Health Economic Analysis Research Articles

Cost-utility analysis for sublingual versus intravenous edaravone in the treatment of amyotrophic lateral sclerosis

BackgroundEdaravone has been widely used in amyotrophic lateral sclerosis (ALS) treatment, and a sublingual (SL) tablet has been developed to offer a more convenient alternative for injection. We present a cost-utility analysis to comprehensively evaluate the costs and health outcomes of oral and intravenous edaravone for the treatment of ALS in Chinese medical context.MethodsCost-utility analysis of SL tablets of edaravone versus intravenous edaravone at home was performed by constructing a 20-year Markov model of ALS stage 1–4 and death. The data were extracted from the literature with model assumptions. Typical sensitivity analysis and scenario analysis for administering SL tablets at home versus intravenous tablets at the hospital were performed.ResultsIn the base case analysis, with SL tablets and intravenous injections both at home, the model estimated an additional cost of ¥12,670.04 and an additional 0.034 QALYs over 20 years (life time) of modeling analysis, and the ICER was ¥372,648.24 per QALY. However, in the scenario of intravenous administration at the hospital, SL tablet was demonstrated dominance to intravenous injection.ConclusionsUsing 3 times the GDP per capita of China in 2023 as the threshold, the SL tablet edaravone was not cost-effective in the context of home treatment for both formulationst, but was dominance to intravenous injection in hospital treatment. The results highlighted the importance of treatment context for health economic analysis.

VI-RADS followed by Photodynamic Transurethral Resection of Non-Muscle-Invasive Bladder Cancer vs White-Light Conventional and Second-resection: the 'CUT-less' Randomised Trial Protocol.

A second transurethral resection of bladder tumour (Re-TURBT) is recommended by European Association of Urology (EAU) Guidelines on non-muscle-invasive bladder cancers (NMIBCs) due to the risk of understaging and/or persistent disease following the primary resection. However, in many cases this may be unnecessary, potentially harmful, and significantly expensive constituting overtreatment. The CUT-less trial aims to combine the preoperative staging accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) and the intraoperative enhanced ability of photodynamic diagnosis (PDD) to overcome the primary TURBT pitfalls thus potentially re-defining criteria for Re-TURBT indications. Single-centre, non-inferiority, phase IV, open-label, randomised controlled trial with 1:1 ratio. The primary endpoint is short-term BC recurrence between the study arms to assess whether patients preoperatively categorised as VI-RADS Score 1 and/or Score 2 (i.e., very-low and low likelihood of MIBC) could safely avoid Re-TURBT by undergoing primary PDD-TURBT. Secondary endpoints include mid- and long-term BC recurrences and progression (i-ii). Also, health-related quality of life (HRQoL) outcomes (iii) and health-economic cost-benefit analysis (iv) will be performed. All patients will undergo preoperative Multiparametric Magnetic Resonance Imaging of the bladder with VI-RADS score determination. A total of 327 patients with intermediate-/high-risk NMIBCs, candidate for Re-TURBT according to EAU Guidelines, will be enrolled over a 3-year period. Participants will be randomised (1:1 ratio) to either standard of care (SoC), comprising primary white-light (WL) TURBT followed by second WL Re-TURBT; or the Experimental arm, comprising primary PDD-TURBT and omitting Re-TURBT. Both groups will receive adjuvant intravesical therapy and surveillance according to risk-adjusted schedules. Measure of the primary outcome will be the relative proportion of BC recurrences between the SoC and Experimental arms within 4.5 months (i.e., any 'early' recurrence detected at first follow-up cystoscopy). Secondary outcomes measures will be the relative proportion of late BC recurrences and/or BC progression detected after 4.5 months follow-up. Additionally, we will compute the HRQoL variation from NMIBC questionnaires modelled over a patient lifetime horizon and the health-economic analyses including a short-term cost-benefit assessment of incremental costs per Re-TURBT avoided and a longer-term cost-utility per quality-adjusted life year gained using 2-year clinical outcomes to drive a lifetime model across the two arms of treatment. ClinicalTrial.gov identifier (ID): NCT05962541; European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) ID: 2023-507307-64-00.

