Supporting Information: Body fluid-based biomarkers in traumatic brain injury

Published: 23 March 2023

Version: 1.0

This document contains information to assist applicants submitting to the call 23/52 Body fluid-based biomarkers in traumatic brain injury. Applications for funding are made online through the NIHR Research Awards Lifecycle Management System (REALMS). You must register or log-in to the REALMS to complete and submit your application.

Please also ensure that you have read the guidance notes fully. We have endeavoured to cover all necessary information relating to the application form through these resources. Incorrectly completed applications may be rejected.

The following additional supporting information is available:

For support developing applications, applicants are encouraged to contact their local NIHR Research Design Service (RDS) or equivalent in the first instance.

Please note, not all information in this document will be relevant to all applications, with some information being applicable to applications more suited to the EME Programme, but not the HTA Programme and vice versa. If you are unsure whether any guidance is relevant, please contact the cross programme secretariat at: crossprogramme@nihr.ac.uk

Eligibility

Researchers in England, Northern Ireland, Scotland and Wales are eligible to apply for funding under this call. Within the United Kingdom anyone who considers that they can carry out high-quality research is likely to be eligible. If you have any concerns regarding your eligibility to apply, we advise that you contact us before completing an application. NIHR programmes welcome applications that are within the programmes' remits from all sectors. Applicants are strongly advised to consider establishing partnerships with other relevant sectors or organisations to demonstrate they have the full breadth of expertise to carry out their proposed research in their applications to NIHR programmes.

If after reviewing this guidance you have any questions about the eligibility of your proposed research, please contact crossprogramme@nihr.ac.uk giving a brief summary of the research proposed. Applicants are asked to:

Follow Good Clinical Practice guidelines when planning how studies, particularly RCTs, will be supervised.
Note that trials involving medicinal products must comply with "The Medicines for Human Use (Clinical Trials) Regulations 2004". In the case of such trials, the Department of Health and Social Care (DHSC) expects the employing institution of the chief investigator to be nominated as the sponsor. Other institutions may wish to take on this responsibility or agree co-sponsorship with the employing institution. The DHSC is prepared to accept the nomination of multiple sponsors. Applicants who are asked to submit a Stage 2 proposal will need to obtain confirmation of a sponsor(s) to complete their application. The DHSC reserve the right to withdraw from funding the project if they are not satisfied with the arrangements put in place to conduct the trial.

Collaboration and team expertise

Proposals should involve a multi-disciplinary team with appropriate skills and experience, including an appropriately experienced statistician on the study team. The involvement of an accredited Clinical Trials Unit (CTU) is strongly encouraged in the design of clinical trials. Where appropriate, applicants are expected to work with suitably accredited clinical research facilities.

Timescales and funding

There are no fixed limits on the duration of projects and proposals should be tailored to fully address the questions posed. Applicants should be aware that they are competing for limited funds and proposals should represent good value for money. All funding requested should be clearly justified, but there is no upper limit.

Other programmes' proposal resubmission policy

We doe not prohibit the submission of research project applications that were previously unsuccessful but applicants will be encouraged not to re-apply until they have re-worked their application and responded to the feedback provided. If they do re-apply their application will be treated as a new application and considered on its merits at the time.

We will not accept the same or substantially similar applications to more than 1 NIHR programme. If 2 similar applications are submitted, once the overlap is identified, the application that is most advanced through the funding process will continue and the second will not be taken further.

Similar applications will only be considered by two programmes concurrently if:

the aims and research proposals are substantially different
if successful, we would be prepared to fund both proposals
the successful delivery of one project is not dependent on the other

Data protection

We have an obligation to keep data secure and to use it appropriately. To fulfil our obligations under law and as a result of our contract with the Department of Health and Social Care (DHSC), we adopt various procedures to use and protect data. This will impact on how we deal with you and your joint applicants.

The DHSC NIHR is the Data Controller under the Data Protection Act 1998 ('the Act'). Under the Data Protection Act, we have a legal duty to protect any information we collect from you. You should be aware that information given to us might be shared with other DHSC NIHR bodies for the purposes of statistical analysis and other DHSC NIHR research management purposes. NIHR also reserves the right to share, in confidence, details of your application with other approved research funding organisations outside NIHR in order to coordinate research activity in the UK.

Information collected from you will not be passed to any third party outside the NIHR except specifically as detailed above without your consent except where we are under a statutory obligation or entitled to do so by law. Applicants may be assured that DHSC NIHR is committed to protecting privacy and to processing all personal information in a manner that meets the requirements of the Act.

