Multiway Sensitivity Analysis Research Articles

Cost-effectiveness analysis of acalabrutinib in treatment of patients with relapsed/refractory form of mantle cell lymphoma who previously received at least one line of therapy

Objective: to conduct a clinical and economic study of acalabrutinib for the treatment of adult patients with relapsed/refractory form of mantle cell lymphoma who previously received at least one line of therapy in the Russian Federation.Material and methods. Acalabrutinib and ibrutinib were considered as compared treatment options. Based on the adjusted indirect comparison, they were found to be comparable in terms of overall survival and progression-free survival. Therefore, a cost minimization analysis method was selected for the study. Based on results of ACE-LY-004 clinical trial a distributed survival model was developed. The model was used to calculate drug costs over a 3-year horizon. To explore uncertainty in the results of economic evaluations we conducted a sensitivity analysis. A number of patients in the hypothetical cohort who could be further treated with a less expensive drug was determined during a missed opportunity analysis. Both mean life years gained and mean progression-free life years were calculated too.Results. Based on simulations over a 3-year horizon, the mean life years gained were 2.45, and the mean progression-free life years were 1.75. The average costs of acalabrutinib therapy both over 1 year and in total over 3 years were 36.6% lower compared to ibrutinib. So, in the 1st year, the costs for acalabrutinib were 3,546,237,60 rubles, for ibrutinib – 5,591,391,00 rubles (a difference of 2,045,153,40 rubles). Using acalabrutinib for 3 years was associated with costs of 7,252,980,60 rubles compared to 11,435,852,60 rubles for ibrutinib (a decrease of 4,182,872,00 rubles). Univariate multi-way sensitivity analysis showed the robustness of modeling results to price fluctuations in the range ±10%. For a hypothetical cohort of 100 patients, using acalabrutinib instead of the more expensive ibrutinib within the same budget will provide therapy to additional 57 patients per year.Conclusion. The results of the study demonstrated that acalabrutinib compared to ibrutinib for the treatment of adult patients with relapsed/ refractory form of mantle cell lymphoma can reduce costs for the 1st year of therapy by 2,045,153,40 rubles (36.6%), and by 4,182,872,00 rubles (36.6%) for 3 years. Thus, acalabrutinib is the cost-saving option for previously treated adult patients with relapsed/refractory mantle cell lymphoma in the Russian Federation.

The YODO algorithm: An efficient computational framework for sensitivity analysis in Bayesian networks

Sensitivity analysis measures the influence of a Bayesian network's parameters on a quantity of interest defined by the network, such as the probability of a variable taking a specific value. In the literature, this influence is often measured by computing the partial derivative with respect to the network parameters. However, this can become computationally expensive in large networks with thousands of parameters. We propose an algorithm combining automatic differentiation and exact inference to calculate the sensitivity measures in a single pass efficiently. It first marginalizes the whole network once, using e.g. variable elimination, and then backpropagates this operation to obtain the gradient with respect to all input parameters. Our method can be used for one-way and multi-way sensitivity analysis and the derivation of admissible regions. Simulation studies highlight the efficiency of our algorithm by scaling it to massive networks with up to 100,000 parameters and investigate the feasibility of generic multi-way analyses. Our routines are also showcased over two medium-sized Bayesian networks: the first modeling the country risks of a humanitarian crisis, the second studying the relationship between the use of technology and the psychological effects of forced social isolation during the COVID-19 pandemic. An implementation of the methods using the popular machine learning library PyTorch is freely available.

Economic burden of locoregional and metastatic relapses in resectable early-stage non-small cell lung cancer in Spain