Transient Ischaemic attack Emergency Referral (TIER): randomised feasibility trial results

BackgroundEarly assessment of patients with suspected transient ischaemic attack (TIA) is crucial to provision of effective care, including initiation of preventive therapies and identification of stroke mimics. Many patients with...

A person-centred consultation intervention to improve shared decision-making about, and uptake of, osteoporosis medicines (iFraP): a pragmatic, parallel-group, individual randomised controlled trial protocol

Background Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person’s life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations. Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. Methods The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. Discussion The iFraP trial will answer important questions about the effectiveness of the new ‘iFraP’ osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. Trial registration ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407

Health-related quality of life assessment in health economic analyses involving type 2 diabetes.

Incorporating health-related quality of life (HRQoL) measures into health economic analyses can help to provide evidence to inform decisions about how to improve patient outcomes in the most cost-effective manner. The aim of this narrative review was to assess which HRQoL instruments have been used in economic evaluations of type 2 diabetes management including in Indigenous communities. MEDLINE (Ovid), Embase (Ovid) and Cochrane were searched from inception to June 2022. Studies included patients with type 2 diabetes; economic evaluations, derived scores from direct questioning of individuals; and were in English. Records were assessed for bias using the JBI critical appraisal tools. A total of 3737 records were identified, with 22 publications meeting the criteria for inclusion. Across those 22 articles, nine HRQoL instruments had been utilised. Generic tools were most frequently used to measure HRQoL, including EQ-5D (-3 L and -5 L) (n = 10, 38%); SF-12 (n = 5, 19%); and SF-36 (n = 4, 15%). Two tools addressing the specific stressors faced by people with type 2 diabetes were utilised: Problem Areas In Diabetes tool (n = 1, 4%) and Diabetes Distress Scale (n = 1, 4%). Two publications reported whether the study population included Indigenous peoples. A wide range of HRQoL instruments are used in economic evaluations of type 2 diabetes management, with the most frequent being varying forms of the EQ-5D. Few economic evaluations noted whether Indigenous peoples were featured in the study population. More research into HRQoL in people living with type 2 diabetes is urgently needed to improve evidence on effectiveness and cost-effectiveness of interventions.

S511 Direct Genetic Screening Approach in Hereditary Nonpolyposis Colorectal Cancer: A Health Economics Analysis in High-risk Colorectal Cancer Population; Perspective from Middle-Income Country

S511 Direct Genetic Screening Approach in Hereditary Nonpolyposis Colorectal Cancer: A Health Economics Analysis in High-risk Colorectal Cancer Population; Perspective from Middle-Income Country

Electronic monitoring versus manual paper-based monitoring for hand hygiene compliance: a comprehensive health economic assessment analysis

