Effectiveness of non-pharmaceutical interventions as implemented in the UK during the COVID-19 pandemic: a rapid review
Background: Although non-pharmaceutical inventions (NPIs) were used globally to control the spread of COVID-19, their effectiveness remains uncertain. We aimed to assess the evidence on NPIs as implemented in the UK, to allow public health bodies to prepare for future pandemics. Methods: We used rapid systematic methods (search date: January 2024) to identify, critically appraise and synthesize interventional, observational and modelling studies reporting on NPI effectiveness in the UK. Results: Eighty-five modelling, nine observational and three interventional studies were included. Modelling studies had multiple quality issues; six of the 12 non-modelling studies were high quality. The best available evidence was for test and release strategies for case contacts (moderate certainty), which was suggestive of a protective effect. Although evidence for school-related NPIs and universal lockdown was also suggestive of a protective effect, this evidence was considered low certainty. Evidence certainty for the remaining NPIs was very low or inconclusive. Conclusion: The validity and reliability of evidence on the effectiveness of NPIs as implemented in the UK during the COVID-19 pandemic is weak. To improve evidence generation and support decision-making during future pandemics or other public health emergencies, it is essential to build evaluation into the design of public health interventions.
Practitioners' views on the measurement and management of postural hypotension in general practice: a qualitative inquiry.
BACKGROUND: Postural hypotension (PH) is associated with cognitive decline, falls and allcause mortality, representing a substantial burden on the NHS. PH is often asymptomatic, making detection and treatment difficult. Currently, there is no systematic approach to measuring and managing PH in UK general practice. AIM: To explore barriers and facilitators to improving PH measurement and management. DESIGN AND SETTING: Qualitative interview study with healthcare practitioners in general practices in England. METHODS: We conducted individual, remote, semi-structured interviews with a range of healthcare practitioners (HCPs) who measure blood pressure (BP) in general practice, to explore their views and experiences of measuring and managing PH. Participants were identified from expressions of interest during a national survey. Interviews were video and audio-recorded, transcribed verbatim and analysed thematically. RESULTS: 26 HCPs in 24 practices across nine Clinical Research Networks in England were interviewed between March and July 2023. HCPs checked for PH when patients were older, reported dizziness, fatigue or had chronic conditions. Despite awareness of clinical guidelines, various diagnostic definitions were provided and measurement protocols varied between participants. Sit-to-stand rather than supine-to-stand measurements were considered more feasible due to time constraints and patient mobility. Education and training, as well as incentives and specialist clinics, were suggested as methods to improve PH measurement and management. CONCLUSIONS: This is the first study to explore barriers to, and facilitators of, PH measurement in English general practice. Findings suggest a more systematic approach to measurement is needed to improve detection and management of PH in general practice.
Targeted Interventions to Improve the Systematic Collection of Acute Respiratory Infection Clinical Data from Primary Care Computerised Medical Records
Data quality in primary care is important for surveillance and research projects based on routinely collected computerised medical records data. We present the results of a targeted intervention of incentives and tools to record specific data about acute respiratory infectious disease. As part of an epidemiological study, practices received a template to code this information, which could also act as a consultation template. Use of the template was not restricted to patients taking part in the epidemiological study. We saw significant increases in coded data for patients in the study in the four areas that we examined; oxygen saturation, body temperature, respiratory rate and history of fever. For patients not included in the study we saw only small differences between study practices and non-study practices. There was an increased frequency of recording of measured body temperature in study practices but the effect was small (1.1%) 95% CI [0.56%,1.66%]. Primary care data quality can be improved with targeted interventions and support, but the effect does not transfer out of the specific patients for which it has been incentivised.
