitor and report on accounts for research purposes in accordance with Trusts Financial Policies PIs who work on commercial studies will be a co-signatory on the relevant specialty specific cost codes for research income and will liaise with the R&D Manager throughout the year to discuss expenditure and agree spending plans The R&D Team Leader and R&D Manager will advise researchers on the costing up of grant proposals and the attribution of costs in line with the latest Department of Health cost attribution guidance and will sign post researchers to the Research Design Service (RDS) who can assist researchers prepare research proposals for submission to high quality NIHR funding streams and other national bodies. 11. Clinical trials of investigational medicinal products 11.1 There is a strict legal framework within which clinical trials of Investigational Medicinal Products (CTIMPs) must be conducted. The EU Clinical Trials Directive and GCP Directive (transposed in UK Law through the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 1031) and Amendment Regulations 2006 (SI 1928) and all amendments, state that clinical trials must be carried out to the principles of Good Clinical Practice (GCP) based on Article 2 to 5 of the GCP Directive This legislation states it is against the law to start or conduct, or to recruit participants to a clinical trial involving a medicinal product until there is a favourable opinion from an ethics committee and a Clinical Trials Authorisation from the licensing authority, the Medicines and Healthcare products Regulatory Agency (MHRA) The Trust will not issue Trust R&D approval for a CTIMP study without HRA approval which will evidence that a Clinical Trials Authorisation has been obtained from the MHRA All study team members working on a CTIMP will be required to have current valid Good Clinical Practice (GCP) Training before they are able to work on the study. GCP should remain up to date throughout the lifespan of any related studies. Failure to do so will be considered a breech of the study contract with the sponsor and will result in R&D approval being revoked. An Introduction to GCP is required in the first instance with GCP renewals undertaken every three years The monitoring of GCP status is undertaken by the R&D department. Reminders are sent to anyone within two months of their renewal date and monitored for successful renewal. If a PI/CI/study team member fails undergo training / renewal after two reminders from the R&D department, their Clinical Director will be informed and requested to liaise with the individual concerned and the study will be suspended until evidence of GCP certification is provided Guidance on the decision to sponsor a CTIMP will be provided by the R&D office in line with local SOPs. It is imperative that you contact the R&D office at the early stages of your study design so that a decision on sponsorship can be made. Clear guidance will be given on the process and rationale for any decisions made along with clear responsibilities relating to any clinical trials undertaken. Ref sections 8.2 and 8.3 of this policy. 10 of 21 (Date for review 10 May 2019)

11 12. Use of patient data 12.1 Data and information collected in the course of research must be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification to ensure data integrity. Furthermore, the appropriate use and protection of patient data should be paramount and particular attention must be given to systems for ensuring confidentiality of personal information The handling of personal information in research must be compliant with Trust policies in relation to the Data Protection Act 1998 (IG5, IG9) and any data/confidentiality breaches must be reported in line with the Trust s Data Breech Management Policy (IG30) 12.3 All use of patient data for research purposes requires the consent of the patient. There are some exceptions where patient data can be used without consent, in these instances studies will be referred by the HRA to the Confidentiality Advisory Group (CAG) in line with the Health Service (Control of Patient Information) Regulations 2002 (also known as section 251 support ). The CAG advises the Health Research Authority and the Secretary of State for Health, whether applications to process confidential patient information without consent should or should not be approved To ensure the security data used in research, all uses of patient data for research purposes must be registered with the Trust Information Governance (IG) department As part of the Assess, Arrange, Confirm activities undertaken by us as a participating site, we will review the HRA Statement of Activities for all studies to determine whether transfer of data outside of the organisation requires additional agreements or review. 13. Patient and public involvement Wherever possible, patients, service users and carers should be involved in the design, conduct, analysis and reporting of research. National organisations, such as INVOLVE ( are working to support and promote active public involvement in the NHS and this includes involvement in research. INVOLVE is a national advisory group, which is funded by the National institute for Health Research (NIHR). It supports greater public involvement in NHS, public health and social care research, and provides information, advice and support to both researchers and service users. NTHFT will ensure that for all Trust sponsored studies, Patient and Public Involvement (PPI) is considered and implemented where possible at all stages in the lifecycle of the research study. 14. Study agreements and contracts 14.1 Before research can commence, sponsors and host institutions need to have appropriate agreement in place which set out the responsibilities of the parties involved in research. The UK Clinical Research Collaboration (UKCRC) and stakeholders have developed a suite of model agreements which can be used off the shelf, without modification. As these agreements are subject to modification and change, it is recommended that the following website is consulted to obtain the most up to date model trial agreement The Trust expects the following agreements to be used: 11 of 21 (Date for review 10 May 2019)