BackgroundMonitoring hand hygiene compliance (HHC) of healthcare providers (HCPs) in healthcare facilities is critical for hand hygiene (HH) promotion. However, less is known about the cost and effectiveness of different HHC monitoring tools. In this study, we aimed to compare various health economic indicators corresponding to electronic system-based monitoring (ESM) and manual paper-based monitoring (MPM) for HHC to provide evidence-based advice for HHC monitoring measures targeted selecting.MethodsA before and after study in 40 clinical departments with 4,524 healthcare providers was conducted from December 2022 to January 2023 (MPM implementation phase) and March 2023 to May 2023 (ESM implementation phase). The cost-effectiveness, cost-efficiency, the extent of the Hawthorne effect, and indirect cost-benefit of the two monitoring methods were compared.ResultsThe total cost spent on ESM for the 40 departments (17,702.92 CNY) was 4,123.76 CNY lower than that of MPM (21,826.68 CNY). The HHC of MPM (80.16%) was higher than that of ESM (69.82%) (p < 0.01). In high- and medium-risk departments, the cost-effectiveness ratio of ESM (7,977.90 CNY and 13,794.60 CNY, respectively) was lower than that of MPM (9,039.61 CNY and 14,549.05 CNY, respectively). In low-risk departments, the cost-effectiveness ratio of ESM (3,910.77 CNY) was higher than that of MPM (3,899.06 CNY). Compared with ESM, the incremental cost of MPM in all departments was 4,123.76 CNY, the incremental effectiveness was 10.34%, and the incremental cost-effectiveness ratio was 39,881.62 CNY. Between the two monitoring methods, the efficiency of ESM (48.11%) in all departments was higher than that of MPM (14.20%) (p < 0.01). The cost-efficiency ratio of MPM in all departments (155,775.56 CNY) was higher than that of ESM (36,796.76 CNY). The extent of Hawthorne effect of MPM of HHC in all departments (43.99%) was higher than that of ESM (35.69%) (p < 0.01). When ESM was used as the HHC monitoring approach, the HAI rates (1.39%) in all departments were higher than that when MPM was used (1.34%) (p = 0.562). When the payment willingness was less than 40,000 CNY, the ESM method was the better option for cost-effectiveness; When the input exceeded this threshold, the MPM method was the better option for cost-effectiveness.ConclusionsESM exhibited notable advantages over MPM in terms of cost-effectiveness, cost-efficiency, cost-benefit, and the Hawthorne effect.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK

IntroductionThere remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the...

Abstract B018: UroPanc: A large prospective observational study for validation of urinary biomarker test for the earlier detection of pancreatic adenocarcinoma

Abstract Introduction. A bleak prognosis of Pancreatic ductal adenocarcinoma (PDAC) is largely due to late diagnosis and highly accurate, non-invasive diagnostic tests are urgently needed to improve patients’ survival. Our group has previously reported on urinary biomarker panel, comprising of LYVE1, REG1B and TFF1 (1-2), which distinguished controls from PDAC stages I-II with AUC 0.936 and sensitivity/specificity (SN/SP)&amp;gt;85%. We constructed the logistic regression based algorithm for interpretation of the data, PancRISK (3), which enables the stratification of high- risk patients into those with ‘average’ or ‘elevated’ risk of developing PDAC. Recently, we showed that our panel combined with CA19-9 can detect PDAC up to 2 years before clinical diagnosis (4). Aim. Here, we report on the design and interim analysis of the UroPanc Trial (ClinicalTrials.gov NCT04449406), which aims to evaluate the accuracy of the urinary biomarker panel and the affiliated PancRISK. We plan to recruit two cohorts: the first one comprises asymptomatic individuals that have high risk of developing PDAC due to familial history and genetic syndroms - these will be recruited through the EUropean Registry Of familial PAncreatic Cancer and hereditary pancreatitis (EUROPAC) (PI: Prof W Greenhalf and team, Liverpool, UK). The second cohort comprises patients with symptoms suggestive of PDAC – such patients are recruited at gastrointestinal clinics at University College London Hospitals (UCLH, PI: Prof S Pereira and team), and The Royal London Hospital (PI: Dr P Wilson).Methods. The urinary proteins are assayed by commercially available ELISAs. Plasma CA19-9 is measured at The Doctors Laboratory in London, UK using Cobas601E, Roche platform. The statistical analysis and accuracy of the test is measured by c-statistics, SN/SP and positive/negative predictive value. The results are compared to imaging and histopathology records (where available). Human factor and budget impact analysis of the future inclusion of the urine test into the diagnostic and surveillance pathways for PDAC patients is ongoing (PI: Dr M Z Ni and the team, Imperial College London, UK). Results and conclusions. At present, 1067 patients have been recruited, and urine samples from 825 patients have been assayed. An interim analysis has shown promising results with SP of 91% and SN of 86%, and accuracy of cancer detection of 90%. Combined with the health economic analysis, we currently work towards the future implementation of this test into clinical practice, with the potential to significantly improve the current diagnostic pathway for individuals at risk of pancreatic cancer. 1. Radon, TP, et al. Clin Cancer Res, 2015; 21:3512-21. 2. Debernardi, S, et al. PLOSMed, 17(12); e1003489. 3. Blyuss, O, et al. Br J Cancer, 2020; 122:692-6. 4. Debernardi, S, et al. Int J Cancer, 2023; 152:769–80. Citation Format: Silvana Debernardi, Evelyn Kurotova, Nurshad Ali, Mariam Mahamood, Ismita Chhetri, Steve Pereira, Patrick Wilson, Bill Greenhalf, Melody Z Ni, Oleg Blyuss, Tatjana Crnogorac-Jurcevic. UroPanc: A large prospective observational study for validation of urinary biomarker test for the earlier detection of pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B018.

