Initiation & set-up

This is the planning stage of a research study before the study formally starts.

It is expected that many documents will be generated during the initiation and set-up stage of a research study and these documents should be kept safely and securely by the researcher in a master file. Collectively, these documents will be known as Essential Documents and will help the researcher to demonstrate during an audit or inspection that their study adheres to the Principles of Good Clinical Practice; this is extremely important when conducting NHS research.

First Steps...

Researchers should contact their local R&D Office as soon as they know that they wish to participate in a research project and discuss with the Research Manager the study’s requirements. In having this conversation, the researcher is giving the Research Manager a “heads-up” of their planned research and a rapid assessment of capacity and capability can be undertaken of the impact of the study on the organisation. If there are any “show-stoppers”, this can be determined as soon as possible in the process, preferably before the grant application stage.

Research Capacity and Capability Assessment – is an early and rapid decision-making process conducted as soon as possible following an invitation to join a study. It enables the Research Manager with the local Principal Investigator to assess any operational risks that may delay or have an impact on the delivery of the study. The assessment depends on understanding both the risks associated with the study and the capabilities of the organisation at the time. If during their assessment, a researcher identifies any operational risks that will require additional management action in order to deliver their contribution to the study, the researcher should bring these issues and risks to the attention of the local Principal Investigator who should in turn bring them to the attention of the Research Manager as soon as possible. The assessment does not duplicate the detailed review leading to confirmation of capacity and capability.

Governance & Is It Research?

The UK Policy Framework for Health and Social Care Research outlines principles of good governance that apply to all research within the remit of the Secretary of State for Health and defines roles and responsibilities for organisations and individuals.

Key responsibilities for organisations and individuals are described in the UK Policy Framework for Health and Social Care Research and anyone embarking on a research project that involves NHS staff or patients, their tissue, organs or data should first familiarize themselves with their responsibilities as provided in the Framework. Researchers should also familiarize themselves with their own organisation’s policies and procedures and that of the organisation where the research is located which have been put in place to ensure compliance and that of their employees with the Framework.

Is it Research?

Not all of the projects undertaken within the NHS are research; projects not classified as research are not managed as research within the NHS.

Projects not managed as research:

  • do not require ethical review by a Research Ethics Committee
  • do not require confirmation of capacity and capability from NHS R&D offices
  • may require some other form of approval from the organisation(s) undertaking or hosting the project depending on local arrangements.

In the first instance, if unsure researchers can refer to the HRA Decision Tool; they can also contact their R&D Office.

Further guidance:

HRA leaflet: Defining Research Published October 2017

If the project is audit, service evaluation or public health surveillance, or some other type of non-research activity, such as case study, system/equipment testing or satisfaction survey, researchers should contact the clinical governance office of their local NHS organisation to check what other review arrangements or sources of advice apply to the project.  For example, there may be standard guidelines on the conduct of clinical audit. The Caldicott Guardian will be a source of advice on the use of patient data.

If the project is classified as research then it is likely that the researcher will need to make an application via the “Integrated Research Application System (IRAS)” Integrated Research Application System (IRAS).

To prepare applications in IRAS, the researcher will need an IRAS account. Each project in IRAS is allocated an IRAS ID. This identifier may be used as a point of reference when seeking advice.

Sponsorship

Every research project in the UK and the European Union requires a sponsor; an organisation that is willing to take on the responsibility for putting in place the arrangements to initiate, manage and finance the study (or arrange the financing of the study). It may take some time to secure a sponsor(s) for your study, so start early in the planning process. A group of organisations may take on sponsorship responsibilities and distribute them by agreement among the members of the group, provided that, collectively, they make arrangements to allocate all the sponsor responsibilities that are relevant to the study. For clinical trials that fall under the UK Clinical Trial Regulations (“CTIMPs”) these come under three broad headings: Authorisation; Good Clinical Practice (GCP) Conduct; and Pharmacovigilance.

Researchers should identify a sponsor at an early stage in the research planning process as the sponsor may have requirements related to the protocol to assure themselves of the quality of the study. One of the key responsibilities of being a sponsor is to ensure that the planned research has undergone a satisfactory process of independent scientific review. There are stations in the Clinical Trials Tool Kit and the Data and Tissues Tool Kit that provide further guidance for researchers with regard to sponsorship and the allocation of sponsor responsibilities. Much of the advice is generic and so can be applied to all types of research.