Data security - data about you

Personal information will be held on a database in the NIHR password-protected network that is available only to NIHR staff. Your details and those of your co-applicants will be retained by the NIHR on behalf of the DHSC to facilitate the running of the HTA and EME Programmes. If your application is successful at any stage of our process, your name, and the details of the sponsoring organisation, will appear on the NIHR website. In addition, once funding has been agreed and the contract signed, your details will appear in other literature as a grant holder and will be passed to the DHSC for inclusion in their publicly available databases of research projects.

Your name and those of your co-applicants will be added to our mailing list. This means that you will be sent updates on all the NIHR programmes.

Useful resources

Research Design Service

Applicants are recommended to seek advice from suitable methodological support services, at an appropriate stage in the development of their research idea and application. It is advisable to make contact at an early a stage as possible to allow sufficient time for discussion and a considered response.

The NIHR Research Design Service can advise on appropriate NIHR programme choice, and developing and designing high quality research grant applications.

Clinical Trials Unit support

Clinical Trials Units (CTU) are regarded as an important component of many trial applications and can advise and participate throughout the process from initial idea development through to project delivery and reporting. However, they may not be essential for all types of studies. If you feel this is the case, please justify the reasons on your application.

If you are looking for a CTU to collaborate with in your application, then the following sources can provide more help:

NIHR CTU Support Funding provides information on units receiving funding form the NIHR to collaborate on research applications to NIHR programmes and funded projects
The UKCRC CTU Network provides a searchable information resource on all registered units in the UK, and lists key interest areas and contact information

Clinical Trials Toolkit

Researchers designing or undertaking clinical trials are encouraged to consult the Clinical Trials Toolkit. This NIHR resource is a website designed to help researchers navigate through the complex landscape of setting up and managing clinical trials in line with regulatory requirements. Although primarily aimed at those involved in publicly funded Clinical Trials of Investigational Medicinal Products (CTIMPs), the Toolkit will also benefit researchers and R&D staff working on trials in other areas, who will find useful information and guidance of relevance to the wider trials environment.

The MHRA (contact details are info@mhra.gsi.gov.uk ) can provide guidance as to whether your trial would be covered by the regulations.

Public involvement

The NIHR expects the active involvement of patients and the public in the research it supports, including research undertaken as part of an individual training award. NIHR recognise that the nature and extent of active patient and public involvement is likely to vary depending on the context of each study or award. The term involvement refers to an active partnership between patients, members of the public and researchers in the research process. This can include, for example, involvement in the choice of research topics, assisting in the design, advising on the research project or in carrying out the research.

It is important that you describe in as much detail as possible how patients and the public have been involved in the development of the application as well as plans for involvement in the proposed research. Please note that this does not refer to the recruitment of patients or members of the public as participants in the research.
Further information and resources can be found on the Make a Strong Application page. This includes a detailed definition of patient and public involvement in research, briefing notes for researchers on how to involve patients and the public and payment guidance. The NIHR Research Design Service provide advice on developing research applications including involving patients and the public and the James Lind Alliance has a step-by-step guide on involvement in research identification and priority setting.

Advice on non-standard methodologies

The Methodology Advisory Service for Trials (MAST), offered by the Network of Hubs for Trials Methodology Research, is a resource for resolving non-standard methodological issues. Referrals to MAST, should ideally be made through Clinical Trials Units (CTUs).

Ethics/regulatory approvals

Guidance on the application process for ethical and other approvals can be found on the HRA website. Please note that if your study is led from England and involves the NHS in England you should apply for HRA approval.

If you are using patient information from an existing database, you should check whether the patients have given their consent for their data to be included in that database for research purposes, or if not whether the database is exempt under Section 251 of the NHS Act 2006. Where exemptions are not already in place, approval to use confidential patient information without consent must be requested from the HRA who make decisions with advice from the Confidentiality Advisory Group (CAG).

To take advantage of the growing utility of routine data (such as HES, GP records etc.), we would encourage investigators, where appropriate, to ask study participants to consent to long term follow up (for example beyond the outcomes to be collected in the funded trial) using routinely collected data, and appropriate linkage to allow this data to be best used.

Information on the responsibilities of key research stakeholders including Sponsors, Chief Investigators and Research Teams are summarised in the UK policy framework for health and social care research.

