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Restart Framework

 

Contents

A framework for restarting NIHR research activities which have been paused due to COVID-19

 

Purpose of this paper

The purpose of this paper is to set out a framework to guide the restarting of NIHR research activities which have been paused due to COVID-19. 

The term ‘NIHR research’ refers to research either funded or supported by NIHR in healthcare, social care and public health settings. 

The key aims of the framework are to guide:

  1. the restart of paused NIHR research that was underway in the health and care system prior to the COVID-19 ‘surge’,
  2. the commencement of ‘new’ NIHR research, and 
  3. the prioritisation of resources in the NIHR Clinical Research Network (CRN) and NIHR infrastructure more broadly. 

The framework sets out guiding principles, preconditions, study prioritisation, and local and national roles in implementing this ‘Restart Framework’.

Background

The emergence of the COVID-19 pandemic in early 2020 led the NHS to suspend many routine clinical services and the NIHR to prepare to support the Government’s research response. Subsequently, the decisions taken in March 2020 by research sponsors, funders, investigators and study sites to pause some non-COVID-19 research, and by the NIHR Clinical Research Network to pause set up of new sites or studies, other than for nationally prioritised COVID-19 studies, led to a rapid and significant reduction in NIHR research activity. 

Towards the end of April 2020, there were indications that the pressures on the UK health system were easing in respect of COVID-19, and therefore that paused and new NIHR research might gradually resume. These indications included a steadily falling hospital admission rate for COVID-19, the suspension of some ‘surge’ capacity in the NHS, and the 29 April 2020 letter from the CEO of NHS England and NHS Improvement (“Second phase of response to COVID-19”) asking for a restart of non-COVID-19 urgent services and potentially some routine elective care.  Data from NIHR Local Clinical Research Networks (LCRNs) and NIHR Clinical Research Facilities (CRFs) further indicated that NIHR-funded staff that had been deployed to the clinical ‘front line’ were beginning to return to research roles. 

Consequently, a group representing NIHR Coordinating Centres initiated the development, involving multiple stakeholders, of a framework for restarting paused NIHR research studies and restarting the NIHR Clinical Research Network support to set up new sites and studies.

This framework has been developed with specific reference to the position in England, in cooperation with Devolved Administrations who may produce aligned, but Devolved Administration specific, guidance.

Strategic objectives of ‘Restart’

  1. Restore a fully active portfolio of NIHR research to improve the health and wealth of the nation.

  2. Continue to support COVID-19 NIHR research as part of the Government response to tackle the pandemic.

  3. Provide a structure to guide the restarting of a full range of NIHR research, across all sectors of health, social care and public health, while maintaining local decision-making and flexibility.

  4. Work in close collaboration with key stakeholders, regulators, HRAMHRA, patients and the public, and health and care research organisations to support the pace and coordination of this Restart and to ensure coordinated UK-wide working.

Guiding principles

These principles have guided the content of the Restart Framework:

  1. The framework is intended to support the NIHR in recommencing research activities. It is recognised that guidance will need to be reviewed and refreshed, for example, in the context of learnt experience of restart progress and changes in COVID-19 activity.

  2. The framework is also intended to enable strong local leadership and decision-making in pursuance of proportionate and pragmatic arrangements.

  3. The priority is to restore an open and flourishing clinical research system whilst recognising that the impact of COVID-19, complexity of restart and many other factors will affect the future shape of the portfolio.

  4. In the initial period of Restart, achieving an optimal and national restart/start of research is a higher priority than attaining all the traditional metrics of research performance. 

  5. Patients and the public can play vital roles at both local and national level in supporting restart activities.

  6. COVID-19 related research will form a significant and high-profile component of the NIHR portfolio for the foreseeable future and COVID-19 Urgent Public Health Research studies will continue to be prioritised. Any further surges in COVID-19 could affect the research system again and the potential for a 're-pause' must be considered by sponsors, funders, Chief Investigators and local sites in the plans to restart individual studies.  

  7. The decision on whether to restart a paused study, or commence a new study, rests with the study sponsor, funder, Chief Investigator and the study site(s) legal entity.

  8. The pace of the restart will be influenced by preconditions that must be met prior to restarting research (see 'Preconditions for restarting/starting research') and because prioritisation may be necessary (see 'Prioritisation').