12 Commercial companies are expected to use the national model Clinical Trial Agreement (mcta or CRO mcta) for pharmaceutical companies working in the NHS. The 2011 revised model Clinical Trial Agreement (mcta) is designed to be used without modification for industry-sponsored trials in patients in hospitals throughout the UK Health Service Non-commercial studies: non-commercial partners are expected to use the national non-commercial Clinical Trial Agreement (mnca). The mnca has been developed as a single agreement that ensures compliance with the applicable UK law and institutional arrangements. The clauses in the main body of the Agreement are intended to be used without modification or negotiation whilst the Schedules will need tailoring to the specific research situations Model Clinical Investigation Agreement (mcia) for medical technology industry. This is designed to be used without modification for company-sponsored commercial research involving medical devices in patients in hospitals throughout the UK Health Service. Revised versions in 2014 of the mcia have been developed to ensure compliance with the law in the relevant jurisdiction and to reflect regional institutional arrangements across the UK. The accompanying Guidance Notes cover all versions of the Agreement Model Industry Collaborative Research Agreement (micra). The model Industry Collaborative Research Agreement (micra) aims to support clinical research collaborations involving the pharmaceutical and biotechnology industries, academia and NHS organisations across the UK The Trust encourages the use of model clinical trial agreements. Where a commercial sponsor does not use such agreements, legal review will be undertaken by the Trust s solicitors and the costs borne by the commercial sponsor Appropriate employment arrangements must be in place for research staff. For NHS staff, evidence of their employment status will be required and a copy of a current, signed CV. Researchers not employed by any NHS organisation and requiring access to the Trust will be reviewed in accordance with the NIHR Research Passport Guidance It is the responsibility of the R&D department to ensure staff have the necessary contracts or letters of access in place before staff begin research work within the Trust. The R&D department should be informed by the research team / PI of any changes to study personnel that may affect our contractual obligations with the study sponsor. 15. Risk assessment 15.1 Risk to patient safety is the increased risk arising from the research activity as opposed to the baseline level of risk arising from normal clinical practice Risk assessments should be used during protocol development to eliminate rather than manage risk. Risk will be controlled by systems in place to ensure that: Projects have a sponsor Projects undergo scientific peer-review Projects are submitted for HRA approval which will incorporate Research Ethics (REC) approval 12 of 21 (Date for review 10 May 2019)