Reasonable costs and value for money

The NIHR accepts that some variance in costs is likely to occur between the Stage 1 and Stage 2 applications. The HTA and EME programmes will carefully scrutinise all Stage 2 application costs and any variance from the first stage. All costs need to be fully justified by the applicants to reassure that the study offers good value for money for the NHS.

It is important that consideration is given to all costs in relation to NHS support and treatment costs and the accurate values for these are included. It should be noted that applicants are expected to have contacted the appropriate Trust/s regarding the NHS support and treatment costs that may be required if their research is funded. If the costs are felt to be material, a letter of support may be provided from the Trust/s concerned as part of the Stage 2 proposal.

There are no fixed limits on the duration of projects or funding, and proposals should be tailored to fully address the research problem. Research costs are the costs of the research activity itself. These include data collection, analysis, other activities needed to answer the research questions, trial registration (if required) and the salary and indirect costs of staff employed to carry out the research.

If you are unsure of how to attribute the costs between research and NHS support and treatment costs, please refer to the following guidance on ‘Attributing the costs of health & social care Research & Development (AcoRD)’.

Higher Education Institutions (HEIs) should determine the Full Economic Cost (FEC) of their research using the Transparent Approach to Costing (TRAC) methodology. For HEIs, up to 80% of FEC will be paid, provided that TRAC methodology has been used.

For applications where the contractor is an NHS body or provider of NHS services in England, up to 100% of direct costs will be paid.

The total costs on the Stage 1 form should include the figures at the appropriate rate, so the total should reflect HEI figures at 80% and non-HEI figures at 100%. When completing the Stage 2 form, the figure submitted should be 100%, any reductions to FEC are automatically

UK Biobank

UK Biobank is a major national health resource with the aim of improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses. As such, applicants are encouraged to consider whether Biobank may be able to provide suitable data for their study, rather than request funding for unnecessary new data collection. We do not want to discourage establishment of new cohorts of participants and their data where this is necessary to address the research questions under consideration, our aim is to avoid applications for funding to set up Biobank-like cohorts where the use of Biobank would prevent wasteful duplication of Biobank-like activities.

UK Biobank has recruited 500,000 people aged between 40-69 years in 2006-2010 from across the country to take part in this project. They have undergone measures, provided blood, urine and saliva samples for future analysis as well as detailed information about themselves. The health of members of this large cohort will be followed over the coming years and the participants have consented to be approached about health research.

Please note: Some of the NIHR programmes, including the HTA Programme, are unlikely to fund work which focuses on collection of physiological, biochemical or other information unless there is a clearly defined way in which this will be used for the benefit of patients (either directly or in terms of improving outcomes of other patients).

Systematic reviews and evidence syntheses (HTA Programme)

Methods

Applicants should demonstrate knowledge of current research in the field and of systematic review methods and state how these would apply to the question posed. Valid and reliable methods should be proposed for identifying and selecting relevant material, assessing its quality and synthesising the results. Guidance on choice of appropriate methods is contained in NHS CRD Report Systematic Reviews is available within CRD’s guidance for undertaking reviews in health care (third edition).

Updating

It is the policy of NIHR, HTA that all search strategies undertaken as part of evidence synthesis/secondary research projects must not be more than 12 months out of date when the draft final report is submitted. We expect that most projects will manage to bring their searches up to date prior to analysis and writing up. As research funders we are aware that exceptional circumstances can apply that would not allow this to be case but this must be the exception rather than the rule and will be assessed on a case by case basis. The expectation is that projects funded by the HTA Programme will deliver information that is both relevant and timely.

In addition, in order to inform decisions on whether and when to update the review, researchers will be expected to give some indication of how fast the evidence base is changing in the field concerned, based on the nature and volume of on-going work known at the time the review is completed. Applicants should note that they will not be expected to carry out any future updating as part of the contract to complete the review.

Requirements for systematic reviews to be registered with PROSPERO

Applicants undertaking systematic reviews should note the commitment of NIHR to register them in the PROSPERO database. PROSPERO was developed by the NIHR’s Centre for Reviews and Dissemination (CRD), and is the first online facility to register systematic reviews for research about health and social care from all around the world. Access is completely free and open to the public via the PROSPERO website. PROSPERO registration is a condition of NIHR funding for eligible systematic reviews.

NIHR carbon reduction guidelines and sustainability

The NIHR is committed to playing a role in helping to meet the UK Net Zero carbon targets. The NIHR would therefore encourage all applications to consider, where feasible, addressing issues of environmental sustainability including their impact and appropriate outcomes within the remit of the applying programme. Advice can be obtained from the NIHR Carbon reduction Guidelines.