Digital remote monitoring of chronic retinal conditions-A clinical future tool? : Remote monitoring of chronic retinal conditions

In view of the predicted increase in incidence and prevalence of chronic retinal diseases and undersupply of care in the population, telemedicine could contribute to reducing access barriers to healthcare and improving the results of treatment. A literature review on remote monitoring of chronic retinal diseases was carried out. The medical literature was searched for publications on remote monitoring of chronic retinal diseases. The results were compiled in anarrative overview. The four main topics in the literature are: validation studies, implementation strategies, acceptance/target group analyses and health economic analyses. Remote monitoring systems are based on visual function tests, imaging or patient reports and have been particularly investigated in age-related macular degeneration (AMD) and diabetic eye disease (DED). Studies indicate positive effects regarding an optimization of clinical care and afavorable safety profile but randomized controlled trials are lacking for the majority of monitoring tools. Remote monitoring could complement existing care structures for patients with chronic retinal diseases, especially AMD and DED. Promising systems are based on hyperacuity or optical coherence tomography, while patient-reported data are not commonly used; however, there is currently insufficient evidence justifying the use of remote monitoring systems in chronic retinal diseases in Europe and more research on the validation of remote monitoring systems is needed.

Linking for Impact: Enhancing Linked Data Infrastructure to Meet Clinical Trials Sector Needs

BackgroundAustralia possesses valuable population health data, yet its potential for advancing medical product development remains largely untapped. Transformative growth in the use of linked data in clinical trials will support Australia’s therapeutic development sector to be more responsive in the development of new therapeutics and the monitoring and surveillance of their safety and effectiveness. MethodsWe conducted interviews with clinical trialists and data linkage experts to understand the current state and awareness of linked data within the clinical trials sector, identify existing pain points in the linkage process, and explore opportunities for improving visibility and access for the clinical trials sector. Researchers represented all stages of the medical product development pipeline and had a diverse range of experience with linked data. ResultsInterviews revealed numerous barriers hindering the clinical trials sector from effectively using linked data, limiting its impact. Barriers included a lack of awareness, the complexity of the application and approval process, and lengthy delays in accessing data. Participants readily recognised several ways that linkage of real-world data could be applied to their work in clinical trials, with pre-recruitment data, measurements of primary and secondary endpoints, and health economic analysis being the most consistently noted use cases. ConclusionTo optimise the use of linked data to support clinical trials and medical product development in Australia, increased awareness among the therapeutic development sector regarding available real-world data and its potential is needed urgently. Lowering the barriers to accessing linked data will enhance health services and patient outcomes across Australia.

Linking for Impact: Enhancing Linked Data Infrastructure to Meet Clinical Trials Sector Needs