13 Research proposals are taken through a staged approach of review and approval before the research can commence in line with Trust R&D SOPs. Sponsors and Researchers act within the Research Governance Framework Staff have appropriate training and GCP training where required, training requirements are identified prior to the study commencing and training status of all Trust staff is monitored by the R&D department. Research is appropriately audited and monitored by the R&D Facilitator 15.3 All proposals for Trust sponsored studies will be assessed for risk by the R&D Manager and risk assessment presented to the Trust Research Evaluation and Review Board (TREB). The level of risk will be taken into consideration when deciding to approve or sponsor a project and decisions to sponsor will be in line with the processes in the related R&D SOPs. 16. Monitoring, audit and reports 16.1 Monitoring is a quality control activity which involves a system of ongoing checks on all research projects in order to detect, correct and prevent faults/ failures so that the specified output is produced consistently. Monitoring and audit can be undertaken internally by the R&D department (all studies) or externally by the study sponsor (for CTIMPs and other clinical trials) It is a statutory requirement that CTIMP studies are conducted in accordance with the principles of Good Clinical Practice (GCP). GCP is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting CTIMPs that involve the participation of human subjects. Compliance with GCP provides assurance that the rights, safety and wellbeing of trial subjects are protected and that the results of clinical trial are credible and accurate. Working to GCP standards involves meeting stringent criteria in respect of study documentation, safety monitoring and reporting, data capture and management, study monitoring, training of study personnel and study conduct in general. The Trust R&D SOP for internal monitoring and audit has been developed to ensure that all of these criteria are assessed Internal monitoring and audit by NTHFT operates according to the R&D department Monitoring SOP. Monitoring is self reported and undertaken every 6 months. The R&D department contact the study PI with a monitoring form for completion and return to the R&D department An annual representative sample of studies are selected for more detailed audit. The R&D team will undertake this audit using the Trial Master File (TMF) for Trust sponsored studies and Investigator Site File (ISF) for non-trust sponsored studies and a random selection of patient medical notes / electronic records. An interview with the PI at the end of the audit will highlight any remedial actions or recommendations As a condition of REC approval all CIs/ sponsors are expected to submit an annual report to the REC in addition to an end of study report 16.6 Safety reporting to MHRA is a legal requirement which allows the authority to identify when trial participants are at increased risk and where to assess when a trial should be modified or stopped. Chief Investigators, Principal Investigators and Research Sponsors have responsibilities for the recording and reporting of adverse events or reactions within a CTIMP study. Certain types of events, (Suspected, Unexpected, 13 of 21 (Date for review 10 May 2019)

14 Serious Adverse Reactions SUSARs) have particularly strict requirements from the MHRA with expedited reporting of 7 days (fatal and life-threatening) and 15 days (non fatal or non-life threatening). All CTIMP studies must have appropriate arrangements for safety reporting clearly outlined in the study protocol. It is important to clearly define events in patients within a CTIMP and general healthcare related Incidents as the reporting procedures will differ Safety Reporting Comprehensive guidance to the definitions and reporting requirements of all Adverse events/reactions(ae/ar), serious adverse events/reactions (SAE/SAR), and Suspected Unexpected Serious Adverse Reactions (SUSARs) is contained within the R&D SOP titled Identifying, recording and reporting Serious Adverse Events available from the R&D intranet or researchanddevelopment@nth.nhs.uk. Please consult this SOP for detailed guidance. Specific guidance for Trust sponsored studies (where we retain responsibility for oversight and follow-up) is outlined below. SAEs / SARs should be reported to the R&D office immediately and the process for the reporting of serious adverse healthcare events should be followed (RM14 & RM15) by completion of a DATIX incident form. The SAE may need reporting by the CI/sponsor to the ethics committee. The CI will review whether the SAE is a reaction (SAR) and the expectedness of the relatedness will be evaluated to inform next steps. The decision to escalate the an SAE to a SUSAR will be made by the R&D Department with consultation with the CI and R&D TREB committee the reporting will be carried out by R&D in conjunction with the CI to the regulatory authority via the e-susar reporting system. The R&D Manager acts as administrator. SUSARs These fall within the Trust s definition of a Serious Adverse Healthcare Event, a DATIX incident form should be completed in line with RM15 Policy by the CI and reported to the R&D office immediately The Sponsor should inform: the REC using the safety report form MHRA, within 7 days for death and life-threatening SUSARs and within 15 days for all other SUSARs 16.8 All PIs and CIs should be aware of their responsibilities in the study protocol and indicate they have read the relevant Trust SOP for reporting of adverse events. Written confirmation of this is sought from the PI at study initiation by signature on the Declaration of Adherence form Serious Breaches. Statutory Instrument AA defines a serious breach as a breach which is likely to effect to a significant degree the a) safety or physical or mental integrity of the subjects of the trial; or b) the scientific value of the trial, To ensure compliance with this requirement, for Trust sponsored studies, the Trust is required to notify the licensing authority in writing of any serious breech within 7 days of becoming aware of the breach. Trust R&D SOP on Serious breaches should be consulted. 14 of 21 (Date for review 10 May 2019)

