Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study.

INTRODUCTION: Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics. METHODS AND ANALYSIS: This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results; use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes; survey a stratified random sample of each group about activities and quality of life at 12 months; use routine and newly collected blood data to assess immunity; interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences; collect healthcare resource use data to calculate implementation costs and cost-consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study. ETHICS AND DISSEMINATION: The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks.

Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study

Introduction Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics. Methods and analysis This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results;use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes;survey a stratified random sample of each group about activities and quality of life at 12 months;use routine and newly collected blood data to assess immunity;interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences;collect healthcare resource use data to calculate implementation costs and cost–consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study. Ethics and dissemination The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks.

Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial.

BACKGROUND: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine. METHODS: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248. FINDINGS: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos -1·29%, 95% CI -14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, -6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (-12·9%, -34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, -13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, -5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, -11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. INTERPRETATION: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need. FUNDING: National Institute for Health Research Policy Research Programme.

A systems analysis of the COVID-19 pandemic response in the United Kingdom - Part 1 - The overall context.

The most common reaction to suggesting that we could learn valuable lessons from the way the current pandemic has been/ is being handled, is to discourage the attempt; as it is suggested that it can all be done more accurately and authoritatively after the inevitable Public Inquiry (Slater, 2019). On the other hand, a more constructive approach, is to capture and understand the work that was actually done.This would include normal activities, as well as positive adaptations to challenges and failures that may have occurred. Such an approach aimed at improving what worked, rather than blaming people for what went wrong, has the potential to contribute more successfully to controlling the consequences of the current crisis. Such an approach should thus be aimed at detecting and feeding back lessons from emerging and probably unexpected behaviours and helping to design the system to adapt better to counter the effects. The science and discipline of Human Factors (HF) promotes system resilience. This can be defined as an organisation's ability to adjust its functioning before, during or after significant disturbances (such as a pandemic), enabling adaptation and operation under both anticipated and unanticipated circumstances. A "functional" approach methodology enables the identification of where the system and its various interdependent functions (an activity or set of activities that are required to give a certain output), could be improved and strengthened; if not immediately, at least for the future. Along these lines, suggestions for adding key resilience functions are additionally identified and outlined. The application and insights gained from this functional approach to the 2015 MERS-Cov pandemic in South Korea has been seen as contributing substantially to the effective response to the current crisis in that country (Min, submitted for publication). In this paper, we present an overarching framework for a series of projects that are planned to carry out focussed systems-based analysis to generate learning from key aspects of the COVID-19 pandemic response in the United Kingdom.

Patient-safety incidents during COVID-19 health crisis in France: An exploratory sequential multi-method study in primary care.

BACKGROUND: The COVID-19 pandemic has resulted in the rapid reorganisation of health and social care services. Patients are already at significant risk of healthcare-associated harm and the wholesale disruption to service delivery during the pandemic stood to heighten those risks. OBJECTIVES: We explored the type and nature of patient safety incidents in French primary care settings during the COVID-19 first wave to make tentative recommendations for improvement. METHODS: A national patient safety incident reporting survey was distributed to General Practitioners (GPs) in France on 28 April 2020. Reports were coded using a classification system aligned to the WHO International Classification for Patient Safety (incident types, contributing factors, incident outcomes and severity of harm). Analysis involved data coding, processing, iterative generation of data summaries using descriptive statistical analysis. Clinicaltrials.gov: NCT04346121. RESULTS: Of 132 incidents, 58 (44%) related to delayed diagnosis, assessments and referrals. Cancellations of appointments, hospitalisations or procedures was reported in 22 (17%) of these incidents. Home confinement-related incidents accounted for 13 (10%) reports and inappropriate medication stopping for five (4%). Patients delayed attending or did not consult their general practitioner or other healthcare providers due to their fear of contracting COVID-19 infection at an in-person visit in 26 (10%) incidents or fear of burdening their GPs in eight (3%) incidents. CONCLUSION: Constraints from the first wave of the COVID-19 pandemic have contributed to patient safety incidents during non-COVID-19 care. Lessons from these incidents pinpoint where primary care services in France can focus resources to design safer systems for patients.

Protocol for a feasibility study incorporating a randomised pilot trial with an embedded process evaluation and feasibility economic analysis of ThinkCancer!: a primary care intervention to expedite cancer diagnosis in Wales.

BACKGROUND: Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. METHODS: The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. DISCUSSION: This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04823559 .