BackgroundAustralia possesses valuable population health data, yet its potential for advancing medical product development remains largely untapped. Transformative growth in the use of linked data in clinical trials will support Australia’s therapeutic development sector to be more responsive in the development of new therapeutics and the monitoring and surveillance of their safety and effectiveness. MethodsWe conducted interviews with clinical trialists and data linkage experts to understand the current state and awareness of linked data within the clinical trials sector, identify existing pain points in the linkage process, and explore opportunities for improving visibility and access for the clinical trials sector. Researchers represented all stages of the medical product development pipeline and had a diverse range of experience with linked data. ResultsInterviews revealed numerous barriers hindering the clinical trials sector from effectively using linked data, limiting its impact. Barriers included a lack of awareness, the complexity of the application and approval process, and lengthy delays in accessing data. Participants readily recognised several ways that linkage of real-world data could be applied to their work in clinical trials, with pre-recruitment data, measurements of primary and secondary endpoints, and health economic analysis being the most consistently noted use cases. ConclusionTo optimise the use of linked data to support clinical trials and medical product development in Australia, increased awareness among the therapeutic development sector regarding available real-world data and its potential is needed urgently. Lowering the barriers to accessing linked data will enhance health services and patient outcomes across Australia.

A Three-Day Prehabilitation Program is Cost-Effective for Preventing Pulmonary Complications after Heart Valve Surgery: A Health Economic Analysis of a Randomized Trial.

While prehabilitation (pre surgical exercise) effectively prevents postoperative pulmonary complications (PPCs), its cost-effectiveness in valve heart disease (VHD) remains unexplored. This study aims to evaluate the cost-effectiveness of a three-day prehabilitation program for reducing PPCs and improving quality adjusted life years (QALYs) in Chinese VHD patients. A cost-effectiveness analysis was conducted alongside a randomized controlled trial featuring concealed allocation, blinded evaluators, and an intention-to-treat analysis. In total, 165 patients scheduled for elective heart valve surgery at West China Hospital were randomized into intervention and control groups. The intervention group participated in a three-day prehabilitation exercise program supervised by a physiotherapist while the control group received only standard preoperative education. Postoperative hospital costs were audited through the Hospital Information System, and the EuroQol five-dimensional questionnaire was used to provide a 12-month estimation of QALY. Cost and effect differences were calculated through the bootstrapping method, with results presented in cost-effectiveness planes, alongside the associated cost-effectiveness acceptability curve (CEAC). All costs were denominated in Chinese Yuan (CNY) at an average exchange rate of 6.73 CNY per US dollar in 2022. There were no statistically significant differences in postoperative hospital costs (8484 versus 9615 CNY, 95% CI -2403 to 140) or in the estimated QALYs (0.909 versus 0.898, 95% CI -0.013 to 0.034) between the intervention and control groups. However, costs for antibiotics (339 versus 667 CNY, 95% CI -605 to -51), nursing (1021 versus 1200 CNY, 95% CI -330 to -28), and electrocardiograph monitoring (685 versus 929 CNY, 95% CI -421 to -67) were significantly lower in the intervention group than in the control group. The CEAC indicated that the prehabilitation program has a 92.6% and 93% probability of being cost-effective in preventing PPCs and improving QALYs without incurring additional costs. While the three-day prehabilitation program did not significantly improve health-related quality of life, it led to a reduction in postoperative hospital resource utilization. Furthermore, it showed a high probability of being cost-effective in both preventing PPCs and improving QALYs in Chinese patients undergoing valve surgery. This trial is registered in the Chinese Clinical Trial Registry (URL: https://www.chictr.org.cn/) with the registration identifier ChiCTR2000039671.

An out-of-court community-based programme to improve the health and well-being of young adult offenders: the Gateway RCT.

Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences. To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution). Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters. Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use. Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting. Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe. The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings. This study is registered as ISRCTN11888938. This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

45 Optimising the management of chronic ischemic heart disease by training general practitioners to deliver very brief advice on physical activity (OptiCor)