15 16.10 PIs / research delivery team members are required to inform the R&D department if they have been notified of an external monitor visit to the Trust for their study. Additional access arrangements to the Trust for Trial data monitors is not required as their activities and responsibilities relating to confidentiality and access are fully detailed in the clinical trial agreement for the study An annual report of research activity and funding will be compiled by the R&D Manager for the Patient Safety and Quality Standards Committee (PSQSC) each April. 17. Indemnity 17.1 NTHFT provides standard NHS indemnity to compensate anyone harmed by negligence by its employees. The Trust does not provide compensation for nonnegligent harm. NHS Indemnity may be extended to research partners, e.g. academic researchers, who are not directly employed by the NHS, through honorary research contracts where appropriate (i.e. where the researcher has a direct bearing on the care on the Trust s patients) For commercial CTIMP studies, commercial companies will be expected to provide cover for negligent and non-negligent harm under the standard Clinical Trial Compensation Guidelines recommended by the Association of the British Pharmaceutical Industry. This should be clearly outlined in the Clinical Trial Agreement. 18. Research misconduct Research misconduct includes, but is not limited to, the following, whether deliberate, reckless or negligent Misconduct in relation to grant applications and fund utilisation: Failure to obtain appropriate permission to conduct research Deception in relation to research proposals Fraud or other misuse of research funds or research equipment 18.2 Misconduct in relation to treatment of/dealing with experimental subjects: Unethical behaviour in the conduct of research, e.g. in relation to research subjects Unauthorised use of information which was acquired confidentially Deviation from good research practice, where this results in unreasonable risk of harm to humans, animals or the environment 18.3 Misconduct in relation to analysis and reporting of findings: Fabrication, falsification or corruption of research data Distortion of research outcomes by distortion or omission of data Dishonest misinterpretation of results Publication of data known or believed to be false or misleading Plagiarism, or dishonest use of unacknowledged sources Misquotation or misrepresentation of other authors Inappropriate attribution of authorship 18.4 Misconduct in relation to misconduct of others: Attempting, planning or conspiring to be involved in research misconduct Inciting others to be involved in research misconduct Collusion in or concealment of research misconduct by others 15 of 21 (Date for review 10 May 2019)

16 The system for monitoring and auditing at NTHFT provides a mechanism for detecting any evidence of mismanagement, fraud or other scientific or professional conduct. Suspected fraud or misconduct will be investigated using the Trust s Disciplinary policy and procedure (HR24). 19. Research dissemination 19.1 As part of the HRA s transparency agenda the requirement to register all clinical trials as a requirement of REC favourable condition was implemented in The purpose of creating this line in the sand was to sharpen focus and awareness of the ethical obligation to ensure all trials are registered. The HRA publishes details of all research reviewed by RECs in the UK as a research summary record. This record consists of some basic information about the research (e.g. title, available registry reference numbers) As a condition of REC approval all CIs/ sponsors are expected to submit an annual report to the REC in addition to an end of study report 19.3 Established findings (positive or negative) should be published in a way that allows critical review and dissemination through the accepted scientific and professional channels. Information on research being conducted in the Trust must be accessible to staff, the public and to all those who could benefit from the findings Information about what research is being conducted and what research has been completed will be made available to all staff through the Trust s intranet site. In addition, internal communications such as the Trusts Anthem magazine will be used to inform staff and patients of relevant research developments Research findings will be published in peer-review journals or other relevant publications where possible PIs for hosted studies are expected to disseminate findings, when made available, to their wider clinical team and to review whether changes in practice are required in light of any evidence presented. 20. Intellectual property 20.1 NHS Trusts are required by the Department of Health to protect and manage intellectual property arising from R&D funded by the NHS. The Trust recognises the need for the wider recognition, improved understanding and increased protection of intellectual property facilities All intellectual property will be dealt with in accordance with the Trust s Intellectual Property Policy (C49). 21. Staff training and development 21.1 Staff training and development will be made available by the Trust to increase general awareness of the research process, systems, guidance and support available in an aid to develop capacity, expertise and skills required to undertake research. This will take the form of R&D Seminars in TRAG meetings R&D Conference 16 of 21 (Date for review 10 May 2019)