The decision with regard to whether an organisation should act as a sponsor for a research project or not usually lies with the organisation’s Director of Research or Medical Director (or university equivalent). The Chief Investigator should contact their R&D Office before applying to any authorities such as an external funder or the ethics committee to ensure that the decision regarding whether their employer is willing to be the sponsor for a research project is made early on in the process.

Contract & Budget

Model Agreements

Before a research project can start, the sponsor and participating organisations need to have appropriate agreements in place. Considerable time and effort can be required to draft different versions of such agreements for the various research scenarios. To simplify this process, the Department of Health and representatives from Industry and other stakeholders have developed a suite of model agreements which can be used “off the shelf”, without modification. It is usually the role of the R&D Office to co-ordinate the site review of a proposed research agreement/contract and researchers should forward any agreements/contracts provided to them by the sponsor to their R&D Office as soon as possible in the initiation stage of a research project.

Model Agreements for Industry-sponsored studies

Industry Costing Templates

In conjunction with a number of stakeholders in the NHS and Industry, the National Institute for Health Research Clinical Research Network (NIHR CRN) has specifically developed costing templates for use on Industry-sponsored clinical trials. Using the templates provides a starting point for clear, swift, negotiation discussions. Based on the principles of the NHS Finance Manual, the templates provide cost transparency, consistency and predictability for companies whilst ensuring full cost recovery for the healthcare site. It is the usually the sponsor’s responsibility to complete the costing template and then pass it over to the research site for review and negotiation. It is usually the role of the R&D Office to co-ordinate the site review of the costing template.

NIHR Industry Costing Templates

What is NHS Indemnity and What Does It Cover?

In England, the Clinical Negligence Scheme for Trusts (CNST), administered by the NHS Litigation Authority (NHSLA), provides an indemnity to NHS employees in respect of clinical negligence claims arising from events occurring in the context of NHS employment in England. It meets any damages and claimants’ costs which are found due, and legal defence costs. Similar schemes operate in Scotland (CNORIS), Wales (WRPS), and the Northern Ireland Office runs a risk pooling scheme.

Research is a core NHS activity. It is therefore treated in the same way as any other NHS activity in relation to potential liabilities for clinical negligence. NHS indemnity covers negligent harm to patients and volunteers involved in research.

NHS Litigation Authority
NHS Indemnity – HSG (96)48: NHS indemnity

External Funding

Grant Funding

When applying for grant funding it is important that NHS costs are included in the application. Whilst grant funding may be paid into a university account arrangements must be put in place to refund the NHS any eligible costs. Guidance on what is an eligible cost is available at AcoRD (Attributing the Costs of Health and Social Care Research).

NIHR FundingThe NHIR (The National Institute for Health Research) award NHS research funding through their NIHR schemes via the local networks and is aimed at ensuring that funding follows R&D activity. It is, therefore, important that researchers notify their R&D Office of any staff costs or service support costs that will be incurred as a result of participating in NIHR portfolio projects so that the R&D Office can ensure these costs are reimbursed.

First Steps…

In the first instance, it is important that researchers contact their R&D Office for guidance and support about applying for research funding and costing their research.

There are stations in the Clinical Trials Tool Kit and the Data and Tissues Tool Kit that provide guidance for researchers with regard to funding. Much of the advice is generic and so can be applied to all types of research.

Protocol Development, Risk Assessment & Peer Review

Before seeking approvals for a research project to commence, the protocol should be finalised, as this constitutes part of the application. A protocol should include sufficient detail to enable, if circumstances were to require it, someone previously unfamiliar with the study to continue from the point that another researcher has left it. If support departments are involved, such as pharmacy, pathology or radiology, it is important to discuss the implications of the study during the protocol development stage with them.

For each study a risk assessment should be undertaken at the protocol development stage. This may be used to plan the details of study management and the approach to, and extent of, monitoring in the study. These plans should be documented, together with the risk assessment, so that the management strategy is both transparent and justified. This documentation is intended not only to facilitate the management of the study but also to help prepare for external audit.

Links to guidance on the contents of a protocol are given below. Some of the key elements that should be included in a protocol are the management, monitoring and reporting arrangements, eg, the procedure for recording and reporting adverse events. Also it is useful to include the definition of the end of the study (this is a regulatory requirement for trials that fall under the clinical trial regulations (“CTIMPs”).

It is recommended that researchers develop procedures and systems for study management that meet the principles of Good Clinical Practice, and that these are clearly documented in the protocol so that adherence is readily demonstrated.