  9. There is likely to be variable and rapidly-changing levels of research capacity in differing geographical regions, sites and departments.

  10. The framework also recognises variability in the capacity in universities to support clinical research processes (e.g. sponsor roles, laboratory facilities), emphasising the importance of close working with partner NHS trusts.

  11. Some sites may wish to restart/start a small number of studies in a pilot to quickly gain experience and learning which will help optimise further restart/start processes. 

  12. The NIHR is well-placed to provide guidance, support, communication, liaison with taskforces (e.g. vaccines, therapeutics) and collaboration at local and national levels.

Preconditions for restarting/starting research

The restart of a currently paused study and the start-up of new studies will be dependent on a number of preconditions being met. It is the responsibility of the sponsor, funder, Chief Investigator, the study site(s) legal entity, and, where applicable, the Principal Investigator at each site to assess that these are met before restarting/starting.

There are therefore important roles at local sites and at national level (see sections 'Local level roles' and 'National level roles'). At local sites, the framework suggests an Assessment and Prioritisation panel is established, ideally led by the R&D Director, supported by clinical investigators, R&D team and able to work with sponsors. Sites hosting non-CRN NIHR infrastructure will likely wish to integrate them into their local governance and accountability structures. The NIHR CRN, through the Local Clinical Research Networks, may be able to offer some support alongside the local R&D team, especially to trusts in which there is not an identified R&D Director. Similarly, Local Clinical Research Networks may be well placed to support primary care sites in their region.

Study viability 

Principle: Only research that is still viable should restart/start.

Some studies that have been paused or have not yet started may no longer be viable, for scientific, clinical, financial or practical reasons. It would be unethical and a waste of money to restart/start studies that are no longer viable.

Therefore, at the earliest opportunity, every paused study should undergo a check of its viability before restarting. This reassessment is a responsibility of the sponsor, working with the Chief Investigator, and funder (see sections 'Local level roles' and 'National level roles'). Sponsors and sites will be expected to work together to conduct a preliminary assessment of all paused studies ideally within one month of this framework being issued. At site level, the Assessment and Prioritisation panel would undertake this task. Where this assessment identifies viability issues that require resolution (e.g. funding, changes in resourcing requirements), it is not expected that these issues would necessarily be resolved within the one month period.

For some studies, viability will depend on redesign / protocol amendment. The sponsor / Chief Investigator should confirm that regulatory checks (if needed) and discussions with the funder to accommodate any such amendment have been agreed as part of viability checks. Independent Data and Safety Monitoring Committees, Trial Steering Committees and Clinical Trials Units (where applicable) should advise as appropriate.

Discussion of the optimisation of research processes, though extremely important, is out-of-scope of this framework but it is recommended that in assessing the study viability, the sponsor/Chief Investigator and funder take the opportunity to consider any potential key improvements that might assist restart and completion of the study.

The HRA and MHRA have developed (and frequently update) advice on measures to optimise regulatory processes in anticipation of and in response to COVID-19 and its effects on research. These regulators can advise on flexibilities that may be available.

This framework recognises studies as valid for restart if their funders support any study extensions and/or amendments necessary, and have confirmed a commitment to fund accordingly. This will allow those studies to begin preparations for restart, whilst giving research funders time to allocate the funds necessary to finance the study’s extension/amendment.

Any required changes to Excess Treatment Costs, where they are relevant, must also be identified and documented before restart.

Viability of NIHR CRN Portfolio studies: NIHR will, on request, offer the input and assistance of NIHR CRN National Specialty Leads and NIHR Programme Directors, and their group / committee members to assist in the assessment of study viability.

Viability of NIHR-funded studies: NIHR Programme Directors will review studies where amendments are proposed in each programme portfolio in line with established processes.

Viability of NIHR Infrastructure supported studies: NIHR Infrastructure Directors, in line with their local governance and accountability arrangements, will review studies where amendments are proposed in each programme portfolio in line with established processes.

Safety

Principle: Research should only restart/start when safe to do so.

Safety of research participants and personnel is of paramount importance.

Safety considerations in restarting research include:

  • Risk of exposure to COVID-19 (and measures to mitigate this).

  • Government guidance on social distancing, restart of work, and travel. 

  • Local site policies in respect of COVID-19.

