Base-case Estimates Research Articles

Surgical-decision making in the setting of unsuspected N2 disease: a cost-effectiveness analysis.

Identification of unsuspected nodal metastasis may occur at the time of operation for a stage I non-small cell lung cancer. Guidelines for this scenario are unclear. Our goal was to assess the cost-effectiveness of aborting the operation in an attempt to first provide neoadjuvant systemic therapy compared with upfront resection. A computer simulation Markov model with a lifetime horizon was constructed to compare the costs and clinical outcomes, as measured by quality-adjusted life-years (QALYs), of upfront resection at the time of identification of unsuspected N2 mediastinal disease vs. aborting initial resection and continuing with neoadjuvant therapy prior to resection. Input parameters for the model were derived from published literature with costs measured from the healthcare perspective. The incremental cost-effectiveness ratio (ICER) was evaluated with a willingness-to-pay (WTP) threshold of $150,000/QALY. Both deterministic (one-, two-, and three-way) and probabilistic sensitivity analysis (PSA) were performed to assess the impact of variation in input parameter values on model results. Aborting initial resection in favor of neoadjuvant therapy resulted in both higher costs ($40,415 vs. $29,873) and more QALYs (3.95 vs. 2.84) relative to upfront resection, yielding an ICER of $9,526/QALY. While variation in overall survival had a significant impact on the ICER, perioperative variables did not. As the annual mortality of best-case therapy in the abort group increased from a base-case estimate of 11% to 15%, the ICER exceeded the WTP threshold of $150,000/QALY. Subsequent one- and two-way sensitivity analyses did not find substantially alter the overall results. PSA resulted in aborting resection to be cost-effective in 99.7% of samples, with 13% of samples dominating upfront resection. Treatment of stage IIIa lung cancer requires the input of a multidisciplinary team who must consider cost, quality of life, and overall survival. As new treatments are developed, further analyses should be performed to determine optimal therapy.

An economic evaluation of restorative justice post-sentence in England and Wales.

Participation in restorative justice interventions post-sentence has been shown to reduce reoffending and mitigate harm to victims. Investment in, and access to, restorative justice remains limited in England and Wales. An economic model was developed to synthesize the available evidence in order to develop contemporary and robust estimates of the economic impact of investment in restorative justice interventions. This research focused on direct and indirect restorative justice interventions for victims and offenders post-sentence in England and Wales. Included offences were those with an identifiable victim. A model was developed to estimate the social benefit-cost ratio of restorative justice, as well as the direct financial return to the criminal justice system. The modeled benefits of restorative justice included reductions in reoffending and direct wellbeing benefits for victims. It was not possible to incorporate direct wellbeing benefits for offenders due to evidence gaps. In the model, 8% of referrals to restorative justice resulted in direct restorative justice interventions and 19% resulted in indirect Restorative justice interventions. The modeled cost of the restorative justice pathway per direct intervention was £3,394. The base case estimate for the social benefit-cost ratio of restorative justice was £14 per £1 invested, with a direct return to the criminal justice system of £4 as a result of substantial reductions in reoffending. Scenario analysis suggested a plausible range of £7 to £20 social benefit per £1 invested. Hypothetically, increasing the proportion of eligible cases referred for a restorative justice intervention from 15 to 40% could be associated with an increase in investment of £5 m, and benefits to the criminal justice system totaling £22 m, implying a net saving of £17 m. The research suggests that Restorative justice has the potential to yield a substantial social return on investment (SROI) and direct return on investment to the criminal justice system. The economic case for investment in restorative justice centers on identifying offenders with a high risk of offending and enabling them to participate in an intervention that has been repeatedly demonstrated to help them to change their behavior.

A Telemedicine Solution to Minimize Unnecessary Emergency Department Transfers for Low-acuity Pediatric Orthopaedic Patients: A Model for Cost Minimization.