It is advisable to allocate version numbers and version dates for protocols during the drafting process. The final protocol that is submitted to the ethics committee should ideally be numbered version 1.0 and dated with the date of finalisation of the protocol. If any protocol amendments are made, then the protocol version number and date must be updated accordingly. Similarly, Participant Information Sheets and Consent Forms should be marked with version numbers and dates. The Health Research Authority website provides template participant information sheets and consent forms for researchers to use when setting up a new study.

There are stations in the Clinical Trials Tool Kit and the Data and Tissues Tool Kit that provide guidance for researchers with regard to study management systems and monitoring procedures. Much of the advice is generic and so can be applied to all types of research. Some of the guidance above has been extracted from these toolkits.

Risk Assessment Tool

Researchers should ask their R&D Office whether or not they have a tool for assessing risk in research. Bradford Teaching Hospitals NHS Foundation Trust has developed a risk assessment tool for researchers to use when assessing risk with regard to their protocol. The risk assessment tool has been developed primarily for clinical trials, however, it can be adapted for other types of research studies; the tool is accessible from the Downloads section of the website.

Scientific Review Proforma

If there is no external funding for a research project, the protocol may not have been through the peer review process. If this is the case, applicants will be required to provide documentary evidence (including CVs of reviewers) of two independent expert reviews when applying for research approvals. Bradford Teaching Hospitals NHS Foundation Trust has developed a Scientific Review proforma for researchers to use when arranging review of their protocol; the proforma is accessible from the Downloads section of the website.

Study Management & Monitoring

Appropriate planning before the study and adequate oversight and monitoring during the study will help ensure that study participant safety is maintained throughout the study and that there is accurate reporting of results at its conclusion.

Study Management

It is recommended that researchers develop procedures and systems for study management that meet the principles of Good Clinical Practice (GCP) and are appropriate to the study design and, and that these are clearly documented in the study protocol so that adherence is readily demonstrated.

For each research project a risk assessment should be undertaken at the protocol development stage. This may be used to plan the details of study management and the approach to, and extent of, monitoring in the study. These plans should be documented, together with the risk assessment, so that the management strategy is both transparent and justified. This documentation is intended not only to facilitate the management of the study but also to help prepare for external audit.

Thus for each study there would be:

  • study risk assessment
  • summary of study management systems
  • procedures for monitoring

These would not necessarily be separate documents and may be included in the protocol or in standard operating procedures.

Study Monitoring

The purpose of study monitoring as defined in ICH GCP is to ensure that:

  1. the rights and well-being of trial participants are protected;
  2. the reported trial data are accurate, complete, and verifiable from source documents;
  3. the conduct of the trial is in compliance with the currently approved protocol/amendments, with Good Clinical Practice (GCP), and with the applicable regulatory requirements.

In the past, compliance with ICH GCP has often been interpreted as requiring intensive site monitoring, but there is now an international consensus that a move towards more flexible and targeted monitoring activities is the most effective approach.

There are a number of approaches to study monitoring available, and the procedures for each study should be considered as the study is being developed. Some of these approaches are outlined below.

1 Study Oversight Committees The funding body or sponsor may specify particular oversight arrangements, but even if they do not, some form of oversight is strongly recommended for all studies, although the appropriate structures will vary according to the size, complexity and risks associated with the trial.

Commonly employed oversight committees for a phase III trial include:

  1. Trial Management Group (TMG)
  2. Trial Steering Committee (TSC)
  3. Data Monitoring Committee (DMC)

2 Coordinating Centre ‘Good Housekeeping’ This is the day-to-day monitoring that is carried out by those responsible for running a study. This typically includes the following checks:

  • the data collected are consistent, with adherence to the study protocol
  • the case report forms (CRFs) are only being completed by authorised persons
  • no key data are missing
  • data appear to be valid (for example, range and consistency checks)
  • a review of recruitment rates, withdrawals and losses to follow-up

3 Central Monitoring In large, multi-site trials, central monitoring of data using statistical techniques is particularly useful for the early identification of:

  • Unusual patterns or trends
  • Issues with plausibility or consistency
  • Safety signals
  • Other deviation from protocol/trial requirements such as poor/late completion of CRFs

Although omissions (e.g. failure to report a serious adverse event) or data entry errors cannot be detected directly, it may be possible to compare data from different sites to identify sites that warrant investigation.