Transparency agenda

In line with the government’s transparency agenda, any contract resulting from this tender may be published in its entirety to the general public. Further information on the transparency agenda is at:

Guidance for using the electronic online Stage 1 application form

To access the application form for Stage 1 applications only

Select the call to which you wish to apply for on the funding opportunity page on the NIHR website. From within the call details page press the ‘Click here to apply’ button to access the Stage 1 application form. This also provides call specific supplementary information e.g. the commissioning brief or specification document. This will direct you to the REALMS login page. If you already have a username (email address) and password, enter these details or, if you have not yet registered, complete the short registration process. You will then be directed to the confirmation page for the specific call. If this is the correct call, click on the Apply button and this will start the application process. Clicking Cancel will return you to your ‘home page’.

Applying for a funding opportunity creates a task called ‘Pending Application’. This task will be available for you to complete until 1pm on the closing date as indicated on the research call and on your task list.

The ‘Pending Application’ task can be accessed at any time until you either submit the application (using the Submit button in the application) or the call closes.

Clicking on the relevant Pending Application link takes you to the online application where you can complete your application information.

Additional guidance will be available on most screens as you progress through your application.

REALMS can be accessed directly, on your home page all your applications and other tasks will be listed.

To submit a Stage 1 application

In order to submit a Stage 1 application to the programme you must complete all mandatory fields as indicated with a red asterisk *. When you click the 'Info still required' button at the bottom of the online application page a list of outstanding information (hyperlinked to the relevant section/question) will be displayed at the top of the application screen.

Giving others access to the form

Co-applicants: Access to your application is through your user login to REALMS. This should not be shared. The Stage 1 application does not require co-applicants to complete this form however as lead applicant you must ensure they are aware of being involved in the study team. If you want to share your form with your co-applicants, please create a PDF of the form and send it to them. Options to create a PDF are available on the Home page and the Review and Submit page. Where appropriate to the study a Joint Lead applicant can be added to the application (Stage 1 and Stage 2) and full access can be provided.

Saving your form

As you work through the application, you are asked to 'Save Draft'. This will save all the information you have submitted so far. You can save the form at any point and leave the application prior to submission. The Save Draft button is always located at the bottom of each page of the application.The pending application task will remain on your home page until complete and submitted or the deadline for the application has passed, at which point it will appear as either a Submitted Application or a Past Application task.

It is important to remember to ‘Save Draft’ as you go through the form before navigating away from the page.

There is a security time out set on the REALMS so that after 60 minutes of inactivity, the user will be logged out of the system. It is advisable therefore to save your work at regular intervals using the Save Draft button on any page. REALMS will give you a warning that you are due to be timed out 10 minutes before it times you out. If this message is displayed, you should close the pop-up.

There is a left hand navigation menu in the application so you can select specific parts of the form to complete, however you should always ensure that you save any information entered on your page before using this left hand menu.

Leaving the application task

You can leave your application task at any time. As long as you have saved any new information you have entered for the application, you can navigate to your home page or log out of the REALMS system.

Technical support

If you encounter any problems with the REALMS system, you should contact the programme funding support team via email.

Space restrictions when entering text

You should be aware that there are character limits set for each text box within the application form. For larger text areas these are indicated with ‘xxx characters left’ at the bottom of the text entry box. Please note that the system does not provide a spell checker. Carriage returns and spaces are counted as characters.

The form counts all blank space as a part of the content of each box, so if you are short of space it will help if you delete extra carriage returns and place any bulleted lists into paragraph format.

URL links

You may wish to include URL links to your application or refer to URL links in a body of your text. You are advised not to use any URL shortening service such as ‘tiny.cc’ when completing your application. This type of shortening service is associated with hacking and spamming (as it promotes the sending of links that are unclear where they are pointing).

Un-submitted applications

Seven days prior to the closing date you will receive an email reminder that you have an open application (i.e. not submitted). The HTA Programme no longer supports ‘rolling over’ of applications to a subsequent call.

Assistance

If, after carefully reading all the instructions, you still have difficulties completing your application, please email crossprogarmme@nihr.ac.uk.

Please be aware that while every effort will be made to respond to enquiries in a timely fashion, it is advisable to send queries in as far in advance of the call closing date as possible to ensure we can respond whilst still leaving you enough time to complete your application.

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