Unnecessary emergency department (ED) transfers represent a notable source of excess costs and misutilization of healthcare resources, particularly with management of acute pediatric musculoskeletal injuries. This study used institutional data to create a model investigating the expected costs of a formal peer-to-peer telemedicine intervention designed to triage pediatric orthopaedic transfers, which we hypothesized would decrease healthcare costs by minimizing unwarranted ED-to-ED transfers. In this retrospective modeling analysis, 350 pediatric orthopaedic trauma patients transferred to two in-network referral hospitals from outside facilities were identified and stratified into three groups representing how patients theoretically optimally could have been treated. Group 1 patients required ambulance transfer, group 2 patients required ED-level care but no ambulance transfer, and group 3 patients did not require ED-level care. Base case estimates for the proportions of patients in each group, probability of ambulance transport, and direct costs of care for each patient were derived from the database. A decision tree was developed to evaluate the expected costs of two triaging strategies: (1) transfer everyone or (2) triage first using e-consultation. Probabilistic sensitivity analyses were used to determine how the results of the decision analysis varied across ranges of cost and probability estimates. In the base case analysis, the telemedicine triage strategy was cheaper than the transfer-all strategy ($4,858 versus $6,610). In a 2-way sensitivity analysis comparing cost of a telemedicine visit and proportion of telemedicine triaged patients requiring ambulance transport, the telemedicine triage strategy remained cheaper than the transfer-all strategy across almost all possibilities for both variables. Additional potential benefits of triage before transfer, such as decreased length of time to completion of ED visit, cost to the family, and patient comfort and satisfaction, were not incorporated into this analysis. The potential for misdiagnosis related to telehealth and its potential costs were not included. We revealed substantial cost savings for the healthcare system from implementing a telehealth platform for peer-to-peer consultation when considering patient transfer for musculoskeletal trauma. Initial peer-to-peer e-consultations cost less than reflexive ambulance transfer in most situations. Economic Level II.

The long-term impact and value of curative therapy for HIV: a modelling analysis.

Curative therapies (CTx) to achieve durable remission of HIV disease without the need for antiretroviral therapy (ART) are currently being explored. Our objective was to model the long-term health and cost outcomes of HIV in various countries, the impact of future CTx on those outcomes and the country-specific value-based prices (VBPs) of CTx. We developed a decision-analytic model to estimate the future health economic impacts of a hypothetical CTx for HIV in countries with pre-existing access to ART (CTx+ART), compared to ART alone. We modelled populations in seven low-and-middle-income countries and five high-income countries, accounting for localized ART and other HIV-related costs, and calibrating variables for HIV epidemiology and ART uptake to reproduce historical HIV outcomes before projecting future outcomes to year 2100. Health was quantified using disability-adjusted life-years (DALYs). Base case, pessimistic and optimistic scenarios were modelled for CTx+ART and ART alone. Based on long-term outcomes and each country's estimated health opportunity cost, we calculated the country-specific VBP of CTx. The introduction of a hypothetical CTx lowered HIV prevalence and prevented future infections over time, which increased life-years, reduced the number of individuals on ART, reduced AIDS-related deaths, and ultimately led to fewer DALYs versus ART-alone. Our base case estimates for the VBP of CTx ranged from $5400 (Kenya) up to $812,300 (United States). Within each country, the VBP was driven to be greater primarily by lower ART coverage, lower HIV incidence and prevalence, and higher CTx cure probability. The VBP estimates were found to be greater in countries where HIV prevalence was higher, ART coverage was lower and the health opportunity cost was greater. Our results quantify the VBP for future curative CTx that may apply in different countries and under different circumstances. With greater CTx cure probability, durability and scale up, CTx commands a higher VBP, while improvements in ART coverage may mitigate its value. Our framework can be utilized for estimating this cost given a wide range of scenarios related to the attributes of a given CTx as well as various parameters of the HIV epidemic within a given country.

Impact of Anti-EGFR Therapies on HER2-Positive Metastatic Colorectal Cancer: A Systematic Literature Review and Meta-Analysis of Clinical Outcomes.

HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes. A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses. Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates. While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.

The social cost of methane

A rapid and sustained reduction of methane emissions has been proposed recently as a key strategy to meet the climate targets of the Paris Agreement. The social cost of methane (SCM), which expresses the climate damage cost associated with an additional metric ton of methane emitted, is a metric that can be used to design policies to reduce the emissions of this gas. Here, we extend the DICE-2016R2 model so that it includes an improved carbon cycle and energy balance model as well as methane emissions, methane abatement cost, and an atmospheric methane cycle explicitly to be able to provide consistent estimations of the SCM. We estimate the SCM to lie in the range 880–8100 USD/tCH4 in 2020, with a base case estimate of 4000 USD/tCH4. We find our base case estimate to be larger than the average SCM presented in other studies mainly due to the revised damage function we use. We also estimate the social cost of carbon (SCC) and find that SCM estimates are less sensitive to variations in the social discount rate than the SCC due to the relatively short lifetime of methane. Changes in the parameterization of the damage function have similar relative impacts on both SCM and SCC. Furthermore, we evaluate the ratio of SCM to SCC as an alternative metric to GWP-100 of CH4 to facilitate tradeoffs between these two gases. We find this ratio to lie in the range 7–33 in 2020, with a base case estimate of 21, based on an extensive sensitivity analysis with respect to the discount rate, damage cost, and underlying emission scenarios. We also show that the global warming potential (GWP) and the SCM to SCC ratio are almost the same if the inverse of the effective discounting (in the social cost calculations) is equal to the time horizon used to evaluate the GWP. For comparison, the most widely used GWP, i.e., with a time horizon of 100 years, equals 27, hence in the upper range of the ratio we find using the SCM to SCC ratio.

