Base-case Estimates Research Articles

Adverse Events Do Not Outweigh Benefits of Combination Therapy for Crohn's Disease in a Decision Analytic Model

The Study of Biologic and Immunomodulator-Naïve Patients With Crohn's Disease (SONIC) showed that combination therapy with infliximab and azathioprine (IFX/AZA) is more effective than treatment with IFX alone. Numbers and types of adverse events were roughly equivalent among groups, although enrollment was limited, so it was not clear how rare adverse events might affect overall outcomes in practice. We sought to define the frequency at which a rare adverse event would have to occur for the risks of combination therapy to outweigh the benefits of treatment. We constructed a decision model to compare the risks and benefits of IFX/AZA with IFX monotherapy. Model parameters were taken from SONIC and other published literature. The base-case analysis was patients with active Crohn's disease who are naïve to both medications (similar to those in SONIC) who were treated for 1 year. We used sensitivity analyses to determine the thresholds at which the risks of side effects from IFX/AZA outweigh its benefits. During 1 year, the benefits of IFX/AZA would outweigh the risks, unless serious infections occurred in 20% or more of the population or lymphoma in 3.9% or more. These thresholds are 5-fold and 65-fold higher than base-case estimates, respectively. On the basis of data from 1 year of SONIC, the combination of IFX/AZA was more effective than IFX alone in patients with Crohn's disease who are naïve to either drug. For the risks of combination therapy to outweigh the benefits in this time frame, the incidence of serious adverse events would have to be higher than seems clinically realistic.

The cost-effectiveness of public health interventions

The need to make best use of limited resources in the English National Health Service is now greater than ever. This paper contributes to this endeavour by synthesizing data from cost-effectiveness evidence produced to support the development of public health guidance at the National Institute of Health and Clinical Excellence (NICE). No comprehensive list of cost-effectiveness estimates for public health interventions has previously been published in England. Cost-effectiveness estimates using English cost data were collected and analysed from 21 (of 26) economic analyses underpinning public health guidance published by NICE between 2006 and 2010. Two hundred base-case cost-effectiveness estimates were analysed, 15% were cost saving (i.e. the intervention was more effective and cheaper than comparator). Eighty-five per cent were cost-effective at a threshold of £20,000 per quality-adjusted life year and 89% at the higher threshold of £30,000. A further 5.5% were above £30,000 and 5.5% of the interventions were dominated (i.e. the intervention was more costly and less effective than comparator). The majority of public health interventions assessed are highly cost-effective. The next challenge is to provide commissioners with a framework that allows information from economic analyses to be combined with other criteria that supports making better investment decisions at a local level.

Certolizumab Pegol Compared to Natalizumab in Patients with Moderate to Severe Crohn’s Disease: Results of a Decision Analysis

A significant proportion of patients with Crohn's disease (CD) lose response to antibodies directed against tumor necrosis factor α (TNF). Prior TNF-antagonist failure is associated with lower rates of response to subsequent TNF-antagonist therapy. In patients failing two anti-TNF agents, a choice exists between using a third-anti-TNF therapy or natalizumab (NAT), an α-4 integrin inhibitor. A cost-effectiveness analysis comparing these competing strategies has not been performed. A decision analytic model was constructed to compare the performance of certolizumab pegol (CZP) versus NAT in patients with moderate to severe CD. Previously published estimates of efficacy of third-line anti-TNF therapy and NAT were used to inform the model. Costs were expressed in 2010 US dollars. A 1-year time frame was used for the analysis. In the base case estimate, use of NAT was only marginally more effective [0.71 vs. 0.70 quality adjusted life-years (QALYs)] than CZP but was expensive with an incremental cost-effectiveness ratio (ICER) of $381,678 per QALY gained. For CZP 2 months response rate of at least 24%, NAT had an ICER above the willingness-to-pay (WTP) threshold. The model was sensitive to the costs of both therapies; for all CZP costs below $2,300 per dose, NAT had higher ICER than the WTP threshold. Substituting adalimumab for CZP resulted in similar ICER estimates and thresholds for NAT use. In patients with moderate to severe CD failing two TNF-antagonists, using a third TNF-antagonist therapy appears to be a cost-effective strategy without significantly compromising treatment efficacy.

