An Introduction to Research Governance Dr Gillian Gatenby

An Introduction to Research Governance Dr Gillian Gatenby Research Governance Manager Trust R&D Newcastle Joint Research Office November 2011

Overview of Presentation 2 ¡ Research Governance – What is it? Why does it exist? ¡ Good Clinical Practice ¡ The regulatory background and the legislation which impacts on clinical research in the UK ¡ Defining Research, Audit & Service Evaluation ¡ Gaining the necessary approvals to carry out clinical research in the NHS

What is Research Governance? Research Governance is essentially a term covering the principles and processes by which standards are set in research. According to the Department of Health (DH), Research Governance improves research and safeguards the public by: ¡ ¡ enhancing ethical awareness and scientific quality promoting good practice reducing adverse incidents and ensuring lessons are learned forestalling poor performance and misconduct Research Governance is for all managers and staff, in all professional groups, no matter how senior or junior working in all health and social care research environments who: ¡ ¡ ¡ design research studies participate in research host research in their organisation fund research proposals or infrastructure manage research undertake research

The Research Governance Framework (RGF) was developed by the DH to set out the principles, requirements and standards expected for the conduct of clinical and non clinical research in the UK covering: • Ethics (The dignity, rights, safety & wellbeing of participants must be the primary consideration in any research study) • Science (must ensure only high quality, valid research is conducted as determined by independent scientific review of research proposals) • Health & Safety (research can use potentially dangerous equipment, substances or organisms so patient and researcher safety is paramount) • Information (allow public access to information on research being conducted and the findings from research) • Finance (financial probity, consideration of adequate insurance cover for research, arrangements for intellectual property, contracting) • Quality Research Culture (promotion of excellence in research in the UK)

Good Clinical Practice (GCP) GCP is an international ethical and scientific quality standard for the design, conduct, recording and reporting of trials that involve the participation of human subjects. Its purpose is to: ¡ ¡ ensure the protection of the rights and well being of research participants ensure that results of research are accurate and credible The principles of Good Clinical Practice have their origin in the Declaration of Helsinki and apply to ALL research, not just clinical trials of medicinal products! 5

Why Have Research Governance & GCP? Episodes in history have shaped the regulation of research involving human subjects & led to the introduction of GCP & tight regulations & governance procedures for research. Some examples: Elixir of sulphanilamide disaster in the USA in 1937 (improperly prepared medicine led to mass poisoning and in response the 1938 Food, Drug & Cosmetic Act was created to ensure all drugs safety tested before marketing) • World War II & Nuremberg Trials (Led to the creation of the Declaration of Helsinki in 1946 - the foundation of the ethical principles on which GCP was built) • Tuskegee Syphilis Experiment (US public health study conducted for 40 years to study the progression of syphilis led to changes in the law governing protection of participants in clinical research) • Use of Thalidomide in the 1950 s/1960 s (changes to legislation worldwide to ensure stricter testing for drugs prior to licensing) •

Regulations & Legislation in the UK The following are the key guidance documents, legislation and regulations which govern the conduct of research in the UK: 7 ¡ DH Research governance framework for health and social care (2 nd Edition Sept 2005) ¡ EU Clinical Trials Directive transposed into UK law through the Medicines for Human Use (Clinical Trials) Regulations 2004 ¡ EU Medical Devices Directives implemented in the UK through the Medical Devices Regulations 2002 ¡ Human Tissue Act 2004 (fully implemented Sept 2006) ¡ Mental Capacity Act 2005 (fully implemented Oct 2007) ¡ Data Protection Act 1998 and Freedom of Information Act 2000 ¡ Governance arrangements for NHS Research Ethics Committees (GAf. REC)

Research/Audit/Service Evaluation 8 ¡ Not all clinical projects conducted in the NHS are research. Your study may be RESEARCH, an AUDIT or a SERVICE EVALUATION ¡ However, it is often difficult to differentiate between these three types of study ¡ Helpful guidance is provided by the National Research Ethics Services (NRES) Guidance page – http: //www. nres. nhs. uk/applications/is-your-project-research/