  • People considered ‘clinically extremely vulnerable’ who are ‘shielded’ and who have participated in a paused study or are considered for a new study require special considerations. Their GP and/or specialist should be consulted to ensure they continue to receive the appropriate care with only essential visits to the research site.

  • An assessment of the need for patient testing for COVID-19 and requirements for personal protective equipment (PPE); these requirements may be specified in research protocol/procedures, otherwise local site policies should be used. 

  • Site compliance with protocol and regulatory requirements (e.g. compliance with clinical trials regulations and other relevant legislation and guidance).

  • Protocol amendments to reduce risk (generally not formal substantial amendments).

  • Participants’ concerns about COVID-19; participants need to feel safe and reassured about the research process.

  • Provision of clear guidance on safety issues and measures for participants and staff.

  • Assessment of requirement, processes and safety for study monitors/visits/meetings, and consideration of remote working where possible.

  • That any mitigations or flexibilities put in place to restart a study do not have an adverse impact on participant safety (e.g. reducing clinic visits).

Capacity and site readiness

Principle: The pace of restart and the commencement of new studies should be commensurate with capacity and readiness in local health and care services and the NIHR.

Delivery of research will be dependent on relevant health and care services being ‘open for business’. Capacity is likely to be variably reduced by several factors - type of facility (e.g. acute trusts and care homes often severely impacted by COVID-19), additional ongoing commitment to COVID-19 studies, additional measures required to ensure staff/patient safety, variation in restoration of NHS services and region – and all of which will vary geographically across England and change over time.

Preconditions include:

  • Availability / capacity of health and care study leadership and research / delivery / support staff.

  • Capacity of the health and care site / service to undertake research.

  • Capacity of the necessary research management infrastructure (e.g. R&D offices in health and care organisations, Clinical Trials Units, NIHR Coordinating Centres, LCRNs, Clinical Research Facilities). 
  • Supporting departments, e.g. pharmacy, pathology, radiology have resource and capacity to resume.

  • Physical access arrangements for participants, in light of social distancing, reduced public transport, and reduction in support from third sector organisations or third parties.

  • Clear and explicit confirmation to restart research from the sponsor, and funder where relevant, and reconfirmation of capacity and capability by the site legal entity.

Prioritisation  

If the preconditions for restarting a paused study, or starting a new study, have been met and there is no requirement for NIHR-funded support, the study may be ready to proceed. However, resource, capacity or other constraints may necessitate prioritisation of NIHR-funded support, including the workforce in NIHR CRN and NIHR CRFs.

Where prioritisation is necessary, this should be on the basis of ‘study urgency’, that is, how urgent the study is in the context of the health/care of the participant and the national priorities for health and care research. The framework indicates that prioritisation is irrespective of the type of funder or sponsor; all research funders and sponsors are essential to the improvement of health and care. Prioritisation does not imply that one study is ‘better’ or ‘more important’ than another but does reflect the urgency with which it should be supported. Discussions on prioritisation should be handled carefully, with consideration of any adverse perceptions, especially for study participants.

Three levels for prioritisation of NIHR CRN support should be applied according to study urgency (Level 1 is highest priority/urgency).

Level 1: Essential studies providing evidence for pandemic management, i.e. nationally prioritised COVID-19 Urgent Public Health (UPH) Research studies.

Level 2: Studies where the research protocol includes an urgent treatment or intervention without which patients could come to harm. These might be studies that provide access to potentially life preserving or life-extending treatment not otherwise available to the patient.

Level 3: All other studies (including new COVID-19 studies not in Level 1). 

We expect that directors of other NIHR infrastructure undertaking research not on the NIHR CRN portfolio will work their local Assessment and Prioritisation panel and that the principle of prioritisation in this framework will apply, in alignment with their host organisation's processes.

Notes on Study Urgency:

  1. It should be noted that in its first statement on the impact of COVID-19 on research (issued 16 March 2020), NIHR stated explicitly that “clinical trials or other research studies which are funded or supported by NIHR should continue if discontinuing them will have significant detrimental effects on the ongoing care of individual participants involved in those studies”. 

  2. Where guidance on prioritisation is provided it will be in the context of supporting studies when resource/capacity is constrained. 

