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Even if public health interventions are successful at reducing the spread of COVID-19, there is no guarantee that they will bring net benefits to the society because of the dynamic nature of the pandemic, e.g., the risk of a second outbreak if those interventions are stopped too early, and the costs of a continued lockdown. In this analysis, a discrete-time dynamic model is used to simulate the effect of reducing the effective reproduction number, driven by lockdowns ordered in March 2020 in four European countries (UK, France, Italy and Spain), on QALYs and hospitalisation costs. These benefits are valued in monetary terms (€30,000 per QALY assumed) and compared to productivity costs due to reduced economic activity during the lockdown. An analysis of the optimal duration of lockdown is performed where a net benefit is maximised. The switch to a soft lockdown is analysed and compared to a continued lockdown or no intervention. Results vary for two assumptions about hospital capacity of the health system: (a) under unlimited capacity, average benefit ranges from 8.21 to 14.21% of annual GDP, for UK and Spain, respectively; (b) under limited capacity, average benefits are higher than 30.32% of annual GDP in all countries. The simulation results imply that the benefits of lockdown are not substantial unless continued until vaccination of high-risk groups is complete. It is illustrated that lockdown may not bring net benefits under some scenarios and a soft lockdown will be a more efficient alternative from mid-June 2020 only if the basic reproduction number is maintained low (not necessarily below 1) and productivity costs are sufficiently reduced., (© 2022. The Author(s).)

The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2 years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41-0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT., Competing Interests: Conflict of interest: F.M. Sullivan reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: F.S. Mair reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: W. Anderson has nothing to disclose. Conflict of interest: P. Armory reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: A. Briggs reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and Oncimmune, during the conduct of the study. Conflict of interest: C. Chew has nothing to disclose. Conflict of interest: A. Dorward has nothing to disclose. Conflict of interest: J. Haughney has nothing to disclose. Conflict of interest: F. Hogarth reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and from Oncimmune, during the conduct of the study. Conflict of interest: D. Kendrick has nothing to disclose. Conflict of interest: R. Littleford reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and Oncimmune, during the conduct of the study. Conflict of interest: A. McConnachie reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: C. McCowan has nothing to disclose. Conflict of interest: N. McMeekin reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: M. Patel has nothing to disclose. Conflict of interest: P. Rauchhaus reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: L. Ritchie has nothing to disclose. Conflict of interest: C. Robertson reports personal fees and other funding from Oncimmune, outside the study. Conflict of interest: J. Robertson reports other funding from Oncimmune, during the conduct of the study; and other funding from Oncimmune, outside the study. J. Robertson was a founder of Oncimmune, a company spun out from the University of Nottingham based on his academic research. Between 2003 and 2013 he was Chief Scientific Officer of Oncimmune and a Director of the company. During this time, he was responsible for the original drafting of the ECLS protocol. Since 2013 he has had no involvement in the science or management of the company. He has been and remains a shareholder in the company. Conflict of interest: J. Robles-Zurita reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and Oncimmune, during the conduct of the study. Conflict of interest: J. Sarvesvaran has nothing to disclose. Conflict of interest: H. Sewell reports other funding from Oncimmune, outside the submitted work; and was an external member of the Oncimmune Scientific Advisory Board from 2006 to 2013. Conflict of interest: M. Sproule has nothing to disclose. Conflict of interest: T. Taylor reports grants, nonfinancial support and other funding from Oncimmune, grants and personal fees from the Chief Scientist Office for Scotland, and grants and nonfinancial support from the Scottish Government, outside the submitted work. Conflict of interest: A. Tello reports grants from Oncimmune, during the conduct of the study. Conflict of interest: S. Treweek reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. Conflict of interest: K. Vedhara has nothing to disclose. Conflict of interest: S. Schembri reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study; and nonfinancial support from GlaxoSmithKline and AstraZeneca, outside the submitted work., (Copyright ©ERS 2021.)

