Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care: Protocol for the UK-ROX trial.

Background: In the United Kingdom, around 184,000 adults are admitted to an intensive care unit (ICU) each year with over 30% receiving mechanical ventilation. Oxygen is the commonest therapeutic intervention provided to these patients but it is unclear how much oxygen should be administered for the best clinical outcomes. Methods: The UK-ROX trial will evaluate the clinical and cost-effectiveness of conservative oxygen therapy (the minimum oxygen concentration required to maintain an oxygen saturation of 90% ± 2%) versus usual oxygen therapy in critically ill adults receiving supplemental oxygen when invasively mechanically ventilated in ICUs in England, Wales and Northern Ireland. The trial will recruit 16,500 patients from approximately 100 UK adult ICUs. Using a deferred consent model, enrolled participants will be randomly allocated (1:1) to conservative or usual oxygen therapy until ICU discharge or 90 days after randomisation. Objectives: The primary clinical outcome is all cause mortality at 90 days following randomisation. Discussion: The UK-ROX trial has received ethical approval from the South Central - Oxford C Research Ethics Committee (Reference: 20/SC/0423) and the Confidentiality Advisory Group (Reference: 22/CAG/0154). The trial commenced in May 2021 and, at the time of publication, 95 sites had opened to recruitment.

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

OBJECTIVES: Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. DESIGN: Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. SETTING: Eighteen PICUs across the United Kingdom. PATIENTS: Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. INTERVENTIONS: Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). CONCLUSIONS: Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

Estimating the hospital costs of care for people living with HIV in England using routinely collected data.

BACKGROUND: Understanding the health care activity and associated hospital costs of caring for people living with HIV is an important component of assessing the cost effectiveness of new technologies and for budget planning. METHODS: Data collected between 2010 and 2017 from an English HIV treatment centre were combined with national reference costs to estimate the rate of hospital attendances and costs per quarter year, according to demographic and clinical factors. The final dataset included records for 1763 people living with HIV, which was analysed using negative binomial regression models and general estimating equations. RESULTS: People living with HIV experienced an unadjusted average of 0.028 (standard deviation [SD] 0.20) inpatient episodes per quarter, equivalent to one every 9 years, and 1.85 (SD 2.30) outpatient visits per quarter. The unadjusted mean quarterly cost per person with HIV (excluding antiretroviral drug costs) was £439 (SD 604). Outpatient appointments and inpatient episodes accounted for 88% and 6% of total costs, respectively. In adjusted models, low CD4 count was the strongest predictor of inpatient stays and outpatient visits. Low CD4 count and new patient status (having a first visit at the Trust in the last 6 months) were the factors that most increased estimated costs. Associations were weaker or less consistent for demographic factors (age, sex/sexual orientation/ethnicity). Sensitivity analyses suggest that the findings were generally robust to alternative parameter and modelling assumptions. CONCLUSION: A number of factors predicted hospital activity and costs, but CD4 cell count and new patient status were the strongest. The study results can be incorporated into future economic evaluations and budget impact assessments of HIV-related technologies.

Cost-effectiveness of alternative minimum recall intervals between whole blood donations.

BACKGROUND: The INTERVAL trial showed shorter inter-donation intervals could safely increase the frequency of whole-blood donation. We extended the INTERVAL trial to consider the relative cost-effectiveness of reduced inter-donation intervals. METHODS: Our within-trial cost-effectiveness analysis (CEA) used data from 44,863 whole-blood donors randomly assigned to 12, 10 or 8 week (males), and 16, 14 or 12 week inter-donation intervals (females). The CEA analysed the number of whole-blood donations, deferrals including low- haemoglobin deferrals, and donors' health-related quality of life (QoL) to report costs and cost-effectiveness over two years. FINDINGS: The mean number of blood donation visits over two years was higher for the reduced interval strategies, for males (7.76, 6.60 and 5.68 average donations in the 8-, 10- and 12- week arms) and for females (5.10, 4.60 and 4.01 donations in the 12-, 14- and 16- week arms). For males, the average rate of deferral for low haemoglobin per session attended, was 5.71% (8- week arm), 3.73% (10- week), and 2.55% (12- week), and for females the rates were: 7.92% (12-week), 6.63% (14- week), and 5.05% (16- week). Donors' QoL was similar across strategies, although self-reported symptoms were increased with shorter donation intervals. The shorter interval strategies increased average cost, with incremental cost-effectiveness ratios of £9.51 (95% CI 9.33 to 9.69) per additional whole-blood donation for the 8- versus 12- week interval for males, and £10.17 (95% CI 9.80 to 10.54) for the 12- versus 16- week interval arm for females. CONCLUSIONS: Over two years, reducing the minimum donation interval could provide additional units of whole-blood at a small additional cost, including for those donor subgroups whose blood type is in relatively high demand. However, the significance of self-reported symptoms needs to be investigated further before these policies are expanded.