(441) Quantifying Men with Erectile Dysfunction Potential Candidates for Penile Prosthesis Implantation in the US

Abstract Introduction While penile prosthesis implantation (PPI) is a recommended treatment option per the American Urological Association for men with erectile dysfunction (ED), there are a limited number of urologists performing PPI procedures in the US. Objective This study quantified the number of US men with ED and projected the number of potential candidates for PPI in 2022. Methods An excel-based disease-impact model was constructed using a top-down estimation approach based on two age groups for ED: 18-64 and ≥65 years old. The starting US male population was extracted from the 2022 US Census after the removal of age-specific mortality rates obtained from the National Vital Statistics Reports. Only men who subscribed to public or private health insurance were included in the model using insurance status data from the US Census. ED prevalence rates were obtained from administrative claims data analyses (IBM® MarketScan® Commercial Database [18-64 years] and 5% Medicare Standard Analytical Files [≥65 years]) using relevant International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes to calculate a base-case estimate of men with ED. To quantify the number of PPI candidates, the rate of men with ED but without ED treatment was obtained from the claims data and combined with the proportion of men with moderate-to-severe ED obtained from published research. The ED prevalence obtained from the administrative claims data analyses reflects a documented diagnosis of ED, which may underestimate the actual US prevalence of ED. Therefore, scenario analyses were conducted using patient-reported ED prevalence data obtained from a literature search of Medline. Results Using the ED prevalence obtained from the administrative claims data analyses, an estimated 8.3% of insured men (8,882,548 aged 18-64 and 1,419,992 aged ≥65) had a diagnosis of ED from 124,318,519 eligible US men aged ≥18 in 2022. The base-case estimate using claims data for the untreated ED rate and published literature for the proportion with moderate-to-severe ED showed 17.1% of men with an ED diagnosis claim could benefit from PPI (1,759,248 men aged ≥18). The literature review for the scenario analyses identified 11 publications from 2000 to 2020 with patient-reported ED prevalence. ED prevalence was assessed using different methods: International Index of Erectile Function (IIEF; 3 publications, 27.3%), Massachusetts Male Aging Study (MMAS)-derived questionnaire (3 publications, 27.3%), and other patient self-reported questionnaires (5 publications, 45.5%). Patient self-reported ED prevalence across all ages ranged from 5.1% to 70.2%. Applying the patient self-reported ED prevalence range to the scenario analyses, it was found that as many as 13,436,363 men in the US with ED could benefit from PPI. Conclusions From this disease-impact model, the estimated number of US men with ED is 124,318,519 as of 2022. Between 1.7 and 13.4 million of these men could potentially benefit from PPI. Ensuring sufficient penile prosthesis implanters could mitigate the potential physical, emotional, and social burden of untreated ED. Disclosure Yes, this is sponsored by industry/sponsor: Boston Scientific Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific

Cost-effectiveness of ultrasound before non-invasive prenatal screening for fetal aneuploidy.

To determine the cost-effectiveness of first-trimester ultrasound before fetal aneuploidy screening with cell-free DNA (cfDNA) compared with screening by cfDNA alone. A decision analytic model was constructed for 400 000 pregnant individuals with advanced maternal age who desired first-trimester aneuploidy screening with cfDNA in the USA, to compare two screening strategies: (1) cfDNA only and (2) ultrasound performed within 4 weeks before cfDNA. Input parameters included probability of fetal aneuploidy, cfDNA performance, desire for diagnostic testing, pregnancy outcomes, and pregnancy and lifetime costs and utilities. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), in terms of cost in 2020 US dollars (USD) per quality-adjusted life year (QALY) gained. Secondary outcomes included procedure-related loss, pregnancy termination, live birth with aneuploidy, live birth with structural anomaly and stillbirth. Discounting was performed at 3% per year with an estimated maternal lifespan of 81 years starting at the age of 35 years. One-way, multiway and Monte Carlo probabilistic sensitivity analyses were performed. All base-case estimates and ranges of uncertainty were derived from the literature. The willingness-to-pay threshold was set at 100 000 USD per QALY. In the base-case analysis, ultrasound before cfDNA screening was more cost-effective than cfDNA screening without pretest ultrasound, with an ICER of 12 588 USD and higher net monetary benefit (24 241 vs 20 466). The strategy involving ultrasound before cfDNA was more costly by 544 USD but also more effective (by 0.04 QALY) compared with cfDNA alone. Base-case results were robust in sensitivity analyses with the strategy involving ultrasound before cfDNA always remaining the most cost-effective approach with the highest net monetary benefit. First-trimester ultrasound before cfDNA is a more cost-effective strategy for non-invasive prenatal aneuploidy screening compared with cfDNA alone. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Cost effectiveness of liquid biopsy for colorectal cancer screening.