What is Research? ¡ Research attempts to derive generalizable, new knowledge ¡ Quantitative research is designed to test a hypothesis. Quantitative research may involve evaluating or comparing interventions, particularly new ones. ¡ Qualitative research identifies/explores themes following established methodology. Qualitative research usually involves studying how interventions and relationships are experienced ¡ Research addresses clearly defined questions, aims and objectives ¡ Research usually involves collecting data that are additional to those for routine care but may include data collected routinely. May involve treatments, samples or investigations additional to routine care ¡ Research may involve randomisation ¡ Research normally requires Research Ethics Committee (REC) review. Refer to: www. nres. npsa. nhs. uk/applications/apply/

What is Service Evaluation? ¡ Designed & conducted solely to define or judge current care ¡ Designed to answer: “What standard does this service achieve? ” ¡ Measures current service without reference to a standard ¡ Involves an intervention in use only. The choice of treatment is that of the clinician and patient according to guidance, professional standards and/or patient preference. ¡ Usually involves analysis of existing data but may include administration of interview or questionnaire. ¡ No allocation to intervention ¡ No randomisation ¡ Does not require REC review

What is Audit? ¡ Designed & conducted to produce information to inform delivery of best care ¡ Designed to answer: “Does this service reach a predetermined standard? ” ¡ Involves an intervention in use only. Choice of treatment is that of the clinician & patient according to guidance, professional standards and/or patient preference ¡ Usually involves analysis of existing data but may include administration of simple interview or questionnaire. ¡ No allocation to intervention o No randomisation ¡ Does not require REC review

Undertaking Research in the NHS Having determined you wish to undertake a clinical research project in the NHS you need to: 12 ¡ Be aware of how clinical research is governed in the UK and the approvals that must be in place before the research begins ¡ Obtain permission to conduct the research from NHS R&D. All research conducted in the NHS requires NHS permission at each NHS Trust where the research is to run ¡ Prepare your submission to the REC which is now completed through a system known as IRAS (Integrated Research Application System) ¡ For certain research projects (those hoping for adoption onto the NIHR Portfolio) a new centralised system for NHS approval is used known as NIHR CSP: NHIR Co-ordinated System for gaining NHS Permission (more about CSP later)

Governance Checks & Risk Assessment In accordance with the Research Governance Framework, NHS organisations are responsible for ensuring that the research they host meets the necessary standards – this is achieved through research proposals undergoing governance checks & risk assessment prior to commencing In Newcastle upon Tyne Hospitals NHS Foundation Trust, the Trust R&D team in the Joint Research Office are responsible for carrying out the governance checks & risk assessment for every research project which runs in the Trust.

Governance Checks & Risk Assessment For all research conducted in the Trust the R&D team assesses: 14 l Organisational risk: Sponsorship, insurance & indemnity, duty of care to research participants l Patient safety: e. g. review of informed consent procedures, review by an appropriate ethics committee, appropriate review by regulatory authorities controlling drugs, approval for exposure to radiation where required etc l Risks to the Investigator and other research staff l Arrangements for data collection and storage and maintenance of confidentiality of participants and use of data l Scientific risk: ensuring scientific quality of the research through good design and independent review l Financial risk: ensuring financial probity and appropriate use of NHS resources, contracting, insurance

Organisational Risk - Sponsorship All research conducted in the NHS must have an identified Sponsor. The sponsor is the individual or organisation which takes responsibility for the initiation, management and financing of the research project. The Sponsor must ensure that: 15 l The research team hold the necessary contracts with the Trust and are appropriately qualified to conduct the research l Arrangements are in place locally to deliver the research as proposed in the research protocol l Through independent peer review the scientific quality of the research is assured l All necessary approvals are obtained prior to the research commencing (REC approval, MHRA approval, all local approvals etc) l Responsibilities for the management, monitoring and reporting of the research are delegated appropriately