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Pediatric Intensive Care.

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Sp o2 ) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Sp o2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Sp o2 target of more than 94% or a conservative Sp o2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals.

Has Ebola delayed progress on access to routine care and financial protection in Sierra Leone? Evidence from a difference-in-differences analysis with propensity score weighting.

INTRODUCTION: Covid-19 has highlighted the need to understand the long-term impact of epidemics on health systems. There is extensive evidence that the Ebola epidemic of 2014-16 dramatically reduced coverage of key reproductive, maternal, newborn, child and adolescent health (RMNCAH) indicators during the period of acute crisis in Sierra Leone. However, less is known about the longer lasting effects, and whether patients continue to be deterred from seeking care either through fear or cost some years after the end of the epidemic METHODS: We analysed nationally representative household surveys from before (2011) and after (2018) the Ebola epidemic to estimate the coverage of 11 indicators of access to RMNCAH, and affordability of care. We used a differences-in-differences analysis, exploiting the variation in epidemic intensity across chiefdoms, to identify the effect of epidemic intensity on access and affordability outcomes, with propensity score weighting to adjust for differences in underlying characteristics between chiefdoms. RESULTS: 13537 households were included across both datasets. Epidemic intensity was associated with a significant stalling in progress (-12.2 percentage points, 95% CI: 23.2 to -1.3, p = 0.029) in the proportion of births attended by a skilled provider. Epidemic intensity did not have a significant impact on any other indicator. CONCLUSION: While there is evidence that chiefdoms which experienced worse Ebola outbreaks had poorer coverage of attendance of skilled providers at birth than would have otherwise been expected, more broadly the intensity of the epidemic did not impact on most indicators. This suggests the measures to restore both staffing and trust were effective in supporting the health system to recover from Ebola.

Cost-Effectiveness of Genetic Testing for All Women Diagnosed with Breast Cancer in China.

Unselected multigene testing for all women with breast cancer (BC) identifies more cancer susceptibility gene (CSG) carriers who can benefit from precision prevention compared with family history (FH)/clinical-criteria-based guidelines. Very little CSG testing is undertaken in middle-income countries such as China, and its cost-effectiveness remains unaddressed. We aimed to estimate cost-effectiveness and population impact of multigene testing for all Chinese BC patients. Data from 8085 unselected BC patients recruited to a Peking University Cancer Hospital study were used for microsimulation modeling, comparing three strategies in the Chinese setting: all BC women undergo BRCA1/BRCA2/PALB2 genetic testing, only BC women fulfilling FH/clinical criteria undergo BRCA testing, and no genetic testing. Prophylactic mastectomy and salpingo-oophorectomy would be adopted where appropriate. Societal and payer perspectives with a lifetime horizon along with sensitivity analyses were presented. Incremental cost-effectiveness ratio (ICER): incremental cost per quality-adjusted life-year (QALY) gained is compared to the USD 10,260/QALY (one-times GDP per capita) willingness-to-pay threshold. BC incidence, ovarian cancer (OC) incidence, and related deaths were also estimated. FH/clinical-criteria-based BRCA testing was ruled out on the principle of extensive dominance. Compared with no genetic testing, multigene testing for all BC patients had an ICER = USD 4506/QALY (societal perspective) and USD 7266/QALY (payer perspective), well below our threshold. Probabilistic sensitivity analysis showed unselected multigene testing remained cost-effective for 94.2%/86.6% of simulations from the societal and payer perspectives. One year's unselected multigene testing could prevent 7868 BC/OC cases and 5164 BC/OC deaths in China. Therefore, unselected multigene testing is extremely cost-effective and should be offered to all Chinese women with BC.

An International Comparison of EQ-5D-5L and EQ-5D-3L for Use in Cost-Effectiveness Analysis.