73 Background: Despite established screening guidelines, adherence to colonoscopy is approximately 60%. Blood-based screening tests, or Liquid Biopsies (LB), have the potential to close this screening gap. Our aim was to determine the cost-effectiveness of LB tests for CRC screening in the US. Methods: We developed a Markov model to compare four CRC screening strategies: no screening, or natural history (NH), colonoscopy (Colo) only, LB only, and colonoscopy to LB hybrid (C-LB). US SEER CRC incidence and mortality data were used to develop and validate the model. Many LB tests are in development awaiting validation; we used the preliminary performance characteristics for CRC screening of 82% sensitivity and 99.5% specificity (base case) from the Galleri multi-cancer early detection test (GRAIL). Screening ran from age 45 to 75; polyp surveillance ended at 85. We assumed 60.6% of the US population would undergo a screening colonoscopy, and 100% adherence for LB. In Colo, nonadherent patients were not offered other screening; in C-LB those who refused colonoscopy underwent LB. Primary outcomes were overall survival, total cost, incremental cost-effectiveness ratio (ICER), number of CRCs, and CRC deaths. Results: In the NH strategy, 5.2% of the population developed CRC and 1.8% died from CRC, with a cost of $7,802.15/individual. Compared to NH, in Colo, 40% of CRCs and 44% of CRC deaths were prevented, at a cost of $10,610.43/individual. In C-LB, 42% of CRCs and 50% of CRC deaths were prevented compared to NH, costing $13,762.61/individual. LB only prevented 2.0% of CRCs and 11% of CRC deaths compared to NH, and cost $34,339.85/individual. While LB showed an incremental benefit of 0.01 life years gained compared to NH, the ICER compared to NH is $2,653,770. Colo was most cost-effective with an ICER of $30,191.04. Although C-LB prevented the greatest number of CRCs, this strategy had an ICER of $457,057.64, above the accepted US willingness to pay threshold of $100,000/life year. We performed sensitivity analysis around base case estimates for LB. At both 70% and 90% test sensitivity, all outcomes remained largely constant. Conclusions: CRC screening with LB alone or with LB in conjunction with colonoscopy among nonadherent patients is not cost-effective in the US context. At this time, LB is unable to detect pre-cancerous colon polyps, which may limit its effectiveness as a CRC screening strategy. [Table: see text]

Surveillance of Severe Acute Respiratory Infection and Influenza Vaccine Effectiveness among Hospitalized Italian Adults, 2021/22 Season

Following an extremely low incidence of influenza during the first waves of the ongoing COVID-19 pandemic, the 2021/22 Northern Hemisphere winter season saw a resurgence of influenza virus circulation. The aim of this study was to describe epidemiology of severe acute respiratory infections (SARIs) among Italian adults and estimate the 2021/22 season influenza vaccine effectiveness. For this purpose, a test-negative case-control study was conducted in a geographically representative sample of Italian hospitals. Of 753 SARI patients analyzed, 2.5% (N = 19) tested positive for influenza, most of which belonged to the A(H3N2) subtype. Phylogenetic analysis showed that these belonged to the subclade 3C.2a1b.2a.2, which was antigenically different from the 2021/22 A(H3N2) vaccine component. Most (89.5%) cases were registered among non-vaccinated individuals, suggesting a protective effect of influenza vaccination. Due to a limited number of cases, vaccine effectiveness estimated through the Firth's penalized logistic regression was highly imprecise, being 83.4% (95% CI: 25.8-97.4%) and 83.1% (95% CI: 22.2-97.3%) against any influenza type A and A(H3N2), respectively. Exclusion of SARS-CoV-2-positive controls from the model did not significantly change the base-case estimates. Within the study limitations, influenza vaccination appeared to be effective against laboratory-confirmed SARI.