4 Other Remote Monitoring Checks: It is common practice for the sponsors of small, non-commercial trials to utilise self-assessment checklists/progress updates to help confirm GCP/protocol compliance. For example, sites may be required to complete a checklist confirming the contents/versions of documents held in their investigator site file thereby giving assurance that the site file is up to date and being maintained.

The Study Monitoring Plan

Appropriate procedures to monitor each study should be established during study design. This plan should define the data to be reviewed as well as the types of checks that will be performed by outlining:

  • the extent and nature of monitoring to be employed;
  • the responsibilities of those involved (and any training required);
  • the procedures for monitoring reports including dealing with any issues that arise from monitoring such as;
    • how issues identified are escalated when required
    • how findings may lead to the monitoring plan being adapted

Extent and Nature of Monitoring

The extent and nature of monitoring should be determined prior to the start of the study, preferably at the grant application stage to allow additional monitoring costs to be included in the budget. The study risk assessment may be used to determine the intensity and the focus of the monitoring activity, whilst the study design would inform the methods used for monitoring.

More detailed guidance…

There are stations in the Clinical Trials Tool Kit and the Data and Tissues Tool Kit that provide guidance for researchers with regard to study management systems and monitoring procedures. Much of the advice is generic and so can be applied to all types of research. The guidance above has been extracted from these toolkits.

What is GCP and Which GCP should I be following?

Fact: Clinical Trials with investigational medicinal products should be conducted to Good Clinical Practice standards (the law since May 2004).

What is GCP?

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible (Introduction ICH GCP).

What is ICH GCP?

ICH is the acronym for ‘The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use’. ICH GCP guideline is a consolidated document (finalised in May 1996) setting out a tripartite standard for the conduct of clinical trials across the European Union, Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

The Principles of ICH GCP

  1. Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).
  2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.
  3. The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.
  4. The available nonclinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
  5. Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
  6. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.
  7. The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
  8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).
  9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.
  10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.
  11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
  12. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.
  13. Systems with procedures that assure the quality of every aspect of the trial should be implemented. (Section 2 ICH GCP)

Which GCP should I be following?

There are many courses advertising ICH GCP for investigators and site staff but if these are just ICH GCP courses and are not structured to include both UK and European Regulations they do not fulfil the obligation to inform investigators conducting clinical trials of all their legal responsibilities. In the UK and other European member states we do not just follow ICH GCP we are committed to ‘European GCP’ which is a higher standard than ICH GCP.

Therefore, the GCP standards you should be following when conducting a clinical trial that involves an investigational medicinal product (CTIMP) within the EU are:

The local Laws of each member state for sites set up in that country. In the UK this is the Medicines for Human Use (Clinical Trial) Regulations 2004 Statutory Instrument (SI) 2004 No. 1031 (known as the principal regulation). It was necessary to amend the UK Clinical Trial Regulations in 2006 using SI 2006 No. 1928 in order to implement the GCP Directive 2005/28/EC. Each time that amendments to the Regulations are published, an SI provides details of how the principal regulation (ie, SI 2004 No. 1031) is to be amended. A consolidated version of the UK clinical trial regulations is available for purchase from Canary Ltd and it incorporates the changes specified in the amending SIs into a single document. HYPERLINK “http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html” ICH E6 must be “taken into account”.

It is recommended that researchers develop procedures and systems for trial management that meet the principles of GCP, and that these are clearly documented in the protocol so that adherence is readily demonstrated.

The European Commission website for access to their clinical trial guidelines and reference documents.

Conducting clinical trials outside of Europe

European Union member states must work to European standard GCP, which includes ICH E6, plus the EU Directives, plus national laws.  Other countries, for example Japan, Australia and Canada work to plain ICH GCP which is a legal requirement in those countries, and as they are outside of the EU they obviously do not have to incorporate the requirements of the Directives,  However, studies set up in a member state which include sites in a country outside the EU must also be conducted to European GCP (same standard for all sites) and permission must be obtained prior to study start for the sites in “third countries” to be inspected by European Inspectors.

Studies conducted in the US must follow the FDA (Food and Drug Administration) standards. The FDA was the first Regulatory Authority to publish standards on the conduct of clinical trials. The problem is that the FDA regulations were published in 1977 and have hardly changed since. In 1977 they were “in advance of their time” for the standards that were expected, but now, compared to the new European GCP Regulations they are not such a high standard and this is in itself causing problems on some global studies that involve US and European sites. FDA GCP is only legally enforceable on studies conducted on US sites.