17 Good Clinical Practice Training (GCP) Research Delivery Staff Meetings Training provided by the Clinical Research Network for North East & North Cumbria (CRN:NENC) Evidence based Practice training 21.2 All Principal Investigators (PIs) undertaking research in the Trust should hold a valid certificate of Good Clinical Practice (GCP). Researchers are required to update their GCP training regularly, in line with the Trust R&D SOP 7 to provide assurances to the Trust that they have the necessary skills to implement best research practices For all new research, the member(s) of the project team who will be involved in recruiting participants will be nominated. The Principal Investigator is required to sign a declaration of adherence, listing all study team members and indicating their agreement to follow study related protocols and SOPs The arrangements for recording consent in each patient s Health Care Records must be specified by the Chief Investigator/ Principal Investigator whichever is applicable 21.5 The R&D office must be informed of any changes to the nominated researchers who are engaged in research activity so that records may be amended and approval still valid. Failure to advise the R&D office of changes to personnel may result in unauthorised or untrained individuals working on the study and could invalidate insurance and indemnity related to the study. A minimum period of 30 days notice is required for a change in PI to ensure that the relevant REC processes can be followed to approve a change in PI. 22. Dissemination and implementation 22.1 A PDF copy of this policy is contained in the trust-wide Intranet policy database, accessible to all Trust staff members. Links and references to the policy are contained on the Trust R&D Intranet site A Trust communications will alert all staff to the updated policy and its availability Signature of Principal Investigators are required at the beginning of a research project on the Declaration of Adherence to indicate they are aware of the policy and familiar with it s contents relating to the initiation and conduct of research within North Tees and Hartlepool NHS Foundation Trust. 23. Document control including archiving arrangements 23.1 Active policy documents are contained on the Trust Intranet policy database and are saved in PDF format to restrict editing Archived copies of policies are held in electronic and paper format in the R&D offices at North Tees Hospital. 24. References International Conference on Harmonisation Good Clinical Practice (1996) Guidelines for Good Practice. 17 of 21 (Date for review 10 May 2019)

18 Accessed from: Clinical Trials Directive (2001/20/EC) 1/dir_2001_20/dir_2001_20_en.pdf The UK Clinical Trial Regulations. Medicines for Human Use Clinical Trials Regulations (2004) Good Clinical Practice (The GCP Directive) 2005/28/EC Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031 as amended by SI 2006/1928). Department of Health (April 2005) NHS Research Governance Framework for Health and Social Care: Second Edition. Clinical Trial Compensation Guidelines are available to download here 18 of 21 (Date for review 10 May 2019)

19 Research, Clinical Audit or Service Evaluation Appendix A 19 of 21 (Date for review 10 May 2019)

20 Responsibilities for Conducting Research Appendix B Chief Investigator, Ensure proposals developed are scientifically sound and ethical Investigators and Ensure the study design has been submitted for independent peer review Researchers Ensure a Clinical Trials Authorisation from the MHRA for all CTIMPs studies has been obtained, if applicable, before any research activity begins Prepare and provide patient information sheets for participants that have been reviewed and approved by the REC Ensuring all staff are appropriately trained/ qualified for the tasks delegated Ensure that all staff have appropriate contracts with this NHS (substantive contracts, honorary research contracts or letters of access) before beginning work on the research project. Ensure all research has been approved by a REC and R&D department Comply with any current legislation and policy requirements relating to research and implement effectively Adhere to all NEAS R&D Standing Operating Procedures (SOPs) for research Ensure all participants are appropriately consented before any research activity begins using documents approved by the REC Ensuring participants welfare while in the study Controlling the research budget and ensuring financial probity during the course of the research project Ensure findings and data are accessible following expert review Ensure results of the research are fed back to participants Maintain a record of their research activity being undertaken in the Trust Notify the R&D department of any amendments, adverse incidents or complaints arising from the research Assist with monitoring and auditing when approached Submit progress and final reports to aid research monitoring Promote a quality research culture in the Trust Main Funder Assess the scientific quality of the research as proposed Establish the value for money of the research as proposed Consider the suitability of the research environment in which the research will be undertaken, particularly the experience and expertise of the chief investigator, principle investigator and other key researchers involved Require that a sponsor takes on responsibility before the research begins 20 of 21 (Date for review 10 May 2019)