Economic impact of RSV infections in young children attending primary care: a prospective cohort study in five European countries, 2021 to 2023
Background: Data on economic costs of respiratory syncytial virus (RSV) infections among children in primary care are scarce, although most RSV-infections are managed in this setting. Aim: To estimate outpatient costs for RSV-positive childrenaged <5 years.Methods: In the RSV ComNet prospective cohort, children<5 years with acute respiratory infection were recruited for RSV testing through primary care physicians in Belgium, Italy, the Netherlands, Spain and the United Kingdom (UK) during RSV seasons 2020/21 (UK only), 2021/22 and 2022/23. Outpatient healthcare utilisation and parental work absence were assessed over 30 days through parental questionnaires. Average costs per RSV episode were calculated from outpatient healthcare sector and societal perspectives, stratified by country and age. Results: We included 3,414 children and 1,124 (33%) tested RSV-positive. Physicians completed reports for 878 episodes, with follow-up questionnaire data for 819 (93%). Outpatient costs ranged from EUR 97 (95% CI: 91–104) in the Netherlands to EUR 300 (95% CI: 287–312) in Spain and were higher for infants than children aged 1–5 years. Societal costs ranged from EUR 454 (95% CI: 418–494) in the UK to EUR 994 (95% CI: 938–1,053) in Belgium. For children aged 1–5 years, societal costs were primarily driven by parental work absence. In infants, the main societal cost driver varied by country, but overall outpatient healthcare costs represented a higher proportion of societal costs vs older children. Conclusion: RSV infections in children attending primary care result in substantial economic costs per episode, although differences exist across countries. This study provides essential data to inform cost-effectiveness analyses on novel RSV immunisations.
Association between ketone metabolism and the risk of depression: An observational and Mendelian randomization study.
BACKGROUND: Ketone bodies (KBs) can serve as an alternative fuel source for the brain. Pre-clinical evidence suggests that KBs have neuroprotective properties, which lie in the pathology of depression. AIMS: This study aimed to examine the association between KBs and the risk of depression using observational and genetic approaches. METHOD: Observational studies analyzed data collected between 2006 and 2010 from 245,459 participants in the UK Biobank, with follow-up to 31 October 2022. Genetic studies were firstly performed using one-sample Mendelian randomization (MR) with individual-level data from the UK Biobank; secondly, two-sample MR was performed using summary-level data from the largest available genome-wide association studies. KBs were measured by β-hydroxybutyrate with nuclear magnetic resonance spectroscopy. Depression outcomes were measured by linked hospital-based clinical depression diagnosis and mental health questionnaires. Cox proportional hazard models and linear regression were used to examine the association of KBs with depression and depression severity and to compare the risk between individuals on light nutritional ketosis (≥0.5 mmol/L) and those not. RESULTS: Observational analyses showed that each SD increase in KBs was associated with a 6 % (95 % CI, 1.03-1.08) increase in PHQ-9 scores in the fully adjusted model. Patients with KBs above 0.5 mmol/L had a higher risk of depression (HR 1.57; 95 % CI, 1.13-2.17) compared to those with KBs <0.5 mmol/L. In one-sample MR, there were no significant associations between genetically predicted KBs and depression and PHQ-9 scores. In two-sample MR analyses, we found no evidence of KBs (IVW OR1.06; 95 % CI, 0.91-1.24) with the risk of depression. CONCLUSIONS: There was observational evidence that higher KB concentration was associated with an increased risk of depression, but MR suggests this is not causal. The data do not support the therapeutic role of ketogenic diets in preventing depression.
Development and external validation of a risk prediction score (DASHI) for cardiovascular events following acute respiratory infections: derivation and validation retrospective cohort study
Background: Acute respiratory infections increase the short-term risk of myocardial infarction (MI) and stroke in primary care patients. Clinical guidelines for acute respiratory infections in primary care do not consider the risk of cardiovascular events, and CVD risk prediction tools target long-term risk. We aimed to develop and validate a prediction tool for the risk of cardiovascular disease events within 28-days of acute respiratory infection. Methods: The design was a retrospective cohort study using two different databases of routinely collected data from electronic health records from January 1999 to December 2019. We used Clinical Practice Research Datalink (CPRD) Aurum data to derive models, and CPRD GOLD data from a different population for external validation. This data is from UK primary care, with data linkage to Hospital Episode Statistics, Office of National Statistics mortality data, and Index of Multiple Deprivation data. Participants were patients aged 40 years or older with no history of cardiovascular events, and a first diagnosis with acute respiratory infection. The outcome was a composite of new diagnoses of myocardial ischaemia (myocardial infarction, angina, acute coronary syndromes, or ischaemic cardiomyopathy), stroke or transient ischaemic attack, or deaths with