The NIHR Health Technology Assessment (HTA) Programme is looking to fund target trial emulation studies.
This is a 2-stage, commissioned funding opportunity. To apply for the first stage you should submit an outline application. If invited to the second stage, you will then need to complete a full application.
Methodological sub-studies: Studies Within A Trial/Review/Project
This funding opportunity is eligible for a methodological sub-study, which can help significantly improve methodology of future research as well as the host study. Sub-studies can also support the decarbonisation of research.
Find out more about methodological sub-studies, how to include them in your application, and the requirements of different research programmes.
Introduction
Our Health Technology Assessment (HTA) Programme invites applications in response to specific research questions and priorities. These have been identified, developed and prioritised for their importance to stakeholders including:
- Department of Health and Social Care
- NHS
- patients and public
- local government
Research priority
We are inviting proposals for Target Trial Emulation (TTE) studies to assess the comparative effectiveness and cost-effectiveness of health and social care interventions. This opportunity targets specific areas where Randomised Controlled Trials (RCTs) are not feasible, ethical, or sufficiently agile to inform fast-moving technologies.
Reflecting NIHR’s commitment to the Life Sciences Sector Plan in support of the government’s Growth Mission, our aim is to unlock the potential of the UK’s rich data assets to enable the 3 strategic shifts of the NHS 10 Year Health Plan: moving from hospital to community care, prioritising prevention over treatment, and advancing from analogue to digital methods. We also want to ensure that social care leverages the advantages of TTE studies, particularly in relation to these shifts in emphasis.
Applicants are required to apply rigorous TTE frameworks to existing health, social care, or administrative data. While we acknowledge the significant curation needed to transform raw administrative records into ‘research-ready’ evidence, applicants must justify the TTE approach. They must demonstrate that it is the most appropriate method and that it delivers value for money by generating robust causal evidence from existing resources without the need for prospective recruitment. Comparisons of health and social care interventions where ‘Time Zero’ (eligibility and assignment) can be clearly defined in administrative data. Note: Proposals must acknowledge and mitigate potential limitations or inconsistencies inherent in datasets.
Proposals should focus on interventions that are already widely used or are positioned for widespread adoption, in line with the HTA Programme remit. This is to ensure the results directly address urgent uncertainties in clinical practice or social care.
Examples of topics of interest include, but are NOT limited to:
- evaluations where a lack of equipoise in clinical or social care practice makes randomisation unfeasible (e.g., entrenched practices in care settings or community support)
- interventions involving fast-moving technologies where data are needed rapidly to inform stakeholder decisions, or where RCTs are practically unfeasible
- complex health and social care questions in populations often excluded from RCTs (e.g., those with multi-morbidity, rare diseases, paediatrics, children in need)
- existing RCT evidence is insufficient to inform NHS/social care practice
Study design
For this funding opportunity, a TTE is defined as applying RCT design principles to the analysis of pre-existing observational data. Unlike RCTs, which involve prospective recruitment and randomisation, TTE requires the explicit specification of a hypothetical “target trial” protocol and its subsequent emulation and analysis of routinely collected data to enable robust causal inference.
Applicants must clearly explain why they are choosing to use this specific research method. This should include a detailed explanation of why an RCT, in which participants or service users are randomly allocated to groups, is not the best approach or not possible for their question. For example, an RCT might not be feasible due to ethical constraints, lack of equipoise, or the immediate need for evidence to support decision-making. The plain English summary must explicitly explain the difference between TTE and RCT for a lay audience.
The proposal must show how the researchers will emulate the structure of an RCT using existing data records. They need to describe 7 specific areas:
- who can be in the study
- what the interventions are
- How the interventions will be assigned. In an RCT, this is random; in emulation, participants are assigned based on observed data (e.g. this requires adjustment for baseline confounders to ensure groups are comparable)
- exactly when the study starts for each person (Time Zero), ensuring eligibility and treatment/intervention assignment are synchronised
- how they define the results, including primary and other outcomes (health or social care) and economic outcomes (e.g., resource use, quality of life, cost-consequences)
- what specific effect they are measuring (e.g., treatment or intervention or policy estimand or principal stratum)
- how they will analyse the numbers
Data feasibility: an important requirement is demonstrating that sufficient data are available. Applicants must submit a Data Feasibility Statement (e.g., using the NICE DataSAT tool) that includes preliminary participant counts and an evaluation of data granularity and completeness for both health/care variables and resource-use/costing data. We recognise that data may require curation and processing to be rendered ‘research-ready’. Proposals must explicitly budget for the data engineering and curation work required to transform raw administrative records into analysable datasets. Applicants need to explain the risks to delivering the study (e.g., timeliness of data access) and how these will be mitigated. Proposals must detail how they will work with regulators and legislative frameworks, such as GDPR.