Determining a Research Sponsor 16 ¡ For non-commercial research involving NHS patients it is usual for NHS Trust to act as Research Governance Sponsor as the duty of care for the patients participating in research and the staff conducting the research resides with the NHS Trust ¡ The Sponsor is usually the lead Trust where study is initiated and where the Chief Investigator is employed ¡ Some Trusts/Universities have co-sponsorship arrangements in place ¡ Universities tend not to sponsor research projects which involve patients and are interventional in nature. It is common however for Universities to sponsor non interventional research (e. g. research involving existing collections of tissue samples held in a university research tissue bank or a healthy volunteer study where there is no NHS Trust involvement) ¡ For commercial research the Sponsor is usually the commercial organisation leading the research ¡ In all cases R&D requires evidence of Sponsorship

The Research Team 17 ¡ The Chief Investigator (CI) is the person designated to take overall responsibility for the design, conduct and reporting of a study ¡ For multi-centre studies it is common to have the CI located at the main research site and local Principal Investigators (PI) identified at participating research sites ¡ Honorary Research Contracts (HRCs) are required for non-NHS staff conducing research where they will have direct contact with patients or staff and/or direct bearing on quality of care for patients. Letters of permission/access are required for those working with data or tissue only ¡ A Research Passport scheme now operates for non NHS staff who require access to multiple NHS Trusts as part of their research ¡ A full HRC provides NHS indemnity. The Trust indemnifies for negligent harm under the Clinical Negligence Scheme for Trusts (CNST). ¡ This Trust expects all those conducting research projects to have undertaken training in GCP

Scientific Risk: Independent Peer Review The Research Governance Framework states that all projects should be independently peer reviewed – this is the responsibility of the Sponsor: 18 l If research has been funded by a commercial organisation, DH or an established charitable body for example, it is generally the case that these organisations will have conducted a rigorous peer review prior to funding a study l If a study is designed in house by the research team and has not been funded by a known funding body or another Trust or University, the R&D office would need to arrange an independent peer review of the research proposal in house l R&D must see evidence of a favourable peer review for a research proposal before R&D approval will be granted

Research Ethics • Research Ethics Committees (RECs) safeguard the rights, safety, dignity and well-being of people participating in research in the NHS. They review applications for research and give an opinion about the proposed participant involvement and whether the research is ethical. • RECs are entirely independent of research Sponsors and investigators. • Each year, RECs in the UK review around 6, 000 research applications. On average, they give an opinion after 35 days: well within the maximum allowance of 60 days.

Research Ethics Broadly speaking, legislation requires REC review of research involving: l l l l 20 people who lack (or lose) capacity to give informed consent to take part (or to keep taking part) in the research; processing of confidential patient information without consent where this would otherwise breach confidentiality; material consisting of or including human cells, which has been taken from the living or the deceased patients who are cared for in private and voluntary sector nursing homes (in England, Wales and Northern Ireland) and/or residents of residential care homes (in Northern Ireland only); exposure to ionising radiation; medical devices that are not CE-marked (i. e. not compliant with European Directives) or CE-marked medical devices that have been modified or are being used for a new purpose; investigational medicinal products; protected information from the Human Fertilisation and Embryology Authority

Applying for Ethical Approval 21 ¡ REC review via NHS RECs is under the control of the National Research Ethics Service (NRES) ¡ The application form for the REC is completed online through IRAS (integrated research application system) ¡ The application to the REC is signed by the CI and the Sponsor for the research – this can be done electronically but the form must be authorised before submission to the REC ¡ Now have ‘main REC’ for each study l A favourable opinion for a study must be obtained by the CI from the main REC l If a multi-centre study, each site must have a Site Specific Assessment conducted as part of Trust R&D approval at that site

Data Protection/Caldicott in Research Caldicott refers to a review commissioned by the Chief Medical Officer. Information Management Principles were created to improve how the NHS handles and protects person identifiable information. Think of the following when designing your research: • • • Justify the purpose of why you are using confidential information in your research Only use confidential information when necessary Use the minimum information that is required Access to information should be restricted to only those who need to access it All those handling confidential information must understand their responsibilities Understand & comply with law (Data Protection & Freedom of Information Acts) In this Trust, Caldicott approval is required for research collecting and transferring person identifiable data. The approval process for Caldicott & Data Protection is combined and requires submission of a single form to the Trust Caldicott Guardian. Databases storing identifiable patient/staff information must be registered with the Trust and held on Trust servers. 22

