Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.

BACKGROUND: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. METHODS: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older-or aged 18 years or older with relevant comorbidities-and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. FINDINGS: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81-1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. INTERPRETATION: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. FUNDING: UK National Institute for Health and Care Research.

Operationalising generalism in medical education: a narrative review of international policy and mission documents.

INTRODUCTION: Despite moves across medical education to increase learning of generalist principles, a lack of clarity about what generalism means and how we should train doctors as 'generalists', has remained. This study explores how international, undergraduate and postgraduate, policy and educational mission documents characterise the practice and learning of generalism and how this can inform physician training. METHODS: A narrative literature review was conducted based on policy and mission documents identified through grey literature searches and a wider systematic review looking at empirical texts. Texts published between 1999 and present and related to 'generalism' were eligible for inclusion. Texts were coded and codes were reviewed and grouped into key themes. RESULTS: Thirty-four documents were included. Definitions vary: some described generalism as a basic skill, whilst others emphasised expertise. Factors which support learning generalism include: favourable financial outcomes; ageing populations; coordination of multidisciplinary care; demand for doctors with transferable skills; and patient expectations. Barriers to learning about generalism include: preference for specialisation; structure of undergraduate teaching and assessment; and the hidden curriculum. Solutions may include re-imagining generalists and specialists as being on a continuum as well as increasing exposure throughout medical education. DISCUSSION: Whilst generalism is consistently positioned as valuable, less clarity exists about how best to operationalise this in medical education. Fundamental ideological and structural changes within teaching curricula and assessment, are necessary to improve generalist learning and to promote sustainable practice. Medical education needs careful, considered planning to ensure workforce expertise is meeting population needs.

Do critical illness survivors with multimorbidity need a different model of care?

There is currently a lack of evidence on the optimal strategy to support patient recovery after critical illness. Previous research has largely focussed on rehabilitation interventions which aimed to address physical, psychological, and cognitive functional sequelae, the majority of which have failed to demonstrate benefit for the selected outcomes in clinical trials. It is increasingly recognised that a person's existing health status, and in particular multimorbidity (usually defined as two or more medical conditions) and frailty, are strongly associated with their long-term outcomes after critical illness. Recent evidence indicates the existence of a distinct subgroup of critical illness survivors with multimorbidity and high healthcare utilisation, whose prior health trajectory is a better predictor of long-term outcomes than the severity of their acute illness. This review examines the complex relationships between multimorbidity and patient outcomes after critical illness, which are likely mediated by a range of factors including the number, severity, and modifiability of a person's medical conditions, as well as related factors including treatment burden, functional status, healthcare delivery, and social support. We explore potential strategies to optimise patient recovery after critical illness in the presence of multimorbidity. A comprehensive and individualized approach is likely necessary including close coordination among healthcare providers, medication reconciliation and management, and addressing the physical, psychological, and social aspects of recovery. Providing patient-centred care that proactively identifies critical illness survivors with multimorbidity and accounts for their unique challenges and needs is likely crucial to facilitate recovery and improve outcomes.

A scoping review of the reasons for and approaches to non-uptake of pertussis and influenza vaccinations in pregnant women in the United Kingdom and Ireland.

BACKGROUND: Pertussis and influenza cause significant morbidity and mortality in pregnancy and the neonatal period. Maternal vaccination in pregnancy would reduce harm, but low vaccine uptake is a concern. This scoping review aimed to understand the reasons for, and approaches, to non-uptake of pertussis and influenza vaccinations in pregnant women in the UK and Ireland. METHODS: The inclusion criteria of this scoping review consist of pregnant women who avail of pertussis and influenza vaccines in the UK and Ireland. MEDLINE, EMBASE, Web of Science and CINAHL databases were searched in June 2021 and updated in October 2022. Searches were limited to English language reports published after 2011. We followed the Joanna Briggs Institute guidance on scoping reviews. Data were extracted and charted. RESULTS: Five themes emerged from the literature. Acceptability, as well as organisational and awareness issues, were overarching themes regarding reasons for and approaches to non-uptake of the vaccines respectively. Other themes included healthcare professional factors, information interpretation and pregnancy-related factors. CONCLUSIONS: Women need clear, comprehensible information, ideally provided by their healthcare professionals, in a way that is meaningful and addresses their circumstances and risk perceptions. This research will serve as a base for future work that aims behaviour science interventions at the wider pregnant population as well as the target groups that have been identified in this review.

