This site is optimised for modern browsers. For the best experience, please use Google Chrome, Mozilla Firefox, or Microsoft Edge.

Call for research proposals for a randomised trial to evaluate vaccine clinical effectiveness for the UK COVID-19 immunisation programme

 

Contents

[Revised 17/02/2021]

Introduction 

The Department of Health and Social Care, through the National Institute for Health Research (NIHR), invites proposals for a rapidly implementable randomised clinical trial to develop greater understanding of the UK’s COVID-19 vaccination programme which is currently deploying Pfizer/BioNTech and Oxford University/AstraZeneca vaccines and is likely to deploy other vaccines in the future. Given these complexities, applicants must demonstrate an adaptive approach.

The successful applicant will need to work closely with, and be highly responsive to the needs of, the Department of Health and Social Care and its system partners. One study only will be funded.

Applicants should demonstrate convincingly the ability to commence the study by 1 April 2021. Further details are specified in the Scope and Funding approach sections below.

Background

The United Kingdom has authorised for use several COVID-19 vaccines and initiated an ongoing population immunisation roll out currently using Pfizer/BioNTech (BNT162b2) and Oxford University/AstraZeneca (AZD1222) vaccines. The UK programme is likely to deploy other vaccines in the future as supplies become available and dependent on regulatory approval.

Vaccination policy in the UK is recommended by the Joint Committee on Vaccination and Immunisation (JCVI) and decided upon by Ministers. For Covid-19 vaccines, government is committed to a Phase 1 programme in the following priority order:

  • residents in a care home for older adults and their carers
  • all those 80 years of age and over and frontline health and social care workers
  • all those 75 years of age and over
  • all those 70 years of age and over and clinically extremely vulnerable individuals
  • all those 65 years of age and over
  • all individuals aged 16 years to 64 years with underlying health conditions which put them at higher risk of serious disease and mortality
  • all those 60 years of age and over
  • all those 55 years of age and over
  • all those 50 years of age and over

To extend access to vaccines to priority groups in the shortest time frame, the JCVI has recommended that priority is given to achieving a first dose of vaccine to those listed in its priority groups 1-9 with a permissible interval between prime and booster doses of either BNT162b2 or AZD1222 of up to 12 weeks. This recommendation is supported by extant data suggesting most of the available short-term protection is achieved after the first dose, and evidence that a longer interval between the first and second doses promotes a stronger immune response with the AstraZeneca vaccine. The rationale for JCVI’s advice has been laid out at:

https://www.gov.uk/government/publications/prioritising-the-first-covid-19-vaccine-dose-jcvi-statement.

This policy of priority first dose extended interval (PFDEI) is supported by the UK Chief Medical Officers and a number of expert independent organisations including the Royal College of General Practitioners and the Royal Pharmaceutical Society.

In due course it is expected that a Phase 2 vaccination will be announced aimed broadly at adults age 18-49 not in risk groups.

Evaluation of vaccine effectiveness and programme effectiveness is ongoing via rapidly implemented observational studies. However, there is an opportunity to consider a randomised study to support a more robust scientific evaluation less prone to data biases, and which may inform future international policy development.

Scope

The intention is to fund one single prospective study in the UK setting focused on clinical outcomes, following a light-touch approach using electronic datasets to achieve this wherever possible. The NIHR seeks a rapidly implementable, streamlined, minimalist, adaptive design that will not interfere with smooth execution of the UK vaccine programme. Any clinical trial proposed must dovetail with the UK’s ongoing vaccination programme or will not be eligible. Any study must take into account all of the below:

  1. The proposed trial should not involve patients in groups 1-4 of the priority cohorts; as they are an absolute operational priority.

  2. The proposed trial could involve priority groups 6-9 and/or be undertaken in the Phase 2 programme. If the trial involves groups 6-9 it should not delay the speed of delivery of the first dose of the vaccine (it should not divert limited vaccine to the trial and delay non-trial participants in receiving their first doses) or disrupt NHS operational delivery. Applicants are expected to demonstrate that they have discussed their trial design and vaccine supply with NHS England and NHS Improvement (NHSE/I) and demonstrate that the design will align with NHS operational logistics. Reviewers will seek independent verification that this has occurred.