Conducting other types of research

Just because a research project is not a CTIMP does not mean that the research project does not have to comply to standards of conduct. The Research Governance Framework for Health and Social Care (2nd Edition 2005) Section 2 (with the Annex) sets out the standards for research governance for all types of research in health and social care which includes legislative requirements, Department of Health requirements and other guidance produced from a variety of established sources, eg, codes of conduct, etc. In practice, it is recommended that researchers conducting non-CTIMP studies should also be able to demonstrate adherence to GCP standards.

GCP Training

A key requirement for anyone involved in the conduct of clinical research is Good Clinical Practice (GCP) training. GCP is the standard and guidelines to which all research is conducted.

The NIHR (National Institute for Health Research) provide GCP training as a taught course and as e-learning.

GCP Training

Includes some extracts taken from Clinical Discovery April-May 2004, Joan Perou, GCP Consultant and Trainer.

Honorary Contracts & Letters of Access

NHS organisations are required to ensure that anyone who has no contractual relationship with any NHS organisation, who will interact with individuals in a way that has direct bearing on the care of NHS patients, holds an NHS honorary research contract. The contract should cover the appropriate time period or have arrangements for extension if required. Where such a contract does not exist, this should be arranged with NHS R&D after submitting the form. A Research Passport system is in place to support issuing of honorary research contracts. For more information see https://www.hra.nhs.uk/planning-and-improving-research/best-practice/research-passport/

In the first instance, researchers should contact their R&D Office for local support and advice in the NIHR Research Passport process.

Student Research

Due to the requirement for a full acceptable protocol, HRA Approval and ethical approval, those anticipating conducting research in the NHS should consider building in a lag time of at least three months before they will be able to collect data. The time and effort necessary to gain approval for a study may seem disproportionate to the size and aims of the study. Those conducting a study as part of an undergraduate or taught Masters programme may wish to consider if the requirements for their qualification could not be met as satisfactorily by conducting a clinical audit or service evaluation study. Both these types of study can employ standard research methodologies and, whilst still requiring NHS permission, the processes for gaining this are more easily attainable within the timeframe of such studies.

Patient & Public Involvement

Participants or their representatives should be involved wherever possible in the design, conduct, analysis and reporting of research. Social care research has a long tradition of the involvement of participants in research. Involve, the consumers in NHS research group, has established the principle that major advisory bodies in NHS research and development programmes should normally have at least two consumer representatives.

INVOLVE (formerly Consumers in NHS Research) has a Support Unit which offers information, advice and support to participants and members of the public, researchers and those working in the NHS about participant and public involvement in research in the NHS and in social care and public health:

INVOLVE

http://www.invo.org.uk

Wessex House
Upper Market Street
Eastleigh
Hampshire
SO50 9FD

Tel: 023 8065 1088

Email: admin@invo.org.uk

Intellectual Property

The Dept. of Health have a policy document that provides a framework for intellectual property in the NHS.

The NHS Innovation centre provides a guide on protecting your intellectual property

The NHS Regional Innovation Hubs offer legal and commercial support to NHS staff who have a pre-market product. In doing so, each Hub serves the NHS organisations in its area by identifying, protecting and developing intellectual property (IP) sourced from within the NHS. The innovation hub for Yorkshire and Humber is Medipex.

Medipex work with NHS organisations and their employees to help bring valuable ideas to life. So whether staff have an idea about improvements to patient care, or the development of new products or services, Medipex can help. They can provide guidance, practical support and a proven model of innovation management. Working in partnership, Medipex can help staff develop initial ideas into new products and services and launch them to market. They can help to ensure that innovations and intellectual property are identified and developed.

First Steps…Researchers should contact their R&D Office.

Local Feasibility

What is Local Feasibility?

Local feasibility is the process by which local research teams consult with the relevant departments and managers within their NHS organisation before the application stage in order to assess the likelihood that the organisation will be able to provide the capacity and capability to deliver the study safely and successfully and in a timely manner. Local feasibility includes:

  • The supporting services (eg, Pharmacy, Pathology, Imaging). Can they provide the capacity and capability to undertake the tests/investigations or dispense the medication in the manner the study protocol requires?
  • Can the organisation provide the capacity and capability to deliver/operate the necessary equipment and facilities for the study?
  • Is it likely that the organisation will be able to address legal and regulatory requirements relating to the study? For example, use of the appropriate Standard Operating Procedures, indemnity cover, licences, etc.
  • Is it likely that the organisation will be able to provide additional support (if required) to the local research team in delivering the study, eg, emergency facilities, psychological support, translation services, etc.
  • Is it likely that the organisation will have the appropriate experience/guidance needed for working with any vulnerable groups as part of the study?
  • Is it likely that the organisation will have appropriate cost information and finance staff time to assess and manage financial risks relating to the study?
  • Is there the patient population for the study?
  • Is there the knowledge and experience to conduct the study?
  • Is there staff resource to conduct the research?