Towards accountability-centred practices: governance in OSCEs subordinating patient and practitioner clinical experience.

New public management ideals and standards have become increasingly adhered to in health professions education; this is particularly apparent in high-stakes assessment, as a gateway to practice. Using an Institutional Ethnographic approach, we looked at the work involved in running high-stakes Objective Structured Clinical Exams (OSCEs) throughout an academic year including use of observations, interviews and textual analysis. In our results, we describe three types of 'work'-standardising work, defensibility work and accountability work-summarising these in the discussion as an Accountability Circuit, which shows the organising role of texts on people's work processes. We show how this form of governance mandates a shift towards accountability-centred practices, away from practices which are person-centred; this lens on accountability-centring during high-stakes assessments invites critique of the often-unquestioned emphasis of new public management in health professions education.

Essential workers? An institutional ethnographic lens on pandemic GP placements.

BACKGROUND: Clinical placements for medical students in the United Kingdom (UK) came to an abrupt halt in March 2020. The rapidly evolving Covid19 pandemic created specific challenges for educators, balancing safety concerns for patients, students and healthcare staff alongside the imperative to continue to train future clinicians. Organisations such as the Medical Schools Council (MSC) published guidance to help plan return of students to clinical placements. This study aimed to examine how GP education leads made decisions around students returning to clinical placements for the 20/21 academic year. METHOD: Data collection and analysis was informed by an Institutional Ethnographic approach. Five GP education leads from medical schools throughout the UK were interviewed (over MS TEAMS™). Interviews focused on the work the participants did to plan students' return to clinical placements and how they used texts to inform this work. Analysis focused on the interplay between the interview and textual data. RESULTS AND DISCUSSION: GP education leads actively used MSC guidance which confirmed students to be 'essential workers', an unquestioned and unquestionable phrase at the time. This permitted students to return to clinical placements by affording the GP education leads authority to ask or persuade GP tutors to accept them. Furthermore, by describing teaching as 'essential work' in its own right in the guidance, this extended what the GP tutors came to expect to do as 'essential workers' themselves. CONCLUSION: GP education leads activated authoritarian phrases such as 'essential workers' and 'essential work' contained within MSC guidance to direct students' return to clinical placements in GP settings.

Access to healthcare for people experiencing homelessness in the UK and Ireland: a scoping review.

BACKGROUND: People experiencing homelessness (PEH) have poorer physical and mental health than the general population. They are also more likely to have less access to healthcare. These processes of access can be better understood using Levesque's access framework which addresses both supply (service provision) and demand (user abilities). METHODS: Following the Joanna Briggs Institute (JBI) guidelines, electronic peer-reviewed databases were searched in February 2022 for studies published since 2000 related to access to healthcare for PEH ages 16 and older in the United Kingdom (UK) and Ireland. Retrieved articles were screened and those eligible were selected for data extraction. Qualitative and quantitative studies were included. RESULTS: Fifty-six papers out of 538 identified were selected and aliased. Six main themes were identified: staff education, flexibility of systems, service coordination, patient preparedness, complex health needs and holistic care. These relate to the Levesque access framework. CONCLUSIONS: Improving access to healthcare for PEH requires changes to how services are provided and how service-user abilities are supported.

Do undergraduate general practice placements propagate the 'inverse care law'?