  3. Even when prioritisation is required, sites may still have capacity for some studies that do not compete for resources or support. In these situations, proportionate and pragmatic, local decision-making, led by local Assessment and Prioritisation panels, can enable such research to restart/start (assuming the preconditions listed earlier in this framework have been met).

  4. COVID-19 studies that are not nationally prioritised (i.e. are not in the COVID-19 UPH Research group - Level 1) will be eligible to join the CRN portfolio (if they meet the normal CRN portfolio criteria) and will have equal priority with other ‘Level 3’ non-COVID-19 studies.

  5. It is likely that, over time, changes in COVID-19 activity, new research priorities and other factors may require revision to the prioritisation of studies. Any changes to the prioritisation schema will be managed through the Restart Implementation Group (see section 'National level roles'), in close consultation with the Restart Advisory Group (see section 'National level roles'), before being published and made clear to all stakeholders in an updated version of this Framework. 

  6. This prioritisation guidance is provided to cover the majority of scenarios but, by exception, other factors may need to be taken into account. The NIHR Restart Implementation group may be able to advise in such cases.

  7. The framework does not specify the balance between non-commercial and commercial studies or the complexity or phase of studies that restart/start. Where prioritisation is necessary (see 'Prioritisation'), it should be based on the urgency of the study to the welfare of the patient in the context of national priorities (e.g. Urgent Public Health). The NIHR Restart Implementation group will monitor this balance and offer guidance or direction as necessary.

Local level roles

Sites and local assessment and prioritisation panels will have key roles in restarting research activities as indicated in the table below.

What

 

Who

Study decision

Decision making as to which studies open, when and where (based on Restart Assessment and site intelligence)

Site Assessment and Prioritisation panel


Sponsor


Site legal entity / R&D


Site principal investigator


Local NIHR infrastructure directors and teams

Assessment

Assessment of whether a study should open / re-open at a specific site. The NIHR has developed a template to assist local assessment (example in Annex A).

Site Assessment and Prioritisation panel


Site legal entity / R&D


Lead LCRN


Site principal investigator


Local NIHR infrastructure directors and teams

Confirmation

Reconfirmation of capacity and capability for a specific study to restart / open at a specific site

Site legal entity / R&D

Prioritisation

Where prioritisation is necessary because there are limitations in availability of resource, capacity or other constraints affecting NIHR-funded support, this should be on the basis of ‘study urgency’ (see 'Prioritisation')

Site Assessment and Prioritisation panel


LCRN

 

National level roles

NIHR will provide national leadership to coordinate and ensure best progress of Restart:

What

 

Who

Restart Oversight

NIHR Restart Implementation Group

Convene an NIHR Restart Implementation Group, reporting to DHSC with roles that include:

  • operational coordination of the NIHR activities in this table
  • monitor progress of Restart
  • provide reports to DHSC and NIHR Centres Executive Board
  • manage or escalate factors impeding national restart/start programme
  • provide specific further guidance or direction if required (e.g. during second surge of COVID-19)
  • refresh and renew the framework as necessary
  • support NIHR communications

Restart Advisory Group

Recognising the importance of collaboration, convene a Restart Advisory Group to offer guidance on implementation, show transparency and share expectations. The Advisory Group will have a membership comprising representatives of stakeholders, and patients and the public.

NIHR



















DHSC

Prioritisation

Provide guidance on prioritisation and propose to DHSC any changes if required

NIHR Restart Implementation Group

Communication

Support NIHR Director of Communications:

Clear coordinated messaging to all stakeholders

Joint communications with key stakeholders where appropriate

Patient-facing communications (with PPI input)

Align NIHR policy documents with agreed study prioritisation (e.g. DHSC Eligibility Criteria for CRN Support)

DHSC


NIHR Communications


NIHR CRN Coordinating Centre


NIHR Centre for Engagement and Dissemination

Pre-conditions

Collect intelligence and support ‘local’ parties in their Restart activities, e.g. 

  • exemplar standard Restart Assessment Checklist
  • guidance
  • case examples (e.g. trial restructuring, solutions to common problems)
  • funding issues to be identified to DHSC

NIHR Coordinating Centres

R&D management in health and care organisations

Work with UKRD, NHS R&D Forum and UHA to ensure consistency of approach and messaging, and in ‘unblocking’ ‘blocks’

NIHR CRN Coordinating Centre

Sponsors

Support sponsor activities.