Selective Fetoscopic Laser Photocoagulation or Expectant Management for Stage I Twin-Twin Transfusion: A Cost-Effectiveness Analysis

Background: Selective fetoscopic laser photocoagulation (SFLP) is the preferred intervention for stage II-IV twin-twin transfusion syndrome (TTTS); however, there is no consensus on whether SFLP or expectant management (EM) is the preferred strategy to manage Quintero stage I TTTS. Objective: The objective of this study is to estimate whether SFLP or EM is the cost-effective strategy for management of Quintero stage I TTTS. Study Design: A decision-analysis (DA) model compared SFLP to EM for 1,000 pregnant people with monochorionic-diamniotic twins affected by stage I TTTS. All subjects were assumed to be appropriate candidates for either SFLP or EM. Probabilities, costs, and utilities were derived from the literature. The DA was conducted from a healthcare payor perspective, and the analytic horizon was over the course of an offspring’s lifetime, with primary outcomes of survivorship (i.e., no intrauterine fetal demise or neonatal death) and long-term neurodevelopmental impairment. The model incorporated Markov processes with 4-week cycles throughout pregnancy. Incremental cost-effectiveness ratios (ICER) for each strategy were calculated and compared to estimate marginal cost effectiveness. An ICER of USD 100,000 per quality-adjusted life year was used to define the cost-effectiveness threshold. One-way sensitivity and Monte Carlo analyses (MCA), as well as microsimulations, were performed. Results: For base-case estimates, SFLP was found to be cost-effective compared to EM in the management of stage I TTTS. In one-way sensitivity analysis, varying each variable along pre-specified ranges did not result in changes in the conclusion. MCA projects SFLP as the cost-effective strategy in 100% of runs. Conclusions: With base-case estimates, SFLP is estimated to be the cost-effective strategy for the treatment of Quintero stage I TTTS when compared with EM. This remained true across a wide range of inputs.

Estimating the Health Effects of Expansions in Health Expenditure in Indonesia: A Dynamic Panel Data Approach.

The marginal productivity of a country's healthcare system refers to the health gains produced per unit change in the level of spending. In budget-constrained settings, this metric reflects the opportunity cost, in terms of health gains forgone, of committing additional or existing resources to alternative uses within the healthcare system. It can therefore assist in evidence-based decisions on whether different interventions represent good value for money. The aim of this paper was to estimate the marginal productivity of the Indonesian healthcare system using subnational data, and to use this to inform health opportunity costs in the country. We define a dynamic health production function to model the stream of effects of current and prior public health spending decisions on population under-five mortality. To estimate the model, we use data from the 33 Indonesian provinces for the 2004-2012 period. The estimated elasticity is then translated into gains in terms of cost per DALY (disability-adjusted life-year) averted. We use dynamic panel data methods to address potential endogeneity issues in the model. Our base-case estimates suggest that a 1% expansion in the level of health spending reduces under-five mortality by 0.38% (95% CI 0.00-0.76), which translates into a cost of averting one DALY of $235 (2019 US$). With Indonesia aiming for universal health coverage, our results support these efforts by highlighting the associated benefits resulting from increases in public health expenditure and have the potential to inform the decision-making process about a suitable locally relevant cost-effectiveness threshold.

HIV incidence estimation among female sex workers in South Africa: a multiple methods analysis of cross-sectional survey data

Although numerous studies have investigated HIV risk factors and shown high HIV prevalence among female sex workers in South Africa, no national HIV incidence estimate exists for this potentially important group for HIV transmission. We aimed to estimate HIV incidence among female sex workers in South Africa who could be accessed through sex worker programmes, and to refine and describe the methods that enabled analysis. This study was embedded in a cross-sectional national survey of female sex workers who were linked to sex worker programmes. We aimed to enrol 3000 female sex workers aged at least 18 years who had sold or transacted in sex in the preceding 6 months in 12 randomly selected districts of the 22 districts with sex worker programmes, ensuring coverage of all provinces of South Africa. Women who self-reported as current victims of human trafficking were excluded from enrolment. We used a multistep process to sample districts and then hotspots, and a chain referral method to recruit participants. We collected cross-sectional data for self-reported HIV status, demographic characteristics, and exposure to violence. Two rapid tests were used to ascertain diagnostic markers, a viral load assay was used to ascertain clinical markers, and the Maxim Limiting Antigen Avidity EIA was used to ascertain infection-staging HIV markers. Given the challenges of estimating HIV incidence, especially cross-sectionally, multiple methods of estimation were adapted to our setting, leveraging the age structure of HIV prevalence, recency-of -infection biomarker results (ie, where recent infection is classified as ≤1·5 normalised optical density [ODn] on the avidity assay and viral load of ≥1000 copies per mL), and reported testing histories. Of 3005 female sex workers who were enrolled and interviewed between Feb 4 and June 26, 2019, 2999 who had HIV test results were included in this analysis. The median age of participants was 32 years (IQR 27-38). 1714 (57·2%) of 2999 participants self-reported as being HIV positive, and 1447 (48·3%) of 2993 participants reported client sexual violence in the past year. The measured HIV prevalence was 62·1% (95% CI 60·3-65·7) and peaked at approximately age 40 years. Using recency-of-infection biomarker results, we obtained a base case estimate of HIV incidence of 4·60 cases per 100 person-years (95% CI 1·53-8·45) for the population. Estimates were generally consistent by method, and outlying incidence estimates calculated by self-reported testing histories were considered unreliable. Various sensitivity analyses produced estimates up to 11 cases per 100 person-years, and we did not detect differences by age and region. We found that female sex workers have extraordinarily high HIV incidence of approximately 5 cases per 100 person-years, emphasising the need to sustain and strengthen efforts to mitigate risk and provide adequate care. The notable role that sex work has in HIV transmission demands substantial investment in ongoing epidemiological monitoring. South African Medical Research Council, South African National Treasury, Global Fund, South African Department of Science and Innovation, Wellcome Trust.