  3. The trial should evaluate clinical not serological or immunological endpoints, this could include asymptomatic infections but the most important endpoints are serious infections and hospitalisations due to Covid-19.

  4. The trial should evaluate first-to-second dose intervals of 28 and 84 days (1 and 3 months).

  5. The trial must be capable of evaluating long term effectiveness of 28 and 84 day intervals and effectiveness in the interval between first and second doses.

  6. The trial must be light-touch, using electronic datasets for outcomes wherever possible.

  7. Follow up should be for at least 12 months after second dose.

  8. The trial should be of sufficient size and power to reliably detect differences in vaccine effectiveness against infection of at least 20% absolute. (Larger studies with the ability to detect more fine grained absolute differences are not considered of policy relevance.)

Funding approach

This call is looking to fund one ambitious, comprehensive and multi/interdisciplinary proposal to deliver robust evaluations which will inform policy on existing and future vaccination roll out plans.

Small-scale standalone projects focussing on discrete areas will not be considered. Proposals focusing on immunological endpoints will not be considered.

It is recommended that proposals consider adaptive design and/or consortium development approaches, supported by provision of risk management strategies/milestones to manage research/consortium refinement along the time course.

Proposals should clearly show plans for patient and public involvement (PPI). This should include engagement of participants in the study design, its delivery and in the dissemination of findings, with consideration of representative participation including from social care and underserved and less frequently heard communities.

The study should start as soon as possible taking account of the speed of the national roll out of vaccinations.

Proposals will need to demonstrate awareness of other relevant and related initiatives that have been set up to support the UK response to the pandemic and that might inform or support the delivery of this trial. Successful applicants will be required to use existing datasets wherever possible such as the Clinical Practice Research Datalink (CPRD). The CPRD holds routinely collected electronic health records (EHR) and the data has been used for a range of COVID-19 studies investigating risk factors, health service usage and outcomes. The CPRD’s recently established data-enabled infrastructure can support a large clinical comparator trial.

Eligibility

The expectation is that the lead applicant to this award is from a UK-based Higher Education Institution (HEI), and that organisations from other sectors such as industry, not-for-profit and the NHS service or other health care service providers, and the MHRA (for CPRD access) are allowed as co-applicants/contractors/collaborators.

Specialist services or expertise may be brought into the team through consultancy or sub-contract arrangements, however, appropriate justification must be provided.

Funding available

Up to £10m will be available for this call. Applicants must provide full justification for costs claimed and demonstrate value for money in their proposal.
Requested costs for UK based researchers should be 80% of full economic costs (FEC) and, where relevant, for overseas researchers should be 100% of direct costs only. In line with NIHR funding policy this call will cover 100% direct costs for SME and NHS trusts (across the whole of the UK). There are no set rules on the split between collaborators, however, as the contracted organisation, the lead applicant will receive funding payments and would be required to distribute to co-applicants/contractors/collaborators where applicable.

Please note - SME is defined as registered in the UK, have a staff headcount no greater than 250 and annual turnover no greater than €50 million (including start-up or spin-out companies). Companies must be registered on Companies House prior to being eligible for funding.

How to apply

Applicants must submit an online application via the PMO RMS (template application form will be accessible at call launch for information only). To assist the NIHR in preparing applications for review, research teams should submit an Expression of Interest (EoI) by 17 February 2021 using the online EoI form (link here) in advance of submitting a full application (details to be specified at call launch).


A Word version of the online application form has been made available and can be used to assist research teams developing an application. Please note the Word form cannot be submitted as an application. Only applications submitted online via the PMO RMS will be accepted, however information can be copied from the Word template into the online application form.