Background: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy., Objectives: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations., Design: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial., Setting: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand., Participants: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum., Interventions: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months., Main Outcome Measures: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient., Results: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n  = 3035; 6-month analysis, n  = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p -value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years ( p  < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient., Conclusions: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease., Trial Registration: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894)., Competing Interests: Timothy Iveson reports honoraria from Amgen Inc. (Thousand Oaks, CA, USA), Bayer AG (Leverkusen, Germany), Bristol-Myers Squibb (New York, NY, USA), Celgene Corporation (Summit, NJ, USA), Pierre-Fabre (Paris, France), Roche (Roche Holding AG, Basel, Switzerland) and Servier (Laboratories Servier, Suresnes, France). Kathleen A Boyd reports grants from the Medical Research Council during the conduct of the study. Mark P Saunders reports personal fees from Servier, Amgen, Merck (Merck and Co., Kenilworth, New Jersey, USA), Eisai (Eisai Co., Ltd., Tokyo, Japan) and Roche outside the submitted work. Jim Cassidy reports grants from the Medical Research Council during the conduct of the study and is currently an employee of Celgene Corporation. Josep Tabernero reports personal fees from Array Biopharma (Boulder, CO, USA), AstraZeneca (Cambridge, UK), Bayer AG (Leverkusen, Germany), BeiGene (Beijing, China), Boehringer Ingelheim (Ingelheim am Rhein, Germany), Chugai (Chugai Pharmaceutical Co., Tokyo, Japan), Genentech, Inc. (South San Francisco, CA, USA), Genmab A/S (Copenhagen, Denmark), Halozyme (Halozyme Therapeutics, San Diego, CA, USA), Imugene Limited (Sydney, NSW, Australia), Inflection Biosciences Limited (Blackrock, Dublin), Ipsen (Paris, France), Kura Oncology (San Diego, CA, USA), Eli Lilly and Company (Indianapolis, IN, USA), Merck, Menarini (The Menarini Group, Florence, Italy), Merck Serono (Rockland, MA, USA), Merrimack Pharmaceuticals (MA, USA), Merus (Utrecht, the Netherlands), Molecular Partners (Molecular Partners AG, Zurich, Switzerland), Novartis (Novartis International AG, Basel, Switzerland), Peptomyc, Pfizer Inc. (New York, NY, USA), Pharmacyclics (Pharmacyclics LLC, Sunnyvale, CA, USA), ProteoDesign SL (Barcelona, Spain), Rafael Pharmaceuticals (Stony Brook, NY, USA), F. Hoffmann-La Roche Ltd, Sanofi (Sanofi S. A., Paris, France), Seattle Genetics (Bothwell, WA, USA), Servier, Symphogen (Symphogen A/S, Ballerup, Denmark), Taiho Pharmaceutical (Tokyo, Japan), VCN Biosciences (Barcelona, Spain), Biocartis (Biocartis Group, Mechelen, Belgium), Foundation Medicine (Cambridge, MA, USA), HalioDX (Marseille, France), SAS Pharmaceuticals (Delhi, India) and Roche Diagnostics outside the submitted work. Bengt Glimelius reports support from PledPharma AB for being on advisory boards. Sherif Raouf reports grants, personal fees and non-financial support from Roche, grants and personal fees from Amgen, and grants and personal fees from Merck outside the submitted work. David Farrugia reports that he received honoraria for speaking in educational events and support for meeting attendance from Bristol-Myers Squibb, Novartis, Ipsen, Amgen, AstraZeneca and Merck. David Cunningham reports grants from 4SC (4SC AG, Planegg, Germany), AstraZeneca, Bayer, Amgen, Celgene, Clovis Oncology (Boulder, CO, USA), Eli Lilly and Company, Janssen Pharmaceuticals (Beerse, Belgium), MedImmune (Gaithersburg, MD, USA), Merck, Merrimack and Sanofi, outside the submitted work. Tamish Hickish reports grants from Pfizer, Roche, Pierre Fabre (Paris, France) and personal fees from Eli Lilly and Company during the conduct of the study. John Bridgewater reports funding from the University College London Hospitals NHS Foundation Trust/University College London Biomedical Research Centre. David Cunningham reports funding from the National Institute for Health Research Biomedical Research Centres at the Royal Marsden.

Background: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer., Methods: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken., Results: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant)., Conclusions: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.

Introduction: Emergency percutaneous coronary intervention (PCI) of the culprit lesion for patients with acute myocardial infarctions is an accepted practice. A majority of patients present with multivessel disease with additional relevant stenoses apart from the culprit lesion. In haemodynamically stable patients, there is increasing evidence from randomised trials to support the practice of immediate complete revascularisation. However, in the presence of cardiogenic shock, the optimal management strategy for additional non-culprit lesions is unknown. A multicentre randomised controlled trial, CULPRIT-SHOCK, is examining whether culprit vessel only PCI with potentially subsequent staged revascularisation is more effective than immediate multivessel PCI. This paper describes the intended economic evaluation of the trial., Methods and Analysis: The economic evaluation will be conducted using a pre-trial decision model and within-trial analysis. The modelling-based analysis will provide expected costs and health outcomes, and incremental cost-effectiveness ratio over the lifetime for the cohort of patients included in the trial. The within-trial analysis will provide estimates of cost per life saved at 30 days and in 1 year, and estimates of health-related quality of life. Bootstrapping and cost-effectiveness acceptability curves will be used to address any uncertainty around these estimates. Different types of regression models within a generalised estimating equation framework will be used to examine how the total cost and quality-adjusted life years are explained by patients' characteristics, revascularisation strategy, country and centre. The cost-effectiveness analysis will be from the perspective of each country's national health services, where costs will be expressed in euros adjusted for purchasing power parity., Ethics and Dissemination: Ethical approval for the study was granted by the local Ethics Committee at each recruiting centre. The economic evaluation analyses will be published in peer-reviewed journals of the concerned literature and communicated through the profiles of the authors at www.twitter.com and www.researchgate.net., Trial Registration Number: NCT01927549; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)