these diagnoses, within 28 days of presentation with an acute respiratory infection. We derived a list of 57 potential predictors based on prior studies and asked clinical experts to rank them. We derived two logistic regression models, one with the top ranked variables, and another including additional lower ranked variables. We derived a clinical prediction score from the most parsimonious logistic regression model. We validated each model and the score in the external dataset using C statistics, calibration plots, and expected to observed ratios. We examined clinical utility using decision curve analysis. Findings: The derivation cohort comprised 3.8 million patients with an acute respiratory infection (mean age 56.5 years, (SD 13.7); 57.7% female), of whom 11,996 had a subsequent cardiovascular outcome (0.3%). The validation cohort included 2.6 million patients (mean age 56.7 years, SD 13.6, 58.0% female), of whom 6868 (0.3%) had a subsequent cardiovascular outcome. The DASHI score comprised five clinical variables: Diabetes (1 point, yes/no), Age (40–59, 0 points; 60–79, 2 points; 80+, 4 points), current Smoking (1 point, yes/no), Heart failure (1 point, yes/no), and Infection diagnosis (Upper Respiratory Tract Infection–0 points. Lower Respiratory Tract Infection (LRTI)–1 point, or LRTI with a pneumonia diagnosis—4 points). Upon external validation, each model and the score showed similar performance. The score showed good discrimination (AUC 0.85, IQR 0.848–0.849) and calibration with an expected to observed ratio of 0.85 (IQR 0.85–0.85). Interpretation: The DASHI score allows primary care clinicians to estimate the risk of cardiovascular complications within 28 days in patients with acute respiratory infections. Funding: This research was funded in part by the Wellcome Trust [ 211182/Z/18/Z] and NIHR [ NIHR300738]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
The (Re)-emerging And ePidemic Infectious Diseases (RAPID) Stigma Scales: a cross-outbreak scale development and pyschometric validation study
Reducing stigma during infectious disease outbreaks is crucial for delivering an effective response. However, no validated stigma scales exist for use across outbreaks, and outbreak-specific scales are developed too slowly to guide timely interventions. To enable more real-time monitoring and mitigation of stigma across outbreak contexts, we developed and validated the (Re)-emerging and ePidemic Infectious Diseases (RAPID) Stigma Scales. Field testing and psychometric validation were conducted in communities affected by Ebola disease in Uganda, mpox in the UK, and Nipah virus disease in Bangladesh. Content validity was established through cognitive interviews and expert Delphi scoring. 1008 respondents were included across the three countries. The final RAPID Community Stigma Scale (12 items) captures initial social stigma, provider or authority-related stigma, structural stigma, and enduring social stigma. The RAPID Self Stigma Scale (4 items) is unidimensional. Both scales were found to have robust psychometric properties, including content validity, structural validity (factor loadings ≥0·6), and reliability (ordinal alphas 0·79–0·92). High scores on both scales predicted an increased hesitancy to report symptoms and seek care. The RAPID Stigma Scales are validated tools for real-time assessment of stigma across outbreak settings, enabling responders to design targeted interventions to improve health outcomes and promote equitable care.
Screening for atrial fibrillation with or without general practice involvement: a controlled study
Background: There has been a drive to increase atrial fibrillation (AF) detection in general practice. However, one-off, opportunistic testing can miss paroxysmal AF and requires significant resource. Paroxysmal AF can be detected through screening that involves repeated ECGs over a period of time, although it is unclear whether screening would need to be led by general practice, and how much support participants require. We aimed to investigate whether AF screening can be delivered remotely by a centralised administration instead of general practice, and to determine the level of support required. Methods: We undertook a controlled comparator study with secondary randomisation in three English general practices. We invited people aged ≥ 70 years to use a hand-held ECG device four times daily for three weeks. Participants were allocated to practice-led or administrator-led screening, with administrator-led support randomised to three different levels. We compared quantity and quality of ECGs obtained in each arm. The primary outcome was proportion of screened participants who recorded ≥ 56 adequate-quality ECGs (2/3 of possible ECGs). Results: Of 288 screened participants, 59 participants received practice-led screening with a telephone consultation to explain the device. The remainder received administrator-led screening: 81 were automatically given a consultation; 74 were offered a consultation, and 74 were not offered a consultation. Most screened participants (280/288, 97.2%) recorded ≥ 56 adequate-quality ECGs. This proportion did not vary significantly between practice-led and administrator-led screening (100.0% vs. 98.8%), or between support levels (94.6% to 98.8%). Practice-led screening led to slightly more adequate-quality ECGs (mean: 83.9 vs 78.3, p < 0.001). Conclusions: AF screening can be successfully delivered remotely, outside general practice, with minimal support.