Current practice and proposed intervention: Applicants must clearly describe the intervention strategies to be compared, in line with the TrAnsparent ReportinG of studies Emulating a Target trial (TARGET) reporting guidelines. This requires a detailed specification of both the proposed intervention and the comparator (e.g., current practice, usual care, or non-initiation) that is sufficient to enable their theoretical implementation. Descriptions must address intervention details, including the specific uncertainty the emulation intends to resolve, the intervention’s intensity, method of delivery or administration, frequency, and duration. Descriptions must also address decision rules, including initiation and discontinuation rules; any grace periods after baseline during which interventions must be started; allowable reasons for discontinuation; and allowed concomitant support or care. Furthermore, if the comparator is “usual care” or “non-initiation,” applicants must clearly describe what these terms mean in practice. Proposed interventions must be mature enough to be tested at a national scale and show clear promise of changing practice or policy in health or social care settings.
Methodological learning: To maximise the impact and credibility of the findings, applicants are encouraged to include a methodological sub-study (e.g., SWAT/SWAR). Given that expert opinions often differ on the optimal analysis of observational data, sub-studies should focus on resolving these uncertainties, for instance, by evaluating bias-mitigation strategies and/or alternative analytical approaches, and by demonstrating that findings are consistent across these approaches. This robustness is important to ensure that the evidence can influence practice and support future HTA decision-making.
Expertise required: This funding opportunity is open to coordinated multidisciplinary teams spanning both health, social care and non-health specialities. Teams must include practitioners, health economists, and patient/public representatives. Importantly, the team must include demonstrated methodological expertise in TTE or advanced causal inference.
Background
The HTA Programme is dedicated to generating high-quality evidence regarding the clinical and cost-effectiveness of health technologies for the NHS and social care. While RCTs are the definitive method for establishing causality, they may not always be feasible due to ethical constraints, small patient or service user populations, or the need for immediate data to inform fast-moving technologies.
We have access to a wealth of routine data, but research using this information is often met with caution. This is usually due to confounding variables and errors in how the data are processed and/or analysed. For example, some studies do not align the study period with the start date of treatment or intervention. This results in an inaccurate picture of how well an intervention or treatment actually works.
TTE addresses these issues by applying key aspects of RCTs to existing health, social care, or administrative data. It requires researchers to develop a plan for a hypothetical RCT before analysing the data. Investigators must be very clear about who is in the study, exactly when the intervention begins, clearly define comparators, and how they will measure the results. By following the same structure as an RCT, there is potential to produce results that are reliable enough to inform national health policy.
This funding opportunity serves as a pilot to explore how study designs utilising routine data can support major decision-making across the health and social care landscape. A key objective is to determine whether the resulting evidence is robust enough to be used by bodies such as NICE, SIGN, and social care policymakers when establishing guidelines for NHS and social care provision.
Funding opportunity scope
This funding opportunity seeks proposals that demonstrate responsiveness in generating evidence for urgent health and social care questions. Applicants must demonstrate value for money by maximising the utility of existing data to deliver robust clinical, practice and cost-effectiveness evaluations. The opportunity excludes proposals involving prospective data collection or new participant recruitment. Proposals must remain within the HTA remit; studies focused primarily on service delivery or organisational mechanisms are outside the scope of this funding opportunity. This is a funding opportunity of broader scope from which our programme is interested in potentially funding more than one proposal.
Outputs
Pathways to impact – we are focused on the impact of the research we fund. Applicants are asked to consider the timing and nature of deliverables in your proposals; and encouraged to maximise the impact of your research by explaining how you will mobilise knowledge and ensure that it is useful and relevant to stakeholders such as:
- policy makers
- public health officers
- special interest groups
- charities
- community audiences
- other stakeholders
Duration and costs
We are seeking efficient studies that demonstrate agility in delivering timely answers to support decision-making. Applicants must provide a robust justification for value for money, particularly regarding the efficient use of existing data resources to answer the research question.
You are advised that we are custodians of public funds and value for money is a key criteria that peer reviewers and funding committee members will assess applications against.
Eligibility
Please refer to the overview tab for the funding opportunity specific eligibility.
Inclusive research
You must detail how you have considered inclusive research design and sex and gender throughout the whole research lifecycle and provide information on any associated costs. fully consider inclusion throughout the whole research lifecycle and provide information on any associated costs. For full details see: Inclusive research funding application guidance
This includes (but is not limited to):
- your research design
- research methods
- data and statistical analysis
- knowledge mobilisation and dissemination of findings
Supporting information
The following projects, previously funded by the NIHR HTA programme, demonstrate relevant study design principles. While the examples below are health-focused in adult populations, we also encourage proposals covering Children’s Social Care, Adult Social Care and other populations, such as Paediatrics or rare disease, provided they meet the data feasibility requirements.
- NIHR135559 Community deployment of monoclonal antibody treatment for treatment of COVID: Completed. Used the OpenSAFELY platform to emulate a target trial during a national rollout, explicitly adjusting for complex confounders and mediators in the treatment-outcome relationship.
- NIHR150376 The FOLLOW UP study – a natural experiment estimating the clinical and cost effectiveness of follow up strategies after curative treatment for prostate cancer. Active. A pragmatic, prospective propensity-matched cohort study that mimics a randomised trial to infer causal effectiveness from routine NHS.
Visit funding web page
(https://www.nihr.ac.uk/funding/target-trial-emulation-utilising-routine-data-answer-key-health-and-care-questions/2026384)