Insurance & Indemnity in Research o Indemnity is the “promise” of insurance cover, not the insurance itself. o In the NHS indemnity is provided by the NHS Litigation Authority under the Clinical Negligence Scheme for Trusts (CNST). o The NHS is legally liable for the negligent acts or omissions of its employees o Those substantively employed by the NHS and those holding honorary contracts with the NHS are covered by CNST whilst working in the Trust. o The NHS only covers claims of negligent harm. Non negligent harm is not covered by NHS Indemnity. o University employees conducting research in the NHS need to inform their organisation’s insurance Department as it may be necessary to obtain a certificate of insurance for your research. o For some research projects using a device or medicinal product, product liability may apply – this is usually provided by the product manufacturer o R&D requires confirmation of insurance arrangements for research

Financial Risk 24 ¡ Projects must be fully costed and funded before the research can be approved to commence in the NHS – seek advice from Trust R&D as to the requirements for costing for your study ¡ For externally-funded, non-commercial research involving the NHS see the “Attributing revenue costs of externally funded noncommercial research in the NHS (ARCO)” guidelines produced by DH to assist with costing your research proposal. You will need to consider not only the research costs but also potential service support costs and excess treatment costs. ¡ Commercial projects would be expected to be fully costed and funded by the company sponsoring the research with all appropriate overheads and all necessary set-up fees (e. g. , R&D, Pharmacy, Clinical Research Facility etc) included in the fees for conducting the research

Clinical Trials of Investigational Medicinal Products (ct. IMPs) The EU Clinical Trials Directive ¡ The EU Directive 2001/20/EC was transposed into the legislation of all EU member states from 1 May 2004 ¡ The Medicines for Human Use (Clinical Trials) Regulations 2004 (the Regulations) regulate clinical trials in the UK since they came into force on the 1 May 2004 ¡ The aims of the Directive and the subsequent regulations were to harmonise the regulation of clinical trials, improve the rights, privacy and protection of research participants in accordance with Good Clinical Practice (GCP) 25 ¡ The Directive applies to any clinical trial of an Investigational Medicinal Product (IMP) ¡ Recently Trust R&D has received applications for approval of trials involving ATMPs (Advances Therapy Medicinal Products) as well as CTIMPs

MHRA ¡ UK Competent Authority is the Medicines and Healthcare products Regulatory Agency (MHRA) ¡ The MHRA has the power to inspect organisations conducting clinical trials of IMPs/ATMPs and devices in the UK and indeed elsewhere in the world ¡ There have been various amendments to the Medicines for Human Use (Clinical Trials) Regulations 2004 as listed below: l l 26 The Medicines for Human Use (Clinical Trials) Amendment (No. 1) Regulations SI (2006/1928) provide a legal basis on which the MHRA can inspect clinical trials and transposes into UK Law the EU Directive (2005/28/EC) on Good Clinical Practice The Medicines for Human Use (Clinical Trials) Amendment (No. 2) Regulations SI (2006/2984) make provisions relating to trials involving incapacitated adults in emergency situations The Medicines for Human Use (Clinical Trials) and Blood Safety and Quality (Amendment) Regulations 2008 SI (2008/941) make additional provision relating to trials involving minors in emergency situations The Medicines for Human Use (Miscellaneous Amendments) Regulations 2009 SI (2009/1164)