Selective Application of Routine Preoperative Axillary Ultrasonography Reduces Costs for Invasive Breast Cancers

Preoperative axillary sonography with fine needle aspiration (FNA) in patients with invasive breast cancer identifies patients with nodal metastasis who can be spared further surgery. Indiscriminate use of the diagnostic modality can increase costs and yield inaccurate results. We evaluate the costs associated with the use of highly sensitive axillary ultrasonography in patients with stage ≥T2 tumors. We constructed a decision analysis tree using TreeAge Pro 2009 software comparing direct hospital charges between patients with and without routine use of axillary ultrasound. Base case estimates were derived from our institutional data and compared with those derived from the literature. One- and two-way sensitivity analyses were performed to check the validity of our inferences. We found that, for the base case estimate with 35% lymph node positivity in stage ≥T2 tumors and sensitivity of the axillary ultrasound set at 86% with a specificity of 40%, the strategy to perform preoperative axillary ultrasound yielded rollback costs of $15,215, compared with $15,940 for surgery plus sentinel lymph node biopsy (cost difference, $725 per patient favoring axillary ultrasound). On two-way sensitivity analysis, the cost benefit for axillary ultrasound was not seen in patients with a low risk for nodal metastasis. The adoption of routine preoperative axillary sonography with FNA is a lower-cost strategy than conventional strategies in patients with stage ≥T2 invasive breast cancer.

Trabectedin for the treatment of relapsed ovarian cancer

The paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of trabectedin for the treatment of relapsed platinum-sensitive ovarian cancer, based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submission addressed only part of the decision problem and did not provide evidence to compare trabectedin (Yondelis®, PharmaMar) and pegylated liposomal doxorubicin hydrochloride (PLDH) (Caelyx®, Schering-Plough) with key comparators. The submission's direct comparison evidence came from one reasonable-quality randomised controlled trial (RCT) of trabectedin and PLDH versus PLDH alone (ET743-OVA-301). The results of the RCT were subdivided into the entire platinum-sensitive population (> 6-month relapse after initial platinum-based chemotherapy) and partially platinum-sensitive (≥ 6- to 12-month relapse) and fully platinum-sensitive (> 12-month relapse) populations. The outcomes included were overall survival, progression-free survival measured by three types of assessor, response rates, adverse effects of treatment, health-related quality of life and cost per quality-adjusted-life-year (QALY) gained. A mixed treatment comparison (MTC) meta-analysis comparing trabectedin and PLDH with single-agent PLDH within the entire platinum-sensitive population, with paclitaxel or with topotecan also formed part of the submission. The RCT data showed that trabectedin plus PLDH compared with PLDH monotherapy had a significant effect on overall survival only within the partially platinum-sensitive subgroup. PFS results reported by the independent radiologists showed significant effects in favour of the trabectedin and PLDH arm for the entire and partially platinum-sensitive populations only. Rates of grade 3 and 4 adverse events were mostly higher in the trabectedin and PLDH arm than in the PLDH alone arm. There were several issues regarding the undertaking of the MTC, and thus the data were not considered robust. Furthermore, the ERG did not believe the MTC to be necessary to answer the decision problem. The manufacturer submitted a de novo cost-effectiveness model. The main analysis compared trabectedin in combination with PLDH versus paclitaxel, topotecan and PLDH (each as monotherapy) in the entire platinum-sensitive population, using results estimated from the MTC. Additional analyses were presented comparing trabectedin in combination with PLDH versus PLDH monotherapy using direct evidence from the OVA-301 trial for the fully, partially and entire platinum-sensitive populations. The cost per QALY gained for trabectedin in combination with PLDH versus PLDH monotherapy was estimated to be £ 70,076 in the main analysis. In the additional analyses, the cost per QALY gained for trabectedin in combination with PLDH versus PLDH monotherapy was £ 94,832, £ 43,996 and £ 31,092 for the entire, partially and fully platinum-sensitive populations, respectively. Additional work was undertaken by the ERG using patient-level data and amending some assumptions to provide a better statistical fit to the Kaplan-Meier data than the exponential distribution assumed by the manufacturer. The ERG base-case estimate of the cost per QALY of trabectedin in combination with PLDH ranged from £46,503 to £54,607 in the partially platinum-sensitive population. At the time of writing, trabectedin in combination with PLDH for the treatment of women with relapsed platinum-sensitive ovarian cancer is not recommended by NICE in the final appraisal determination.