OBJECTIVES: To estimate the impact of using EQ5D-5L (5L) compared with EQ5D-3L (3L) in cost-effectiveness analyses in 6 countries with 3L and 5L values: Germany, Japan, Korea, The Netherlands, China, and Spain. METHODS: Eight cost-effectiveness analyses based on clinical studies with 3L provided 11 pairwise comparisons. We estimated cost-effectiveness by applying the appropriate country values for 3L to observed responses. We re-estimated cost-effectiveness for each country by predicting the 5L tariff score for each respondent, for each country, using a previously published mapping method. We compared results in terms of impact on estimated incremental quality-adjusted life-year (QALY) gain and cost-effectiveness ratios. RESULTS: For most countries the impact of moving from 3L to 5L is to lower the incremental QALY gain in the majority of comparisons. The only exception to this was Japan, where 4 out of 11 cases (37%) saw lower QALYs gained when using 5L. The mean and median reductions in health gain, in those case studies where 5L does lead to lower health gain, are largest in The Netherlands (84% mean reduction, 41% median reduction), Germany (68% and 27%), and Spain (30% and 31%). For most countries, those studies where 5L leads to lower health gain see larger reductions than the gains in studies showing the opposite tendency. CONCLUSIONS: Overall, 3L and 5L are not interchangeable in these countries. Differences between results are large, but the direction of change can be unpredictable. These findings should prompt further investigation into the reasons for differences.

Cost-Utility Analysis of a Complex Intervention to Reduce School-Based Bullying and Aggression: An Analysis of the Inclusive RCT.

OBJECTIVES: Bullying and aggression among children and young people are key public mental health priorities. In this study, we evaluated the cost-effectiveness of a complex school-based intervention to address these outcomes within a large-cluster randomized trial (Inclusive). METHODS: Forty state secondary schools were randomly allocated (1:1) to receive the intervention or continue with current practice as controls. Data were collected using paper questionnaires completed in classrooms including measures of their health-related quality of life using the Childhood Utility Index and police and National Health Service resource use. Further detailed data were collected on the cost of delivering the intervention. We calculated incremental cost-effectiveness ratios following the intention-to-treat principle using multilevel linear regression models that allowed for clustering of pupils at the school level. RESULTS: Overall, we found that the intervention was highly cost-effective, with cost-per quality-adjusted life year thresholds of £13 284 and £1875 at 2 years and 3 years, respectively. Analysis of uncertainty in the result at 2 years revealed a 65% chance of being cost-effective, but after 3 years there was a 90% chance that it was cost-effective. CONCLUSION: This study provides strong evidence collected prospectively from a randomized study that this school-based intervention is highly cost-effective. Education- and health-sector policy makers should consider investment in scaling up this intervention.

Costs of Early Invasive Breast Cancer in England Using National Patient-Level Data.

OBJECTIVES: This study aimed to use patient-level data to provide up-to-date estimates of early invasive breast cancer care costs by stage in England and to explore to what extent these costs varied based on patients' ages and geographic regions. METHODS: This study identified women aged 50 years and older who had been diagnosed with early invasive breast cancer between January 1, 2014, and December 31, 2015, using linked cancer registrations and routine hospital data sets generated from the usual care for all National Health Service trusts in England. Cost estimates were derived from hospital records in Hospital Episodes Statistics with additional chemotherapy and radiotherapy information from the national data sets. We fitted general linear regression models to analyze the cost data. The model that best fit the data was selected using the model selection criteria of Akaike information criterion. RESULTS: 55 662 women with early invasive breast cancer in England were included. The generalized linear model with log-gamma distribution fit the data best. The costs of breast cancer care for 1 year after diagnosis were strongly dependent on stage at diagnosis, controlling for other covariates. The estimated average per-patient hospital-related costs were £5167 at stage I, £7613 at stage II, and £13 330 at stage IIIA. Costs decreased with increasing age (P < .001) and varied across region (P < .001), deprivation level (P < .001), referral source (P < .01), presence of comorbidities (P< .001), and tumor receptor (ER/PR/HER2) status (P < .001). CONCLUSIONS: In England, the costs of breast cancer care increased with advancing stage of the disease at diagnosis. Breast cancer costs varied by age and geographic region.

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems.