Agreement and utility of coded primary and secondary care data for long-term follow-up of clinical trial outcomes
Abstract Background Whilst interest in efficient trial design has grown with the use of electronic health records (EHRs) to collect trial outcomes, practical challenges remain. Commonly raised concerns often revolve around data availability, data quality and issues with data validation. This study aimed to assess the agreement between data collected on clinical trial participants from different sources to provide empirical evidence on the utility of EHRs for follow-up in randomised controlled trials (RCTs). Methods This retrospective, participant-level data utility comparison study was undertaken using data collected as part of a UK primary care-based, randomised controlled trial (OPTiMISE). The primary outcome measure was the recording of all-cause hospitalisation or mortality within 3 years post-randomisation and was assessed across (1) Coded primary care data; (2) Coded-plus-free-text primary care data; and (3) Coded secondary care and mortality data. Agreement levels across data sources were assessed using Fleiss’ Kappa (K). Kappa statistics were interpreted using an established framework, categorising agreement strength as follows: <0 (poor), 0.00–0.20 (slight), 0.21–0.40 (fair), 0.41–0.60 (moderate), 0.61–0.80 (substantial), and 0.81–1.00 (almost perfect) agreement. The impact of using different data sources to determine trial outcomes was assessed by replicating the trial’s original analyses. Results Almost perfect agreement was observed for mortality outcome across the three data sources (K = 0.94, 95%CI 0.91–0.98). Fair agreement (weak consistency) was observed for hospitalisation outcomes, including all-cause hospitalisation or mortality (K = 0.35, 95%CI 0.28–0.42), emergency hospitalisation (K = 0.39, 95%CI 0.33–0.46), and hospitalisation or mortality due to cardiovascular disease (K = 0.32, 95%CI 0.19–0.45). The overall trial results remained consistent across data sources for the primary outcome, albeit with varying precision. Conclusion Significant discrepancies according to data sources were observed in recording of secondary care outcomes. Investigators should be cautious when choosing which data source(s) to use to measure outcomes in trials. Future work on linking participant-level data across healthcare settings should consider the variations in diagnostic coding practices. Standardised definitions for outcome measures when using healthcare systems data and using data from different data sources for cross-checking and verification should be encouraged.
The importance of experience: insights into optimal home-blood pressure monitoring regimens from the TASMINH4 Trial
Objectives: This study investigates how prior home blood pressure monitoring (HBPM) experience affects blood pressure variability and evaluates if reduced HBPM regimens could be recommended for experienced patients. Methods: This posthoc analysis of the TASMINH4 trial included self-monitored blood pressure (BP) data from 225 patients. The standard deviation of systolic BP recordings was calculated for each patient-week to assess how BP variability changes with HBPM duration. A subgroup of 84 patients, who submitted at least 1 reading a day for 7days at months 1, 3, and 6, was analysed to assess the impact of reduced HBPM regimens on BP estimates. Results: Day 1 readings were significantly higher than day 2–7 in the first 3months of HBPM: 1.1 (95% CI 1.8, 0.4) day 1 vs. day 2. This effect diminished after 6months: 1.0 (95% CI -0.8, 2.8) day 1 vs. 2. Long term monitoring significantly reduced intra-week BP variability, with the standard deviation of systolic BP recordings within each patient-week significantly reduced after 6months. After 6months of HBPM, the inclusion of day 1 readings or use of an abbreviated monitoring regimen had a reduced impact on estimates of mean systolic and diastolic blood pressure. Conclusions: Long-term HBPM reduces intra-week BP variability, making day 1 readings insignificantly raised after 6months of HBPM. This provides rationale for different HBPM recommendations: longer regimes, excluding day one readings, for diagnosis and short-term monitoring; and abbreviated regimes including day 1 for longer term monitoring in those with HBPM experience.
A framework for considering the use of generative AI for health
This perspective provides a critical framework for evaluating the use of Generative AI (GenAI) in healthcare, informed by two roundtable events and a series of semi-structured expert interviews. By outlining key principles and risks—including mapping applications to GenAI strengths, ensuring rigorous evaluation frameworks, and fostering transparency and collaboration—it will support healthcare professionals and policymakers in navigating the ethical and impactful integration of GenAI into healthcare.