Please note that successful applicants will be required to return their award acceptance within five working days of receipt

Evaluation process

Proposals will be reviewed firstly by the NIHR office for fit to scope and eligibility. Eligible applications within scope of the call will then be reviewed by an Expert Funding Committee who will make a funding recommendation to DHSC. Applicants will not have an opportunity to respond to Committee comments in instances where feedback is provided, except where clarifications and/or changes are required as part of the award process.
Applicants are expected to include in their application relevant information in line with the assessment criteria outlined below:

  • Impact of the proposed work. (Will the proposal have an impact within the period of the award and to provide a unique value-added research against the call scope? Are the necessary academic, clinical, and organisational links needed to support the research in place? Are dissemination and stakeholder engagement plans clearly described and credible? Are the identified audiences appropriate and their needs considered? Are the specific resources and competencies dedicated to these activities?)
  • Relevance of the proposed research to the research specification. (How relevant is the proposal in relation to the research brief? Does it address the call’s strategic endpoints/objectives? Does the application demonstrate an awareness and understanding of previous relevant research or developments in this area? To what extent does the proposed research add distinct value or advance existing knowledge?)
  • Applicant expertise and evidence of delivering similar work, and demonstrating ability to work collaboratively with a wide range of organisations and with a multidisciplinary team. (Is the Principal Investigator suitably qualified and experienced to lead the proposed work. Are the leadership and management arrangement convincing and coherent? Does the PI show awareness of policy priorities and demonstrate ability to work with policy makers. Are the roles of the team members clearly described? Does the research team provide the necessary breadth and depth of expertise to deliver the proposed work?
  • Quality of the research design and feasibility of project plan. (How appropriate is the research design in relation to the stated objectives? To what extent is the proposed design and methodology for all elements of the research well defined, appropriate, valid and feasible within the timeframe and resources requested? To what extent does the research show originality and innovation? To what extent does the proposed work add to or complement initiatives at a national/international level?)
  • Quality and appropriateness of the project management structure including Governance arrangements. (Has the Applicant demonstrated they have appropriate access and rights to the required resources? Are work packages coherent, fully justified, and aligned with the overall vision of the proposal? How appropriate are the work plan and management arrangements? Have clear milestones been proposed? How likely is it that these will be met within the specified timeframe? Have the applicants identified key risks to delivery (e.g. ethical, technical, and organisational)? Have these been adequately addressed? Are plans to secure access to relevant sources of evidence and data sets and to work with relevant data providers/custodians sufficiently described? Are governance and data management arrangements robust?)
  • Value for money. (Does the proposal sufficiently justify the resources required to deliver the proposed work? Does the proposed costs demonstrate value for money; and is the time committed by the applicants realistic to ensure delivery?)
  • Patient and Public Involvement. (Have the applicants carefully considered ways to embed input from patients and the public in the design and the delivery of the research? Have adequate, well justified training and support measures for PPI representatives been described in the proposal? Does the budget reflect the proposed research ambitions for PPI?)

The decisions of the Committee will not be open to appeal and the NIHR reserve the right to amend the application process.

Ethics and governance

The NIHR does not require ethics permissions and regulatory approvals to be in place when an application is submitted. If an application is successful, it is the responsibility of the host organisation to ensure that the appropriate ethics approval(s) has been obtained and that no research requiring such approval is initiated before it has been granted.

Key call dates

Expression of Interest (EoI) opens 8 February 2021
Call launch 12 February 2021
Expression of Interest submissions closes 17 February 2021
Online application form live from 12 February 2021
Call close 24 February 2021, 1pm
Notification of outcome Mid-March 2021
Project start 1 April 2021

 

Contact information

For general and scientific queries relating to the call, including queries relating to the administrative process of applying, please contact ccf-nCoV@nihr.ac.uk.

Other Information

The information collected throughout the application and assessment process will be used to support the assessment process and inform NIHR funding decisions, for the management and monitoring of awards, and the evaluation of the funding programme.

Proposal information is treated confidentially and in line with our privacy notice. Information relating to proposals may be shared, on a confidential basis, across DHSC/NIHR, and with other organisations to support the national and international coordination of research to combat COVID-19 and to seek funding contributions from third parties.