INTRODUCTION: Fifty years since Dr Tudor-Hart's publication of the 'Inverse Care Law', all-cause mortality rates and COVID-19 mortality rates are higher in more deprived areas. Part of the solution is to increase access and availability to healthcare in underserved and deprived areas. This paper examined how socio-economically representative the undergraduate general practice placements are in Northern Ireland (NI). METHODS: A quantitative study of general practices involved in undergraduate medical placements through Queen's University Belfast, comparing practice lists by deprivation indices, examining both blanket deprivation and deprivation quintile trends for teaching and non-teaching practices. RESULTS: Deprivation data for 135 teaching practices were compared against the 323 NI practices. Teaching practices had fewer patients living in the most deprived quintiles compared with non-teaching practices. Fewer practices with blanket deprivation were involved in undergraduate medical education, 32% compared with 42% without blanket deprivation. Practices in areas of blanket deprivation were under-represented as teaching practices, 10%, compared to 14% of NI general practices that met this criterion. CONCLUSION: Practices with blanket deprivation were under-represented as teaching practices. Exposure to general practice in deprived areas is an essential step to improving future workforce recruitment and ultimately to closing the health inequalities gap. Ensuring practices in high-need areas are proportionately represented in undergraduate placements is one way to direct action in addressing the 'Inverse Care Law'. This study is limited to NI and further work is required to compare institutions across the UK and Ireland.

Sedentary behaviour among general practitioners: a systematic review.

BACKGROUND: Sedentary behaviour is when someone is awake, in a sitting, lying or reclining posture and is an independent risk factor for multiple causes of morbidity and mortality. A dose-response relationship has been demonstrated, whereby increasing sedentary time corresponds with increasing mortality rate. This study aimed to identify current levels of sedentary behaviour among General Practitioners (GPs), by examining and synthesising how sedentary behaviour has been measured in the primary care literature. METHODS: A systematic review was conducted to identify studies relating to levels of sedentary behaviour among GPs. Searches were performed using Medline®, Embase®, PscycINFO, Web of Science and the Cochrane Library, from inception of databases until January 2020, with a subsequent search of grey literature. Articles were assessed for quality and bias, with extraction of relevant data. RESULTS: The search criteria returned 1707 studies. Thirty four full texts were reviewed and 2 studies included in the final review. Both were cross-sectional surveys using self-reported estimation of sedentary time within the International Physical Activity Questionnaire (IPAQ). Keohane et al. examined GP trainees and GP trainers in Ireland. 60% reported spending in excess of 7 h sitting each day, 24% between 4 and 7 h, and 16% less than or equal to 4 h. Suija et al. examined female GPs in Estonia. The mean reported daily sitting time was 6 h and 36 min, with 56% sitting for over 6 h per day. Both studies were of satisfactory methodological quality but had a high risk of bias. CONCLUSION: There is a paucity of research examining current levels of sedentary behaviour among GPs. Objective data is needed to determine GPs' current levels of sedentary behaviour, particularly in light of the increase in remote consulting as a result of the COVID-19 pandemic.

Training Primary Care Physicians in Dermoscopy for Skin Cancer Detection: a Scoping Review.

In many countries, patients with concerning skin lesions will first consult a primary care physician (PCP). Dermoscopy has an evidence base supporting its use in primary care for skin cancer detection, but need for training has been cited as a key barrier to its use. How PCPs train to use dermoscopy is unclear. A scoping literature review was carried out to examine what is known from the published literature about PCP training in dermoscopy. The methodological steps taken in this review followed those described by Arksey and O'Malley, as revised by Levac et al. Four electronic databases were searched for evidence published up to June 2018. Sixteen articles were identified for analysis, all published since 2000. Ten training programs were identified all of which addressed dermoscopy of pigmented skin lesions, among other topics. Ten articles reported on a range of outcomes measured after training and showed generally positive results in terms of improved diagnostic performance, although no meta-analysis was conducted. However, it was unclear whether trained PCPs continued to use dermoscopy after training. Observational questionnaire data revealed that many PCPs use dermoscopy in practice without any formal training. The literature generally supports the use of dermoscopy by PCPs, but it is unclear whether current training leads to long-term change in PCPs' use of dermoscopy in clinical practice. Understanding this problem, as well as exploring PCPs' training needs, is essential to develop training programs that will facilitate the uptake and use of dermoscopy in primary care.