CRN National Specialty Leads / Groups, NIHR Translational Research Collaborations, NIHR Statistics Group and NIHR Programme Directors can provide ‘big picture’ in each specialty, advising on priorities and regional situations

NIHR Coordinating Centres

Clinical Trials Units

Support study assessments, viability checks, advise regarding protocol amendments

UKCRC Registered Clinical Trials Unit Network

Charities

Support AMRC and specific charities as appropriate, e.g. to support discussions on study viability and progress in Restart

NIHR Coordinating Centres

Industry

Support life sciences industry Trade Associations and individual companies, e.g. support discussions on study viability and progress in Restart.

Coordinate messaging through international networks with OLS, BEIS, DIT, Healthcare UK, etc

NIHR CRN Coordinating Centre

NOCRI

Monitoring and Reporting

Monitor Restart progress and report to DHSC regularly.

NIHR Programme and Infrastructure teams will continue to monitor projects including managing variations to contract, milestones and, where appropriate, closing project support.

NIHR Restart Implementation Group


NIHR Coordinating Centres

Patient and Public Involvement and Engagement

PPIE can assist at both national and local levels to add value to Restart


 


 

NIHR Centre for Engagement and Dissemination


Other NIHR Coordinating Centres


NIHR Communications


AMRC


HRA

Organisational learning

Contribute to a review of what has been learned in the research response to the COVID-19 to inform any further optimisation of the health research ecosystem.

NIHR Restart Advisory Group - feeding into the ABPI Clinical Research Working Group

COVID-19 

Manage or collaborate with new programmes of COVID-19 research (e.g. mental health, vaccines, long-term effects, applied research) and consider potential impacts of subsequent COVID-19 waves on NIHR research

NIHR Restart Implementation Group

 

Phasing and timescales

The NIHR wishes to restart paused and new research as soon as possible, and to support the energetic restoration of a fully active portfolio of NIHR research. The NIHR Restart Implementation Group will monitor the progress and pace of Restart.

In light of the fluidity of the COVID-19 situation and the variable levels of capacity and readiness for non-COVID research across health and care services we do not, beyond setting a one month period for sites to complete preliminary restart assessments, propose a ‘timetable’ or any fixed phasing for the completion of Restart. The pace of restart of paused studies and commencement of new studies will be dependent on the preconditions set out in section 5 of this paper being met on a case-by-case basis.

 

Annex A - Study Local Restart Assessment Checklist (example)

This checklist could be provided to assist local Assessment and Prioritisation panels as part of comprehensive local site governance procedures.

#

Factor

Requirement

1

Study viability

  • Sponsor and funder have assessed and agreed to restart
  • Regulatory approvals in place
  • No impact on support for UPH COVID-19 studies
  • All necessary research funding is confirmed
  • Funding to meet any Excess Treatment Costs has been confirmed
  • Sponsor and funder are satisfied with the arrangements for patient and public involvement in the study

2

Safety

  • Risk of exposure to COVID-19 for patients and staff has been mitigated
  • Physical access complies with government restrictions on social distancing
  • Assessment of COVID-19 testing and PPE requirements completed
  • Study arrangements comply with local organisation / site policies in respect of COVID-19
  • Site compliance with regulatory requirements has been confirmed by the organisation’s R&D Director or equivalent
  • Clear guidance on safety issues and precautions has been provided to participants and staff
  • Participants are asked and reassured about any concerns regarding COVID-19 - participants need to feel safe and confident

3

Capacity and site readiness

  • Local clinical lead (Principal Investigator) confirmed and in place
  • Research staff in place
  • Health and care site / service ‘open for business’ to the full extent required for the study
  • Research management and support in place (site R&D office, CTU, LCRN)
  • All necessary supporting departments (e.g. pharmacy, pathology, radiology) have resource and capacity. Assess study dependencies. 
  • All necessary supplies have been procured and are in place (including IMPs and PPE)
  • For paused studies, study data have been checked for data integrity to ensure that data remain robust and/or fit for purpose
  • Physical access arrangements for participants have been assessed and are satisfactory
  • Permission to restart from site legal entity 

4

Prioritisation

  • Not required if the study does not require NIHR-funded support
  • Where prioritisation is necessary, this should be on the basis of ‘study urgency’ (section 6)