Universal first-trimester cytomegalovirus screening and valaciclovir prophylaxis in pregnant persons: a cost-effectiveness analysis

BACKGROUNDRecent studies have suggested a possible benefit of valaciclovir prophylaxis to prevent vertical transmission after a positive serologic screen for primary maternal cytomegalovirus infection during pregnancy, although its cost-effectiveness remains uncertain. OBJECTIVEThis study aimed to determine the circumstances under which universal first-trimester maternal serologic screening for maternal cytomegalovirus infection, with valaciclovir prophylaxis to prevent congenital cytomegalovirus, is cost-effective. STUDY DESIGNThis study was a decision analysis from the perspective of the pregnant person to assess whether universal maternal screening in the first trimester of pregnancy, with subsequent valaciclovir prophylaxis (8 g/day from the time of positive serologic screen for primary maternal cytomegalovirus infection to 21 weeks of gestation) for those who are acutely infected, is cost-effective compared with usual care (ie, no routine serologic screening but with amniocentesis if midtrimester sonographic findings suggest cytomegalovirus). For baseline estimates, this study assumed a 35% risk of congenital cytomegalovirus after primary maternal infection and a 71% risk reduction with valaciclovir. This study varied valaciclovir's efficacy to identify whether and at what threshold universal screening would be estimated to be cost-effective, compared with usual care. Monte Carlo analyses were performed. A willingness-to-pay threshold of $100,000/quality-adjusted life year was used to define cost-effectiveness. RESULTSUnder base case estimates, first-trimester universal screening and valaciclovir prophylaxis for seropositive pregnant persons with acute cytomegalovirus infection were not cost-effective, with a cost of $137,854 per maternal quality-adjusted life year but resulted in 14 fewer children affected with cytomegalovirus per 100,000 pregnancies compared with usual care. In 1-way sensitivity analysis, universal screening and treatment were estimated to be the cost-effective strategy if the incidence of primary maternal cytomegalovirus infection exceeds 2.6%, the baseline risk of vertical transmission of cytomegalovirus without prophylaxis is greater than 36.8%, and the risk reduction of vertical transmission of cytomegalovirus with valaciclovir prophylaxis exceeds 75.9%. In Monte Carlo analyses, first-trimester universal serologic screening with valaciclovir prophylaxis was estimated to be the cost-effective strategy in 46.8% of runs. CONCLUSIONUniversal first-trimester serologic screening with valaciclovir prophylaxis is not the cost-effective strategy for antenatal management of cytomegalovirus under the base case estimates. Although universal screening is cost-effective in certain circumstances when the efficacy of valaciclovir exceeds the base case, that result was not robust to variation of estimates across their reasonable ranges. These data can inform future studies to evaluate screening and treatment to prevent congenital cytomegalovirus.

Cost-effectiveness of adjuvant chemotherapy for patients with high-risk stage II and stage III colon cancer in South Africa.