Local feasibility should not be too burdensome for the researcher undertaking the local feasibility checks and same for the relevant head of department and services.  Local feasibility should be a ‘discussion’ between the researcher, managers and the support departments (if applicable) and should not involve sending various documents around the organisation for ‘blanket’ review.  The feasibility discussions should be specific and tailored to the needs of the manager with an exchange of information that results in the manager understanding the impact of the research on their service.

Local feasibility is intended to be undertaken prior to the local site submission when the Trust is the participating organisation.  If the Chief Investigator is employed and located at the Trust, local feasibility should be undertaken prior to ethics and regulatory submission(s).

Research feasibility has always been good practice. The R&D Office should be able to provide advice and support about undertaking local feasibility checks. If local research teams engage fully in this feasibility process then it should help:

  1. Confirmation of Capacity and Capability being granted in a timely manner.
  2. The local research teams are more likely to be able to commence recruitment on time in the knowledge that the organisation is ready to support the research.
  3. The successful delivery of the study “to time and target” as agreed with the Chief Investigator/sponsor.

Research Performance

In the past, there was little consequence to poor research performance, but this is no longer the case and future funding and research reputation is dependent on the NHS organisation’s research performance.

Department of Health– performance in initiating and delivering clinical research

The Government wishes to see a dramatic and sustained improvement in the performance of providers of NHS services in initiating and delivering clinical research. The aim is to increase the number of patients who have the opportunity to participate in research and to enhance the nation’s attractiveness as a host for research. The Government’s Plan for Growth, published in March 2011, announced the transformation of incentives at local level for efficiency in initiation and delivery of research.

National Institute for Health Research (NIHR) and Clinical Research Network (NIHR CRN) – research performance measures

The NIHR via the local networks provides funding to support research activity adopted onto the NIHR portfolio. A condition of continued receipt of this funding is that research teams must meet the performance targets set by the local networks, recruit to time and target and recruit the first patient into a study within the benchmark.

In practice, this means that in NHS organisations –

Divisional General Managers/Directors/Heads of Service are ensuring that they have a good understanding of the research that is being undertaken within their organisation and, with support from the R&D Office, put processes in place to ensure research performance indicators are met.

Researchers/ Research Teams are conducting local project feasibility with support from the R&D Office prior to submission of a research application; this assists in ensuring the NHS organisation can host the research and that the project can start as soon as formal organisational capacity and capability has been confirmed. Researchers should contact their R&D Office as soon as they are thinking of conducting a research project.

Discussions about target setting will include –

  • Ensure agreed recruitment targets are achievable and are not over-estimated
  • Put the necessary arrangements in place to ensure that recruitment targets are met
  • Communicate regularly with the R&D Office regarding new and on-going projects
  • Provide information as necessary on research activity

The R&D Office will –

  • Confrim organisational capacity and capability to deliver the research.
  • Co-ordinate the performance management of research activity
  • Provide advice and support to research teams on conducting local research feasibility and ensuring performance targets are met
  • Develop systems to collect performance information
  • Co-ordinate submissions to the DH/ NIHR on research performance as required.

Research Approvals

Study approval includes those approvals needed for the study as a whole and will include HRA Approval, Research Ethics Committee (REC) approval and, where required, regulatory approval, for example, a clinical trial authorisation (CTA) from the Medicines and Healthcare Products Regulatory Agency (MHRA) for clinical trials involving medicinal product(s) or approval from the Confidentiality Advisory Group (CAG) for studies which involve the use of data without gaining the patient’s consent.It is a condition of HRA Approval that ‘Confirmation of Capacity and Capability is obtained from each NHS organisation before the research begins’

Guidance on applying for NHS confirmation of capacity and capability for research is available on the HRA website and researchers should contact either their local R&D Office or local network for advice and assistance in setting up their research project.

Where a NHS organisation’s role in the study is limited to identifying and referring potential participants to research sites (“participant identification centre”), guidance should be sought from the R&D Office on the information it requires to give permission for this activity.