Trabectedin for the treatment of relapsed ovarian cancer

The paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of trabectedin for the treatment of relapsed platinum-sensitive ovarian cancer, based upon a review of the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submission addressed only part of the decision problem and did not provide evidence to compare trabectedin (Yondelis®, PharmaMar) and pegylated liposomal doxorubicin hydrochloride (PLDH) (Caelyx®, Schering-Plough) with key comparators. The submission’s direct comparison evidence came from one reasonable-quality randomised controlled trial (RCT) of trabectedin and PLDH versus PLDH alone (ET743-OVA-301). The results of the RCT were subdivided into the entire platinum-sensitive population (> 6-month relapse after initial platinum-based chemotherapy) and partially platinum-sensitive (≥ 6- to 12-month relapse) and fully platinum-sensitive (> 12-month relapse) populations. The outcomes included were overall survival, progression-free survival measured by three types of assessor, response rates, adverse effects of treatment, health-related quality of life and cost per quality-adjusted-life-year (QALY) gained. A mixed treatment comparison (MTC) meta-analysis comparing trabectedin and PLDH with single-agent PLDH within the entire platinum-sensitive population, with paclitaxel or with topotecan also formed part of the submission. The RCT data showed that trabectedin plus PLDH compared with PLDH monotherapy had a significant effect on overall survival only within the partially platinum-sensitive subgroup. PFS results reported by the independent radiologists showed significant effects in favour of the trabectedin and PLDH arm for the entire and partially platinum-sensitive populations only. Rates of grade 3 and 4 adverse events were mostly higher in the trabectedin and PLDH arm than in the PLDH alone arm. There were several issues regarding the undertaking of the MTC, and thus the data were not considered robust. Furthermore, the ERG did not believe the MTC to be necessary to answer the decision problem. The manufacturer submitted a de novo cost-effectiveness model. The main analysis compared trabectedin in combination with PLDH versus paclitaxel, topotecan and PLDH (each as monotherapy) in the entire platinum-sensitive population, using results estimated from the MTC. Additional analyses were presented comparing trabectedin in combination with PLDH versus PLDH monotherapy using direct evidence from the OVA-301 trial for the fully, partially and entire platinum-sensitive populations. The cost per QALY gained for trabectedin in combination with PLDH versus PLDH monotherapy was estimated to be £70,076 in the main analysis. In the additional analyses, the cost per QALY gained for trabectedin in combination with PLDH versus PLDH monotherapy was £94,832, £43,996 and £31,092 for the entire, partially and fully platinum-sensitive populations, respectively. Additional work was undertaken by the ERG using patient-level data and amending some assumptions to provide a better statistical fit to the Kaplan–Meier data than the exponential distribution assumed by the manufacturer. The ERG base-case estimate of the cost per QALY of trabectedin in combination with PLDH ranged from £46,503 to £54,607 in the partially platinum-sensitive population. At the time of writing, trabectedin in combination with PLDH for the treatment of women with relapsed platinum-sensitive ovarian cancer is not recommended by NICE in the final appraisal determination.

Cost-Effectiveness of Third-Line Anti-TNF Therapy Compared to Natalizumab in Patients With Moderate-to-Severe Crohn's Disease With Two Prior Anti-TNF Failures

Introduction: Infliximab, adalimumab, and certolizumab pegol (CZP) are approved for use in inducing andmaintaining remission inmoderate-to-severe Crohn's disease (CD). However, a significant proportion of patients either fail to respond to these agents or lose response over time. Prior failure is associated with lower rates of response to subsequent anti-TNF therapy. In patients who fail two anti-TNF agents, a choice exists between using a thirdanti TNF therapy vs. initiating natalizumab (NAT), an integrin inhibitor that acts through a distinct biologic mechanism. The cost-effectiveness of these two competing strategies in patients with loss of response to two prior anti-TNF therapies has not been examined. Methods: A decision analysis model was constructed to compare the performance of CZP as the third-line anti-TNF therapy vs. NAT in patients withmoderate-to-severe CD. Previously published estimates of efficacy of third-line anti-TNF therapy (Allez M, APT 2010) and NAT (Sandborn WJ, NEJM 2005) were used to inform the model. Costs were expressed in 2010 US dollars. A 1 year time frame was used for the analysis. The incremental cost-effectiveness ratio (ICER) was calculated and sensitivity analyses were performed by varying cost and efficacy estimates. Results: For the base case scenario, we assumed a response rate at 2 months of 61% for CZP among whom 54% were able to maintain response or remission at the end of the year (Allez M, APT 2010). From the ENACT trials, a 2 month response rate of 58% was estimated for NAT; 39% of these patients maintained remission at 12 months with 15% achieving clinical response. At the base case estimate, use of NAT was more effective (0.72 vs. 0.71 QALYs) but was associated with an incremental cost of $1,502 yielding an ICER of $120,976/QALY. For 2 month response rate with CZP of 50% or lower, NAT had an acceptable ICER at a willingness-to-pay threshold of $80,000/QALY or lower(Figure). Reduction in CZP costs by 25% yielded high ICER for NAT at all CZP response rates > 10%. In a hypothetical cohort of 100,000 patients, both strategies resulted in similar proportion of patients achieving clinical remission or response (61,051 with CZP compared to 60,111 with NAT) at the end of 1 year. Conclusion: In patients with moderateto-severe CD failing two-anti TNF therapies, using a third-anti TNF (CZP) appears to be a cost-effective strategy if response rates of at least 50% can be achieved at 2 months.