Clinical criteria/Family history-based BRCA testing misses a large proportion of BRCA carriers who can benefit from screening/prevention. We estimate the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. A Markov model comparing the lifetime costs and effects of BRCA1/BRCA2 testing all general population women ≥30 years compared with clinical criteria/FH-based testing. Separate analyses are undertaken for the UK/USA/Netherlands (high-income countries/HIC), China/Brazil (upper-middle income countries/UMIC) and India (low-middle income countries/LMIC) using both health system/payer and societal perspectives. BRCA carriers undergo appropriate screening/prevention interventions to reduce breast cancer (BC) and ovarian cancer (OC) risk. Outcomes include OC, BC, and additional heart disease deaths and incremental cost-effectiveness ratio (ICER)/quality-adjusted life year (QALY). Probabilistic/one-way sensitivity analyses evaluate model uncertainty. For the base case, from a societal perspective, we found that population-based BRCA testing is cost-saving in HIC (UK-ICER = $-5639/QALY; USA-ICER = $-4018/QALY; Netherlands-ICER = $-11,433/QALY), and it appears cost-effective in UMIC (China-ICER = $18,066/QALY; Brazil-ICER = $13,579/QALY), but it is not cost-effective in LMIC (India-ICER = $23,031/QALY). From a payer perspective, population-based BRCA testing is highly cost-effective in HIC (UK-ICER = $21,191/QALY, USA-ICER = $16,552/QALY, Netherlands-ICER = $25,215/QALY), and it is cost-effective in UMIC (China-ICER = $23,485/QALY, Brazil-ICER = $20,995/QALY), but it is not cost-effective in LMIC (India-ICER = $32,217/QALY). BRCA testing costs below $172/test (ICER = $19,685/QALY), which makes it cost-effective (from a societal perspective) for LMIC/India. Population-based BRCA testing can prevent an additional 2319 to 2666 BC and 327 to 449 OC cases per million women than the current clinical strategy. Findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across HIC/UMIC health systems, is cost-saving for HIC health systems from a societal perspective, and can prevent tens of thousands more BC/OC cases.

Delivering a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: a descriptive costing study.

The Syrian conflict has caused enormous displacement of a population with a high non-communicable disease (NCD) burden into surrounding countries, overwhelming health systems' NCD care capacity. Médecins sans Frontières (MSF) developed a primary-level NCD programme, serving Syrian refugees and the host population in Irbid, Jordan, to assist the response. Cost data, which are currently lacking, may support programme adaptation and system scale up of such NCD services. This descriptive costing study from the provider perspective explored financial costs of the MSF NCD programme. We estimated annual total, per patient and per consultation costs for 2015-17 using a combined ingredients-based and step-down allocation approach. Data were collected via programme budgets, facility records, direct observation and informal interviews. Scenario analyses explored the impact of varying procurement processes, consultation frequency and task sharing. Total annual programme cost ranged from 4 to 6 million International Dollars (INT$), increasing annually from INT$4 206 481 (2015) to INT$6 739 438 (2017), with costs driven mainly by human resources and drugs. Per patient per year cost increased 23% from INT$1424 (2015) to 1751 (2016), and by 9% to 1904 (2017), while cost per consultation increased from INT$209 to 253 (2015-17). Annual cost increases reflected growing patient load and increasing service complexity throughout 2015-17. A scenario importing all medications cut total costs by 31%, while negotiating importation of high-cost items offered 13% savings. Leveraging pooled procurement for local purchasing could save 20%. Staff costs were more sensitive to reducing clinical review frequency than to task sharing review to nurses. Over 1000 extra patients could be enrolled without additional staffing cost if care delivery was restructured. Total costs significantly exceeded costs reported for NCD care in low-income humanitarian contexts. Efficiencies gained by revising procurement and/or restructuring consultation models could confer cost savings or facilitate cohort expansion. Cost effectiveness studies of adapted models are recommended.

Economic impact of Ebola virus disease outbreak on an extractive firm: a case study.

Purpose: The recent Ebola virus disease (EVD) epidemic was one of the most severe public health emergencies in modern times. The economic impact of epidemics has mostly been analysed at the macroeconomic level. Conversely, we aimed to estimate the economic costs of preventive measures of the epidemic to an extractive firm, ArcelorMittal (AM), using data in the epidemic region from March 2014 to December 2015. AM is the world's largest steel producer and is particularly important in West Africa, where the extractive industry is economically crucial. Methods: Qualitative methods, in-depth interviews (IDIs) and focus group discussions (FGDs), were used to investigate the events and channels of impact of the epidemic on the firm, as perceived by employees and contractors. Quantitative data regarding these costs were also collected. Retrospective cost analysis estimated the actual cost of preventive methods adopted. Results: Most respondents indicated the largest cost impact was suspension of the Phase II expansion, a series of projects designed to increase iron ore production in Liberia. The next largest cost was the preventive measures adopted to counter disease spread. Total costs incurred for adopting preventive measures were USD 10.58-11.11 million. The overall direct costs of preventive measures adopted within the fence, meaning within the physical boundary of the firm's sites, shared 30-31% of the total costs incurred. The share of external donations supporting humanitarian response was 11-12% of the total costs, followed by 7-12% of relational costs. Conclusions: The firm's response during the EVD epidemic focussed on its employees and operations, which was later expanded to the wider community and then in supporting the international humanitarian response.