For non-NHS sites, site management permission should be obtained in accordance with the procedures of the relevant host organisation. Sponsors are not required to notify the ethics committee of approvals from host organisations.

It is the responsibility of the sponsor to ensure that all the conditions are complied with before the start of the study or its initiation at a particular site (as applicable).

What is IRAS?

The Integrated Research Application System (IRAS) is a single system for applying for the approvals for health and social care / community care research in the UK.

The method for researchers to apply to R&D Offices is not affected by IRAS itself. However, IRAS is able to support different review processes developed across the UK. Researchers need to seek confirmation of capacity and capability to deliver research from the R&D Office for each site.

IRAS is not a form, but a set of information that is used to create the various forms needed for the relevant approvals. It consists of a single dataset (i.e. a set of questions and answers) for all the questions in all the application forms included in the system. The set of questions that need to be answered by a researcher will depend on the type of study and the types of applications required. Many questions will be disabled when the researcher has completed the initial Project Filter. The actual application forms for each reviewing body are generated from the single dataset, ie, all the forms cross-populate. This means that there are separate application forms but only one set of questions. As an example, each form requires the Chief Investigator’s name but the dataset includes the question for the Chief Investigator’s name only once, and the researcher will only need to answer the question once and the name will be entered in all the relevant forms for that project. There is question specific guidance easily accessible with each question. An XML file can be created to support transfer of data to management systems.

The process of completing the online application forms on IRAS should trigger researchers to apply for approvals relevant to their study. The most common study approvals and legislation/regulation are:

  • A clinical trial involving the use of medical product(s) will require MHRA authorisation
  • A study involving the use of medical device(s) without CE marking may require a letter of NO OBJECTION from the MHRA
  • A study involving the use of data must be compliant with the Data Protection Act 1998 and in accordance with the rules on NHS patient confidentiality.
  • A study involving the use of data without the patient’s consent may require CAGapproval
  • A study involving the use of human tissue must be compliant with the Human Tissue Act 2004 and should be conducted in accordance with the Human Tissue Authority (HTA) codes of good practice.
  • A study involving the use of ionising radiation must be assessed by a Medical Physics Expert to ensure local compliance with the IRMER regulations.
  • A study involving persons who lack capacity to consent must be compliant with the Mental Capacity Act 2005 and should follow the code of practice.
  • A study seeking adoption onto the NIHR (National Institute for Health) Clinical Research Network Portfolio

Is my study eligible for NIHR Clinical Research Network Portfolio?

Please refer to the full eligibility criteria for details on the inclusion of studies in the NIHR CRN Portfolio: https://www.nihr.ac.uk/documents/eligibility-for-nihr-clinical-research-network-support/11604

What should I do if my study is not eligible for the NIHR Portfolio?

If your study has not been successful in being adopted onto the NIHR CRN Portfolio or is not eligible for the NIHR CRN Portfolio, an R&D submission should be prepared for each research site and submitted in accordance with each NHS organisation’s submission procedures; guidance is available on the HRA website.

Confirming capacity and capability at the Trust

After HRA Approval has been granted, the sponsor is responsible for sending a local document package in accordance with HRA guidance to each participating site. Each participating site is required to confirm their organisations capacity and cabaility to deliver the research.

Click here for guidance on making a local site submission. For guidance on local procedures contact the relevant R&D office.

Assessment

The confirmation of capacity and capability process will:

  • Review the feasibility of undertaking the research locally, assess the logistics for the local supporting departments, undertake contract and budget negotiations, assess local research team suitability, and issue Letters of Access or Honorary Research Contracts
  • Arrange access to research nurse or other resources or financial support, as appropriate
  • Support the process where research involves NHS patients taking part through private or charity providers

You should note the following points to avoid unnecessary delays in the review process:

  • Contracts – It is strongly recommended that you use the NHS model agreements. Failure to do so is likely to delay your project while a legal review is undertaken, and may incur a charge.
  • Finance – For commercially funded research you are recommended to use the Industry Costing Template.
  • Research Passports and Honorary Contracts or Letters of Access – The local R&D office will determine the necessary contractual arrangements for the research team.
  • Radiation – For research involving ionising radiation (eg X-rays and CT scans), whether additional or standard practice, the NHS organisation is legally required to assess each individual study.

When will I get the go ahead?