Good Clinical Practice in ct. IMPs (Amendment Regulations 2006) Summary of main GCP Responsibilities: l l l 27 l Trial documents: Master Trial Files/Investigator site file must be maintained Adequate resources must be available (time, facilities, staff, training, potential to recruit) Recorded evidence of investigators qualifications (signed CV), GCP training etc Rights/well-being of trial subjects (ethical approval and medical care ensured) Compliance with protocol as set out in initial application to MHRA/REC or amendments as approved by MHRA & Ethics (non adherance to the protocol is a serious breach of GCP) IMPs to be stored, labelled and used in accordance with protocol Data recorded & stored appropriately (eg changes to case report forms must be dated and initialled (no tippex!) Informed consent essential - patient MUST sign and DATE informed consent form as per protocol and ethics approval – MUST show that all staff taking consent are trained in obtaining consent Regular monitoring – establishing data monitoring committees and evidence of decisions made (minutes) Progress reports to Ethics and MHRA (copy to sponsor) – yearly and end of trial Safety reporting – very specific for ct. IMPs regarding reporting of Serious Adverse Events (guidance available regarding legal requirements) Records retention and archiving – patient confidentiality issues/integrity of the record of the trial to be maintained

Permissions Needed for ct. IMPs ¡ All ct. IMPs must be registered with the European clinical trials database to obtain unique Eudra. CT number to be used on all correspondence with the MHRA ¡ The investigator must obtain a Clinical Trial Authorisation (CTA) from Medicines and Healthcare Products Regulatory Agency (MHRA) prior to commencing the trial ¡ For ct. IMPs the is a requirement in the Trust that the trial will be regularly monitored (ideally by a registered Clinical Trial Unit or a Contract Research Organisation) to ensure that the trial is running safely and is GCP compliant at all times l l 28 For commercial studies the commercial sponsor arranges monitoring For non-commercial trials, monitoring should be arranged through an accredited clinical trials unit

EU Medical Devices Directive The Medical Devices directive defines a medical device as: Any instrument, apparatus, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application intended by the manufacturer to be used for human beings for the purpose of: l l l 29 diagnosis, prevention, monitoring, treatment or alleviation of disease, diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap, investigation, replacement or modification of the anatomy or of a physiological process, control of conception, and which does not achieve its principle intended action in or on the human body by pharmacological, immunological or metabolic means, but may be assisted in its function by such means.

Permissions Needed for Device Trials 30 ¡ Devices are regulated in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) ¡ The legislation covers the placing on the market and putting into service of medical devices ¡ This enables the device to obtain a CE mark – manufacturer's claim that the device satisfies the relevant Essential Requirements in the Directives and is fit for its intended purpose ¡ If using CE marked devices in research then no need to register with MHRA ¡ Clinical devices developed and used within an NHS setting only (eg, made by and used in Medical Physics) do not fall under the regulations – CE mark not necessary unless placing on the market ¡ GREY areas – does it cross-over into medicinal products legislation (eg, device administers a medicinal product)

Human Tissue Act 2004 31 ¡ Implemented Sept 2006 the HT Act is regulated in the UK by The Human Tissue Authority (HTA) for the removal, storage, use and disposal of human bodies, organs and tissue from the living and deceased. ¡ Consent is the fundamental principle of the Act Under the Act, consent is broadly required to store and use relevant material from the living for a number of ‘scheduled purposes’, including ‘research in connection with disorders, or the functioning of, the human body’. Consent is also required to remove, store and use relevant material from a deceased person. This consent must be both appropriate and valid. ¡ The HTA has the authority to inspect organisations that store and use tissues for the purposes covered by the HT Act. ¡ What does the Act do? l Identifies the range of activities for which a licence will be required (the Trust and the University hold licences from the HTA) l Prohibits the conduct of certain activities without a licence l Establishes penalties (including custodial sentences) l Prohibits commercial dealing in human material

Definition of Relevant Material The material that the HT Act covers is called ‘relevant material’, which is material that consists of or includes human cells (even a single cell!). ‘Relevant material’ includes blood, tissues and organs. It does not include: • Material which contains no cells e. g. serum. • Gametes (ova and sperm). • Material created outside of the body e. g. embryos, cell lines. Information about relevant material can be found on the HTA website and supplementary list of relevant materials: http: //www. hta. gov. uk/legislationpoliciesandcodesofpractice/defini tionofrelevantmaterial. cfm 32