Safety in primary care (SAP-C): a randomised, controlled feasibility study in two different healthcare systems.

BACKGROUND: Patient safety research is conducted predominantly in hospital settings, with a dearth of insight from primary care, despite suggestions that 2.2% of primary care consultations result in a patient safety incident. This study aimed to assess the feasibility of an intervention intended to improve patient safety in general practice. METHODS: A randomised controlled feasibility study was conducted with general practices in the Republic of Ireland (N = 9) and Northern Ireland (N = 2), randomly assigned to the intervention (N = 5) or control (N = 6) group. The nine-month intervention consisted of: 1) repeated safety climate (SC) measurement (using GP-SafeQuest questionnaire) and feedback (comparative anonymised practice-level SC data), and 2) patient record reviews using a specialised trigger tool to identify instances of undetected patient harm. For control practices, SC was measured at baseline and study end only. The intervention's perceived usefulness and feasibility were explored via an end-of-study questionnaire and semi-structured interviews. RESULTS: Thirteen practices were invited; 11 participated; 10 completed the study. At baseline, 84.8% of intervention practice staff (39/46) and 77.8% (42/54) of control practice staff completed the SC questionnaire; at the study terminus, 78.3% (36/46) of intervention practice staff and 68.5% (37/54) of control practice staff did so. Changes in SC scores, indicating improvement, were observed among the intervention practices but not in the control group. The trigger tool was applied to 188 patient records; patient safety incidents of varying severity were detected in 19.1% (36/188). Overall, 59% of intervention practice team members completed the end-of-study questionnaire, with the majority in both healthcare systems responding positively about the intervention. Interviews (N = 9) identified the intervention's usefulness in informing practice management and patient safety issues, time as a barrier to its use, and the value of group discussion of feedback. CONCLUSION: This feasibility study suggests that a definitive randomised controlled trial of the intervention is warranted. Our findings suggest that the intervention is feasible, useful, and sustainable. Practices were willing to be recruited into the study, response and retention rates were acceptable, and there is possible evidence of a positive effect of the intervention. TRIAL REGISTRATION: The trial registration number is: ISRCTN11426121 (retrospectively registered 12th June 2018).

Knowledge or noise? Making sense of General Practitioners' and Consultant use of 2-week-wait referrals for suspected cancer.

BACKGROUND: Early diagnosis and treatment of cancer is the goal of the 2-week-wait referral pathway (2WW). Variation exists between General Practice use of 2WW and rates of consultant reprioritisation of GP referral from routine to 2WW (Consultant Upgrade). We investigated variation in General Practice and Consultant Upgrade 2WW referral activity. METHODS: Data from 185 000 referrals and 29 000 cancers recorded between 2011 and 2013 from the Northern Ireland Cancer Waiting Time database (CaPPS) were analysed to ascertain standardised referral rate ratios, detection rate (DR) (=sensitivity) and conversion rate (CR) (=positive predictive value) for Practice 2WW referrals and Consultant Upgrade 2WW. Metrics were compared using Spearman's rank correlation co-efficients. RESULTS: There was consistency in Practice and Consultant Upgrade 2WW referral rates over time, though not for annual DR (Spearman's ρ<0.37) or CR (Spearman's ρ<0.26). Practice 2WW referral rates correlated negatively with CR and positively with DR while correlations between DR and CR were restricted to single-year comparisons in Practice 2WW. In Consultant Upgrade, 2WW CR and DR were strongly correlated but only when the same cancers were included in both rates. CONCLUSIONS: Results suggest 'random case mix' explains previously reported associations between CR and DR with more 'hard to detect' cancers in some Practices than in others in a given year corresponding to lower DR and CR. Use of Practice and Consultant Upgrade 2WW referral metrics to gauge General Practice performance may be misleading.

Preparation for practice: a novel role for general practice in pre-foundation assistantships.