Examining the use of economic evaluations in health-related humanitarian programmes in low- and middle-income countries: a systematic review.

The costly nature of health sector responses to humanitarian crises and resource constraints means that there is a need to identify methods for priority setting and long-term planning. One method is economic evaluation. The aim of this systematic review is to examine the use of economic evaluations in health-related humanitarian programmes in low- and middle-income countries. This review used peer-reviewed literature published between January 1980 and June 2018 extracted from four main electronic bibliographic databases. The eligibility criteria were full economic evaluations (which compare the costs and outcomes of at least two interventions and provide information on efficiency) of health-related services in humanitarian crises in low- and middle-countries. The quality of eligible studies is appraised using the modified 36-question Drummond checklist. From a total of 8127 total studies, 11 full economic evaluations were identified. All economic evaluations were cost-effectiveness analyses. Three of the 11 studies used a provider perspective, 2 studies used a healthcare system perspective, 3 studies used a societal perspective and 3 studies did not specify the perspective used. The lower quality studies failed to provide 7information on the unit of costs and did not justify the time horizon of costs and discount rates, or conduct a sensitivity analysis. There was limited geographic range of the studies, with 9 of the 11 studies conducted in Africa. Recommendations include greater use of economic evaluation methods and data to enhance the microeconomic understanding of health interventions in humanitarian settings to support greater efficiency and transparency and to strengthen capacity by recruiting economists and providing training in economic methods to humanitarian agencies.

Management of diabetes and associated costs in a complex humanitarian setting in the Democratic Republic of Congo: a retrospective cohort study.

OBJECTIVE: We aimed to evaluate an Integrated Diabetic Clinic within a Hospital Outpatient Department (IDC-OPD) in a complex humanitarian setting in North Kivu, Democratic Republic of Congo. Specific objectives were to: (1) analyse diabetes intermediate clinical and programmatic outcomes (blood pressure (BP)/glycaemic control, visit volume and frequency); (2) explore the association of key insecurity and related programmatic events with these outcomes; and (3) describe incremental IDC-OPD programme costs. DESIGN: Retrospective cohort analysis of routine programmatic data collected from January 2014 to February 2017; analysis of programme costs for 2014/2015. SETTING: Outpatient diabetes programme in Mweso hospital, supported by Médecins sans Frontières, in North Kivu, Demographic Republic of Congo. PARTICIPANTS: Diabetes patients attending IDC-OPD. OUTCOME MEASURES: Intermediate clinical and programmatic outcome trends (BP/ glycaemic control; visit volume/frequency); incremental programme costs. RESULTS: Of 243 diabetes patients, 44.6% were women, median age was 45 (IQR 32-56); 51.4% were classified type 2. On introduction of IDC-OPD, glucose control improved and patient volume and visit interval increased. During insecurity, control rates were initially maintained by a nurse-provided, scaled-back service, while patient volume and visit interval decreased. Following service suspension due to drug stock-outs, patients were less likely to achieve control, improving on service resumption. Total costs decreased 16% from 2014 (€36 573) to 2015 (€30 861). Annual cost per patient dropped from €475 in 2014 to €214 in 2015 due to reduced supply costs and increased patient numbers. CONCLUSIONS: In a chronic conflict setting, we documented that control of diabetes intermediate outcomes was achievable during stable periods. During insecure periods, a simplified, nurse-led model maintained control rates until drug stock-outs occurred. Incremental per patient annual costs were lower than chronic HIV care costs in low-income settings. Future operational research should define a simplified diabetes care package including emergency preparedness.

A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer.