Using Human Tissue Samples in Research ¡ Consent l l ¡ Ethics review from an NHS REC l ¡ A licence is required for storage of tissue for research purposes only if you are storing licensable tissue (relevant material) for unspecified research purposes Transfer of tissue l 33 Ethical approval from an NHS REC can be project specific or generic if it is obtained for the initiation of a Research Tissue Bank (RTB) HTA Licence l ¡ Need consent to collect and use tissue in research in most cases (exceptions if held before 01 Sept 2006, ‘surplus’ tissue if anonymised and research approved by an NHS REC, 100 year rule) Consent can be for use of tissue samples in a specific research project or generic to allow for use of samples in future unspecified research Material Transfer Agreements (MTA) are required for the transfer of tissue to or from an RTB or other organisation

Mental Capacity Act 2005 34 ¡ Became law in Oct 2007 ¡ The Mental Capacity Act 2005 (MCA) provides a statutory framework to empower and protect vulnerable people who are not able to make their own decisions. ¡ It makes clear who can take decisions, in which situations, and how they should go about this. ¡ It enables people to plan ahead for a time when they may lose capacity.

Five Key Principles of the MCA 35 ¡ A presumption of capacity ¡ The right for individuals to be supported to make their own decisions ¡ That individuals must retain the right to make what might be seen as eccentric or unwise decisions ¡ Anything done for or on behalf of people without capacity must be in their best interests ¡ Least restrictive intervention of the person’s basic rights and freedoms

Research and the MCA 36 ¡ The Act sets out a single clear test for assessing whether a person lacks capacity to make a particular decision at a particular time ¡ The Act sets out clear parameters for research: l Research involving, or in relation to, a person lacking capacity may be lawfully carried out if an ‘appropriate body’ (a Research Ethics Committee designated to review MCA applications) agrees that the research is safe, relates to the person’s condition and cannot be done as effectively using people who have mental capacity. l Carers or nominated third parties must be consulted and agree that the person would want to join an approved research project l A personal consultee is identified in the case of loss of capacity during research l Nominated consultee if no personal consultee available – see http: //www. dh. gov. uk/en/Publicationsandstatistics/Publications/Public ations. Policy. And. Guidance/DH_083131 for guidance

Research Involving Radiation IRMER: The Ionising Radiation (Medical Exposure) Regulations 2000 as amended by the Ionising Radiation (Medical Exposure) (Amendment) Regulations 2006 Scope of IRMER governs the exposure to ionising radiation of patients or other persons voluntarily participating in medical or biomedical, diagnostic or therapeutic research programmes. The research provisions of IRMER apply to any research exposure involving ionising radiation, not only to exposures that are additional to routine care Procedures involving ionising radiation include: ¡ Diagnostic X-rays, CT scans or DXA scans ¡ Radiotherapy ¡ Radionuclide imaging (including diagnostic imaging) ¡ NB: Magnetic Resonance Imaging (MRI) or ultrasound does not involve ionising radiation. R&D requires evidence of IRMER review if studies involve ionising radiation

Research Involving Radiation ARSAC: The Administration of Radioactive Substances Advisory Committee • The administration of radioactive substances is governed by the Medicines (Administration of Radioactive Substances) Regulations 1978 (MARS) as well as by IRMER. Regulation 2 of MARS requires that any doctor or dentist wishing to administer radioactive medicinal products to humans should hold a certificate issued by Health Ministers. • In the case of research involving administration of radioactive substances (nuclear medicine), preparatory work may include application for a research ARSAC certificate from the Department of Health in order to comply with MARS • R&D requires a copy of the ARSAC certificate where research involves the administration of radioactive substance to a research participant

Clinical Trial Agreements It is sometimes necessary to execute an agreement to cover the financial arrangements and division of responsibilities between Parties for the conduct of a project: • For commercially sponsored and funded trials the ABPI model Clinical Trial Agreement (m. CTA) is generally used. • For non commercially sponsored research there is the national model agreement for non commercial research (m. NCA) • Where a project involves the transfer of tissues between organisation a Material Transfer Agreement (MTA) may be necessary.