Abstract Purpose The German treatment guideline “chronic ischemic/coronary heart disease (IHD)” recommends that general practitioners (GPs) deliver advice on physical activity (PA) to IHD patients. This recommendation is inadequately implemented, often due to GP’s insufficient specific training. International guidelines recommend training GPs in how to deliver PA advice effectively and efficiently. Evidence is lacking on how such training should be designed to match the recipients’ needs, and whether it improves the frequency and quality of advice. With OptiCor we aim to systematically develop and evaluate such a training for GPs to optimise the routine care of IHD patients. Project OptiCor has started in 2022. It comprises three phases over five years. The methodology matches the Medical Research Council framework recommendations for complex interventions. GPs and patients are substantially involved throughout the entire project. OptiCor (funded by the German Ministry of Education and Research) will be presented internationally for the first time. Phase 1 (needs analysis/development)–completed: A nationwide, face-to-face household survey was used to collect data on the receipt of GP-delivered PA advice in people with IHD. Focus group discussions and problem-centred interviews were conducted with GPs and patients with IHD to explore attitudes and motivation towards, experiences with, and barriers and facilitators of PA advice implementation or reception, respectively. The findings are now being used to inform the theory-based training development. Phase 2 (pilot): A pragmatic cluster randomised controlled trial (cRCT) on the effectiveness of the GP training on delivered PA advice during routine care of IHD patients will be pilot tested in summer 2024. Phase 3 (evaluation): A full pragmatic cRCT will be conducted from 2025 onwards (primary endpoint: patient-reported proportions of GP-delivered PA advice). Health economic and process-related analyses will facilitate a potential future broad dissemination and health economic evaluation of the training. Conclusions If our training successfully enhances the proportions and quality of delivered PA advice to IHD patients, it represents a low-threshold strategy for a broad implementation in general practice. The training could extend existing projects on PA referral/prescription schemes, and it could be transferred to the management of other diseases or to other healthcare settings.

Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.

68. Health economic analysis of neurologically intact thoracolumbar A3 and A4 fractures is dominant in supporting surgery over nonsurgical treatment

68. Health economic analysis of neurologically intact thoracolumbar A3 and A4 fractures is dominant in supporting surgery over nonsurgical treatment

Development and validation of prediction models for fetal growth restriction and birthweight: an individual participant data meta-analysis.

Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Maternal clinical characteristics, biochemical and ultrasound markers. fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight. First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance (c-statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model. Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c-statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g). We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data. International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation. The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management. This study is registered as PROSPERO CRD42019135045. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Assessing economic investment required to scale up bariatric surgery capacity in England: a health economic modelling analysis

ObjectivesTo quantify the economic investment required to increase bariatric surgery (BaS) capacity in National Health Service (NHS) England considering the growing obesity prevalence and low provision of BaS in England...

Health economic evaluation of an electronic mindfulness-based intervention (eMBI) to improve maternal mental health during pregnancy – a randomized controlled trial (RCT)

BackgroundAnxiety and depression are the most prevalent psychiatric diseases in the peripartum period. They can lead to relevant health consequences for mother and child as well as increased health care resource utilization (HCRU) and related costs. Due to the promising results of mindfulness-based interventions (MBI) and digital health applications in mental health, an electronic MBI on maternal mental health during pregnancy was implemented and assessed in terms of transferability to standard care in Germany. The present study focused the health economic outcomes of the randomized controlled trial (RCT).MethodsThe analysis, adopting a payer’s and a societal perspective, included women of increased emotional distress at < 29 weeks of gestation. We applied inferential statistics (α = 0.05 significance level) to compare the intervention group (IG) and control group (CG) in terms of HCRU and costs. The analysis was primarily based on statutory health insurance claims data which covered the individual observational period of 40 weeks.ResultsOverall, 258 women (IG: 117, CG: 141) were included in the health economic analysis. The results on total health care costs from a payer’s perspective indicated higher costs for the IGi compared to the CG (Exp(ß) = 1.096, 95% CI: 1.006–1.194, p = 0.037). However, the estimation was not significant after Bonferroni correction (p < 0.006). Even the analysis from a societal perspective as well as sensitivity analyses did not show significant results.ConclusionsIn the present study, the eMBI did neither reduced nor significantly increased health care costs. Further research is needed to generate robust evidence on eMBIs for women suffering from peripartum depression and anxiety.Trial registrationGerman Clinical Trials Register: DRKS00017210. Registered on 13 January 2020. Retrospectively registered.