6599 Background: Colon cancer (CC) incidence is rising globally, and case fatality rates are greatest in low-income settings, such as South Africa (SA). Adjuvant chemotherapy is standard of care for high-risk stage II and stage III CC in the US. We evaluated the cost-effectiveness of adjuvant chemotherapy for CC in SA public hospitals. Methods: We developed a decision-analytic Markov model comparing lifetime costs and outcomes for 60-year-old high-risk stage II and stage III CC patients treated in a SA public hospital with no adjuvant chemotherapy, versus: capecitabine and oxaliplatin (CAPOX) for 3 or 6 months or capecitabine for 6 months. High-risk stage II was defined as ≥1 of: T4 disease; poorly differentiated tumor; lymphovascular/perineural invasion; <12 lymph nodes dissected, bowel obstruction/perforation. Transition probabilities were derived from clinical trials estimating toxicity, disease recurrence, and survival. Costs from a SA societal perspective and utility estimates were obtained from literature and local expert opinion. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life year (DALY) averted, with a willingness-to-pay (WTP) threshold equal to 2021 GDP/capita of SA (I$13,764). Results: CAPOX for 3 months was the cost-effective strategy for stage III CC at a lifetime cost of I$5,284 and 5.55 DALYs averted, compared to no adjuvant treatment. All other strategies were absolutely dominated. For high-risk stage II CC, CAPOX for 3 months was the cost-effective strategy (ICER = I$711/DALY averted). No adjuvant chemotherapy was on the efficiency frontier, with a lower lifetime cost, but no DALYs averted. The results of one-way deterministic sensitivity analyses showed that the model is most sensitive to CC recurrence rate. In a probabilistic sensitivity analysis, CAPOX for 3 months was optimal in 88% of iterations for high-risk stage II CC and 79% of iterations for stage III CC. Conclusions: CAPOX for 3 months is the cost-effective adjuvant treatment for high-risk stage II and stage III CC in SA public hospitals. This strategy offers the highest quality of life benefit for the lowest cost and is well within the WTP threshold for SA. The optimal strategy in other settings will vary according to local WTP thresholds. Base case estimates of cost-effectiveness, in order of cost. [Table: see text]

Cost-effectiveness of multicomponent interventions in type 2 diabetes mellitus in a cluster randomised controlled trial: the INDICA study

ObjectiveTo analyse the cost-effectiveness of multicomponent interventions designed to improve outcomes in type 2 diabetes mellitus (T2DM) in primary care in the Canary Islands, Spain, within the INDICA randomised clinical...

An integrated approach to evaluate different tetracycline derivatives for formulary decisions

Stenotrophomonas maltophilia has emerged as a critical opportunistic pathogen associated with significant morbidity and mortality. Tetracycline derivatives have been recognized as alternative treatment options, but they have varied pharmacokinetic properties. An integrated approach to different tetracycline derivatives for formulary decisions is reported. The minimum inhibitory concentration (MIC) data from clonally diverse bloodstream S. maltophilia isolates were examined, along with the pharmacokinetic profiles of 4 tetracycline derivatives, to predict achievable pharmacodynamic exposures with standard intravenous dosing regimens. Antimicrobial therapy was assessed using the ratio of daily drug acquisition cost relative to the ratio of the free-drug area under the time-concentration curve (fAUC) to minimum inhibitory concentration (MIC) for 90% of isolates (fAUC/MIC90). In our analysis, minocycline had the greatest fAUC/MIC90. Doxycycline was the most financially preferred agent, as calculated using 2020 average wholesale price for base-case estimates of drug acquisition cost. An integrated evaluation for antimicrobial formulary decision-making addressed local susceptibility data, pharmacokinetics, pharmacodynamics, dosing regimens, and drug acquisition costs. This comprehensive method is more objective than the conventional approach and warrants validation.

Cost of illness of invasive meningococcal disease caused by serogroup B Neisseria meningitidis in Spain

IntroductionInvasive meningococcal disease (IMD) is a severe infectious disease, mainly affecting children under 5 years, associated with long-term physical, neurological and psychological sequelae. In Spain, most IMD cases are caused by meningococcal serogroup B (MenB). This study estimates its economic burden from a societal perspective in Spain. MethodsA previously published bottom-up, model-based incidence costing approach by Scholz et al. (2019) to estimate the economic burden of MenB in Germany was adapted to the Spanish setting. Diagnosis and age-related costs for a hypothetical Spanish cohort were calculated over a lifetime horizon. Official Spanish databases, literature and expert opinion were used as data sources. The costs were updated to 2019 prices, and a 3% discount rate was applied. Direct costs related to the acute IMD phase, long-term sequelae, rehabilitation and public health response were considered. Indirect costs included productivity losses and premature mortality and were calculated using the human-capital approach (HCA) and friction-cost approach (FCA). Deterministic and probabilistic sensitivity analyses were also performed. ResultAt base-case, the total cost for a cohort of 142 patients (2017–2018 period) was €4.74 million (€33,484/case) using the FCA and €13.14 million (€92,768/case) using the HCA. Direct costs amounted to €4.65 million (€32,765/case). Sequelae costs represented 62.46% of the total cost using the FCA and 77.63% using the HCA. Deterministic sensitivity analysis showed that variation of ± 20% in the input parameter values (population, epidemiology, productivity, costs) had the greatest influence on the base-case results, and the probabilistic sensitivity analysis showed the probability of fitting base-case estimates was > 99%, both for FCA and HCA. DiscussionMenB IMD is an uncommon but severe disease, with a high economic burden for Spanish society. The elevated costs per IMD case reflect its severity in each patient suffering this disease, especially due to the development of sequelae.