Commercial Importation of Prescription Drugs in the United States: Short-Run Implications

The option of legalizing the commercial importation of prescription drugs is of continued policy interest as a way to reduce U.S. drug spending. Using IMS data, we estimate potential savings from commercial drug importation under assumptions about percentage of drugs likely to attract imports; potential supply from foreign countries; and share of savings passed on to payers. Our base case estimate is that $1.7 billion per year, or 0.6 percent of total drug spending, would be saved by payers; sensitivity analyses range from 0.2 to 2.5 percent under plausible assumptions and up to 17.4 percent under unrealistic assumptions about unlimited foreign supply, costless trade, and zero profits for intermediaries. Estimated savings to payers are less than the average price differentials between the United States and foreign countries because proposed legislation exempts certain drugs from importation; foreign markets are small relative to the United States; regulatory and other constraints may limit the volume of exports; trade is costly; and intermediaries will retain some savings. Although savings to U.S. payers/consumers would likely be small and have minimal impact on total U.S. health care spending, costs to other countries could be significant, due to reduced access and possibly higher prices. In the long run, reduced investment in R&D could adversely affect consumers globally.

An economic evaluation of early assessment for Alzheimer's disease in the United Kingdom

Diagnosing and treating patients with Alzheimer's disease (AD) at an early stage should improve the quality of life of the patient and caregiver. In the United Kingdom, cost-effectiveness of early assessment of individuals presenting with subjective memory complaints and treating those with AD with donepezil was evaluated. A discrete event simulation of AD progression and the effect of treatment interventions was developed. Patient-level data from donepezil trials and a 7-year follow-up registry were used to model correlated longitudinal rates of change in cognition, behavior, and function. Other epidemiological and health services data, including estimates of undiagnosed dementia and delays in diagnosis, were based on published sources. Simulated individuals were followed up for 10 years. In the base-case estimates, 17 patients need to be assessed to diagnose one patient with AD, resulting in an average assessment cost of £4100 ($6000; $1 US = £0.68 UK) per patient diagnosed (2007 cost year). In comparison with a scenario without early assessment or pharmacologic treatment, early assessment reduces health care costs by £3600 ($5300) per patient and societal costs by £7750 ($11,400). Savings are also substantial compared with treatment without early assessment, averaging £2100 ($3100) in health care costs, and £5700 ($8400) in societal costs. Results are most sensitive to estimates of patient care costs and the probability of patients reporting subjective memory complaints. In probabilistic sensitivity analysis, early assessment leads to savings or is highly cost-effective in the majority of cases. Although early assessment has significant up-front costs, identifying AD patients at an early stage results in cost savings and health benefits compared with no treatment or treatment in the absence of early assessment.

The marginal cost of public funds and tax reform in Africa

In this paper we propose estimates of the marginal cost of public funds (MCF) in 38 African countries. We develop a simple general equilibrium model that can handle taxes on five major tax classes, and can be calibrated with little more than national accounts data. A key feature of our model is the explicit recognition of the informal economy. Our base case estimate of the average MCF from marginal increases in all five tax instruments is 1.2. Focusing on the lowest cost tax instruments in each country, commonly the VAT but not always, the average MCF is 1.1. Finally extending the tax base to include sections of the informal economy by removing some tax exemptions offers the potential for a low MCF source of public funds, and a lowering of MCFs on other tax instruments.