Importance: Moving to multigene testing for all women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, the cost-effectiveness of this approach remains unaddressed. Objective: To estimate incremental lifetime effects, costs, and cost-effectiveness of multigene testing of all patients with BC compared with the current practice of genetic testing (BRCA) based on family history (FH) or clinical criteria. Design, Setting, and Participants: This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations. Data were obtained from 11 836 patients in population-based BC cohorts (regardless of FH) recruited to 4 large research studies. Data were collected and analyzed from January 1, 2018, through June 8, 2019. The time horizon is lifetime. Payer and societal perspectives are presented. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty. Interventions: In strategy A, all women with BC underwent BRCA1/BRCA2/PALB2 testing. In strategy B, only women with BC fulfilling FH or clinical criteria underwent BRCA testing. Affected BRCA/PALB2 carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO). Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention, or risk-reducing mastectomy for BC risk and RRSO for ovarian cancer (OC) risk. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with standard £30 000/QALY and $100 000/QALY UK and US thresholds, respectively. Incidence of OC, BC, excess deaths due to heart disease, and the overall population effects were estimated. Results: BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost £10 464/QALY (payer perspective) or £7216/QALY (societal perspective) in the United Kingdom or $65 661/QALY (payer perspective) or $61 618/QALY (societal perspective) in the United States compared with current BRCA testing based on clinical criteria or FH. This is well below UK and US cost-effectiveness thresholds. In probabilistic sensitivity analysis, unselected multigene testing remained cost-effective for 98% to 99% of UK and 64% to 68% of US health system simulations. One year's unselected multigene testing could prevent 2101 cases of BC and OC and 633 deaths in the United Kingdom and 9733 cases of BC and OC and 2406 deaths in the United States. Correspondingly, 8 excess deaths due to heart disease occurred in the United Kingdom and 35 in the United States annually. Conclusions and Relevance: This study found unselected, high-risk multigene testing for all patients with BC to be extremely cost-effective compared with testing based on FH or clinical criteria for UK and US health systems. These findings support changing current policy to expand genetic testing to all women with BC.

Cost-effectiveness of breast cancer screening programme for women in rural China.

In low and middle-income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China launched a breast cancer screening programme for rural women aged 35-64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost-effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non-screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality-adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost-effectiveness ratio (ICER) of $-916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost-effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.

Psychological outcomes following a nurse-led preventative psychological intervention for critically ill patients trial: Statistical and health economic analysis plan.

The Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients trial is a cluster-randomised controlled trial of the clinical and cost-effectiveness of a complex nurse-led preventative psychological intervention compared with usual care in reducing patient-reported post-traumatic stress disorder symptom severity, and other reported psychological morbidities, at six months among Level 3 (intensive care) patients in adult general critical care units in England, Wales and Northern Ireland. This paper describes the proposed statistical and health economic analyses for the Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients trial. It is important to complete and publish this plan before inspecting and locking the trial data to ensure that post hoc and data-derived decisions are avoided. Trial registration: ISRCTN53448131.

Global treatment costs of breast cancer by stage: A systematic review.

BACKGROUND: Published evidence on treatment costs of breast cancer varies widely in methodology and a global systematic review is lacking. OBJECTIVES: This study aimed to conduct a systematic review to compare treatment costs of breast cancer by stage at diagnosis across countries at different levels of socio-economic development, and to identify key methodological differences in costing approaches. DATA SOURCES: MEDLINE, EMBASE, and NHS Economic Evaluation Database (NHS EED) before April 2018. ELIGIBILITY CRITERIA: Studies were eligible if they reported treatment costs of breast cancer by stage at diagnosis using patient level data, in any language. STUDY APPRAISAL AND SYNTHESIS METHODS: Study characteristics and treatment costs by stage were summarised. Study quality was assessed using the Drummond Checklist, and detailed methodological differences were further compared. RESULTS: Twenty studies were included, 15 from high-income countries and five from low- and middle-income countries. Eleven studies used the FIGO staging system, and the mean treatment costs of breast cancer at Stage II, III and IV were 32%, 95%, and 109% higher than Stage I. Five studies categorised stage as in situ, local, regional and distant. The mean treatment costs of regional and distant breast cancer were 41% and 165% higher than local breast cancer. Overall, the quality of studies ranged from 50% (lowest quality) to 84% (highest). Most studies used regression frameworks but the choice of regression model was rarely justified. Few studies described key methodological issues including skewness, zero values, censored data, missing data, and the inclusion of control groups to estimate disease-attributable costs. CONCLUSIONS: Treatment costs of breast cancer generally increased with the advancement of the disease stage at diagnosis. Methodological issues should be better handled and properly described in future costing studies.