Take Your Best Shot: Which SARS-CoV-2 Vaccine Should I Get?

Background. Three vaccines against SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) have now received emergency use authorization by the US Food and Drug Administration. Patients may have the opportunity to make a choice about which vaccine they prefer to receive. Vaccine hesitancy is a hurdle to the development of widespread immunity, with many patients struggling to decide whether to get vaccinated at all. Objective. Develop a decision model exploring the question, “Should I get vaccinated with mRNA or adenovirus vector vaccine (AVV) if either is available now?”Design. Markov state transition model with lifetime time horizon. Data Sources. MEDLINE searches, bibliographies from relevant English-language articles. Setting. United States, ambulatory clinical setting. Participants. Previously uninfected, nonimmunized adults in the United States. Interventions. 1) Do Not Vaccinate, 2) Vaccination with mRNA Vaccine, 3) Vaccination with Adenovirus Vector Vaccine. Main Measures. Quality-adjusted life years (QALYs). Key Results. Base case—for a healthy 65-year-old patient, both vaccines yield virtually equivalent results (difference of 0.0028 QALYs). In sensitivity analyses, receiving the AVV is preferred if the short-term morbidity associated with each vaccine dose exceeds 1.8 days. Both vaccines afford an even greater benefit compared with Do Not Vaccinate if the pandemic is in a surge phase with a rising incidence of infection or if the current 7-day incidence is greater than the base case estimate of 105 cases per 100,000. Conclusions. Preferred vaccination strategies change under differing assumptions, but differences in outcomes are negligible. The best advice for patients is to get vaccinated against COVID-19 disease with whatever vaccine is available first. Providing mRNA vaccine to the remaining eligible US population would result in an aggregate gain of 3.92 million QALYs. Highlights Question: Now that three vaccines have received emergency use authorization to prevent SARS-CoV-2, should I get vaccinated with either the mRNA (Moderna or Pfizer) or the adenovirus vector (Janssen/Johnson & Johnson) vaccine if either one is available now?Findings: In our base case, for a healthy 65-year-old patient, an mRNA vaccine is very slightly preferred over the adenovirus vector vaccine by 0.0028 QALYs, or slightly more than 1 day. However, both vaccines afford a substantial benefit compared with not getting vaccinated.Meaning: In conclusion, although different vaccine strategies are preferred under different modeling assumptions, in the final analysis the differences in outcomes are extremely small. Our best advice is to simply get vaccinated with whatever is available the soonest!

Cost-Effectiveness of Repository Corticotropin Injection versus Standard of Care for the Treatment of Active Rheumatoid Arthritis.

IntroductionPatients with active rheumatoid arthritis (RA) often have inadequately controlled symptoms and are unable to achieve remission or low disease activity despite aggressive treatment. This results in irreversible joint damage, adversely affecting patients’ physical and social functioning. The objective was to estimate the cost-effectiveness of repository corticotropin injection (RCI) versus standard of care (SoC) in patients with active RA from the United States (US) payer and societal perspectives over two to three years.MethodsAn individual-level microsimulation was developed to generate individual trajectories for patients with RA, using data from a published Phase 4 trial of RCI. These trajectories report a patient’s disease pathway and associated cost and quality-of-life outcomes. The incremental cost-effectiveness ratio (ICER) of RCI versus SoC was assessed using the literature-derived direct medical and indirect costs, and quality-adjusted life-years (QALY) derived from a Phase 4 trial of RCI. The uncertainty in base case estimates of the parameters was evaluated in the sensitivity analysis.ResultsOver two years, RCI has an incremental QALY gain of 1.591 and incremental cost of $183,965 and $117,443 from payer and societal perspective, respectively, resulting in an ICER of $115,629/QALY and $73,817/QALY compared to SoC. Over three years, RCI has an incremental QALY gain of 2.336 and incremental cost of $202,315 and $104,506 from payer and societal perspective, respectively, resulting in an ICER of $86,607/QALY and $44,737/QALY compared to SoC. Results from the probabilistic sensitivity analysis are consistent with those of the base case model.ConclusionRCI is a cost-effective strategy for patients with persistently active RA who are previously treated with disease-modifying anti-rheumatic drugs and corticosteroids compared to SoC over two to three years from the payer and societal perspectives at a US willingness-to-pay threshold of $150,000/QALY. Further, the economic benefit of RCI is realized with improvement in a patient’s clinical and health outcomes.