Health care use and costs of adverse drug events emerging from outpatient treatment in Germany: a modelling approach.

BackgroundThis study's aim was to develop a first quantification of the frequency and costs of adverse drug events (ADEs) originating in ambulatory medical practice in Germany.MethodsThe frequencies and costs of ADEs were quantified for a base case, building on an existing cost-of-illness model for ADEs. The model originates from the U.S. health care system, its structure of treatment probabilities linked to ADEs was transferred to Germany. Sensitivity analyses based on values determined from a literature review were used to test the postulated results.ResultsFor Germany, the base case postulated that about 2 million adults ingesting medications have will have an ADE in 2007. Health care costs related to ADEs in this base case totalled 816 million Euros, mean costs per case were 381 Euros. About 58% of costs resulted from hospitalisations, 11% from emergency department visits and 21% from long-term care. Base case estimates of frequency and costs of ADEs were lower than all estimates of the sensitivity analyses.DiscussionThe postulated frequency and costs of ADEs illustrate the possible size of the health problems and economic burden related to ADEs in Germany. The validity of the U.S. treatment structure used remains to be determined for Germany. The sensitivity analysis used assumptions from different studies and thus further quantified the information gap in Germany regarding ADEs.ConclusionsThis study found costs of ADEs in the ambulatory setting in Germany to be significant. Due to data scarcity, results are only a rough indication.

Capacity Factor Risk at Nuclear Power Plants

We develop a model of the dynamic structure of capacity factor risk. It incorporates the risk that the capacity factor may vary widely from year-to-year, and also the risk that the reactor may be permanently shutdown prior to the end of its anticipated useful life. We then fit the parameters of the model to the IAEA’s PRIS dataset of historical capacity factors on reactors across the globe. The estimated capacity factor risk is greatest in the first year of operation. It then quickly declines over the next couple of years, after which it is approximately constant. Whether risk is constant or increasing in later years depends significantly on the probability of a premature permanent shutdown of the reactor. Because these should be very rare events, the probability is difficult to estimate reliably from the small historical sample of observations. Our base case is parameterized with a conservatively low probability of a premature permanent shutdown which yields the approximately constant variance. Our model, combined with the global historical dataset, also yields relatively low estimates for the expected level of the capacity factor through the life of the plant. Our base case estimate is approximately 74%. Focusing on alternative subsets of the data raises the estimated mean capacity factor marginally, but not significantly, unless the sample chosen is restricted to selected countries over select years. This emphasizes the need for judgment in exploiting the historical data to project future probabilities.

The health and economic effects of HPV DNA screening in The Netherlands

We studied the health and economic effects of human papillomavirus (HPV) DNA testing in cervical screening using a simulation model. The key data source was a Dutch longitudinal screening trial. We compared cytological testing with repeat cytology (for borderline/mildly abnormal smears) to HPV testing with cytology triage (for HPV-positive smears), combination testing (combined HPV and cytology) and cytological testing with HPV triage (for borderline/mildly abnormal smears). We varied the screening interval from 5 to 10 years. The main outcome measures were the number of cervical cancer cases, the number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The base-case estimates were accompanied with ranges across 118 calibrated parameter settings (calibration criteria: cervical intraepithelial neoplasia 2/3, cancer and mortality rates). In comparison to 5-yearly cytology, 5-yearly HPV testing with cytology triage gave a reduction in the number of cancer cases of 23% (range, 9-27%). The reduction was 26% (range, 10-29%) for combination testing and 3% (range, -1 to 8%) for cytology with HPV triage. For strategies with primary HPV testing, the model also estimated a reduction in cancer cases when the screening interval was extended to 7.5 years. Five-yearly cytology with HPV triage and 5 to 7.5-yearly HPV testing with cytology triage were cost effective for the base-case settings and the majority of calibrated parameter settings (ICER below Dutch willingness-to-pay threshold of euro20,000/QALY). Our model indicates that HPV testing with cytology triage is likely to be cost effective. An extension of the screening interval may be considered to control costs.