BACKGROUND: Hospital-based undergraduate assistantships are now widely established in medical school curricula. They are considered to improve graduates' preparedness for practice in their role as a foundation doctor. Foundation doctors play a key team role in ensuring patient safety during complex transitions across the hospital/primary care interface, and their self-reported preparedness for practice still varies considerably. AIMS: We sought to explore what spending one week of the pre-foundation assistantship in General Practice might add. METHODS: We solicited reflective audio diaries from final year students during a one-week pilot attachment delivered during the post-finals, pre-foundation assistantship period, and performed an iterative thematic analysis on the acquired data. RESULTS: From this attachment in General Practice, students described diverse learning, resulting in improved preparedness for (hospital) foundation practice across several domains, impacting positively on how they might approach patients in the future. Self-confidence improved due to affirming outcomes and tutor mentorship. Students deepened their understanding of community healthcare and General Practice; and seeing the 'Patient Journey' across the interface from the patient's perspective helped them contextualise their forthcoming role as foundation doctors in managing it. DISCUSSION: We believe that this novel intervention distinctively contributed to preparedness for practice. It aligns with published recommendations about extending the current assistantship model. We suggest it should be incorporated more widely into pre-foundation assistantship curricula.

Development of a survey instrument to investigate the primary care factors related to differences in cancer diagnosis between international jurisdictions.

BACKGROUND: Survival rates following a diagnosis of cancer vary between countries. The International Cancer Benchmarking Partnership (ICBP), a collaboration between six countries with primary care led health services, was set up in 2009 to investigate the causes of these differences. Module 3 of this collaboration hypothesised that an association exists between the readiness of primary care physicians (PCP) to investigate for cancer - the 'threshold' risk level at which they investigate or refer to a specialist for consideration of possible cancer - and survival for that cancer (lung, colorectal and ovarian). We describe the development of an international survey instrument to test this hypothesis. METHODS: The work was led by an academic steering group in England. They agreed that an online survey was the most pragmatic way of identifying differences between the jurisdictions. Research questions were identified through clinical experience and expert knowledge of the relevant literature.A survey comprising a set of direct questions and five clinical scenarios was developed to investigate the hypothesis. The survey content was discussed and refined concurrently and repeatedly with international partners. The survey was validated using an iterative process in England. Following validation the survey was adapted to be relevant to the health systems operating in other jurisdictions and translated into Danish, Norwegian and Swedish, and into Canadian and Australian English. RESULTS: This work has produced a survey with face, content and cross cultural validity that will be circulated in all six countries. It could also form a benchmark for similar surveys in countries with similar health care systems. CONCLUSIONS: The vignettes could also be used as educational resources. This study is likely to impact on healthcare policy and practice in participating countries.

"What script am I meant to use?": a qualitative study in chronic primary pain.

BACKGROUND: Chronic primary pain (CPP) as a diagnosis has been introduced in the recent International Classification of Diseases, 11th Revision (ICD-11). CPP captures the experience of pain as the primary problem, without an underlying attributable cause. Dissemination of UK guidance regarding CPP represents the first time it has been recognised as a condition in its own right. Little is known regarding General Practitioner (GP) views concerning caring for patients with CPP and how related guidance is viewed and applied in practice. AIM: To explore GP perspectives in relation to caring for people with CPP, including challenges encountered and use of related guidelines in practice. DESIGN & SETTING: A UK-wide qualitative interview study in primary care. METHOD: Purposive and snowball sampling were used to recruit 15 GP participants from England, Northern Ireland, Wales and Scotland. Semi-structured interviews were undertaken and analysed using reflexive thematic analysis. RESULTS: Three main themes were generated: (1) "How to start? Problematic beginnings" referred to difficulties regarding diagnosis; (2) "Where to go? Mapping the management challenge" and (3) "How to get there? Navigating strategies and response", explored GP awareness and acceptability of UK guidelines for chronic pain. Areas identified for potential improvement included increased access to NPM and secondary care services, support with de-prescribing and an expanded multidisciplinary team input. CONCLUSION: CPP is complex to both diagnose and manage. Although guidelines provide a useful framework, they pose challenges when translating into day-to-day practice.