Developing prediction models for electrolyte abnormalities in patients indicated for antihypertensive therapy: evidence-based treatment and monitoring recommendations
Objectives: Evidence from clinical trials suggests that antihypertensive treatment is associated with an increased risk of common electrolyte abnormalities. We aimed to develop and validate two clinical prediction models to estimate the risk of hyperkalaemia and hyponatraemia, respectively, to facilitate targeted treatment and monitoring strategies for individuals indicated for antihypertensive therapy. Design and methods: Participants aged at least 40 years, registered to an English primary care practice within the Clinical Practice Research Datalink (CPRD), with a systolic blood pressure reading between 130 and 179 mmHg were included the study. The primary outcomes were first hyperkalaemia or hyponatraemia event recorded in primary or secondary care. Model development used a Fine-Gray approach with death from other causes as competing event. Model performance was assessed using C-statistic, D-statistic, and Observed/Expected (O/E) ratio upon external validation. Results: The development cohort included 1 773 224 patients (mean age 59 years, median follow-up 6 years). The hyperkalaemia model contained 23 predictors and the hyponatraemia model contained 29 predictors, with all antihypertensive medications associated with the outcomes. Upon external validation in a cohort of 3 805 366 patients, both models calibrated well (O/E ratio: hyperkalaemia 1.16, 95% CI 1.13-1.19; hyponatraemia 1.00, 95% CI 0.98-1.02) and showed good discrimination at 10 years (C-statistic: 0.69, 95% CI 0.69-0.69; 0.80, 95% CI 0.80-0.80, respectively). Conclusion: Current clinical guidelines recommend monitoring serum electrolytes after initiating antihypertensive treatment. These clinical prediction models predicted individuals' risk of electrolyte abnormalities associated with antihypertensive treatment and could be used to target closer monitoring for individuals at a higher risk, where resources are limited.
Risk of bias in routine mental health outcome data: the case of Health of the Nation Outcome Scales
BackgroundRoutine outcome data in secondary mental health services have significant potential for service planning, evaluation and research. Expanding the collection and use of these data is an ongoing priority in the National Health Service (NHS), but inconsistent use threatens their validity and utility. If recording is more likely among certain patient groups or at specific stages of treatment, measured outcomes may be biased and unreliable.ObjectiveThe objective is to assess the scale, determinants and implications of incomplete routine outcome measurement in a secondary mental health provider, using the example of the widely collected Health of the Nation Outcome Scores (HoNOS).MethodsA retrospective cohort study was conducted using routine HoNOS assessments and episodes of care for patients receiving secondary mental healthcare from an NHS Trust in Southeast England between 2016 and 2022 (n=30 341). Associations among demographic, clinical and service factors, and rates and timings of HoNOS assessments were explored with logistic regressions. Relationships between total HoNOS scores and related mental health outcomes (costs, relapse and improvement between assessments) were estimated after adjusting for the likelihood of assessment.Findings66% of patients (n=22 288) had a recorded HoNOS assessment. Of the distinct episodes of care for these patients (n=65 439), 43% (n=28 170) were linked to any assessment, 25% (n=16 131) were linked to an initial baseline assessment, while 4.7% (n=3 094) were linked to multiple HoNOS assessments, allowing for evaluation of clinical progress. Likelihood and timing of assessment were significantly associated with a range of factors, including service type, diagnosis, ethnicity, age and gender. After adjusting for observed factors determining the likelihood of assessment, the strength of association between HoNOS scores and overall costs was significantly reduced.ConclusionMost of the activity observed in this study cannot be evaluated with HoNOS. HoNOS assessments are highly unlikely to be missing at random. Without approaches to correct for substantial gaps in routine outcome data, evaluations based on these may be systematically biased, limiting their usefulness for service-level decision-making.Clinical implicationsRoutine outcome collection must increase significantly to successfully implement proposed strategies for outcome assessment in community mental healthcare without inconsistent records undermining the use of resulting data.
Preferences for multi-cancer tests (MCTs) in primary care: discrete choice experiments of general practitioners and the general public in England.
BACKGROUND: Multi-Cancer tests (MCTs) hold potential to detect cancer across multiple sites and some predict the origin of the cancer signal. Understanding stakeholder preferences for MCTs could help to develop appealing MCTs, encouraging their adoption. METHODS: Discrete Choice Experiments (DCEs) conducted online in England. RESULTS: GPs (n = 251) and the general public (n = 1005) preferred MCTs that maximised negative predictive value, positive predictive value, and could test for a larger number of cancer sites. A reduction of the NPV of 4.0% was balanced by a 12.5% increase in the PPV for people and a 32.5% increase in PPV for GPs. People from ethnic minority backgrounds placed less importance on whether MCTs can detect multiple cancers. People with more knowledge and experience of cancer placed substantial importance on the MCT being able to detect cancer at an early stage. Both GPs and members of the public preferred the MCT reported in the SYMPLIFY study to FIT, PSA, and CA125, and preferred the SYMPLIFY MCT to 91% (GPs) and 95% (people) of 2048 simulated MCTs. CONCLUSIONS: These findings provide a basis for designing clinical implementation strategies for MCTs, according to their performance characteristics.