Confirmation of capacity and capabilty will be provided once the following are in place:

  1. Allocation of adequate arrangements & resources are in place
  2. Appropriate contractual arrangements are in place
  3. Allocation of responsibilities agreed and documented
  4. MHRA approval in place (where required)
  5. Local IRMER or ARSAC approval (where required)
  6. Appropriate internal authorisation to conduct the study locally is in place.
  7. Appropriate insurance or indemnity arrangements are in place.
  8. HRA Approval is in place.

Guidance Flow Charts

  • Confirmation of capacity and capability (Link TBC)
  • Amendments (Link TBC)
  • Contract review (Link TBC)

Set-up Activities

The following activities are the responsibility of the Chief Investigator/sponsor before a study commences –

  • Ensuring that the Protocol has undergone independent scientific and statistical review and is compliant with the relevant legislation/regulations and guidelines.
  • Ensuring that appropriate and robust methods of randomisation are used and documented in the protocol and advice from a suitable statistician or other appropriate expert with regard to methods for randomisation and un-blinding should be used.
  • Securing and administering the necessary funding for the Study and ensuring appropriate contracts/agreements are in place.
  • Putting in place appropriate monitoring activities. Developing a Study Monitoring Plan and ensuring it is in place prior to the start of the study that is proportionate to the risks of the study and requires monitoring activities to be documented and assessed for trends periodically.
  • For a clinical trial involving a medicinal product (CTIMP), ensuring that management of the Investigational Medicinal Product(s) (IMP) is agreed with the Pharmacy Department and that a suitable pharmacist is involved in completing the application form for a Clinical Trial Authorisation (CTA) with regard to assessing Qualified Person (QP) Declarations and QP Certification; and Assessing (with Pharmacy Department) the IMP manufacturer’s ability to comply with regulatory requirements and that the IMP is provided and labelled in accordance with the UK Clinical Trial Regulations (Part 7, Regulation 46).
  • Establishing a Trial Master File (TMF) which contains the Study’s Essential Documents. The Essential Documents are those which enable both the conduct of the Study and the quality of the data produced to be evaluated and show whether the Study is or has been conducted in accordance with regulatory and good clinical practice requirements (ICH GCP Handbook Section 8). The TMF should be appropriately labelled and sectioned with a contents page. The TMF should be kept for a minimum of five years in a safe and secure place after the study has ended. For a CTMP, the sponsor is responsible for compliance with Regulation 31A (Trial Master File and Archiving) of the UK Clinical Trial Regulations.
  • Carrying out a consistency check to ensure there are no conflicting/inappropriate statements being made in the Study’s documentation.prior to submitting the application to the Research Ethics Committee (REC) and the Medicines and Healthcare Products Regulatory Agency (MHRA) or any other authority.
  • Arranging site initiation visits and ensuring all research approvals and permissions are in place before a research site is activated. A site initiation visit will include review of roles and responsibilities, training, contracts and monitoring and reporting procedures.
  • Checking that contractors are adequate with respect to the standards to which the work would be conducted and ensure contracts are in place prior to undertaking activities. Sub-contracting should be undertaken through the organisation’s standard processes for sub-contracting and should be adequately documented.
  • Putting in place written procedures to allow all investigators to conduct the Study in accordance with the Protocol. It is strongly recommended that as many study procedures as possible are included in the protocol. However, additional Standard Operating Procedures (SOPs) may be needed where it is difficult or not appropriate to include them in the protocol.
  • Ensuring that the Study’s database is assessed as fit for purpose and that the assessment is documented.
  • Ensuring that training is done and quality control procedures for data entry are in place and these are documented and a log is maintained during the life of the Study.

Standard Operating Procedures

Bradford Teaching Hospitals NHS Foundation Trust (BTHfT) Policy for Research delegates to the Research Management & Support Office the responsibility of providing guidance and written procedures for its staff and researchers in order to demonstrate regulatory compliance when conducting research.

Access to BTHfT’s Policy for Research and BTHfT’s Research Standard Operating Procedures (SOPs) is via BTHfT’s Intranet which is available to all BTHfT’s staff.

If you have any queries about our policies and procedures and you do not have access to BTHfT’s Intranet, please contact the Research Management & Support Office using the contact details below –

Bradford Teaching Hospitals NHS Foundation Trust (BTHfT)

Research Management & Support Office
Bradford Institute for Health Research
Bradford Royal Infirmary
Duckworth Lane
Bradford
BD9 6RJTel: (01274) 383418/ 366808/364687
Fax: (01274) 382640
Email: Bradfordresearch.applications@bthft.nhs.uk