Revenue implications to the Vietnamese government of using taxes to curb cigarette smoking

This study explores the impact on government taxation revenue from increasing excise on cigarettes in Vietnam. A dynamic population model is used to estimate future patterns (both prevalence and consumption) of tobacco use in Vietnam, with and without changes to tobacco excise for the period 2006–2016. Three increases in the base case excise tax rate of 55% are modelled: 65%, 75% and 90%. Various price elasticities are used to examine variations in cigarette consumption while cross price elasticities are used to explore shifts from cigarette to other forms of tobacco. Revenue implications for the period 2006–2016 are reported as discounted net present values (NPV) in 2006 values. The model predicts that smoking rates in 2016, for both males and females, are marginally lower than base case estimates for all taxation excise options with higher price elasticities generating greater reductions in prevalence. In all cases, compared to base case estimates, the results indicate a fall in number of smokers, a reduction in amount of tobacco consumed and an increase in overall taxation revenue. The additional gain in government revenue, expressed in NPV terms, ranges from a low of VND 69,579 billion (or USD $4.35 billion) to a high of VND 108,492 billion (or USD $6.79 billion). Increases in tobacco excise provide an opportunity for the Vietnamese government to increase revenue at the same time as reducing tobacco consumption. Further research into the wider social and economic consequences of increasing tobacco excise in Vietnam is warranted.

Drug development costs when financial risk is measured using the Fama–French three‐factor model

In a widely cited article, DiMasi, Hansen, and Grabowski (2003) estimate the average pre-tax cost of bringing a new molecular entity to market. Their base case estimate, excluding post-marketing studies, was $802 million (in $US 2000). Strikingly, almost half of this cost (or $399 million) is the cost of capital (COC) used to fund clinical development expenses to the point of FDA marketing approval. The authors used an 11% real COC computed using the capital asset pricing model (CAPM). But the CAPM is a single factor risk model, and multi-factor risk models are the current state of the art in finance. Using the Fama-French three factor model we find that the cost of drug development to be higher than the earlier estimate.

Intravesical Botulinum a Toxin is More Cost-Effective Than Sacral Neuromodulation for Treatment of Refractory Urge Incontinence

A Markov decision model was constructed for urge incontinence using two treatment algorithms: sacral neuromodulation and botulinum A toxin injection(s). In each scenario, the “patients” were observed and treated, if necessary, every 3 months for 2 years. Rates of efficacy and treatment-specific adverse event rates were extracted from the MEDLINE database by identifying relevant articles from 1980 to 2008. Comparison of cost and effectiveness, measured in quality-adjusted life-years (QUALYs), between the two treatments was accomplished by developing base case estimates and utility scores for outcomes. The primary outcome was the incremental costeffectiveness ratio calculated in the following manner:

650: Cost-effectiveness of prenatal HIV screening strategies in Uganda

Estimate the cost-effectiveness of HIV screening strategies for the prevention of mother-to-child transmission (MTCT) in Uganda, a resource-limited country with high HIV prevalence and incidence. We designed a decision analytic model from a health care system perspective to assess the cost-effectiveness of 4 different HIV screening strategies in pregnancy: 1. Antibody (Ab) at initial visit (current standard of care); 2. Strategy 1 + RNA at initial visit (adds detection of acute HIV); 3. Strategy 1 + repeat Ab at delivery (adds detection of incident HIV); 4. Strategy 3 + RNA at delivery (adds detection of acute HIV at delivery). Model estimates were derived from the literature and local sources, and life years saved were discounted at a rate of 3% per year. Based on World Health Organization guidelines, we defined our cost-effective threshold as 3 times the gross domestic product per capita, which for Uganda was US$3300 in 2008. Using base case estimates of 10% HIV prevalence among women entering prenatal care and 3% incidence during pregnancy, strategy 3 was incrementally the most cost-effective option. Strategy 3 remained the most cost-effective option in sensitivity analysis until the pregnancy incidence rate was >14%, at which point strategy 4 became cost-effective at <$3, 300 per life-year gained. Repeat HIV Ab testing at time of birth is a cost-effective strategy even in a resource-limited setting. Additionally, adding acute HIV testing becomes cost-effective when HIV incidence is >14% in pregnancy.