Clinical and cost-effectiveness of detailed anomaly ultrasound screening in the first trimester: a mixed-methods study.
BACKGROUND: In the United Kingdom, pregnant women are offered two scans: at 11-14 and 18-20 weeks' gestation. Current guidance supports fetal anatomical screening at the second scan, but evidence suggests earlier detection is possible. OBJECTIVES: To determine clinical and cost-effectiveness of a detailed two-dimensional ultrasound scan in the first trimester for detection of fetal anomalies, in addition to usual practice. DESIGN: Systematic review and meta-analysis. Nationwide survey. Analysis of National Congenital Anomaly Disease Registry data. Consensus procedure. Prospective survey of parental opinions. Probabilistic decision-analytic model for cost-effectiveness. Value-of-information analysis. SETTING: United Kingdom National Health Service. PARTICIPANTS: Pregnant women and partners. INTERVENTIONS: Detailed anomaly ultrasound at 11-14 weeks' gestation, in addition to usual practice. MAIN OUTCOME MEASURES: Diagnostic accuracy, protocol development, health economic modelling and value-of-information analysis. DATA SOURCES: MEDLINE (OvidSP), EMBASE (OvidSP), Science Citation Index and Conference Proceedings Citation Index-Science (Web of Science Core Collection); National Congenital Anomaly Disease Registry; European Congenital Anomalies Registry; Surveys of National Health Service Trusts; screening sonographers, midwives and doctors; and parents; National Schedule of National Health Service Costs (2019-20). REVIEW METHODS: Systematic review and meta-analysis for diagnostic accuracy. RESULTS: First-trimester ultrasound detects 93.3% (95% confidence interval 90.4% to 95.7%) of a pre-selected group of eight major anomalies with specificity of 99.99% (95% confidence interval 99.98% to 99.99%) and positive predictive value of 96.5% (95% confidence interval 93.3 to 98.8, 416,877 fetuses, 40 studies). For major cardiac anomalies, the respective data are 55.8% (95% confidence interval 45.9% to 65.5%), 99.98% (95% confidence interval 99.97% to 99.99%) and 94.85% (95% confidence interval 91.63% to 97.32%, 306,872 fetuses, 45 studies). Of NHS trusts surveyed, 77% currently perform first-trimester anatomy assessment, with evidence of inequity of care; earlier screening resulted in more diagnoses before 16 weeks' gestation. A consensus procedure (n = 172) developed an anatomical protocol and minimum targets for diagnosis. Parental survey (n = 1374) indicated that over 90% would opt for such screening. Modelling of singleton pregnancies undergoing earlier anomaly screening using two-dimensional ultrasound was associated with increased mean healthcare costs per woman (£11, 95% confidence interval £1 to £29) and maternal quality-adjusted life-years (0.002065, 95% confidence interval 0.000565 to 0.00358), an incremental cost per quality-adjusted life-year of £5270, with likelihood of being cost-effective at £20,000 per quality-adjusted life-year of over 95%. Additional modelling predicted reductions in infant healthcare costs and quality-adjusted life-years. Decision uncertainty was low. Value-of-information analysis of cost-effectiveness results showed no groups of parameters for which further research to reduce uncertainty would likely prove cost-effective. LIMITATIONS: Study heterogeneity; the lack of a universal reference standard; simplifying assumptions relating to economic model structure; and estimation of some parameters are documented and justified. The rarity of the conditions made estimation of longer-term maternal and infant costs and quality-adjusted life-years challenging, resulting in likely under-estimation of healthcare costs. CONCLUSIONS: With standardisation and training, first-trimester ultrasound screening for fetal anomalies is clinically effective with over 90% detection for eight major conditions and low false-positive rates. Decision uncertainty around implementation is low and a prospective study would not be an efficient investment. Adding first-trimester anomaly screening to the current screening likely represents a cost-effective use of resources and is acceptable to parents. FUTURE WORK: Focus on developing an implementation framework to modify the current United Kingdom Fetal Anomaly Screening Programme. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018111781 and CRD42018112434. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/19/10) and is published in full in Health Technology Assessment; Vol. 29, No. 22. See the NIHR Funding and Awards website for further award information.