Integrated Research Application System (IRAS) ¡ Web based system at www. myresearchproject. org. uk ¡ A single system for applying for the permissions and approvals for health and social care / community care research in the UK ¡ Enables you to enter the information about your project once instead of duplicating information in separate application forms ¡ Uses filters to ensure that the data collected and collated is appropriate to the type of study, and consequently the permissions and approvals required ¡ Helps you to meet regulatory and governance requirements

Integrated Research Application System (IRAS) IRAS captures the information needed for the relevant approvals from the following review bodies: ¡ ¡ ¡ ¡ 41 ¡ Administration of Radioactive Substances Advisory Committee (ARSAC) Gene Therapy Advisory Committee (GTAC) Medicines and Healthcare products Regulatory Agency (MHRA) Ministry of Justice NHS / HSC R&D offices NRES/ NHS / HSC Research Ethics Committees National Information Governance Board (NIGB) National Offender Management Service (NOMS) Social Care Research Ethics Committee

Entry page for IRAS 42

When to Apply for Approvals It can be confusing as to when to apply for certain approvals… 43 ¡ It is now a requirement of final R&D approval that there is evidence of other approvals having been granted before giving final R&D approval ¡ Ideally you should apply for ethics, MHRA, other approvals (eg Caldicott) at the same time as applying for R&D approval so the applications can be processed in parallel – you should NOT wait for R&D approval before applying for ethics, MHRA etc (integrated application process) ¡ The new CSP system helps with order of approvals ¡ You CANNOT begin your research in an NHS Trust without the final letter of approval from that organisation

The NIHR Portfolio The goal of the National Institute for Health Research (NIHR) is to create a health research system in which the NHS supports outstanding individuals, working in world class facilities, conducting leading edge research focused on the needs of patients and the public The Institute manages its activities through four main work strands: ¡ ¡ NIHR Faculty: supporting the individuals carrying out and participating in research NIHR Research: commissioning and funding research (e. g. NIHR programme grants, Rf. PB etc) NIHR Infrastructure: providing the facilities for a thriving research environment (e. g. BRUs & BRCs) NIHR Systems: creating unified, streamlined and simple knowledge management systems (RDMIS CSP Module) The National Institute for Health Research Clinical Research Network (NIHR CRN) Portfolio is a database of high-quality clinical research studies that are eligible for support from the NIHR Clinical Research Network in England.

Applying for Portfolio Adoption The NIHR Coordinated System for gaining NHS Permission (NIHR CSP) is the entry point for non-commercial studies applying for portfolio adoption and Clinical Research Network (CRN) support. Studies automatically eligible for consideration for NIHR CRN support are those that: ¡ Have some of their research funding provided by the NIHR, other areas of central Government and NIHR non-commercial Partners; and ¡ Fulfil the Eligibility Criteria definition of a ‘research study’ which is "the attempt to derive generalisable (i. e. of value to others in a similar situation) new knowledge by addressing clearly defined questions with systematic and rigorous methods". Studies potentially eligible for consideration for NIHR CRN support are those that are: ¡ Commercially funded and commercially sponsored (i. e. commercial contract research) ¡ Non-commercial studies o Investigator initiated trials (i. e. commercial collaborative research) o Funded by overseas Governments o Funded by overseas charities NHS REC approval and NHS permission are prerequisites for research to be supported via the CRN.

Clinical Research Networks in the UK Studies on the NIHR Portfolio have the following support: l Access to local network of dedicated research support staff including research nurses and other allied health professionals, who can help identify eligible patients, arrange consent to participate in the study and monitor patients as they progress through the study l Support to ensure your study can be successfully undertaken in the NHS including pharmacy, imaging and pathology services and the possibility of securing protected time for NHS staff to conduct research l Access to experienced RM&G staff that can advise on governance aspects of undertaking research in the NHS and facilitate rapid approval of your study through the NIHR Coordinated System for gaining NHS Permission (NIHR CSP). Although the CRN operates as one organisation, it is made up of a number of parts: l Six “Topic” Research Networks (covering Cancer, Dementia and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health & Stroke) l A Primary Care Research Network l A Comprehensive Clinical Research Network, which covers all other areas. Our researchers are supported by Northumbria Tyne & Wear Comprehensive Local Research Network (NTW CLRN), one of 25 CLRNs in England.