"Challenging but ultimately rewarding": A qualitative analysis of Deep End GPs' experiences.

Background Living in socioeconomically deprived areas is associated with shorter lives, in worse health. GPs working in these areas face additional challenges. Aim Establishing GPs' motivation for working in these areas, what the challenges are, and insights from GPs on potential improvements and changes. Design and Setting An Interpretative Phenomenological Analysis of GPs' lived experiences of working in the most socioeconomically deprived practices, in Northern Ireland (NI), the most deprived country within the UK. Method Interviews with GPs finding out the challenges facing them, why they work in a "Deep End" area and what suggestions, ideas and solutions they have to improve patient care and GP experience at NI's 'Deep End'. Results The challenges related to wider health service failures including the increased demand on GPs and feelings of powerlessness. Patient population challenges included 'missingness', late or crisis presentations, alongside the clinical difficulties of a highly 'medicalised' patient population, as well as the high prevalence of mental health problems. However, GPs choose to work in 'Deep End' areas because it's clinically stimulating and rewarding, as well as feelings of belonging and fulfilling a duty to 'their' area. Improvements focused on providing more flexible access, increased mental health provision and future training and recruitment, particularly around widening participation in medicine. Conclusion Improving the environmental conditions, empowering individuals and investing in communities are essential to achieving health. The current model of providing reactionary acute care is leading to GPs experiencing powerlessness and feelings of helplessness at the 'Deep End'.

The relationship between general practitioner movement behaviours with burnout and fatigue.

BACKGROUND: Physical inactivity is associated with feelings of burnout and fatigue, which in turn are associated with reduced performance among healthcare practitioners. This study explored movement behaviours of general practitioners (GPs) and the association between these behaviours with burnout and fatigue. METHODS: GPs in Northern Ireland were asked to wear a thigh-worn accelerometer for seven days and complete validated questionnaires to assess the association between daily number of steps, time spent sitting and standing with feelings of burnout and fatigue. RESULTS: Valid accelerometer data were obtained from 47 (77.0%) participants. Average workday sitting time, standing time and number of steps were 10.6 h (SD 1.5), 3.8 h (SD 1.3), and 7796 steps (SD 3116) respectively. Participants were less sedentary (8.0 h (SD 1.6)) and more active (4.7 h (SD 1.4) standing time and 12,408 steps (SD 4496)) on non-workdays. Fourteen (30.4%) participants reported burnout and sixteen (34.8%) reported severe fatigue. There were no significant associations between sitting, standing and step counts with burnout or fatigue (p > 0.05). CONCLUSION: GPs were less active on workdays compared to non-workdays and exhibited high levels of sitting. Feelings of burnout and fatigue were highly prevalent, however movement behaviours were not found to be associated with burnout and fatigue. Given the increased sedentariness among GPs on workdays compared to non-workdays, GPs should consider how they can improve their movement behaviours on workdays to help optimise their wellbeing.

Cost-utility analysis of molnupiravir for high-risk, community-based adults with COVID-19: an economic evaluation of the PANORAMIC trial.

BACKGROUND: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. AIM: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over 6 months. DESIGN AND SETTING: An economic evaluation of the PANORAMIC trial in the UK. METHOD: A cost-utility analysis that adopted a UK NHS and personal social services perspective and a 6-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. RESULTS: In the base-case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] = 445 to 453) and higher mean QALYs of 0.0055 (95% CI = 0.0044 to 0.0067) than usual care (mean incremental cost per QALY of £81 190). Sensitivity and subgroup analyses showed similar results, except for those aged ≥75 years, with a 55% probability of being cost-effective at a £30 000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15 000 per QALY threshold. CONCLUSION: At the current cost of £513 per course, molnupiravir is unlikely to be cost-effective relative to usual care over a 6-month time horizon among mainly vaccinated patients with COVID-19 at increased risk of adverse outcomes, except those aged ≥75 years.