Cost-Consequences of Ultrafiltration for Acute Heart Failure

Ultrafiltration for heart failure may reduce costs associated with acute heart failure by decreasing rehospitalization rates compared to intravenous diuretics. We developed a decision-analytic model to explore the clinical outcomes and associated costs of ultrafiltration compared to intravenous diuretics for index and subsequent acute heart failure hospitalizations to 90 days from index hospitalization. We evaluated the model from societal, Medicare, and hospital payer perspectives. Base-case probabilities and costs were derived from the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure clinical trial, Medicare reimbursement schedules, and published data. From a societal perspective, treatment with ultrafiltration had an 86% probability of being more expensive than intravenous diuretics in probabilistic sensitivity analysis, with a base-case estimate of $13 469 per patient treated with ultrafiltration compared to $11 610 per patient treated with intravenous diuretics. Cost estimates were most influenced by length of index hospitalization, daily cost of rehospitalization, number of days rehospitalized, and number and cost of ultrafiltration filters. From a Medicare payer perspective, ultrafiltration had a >99% probability of being cost saving. From a hospital perspective, there was a 97% probability ultrafiltration was more expensive. Our model suggested similar 90-day mortality rates between treatment arms. Despite a reduction in rehospitalization rates, it is unlikely ultrafiltration results in cost savings from a societal perspective. The discordance in cost between societal, Medicare, and hospital perspectives underscores the importance of payer perspective in formulating strategies and reimbursement structures to reduce heart failure hospitalizations.

Screening and Early Treatment of Migrants for Chronic Hepatitis B Virus Infection Is Cost-Effective

Persons with chronic hepatitis B virus (HBV) infection are at risk of developing cirrhosis and hepatocellular carcinoma. Early detection of chronic HBV infection through screening and treatment of eligible patients has the potential to prevent these sequelae. We assessed the cost-effectiveness in The Netherlands of systematically screening migrants from countries that have high and intermediate HBV infection levels. Epidemiologic data of the expected numbers of patients with active chronic HBV infection in the target population and information about the costs of a screening program were used in a Markov model and used to determine costs and quality-adjusted life years (QALY) for patients who were and were not treated. Compared with the status quo, a 1-time screen for HBV infection can reduce mortality of liver-related diseases by 10%. Using base case estimates, the incremental cost-effectiveness ratio (ICER) of screening, compared with not screening, is euros (euro) 8966 per QALY gained. The ICER ranged from euro7936 to euro11,705 based on univariate sensitivity analysis, varying parameter values of HBV prevalence, participation rate, success in referral, and treatment compliance. Using multivariate sensitivity analysis for treatment effectiveness, the ICER ranged from euro7222 to euro15,694; for disease progression, it ranged from euro5568 to euro60,418. Early detection and treatment of people with HBV infection can have a large impact on liver-related health outcomes. Systematic screening for chronic HBV infection among migrants is likely to be cost-effective, even using low estimates for HBV prevalence, participation, referral, and treatment compliance.

Oseltamivir for Influenza Postexposure Prophylaxis: Economic Evaluation for Children Aged 1–12 Years in the U.S.

Postexposure prophylaxis (PEP) with oseltamivir (Tamiflu) has been shown to be effective and is approved in children exposed to a case of influenza in a household setting. Given limited healthcare budgets, it is important to understand the costs and cost effectiveness of PEP in children. This study aims to estimate the cost effectiveness of oseltamivir PEP for children aged 1-12 years in the U.S. A decision-tree model with a 1-year time horizon was used to assess the cost effectiveness of oseltamivir PEP for 10 days at approved doses compared with no prophylaxis for children aged 1-12 years who were exposed to a household index case of influenza from the U.S. societal and payer perspectives. Model inputs included U.S. influenza epidemiology data, efficacy data from oseltamivir PEP clinical trials, direct medical resource use and costs for PEP and influenza treatment derived from large U.S. databases, and indirect costs based on caregiver lost productivity. Base-case estimates were tested in extensive sensitivity analyses. For the societal perspective, the model estimated 12,184 fewer cases of influenza per 100,000 children exposed and an incremental cost-effectiveness ratio of $41,452 per quality-adjusted life-year (QALY) gained. Results were most sensitive to the influenza attack rate, PEP protective efficacy, and prescribing patterns for initiating PEP. Probabilistic sensitivity analyses showed that oseltamivir PEP was likely to be cost effective for all willingness-to-pay threshold values above $34,300 per QALY gained. Results were similar for the payer perspective. Although there is no official cost-effectiveness threshold in the U.S., results from the current study show that when compared with no prophylaxis, oseltamivir PEP for children has cost-effectiveness ratios similar to those of vaccines for preventing influenza.