Research Design Service ¡ National Institute for Health Research Design Services' (NIHR RDSs) aim is to increase the volume and quality of successful grant applications for NIHR funding ¡ In Newcastle RDS North East provides expert advice to help local researchers to develop and design high quality research proposals for submission to national, peer-reviewed funding competitions for applied health or social care research ¡ The RDS is part of the NIHR infrastructure and is a national service regionally delivered working to the maxim "consistency where possible, flexibility where appropriate". ¡ The support is provided free of charge

To recap… You need to: 48 ¡ Register your research with Trust R&D & obtain R&D approval from each research site, including all local approvals required from Support Depts (Pharmacy, Labs, Imaging, etc Finance etc) ¡ Obtain favourable ethical opinion from an NHS REC (where the NHS is involved in the research) or a UREC (if applicable) ¡ Honorary Research Contracts/ necessary permissions for non NHS staff ¡ Obtain Data protection/Caldicott approval ¡ Obtain MHRA approval for ct. IMPs or device trials ¡ Agree arrangements for collection, use & storage of tissue samples ¡ Other certificates/approvals as appropriate (eg, GTAC – for gene therapy; ARSAC – radiation; NIGB if accessing clinical information without consent) ¡ Signed agreements where required (m. CTA/m. NCA, MTAs etc)

List of Common Acronyms in Research ¡ ¡ ¡ ¡ ¡ 49 ¡ ARSAC: Administration of Radioactive Substances Advisory Committee ATMP: Advanced Therapy Medicinal Products NIHR CSP: Coordinated System for gaining NHS Permission ct. IMP: clinical trial of an Investigational Medicinal Product Eudra. CT: European Union Drug Regulating Authorities Clinical Trials GAf. REC: Governance Arrangements for Research Ethics Committees GTAC: Gene Therapy Advisory Committee IRAS: Integrated Research Application System IRMER: The Ionising Radiation (Medical Exposure) Regulations 2000 m. CTA: model Clinical Trial Agreement m. NCA: model agreement for non commercial research MHRA: Medicines and Healthcare product Regulatory Agency MTA: Material Transfer Agreement NIGB: National Information Governance Board NIHR: National Institute for Health Research NPSA: National Patient Safety Agency NRES: National Research Ethics Service PIAG: Patient Information Advisory Group

Useful Websites 50 ¡ Department of Health – Research Governance Framework http: //www. dh. gov. uk/en/Policyandguidance/Researchanddevelopment/AZ/Researchgovernance/index. htm ¡ NRES http: //www. nres. npsa. nhs. uk/ ¡ IRAS https: //www. myresearchproject. org. uk/ ¡ MHRA for trials of Medical Devices and Medicinal Products http: //www. mhra. gov. uk/index. htm ¡ Eudra. CT for registering a ct. IMP http: //eudract. emea. europa. eu/ ¡ Clinical Trials Toolkit http: //www. ct-toolkit. ac. uk/

Useful Websites 51 ¡ Mental Capacity Act information – Department of Health http: //www. dh. gov. uk/en/Social. Care/Deliveringsocialcare/Me ntal. Capacity/Mental. Capacity. Act 2005/index. htm ¡ Information about Research Passports http: //www. nihr. ac. uk/systems_research_passports. aspx ¡ NIHR Portfolio information: http: //www. crncc. nihr. ac. uk/about_us/processes/portfolio ¡ NIHR Portfolio information for Commercial projects http: //www. crncc. nihr. ac. uk/Life+sciences+industry ¡ Human Tissue Authority http: //www. hta. gov. uk/

ANY QUESTIONS?

Contact Details Dr Gillian Gatenby Research Governance Manager Joint Research Office 6 th Floor, Leazes Wing Royal Victoria Infirmary Queen Victoria Road Newcastle upon Tyne NE 1 4 LP Trust R&D main office: 0191 2825959 53