BackgroundThere are scarce data of the costs of non-small cell lung cancer (NSCLC) recurrence in Spain. The objective of this study is to assess the economic burden of disease recurrence, for both locoregional and/or metastatic relapses, after appropriate early-stage NSCLC treatment in Spain.Materials and methodsA two-round consensus panel of Spanish oncologists and hospital pharmacists was conducted to collect information on patient’s flow, treatments, use of healthcare resources and sick leaves in patients with relapsed NSCLC. A decision-tree model was developed to calculate the economic burden of disease recurrence after appropriate early-stage NSCLC. Both direct and indirect costs were considered. Direct costs included drug acquisition and healthcare resources costs. Indirect costs were estimated using the human-capital approach. Unit costs were obtained from national databases (euros of 2022). A multi-way sensitivity analysis was performed to provide a range to the mean values.ResultsAmong a cohort of 100 patients with relapsed NSCLC, 45 patients would have locoregional relapse (36.3 would eventually progress to metastasis and 8.7 would be considered in remission) and 55 patients would have metastatic relapse. Over time, 91.3 patients would experience a metastatic relapse (55 as first relapse and 36.6 after previous locoregional relapse). The overall cost incurred by the 100-patients cohort is €10,095,846 (€9,336,782 direct costs, €795,064 indirect costs). The average cost of a locoregional relapse is €25,194 (€19,658 direct costs, €5536 indirect costs), while the average cost a patient with metastasis who receives up to 4 lines of treatment is €127,167 (€117,328 direct, €9839 indirect).ConclusionsTo our knowledge, this is the first study that specifically quantifies the cost of relapse in NSCLC in Spain. Our findings shown that the overall cost of a relapse after appropriate treatment of early-stage NSCLC patients is substantial, and it increases considerably in the metastatic relapse setting, mainly due to the high cost and long duration of first-line treatments.

Active Learning for Multi-way Sensitivity Analysis with Application to Disease Screening Modeling.

Sensitivity analysis is an important aspect of model development as it can be used to assess the level of confidence that is associated with the outcomes of a study. In many practical problems, sensitivity analysis involves evaluating a large number of parameter combinations which may require an extensive amount of time and resources. However, such a computational burden can be avoided by identifying smaller subsets of parameter combinations that can be later used to generate the desired outcomes for other parameter combinations. In this study, we investigate machine learning-based approaches for speeding up the sensitivity analysis. Furthermore, we apply feature selection methods to identify the relative importance of quantitative model parameters in terms of their predictive ability on the outcomes. Finally, we highlight the effectiveness of active learning strategies in improving the sensitivity analysis processes by reducing the total number of quantitative model runs required to construct a high-performance prediction model. Our experiments on two datasets obtained from the sensitivity analysis performed for two disease screening modeling studies indicate that ensemble methods such as Random Forests and XGBoost consistently outperform other machine learning algorithms in the prediction task of the associated sensitivity analysis. In addition, we note that active learning can lead to significant speed-ups in sensitivity analysis by enabling the selection of more useful parameter combinations (i.e., instances) to be used for prediction models.

KEPT-app trial: a pragmatic, single-blind, parallel, cluster-randomised effectiveness study of pelvic floor muscle training among incontinent pregnant women: study protocol

IntroductionPelvic floor muscle training (PFMT) strongly recommended to incontinent pregnant women. The Kegel Exercise Pregnancy Training-app trial is a multicentre cluster-randomised study aims to assess the effectiveness and its cost-effectiveness...

2000. Rapid, Point-of-care Diagnosis of Tuberculosis with Novel Truenat Assay: Cost-Effectiveness and Budgetary Impact Analysis for India’s Public Sector

BackgroundPoint-of-care (POC) tuberculosis (TB) diagnostics may dramatically improve TB outcomes. Truenat is a new, battery-powered RT-PCR device that rapidly detects TB and rifampin resistance. Due to its portability, it may be valuable in peripheral healthcare settings. We evaluated the cost-effectiveness of Truenat in peripheral laboratories (designated microscopy centres [DMCs]) and public healthcare facilities in India.MethodsWe used the CEPAC-International microsimulation model to compare four TB diagnostic strategies for adult, HIV-negative patients with suspected TB: (1) sputum smear microscopy in DMCs (SSM); (2) Xpert MTB/RIF in DMCs (Xpert); (3) Truenat in DMCs (Truenat DMC); and (4) Truenat in public healthcare facilities (Truenat POC). We projected life expectancy (LE), costs, incremental cost-effectiveness ratios (ICERs), and 5y budget impact of full scale-up. A strategy was cost-effective if its ICER was <US$990/year of life saved (YLS) (i.e., <50% of India annual per capita GDP). Model inputs included: TB prevalence, 20%; sensitivity for TB detection, 92% for Xpert and 89% for Truenat; costs per test, $12.70 for Xpert and $13.20 for Truenat; linkage to care after diagnosis, 84% for DMC-based tests and 95% for POC. We varied these parameters in sensitivity analyses.ResultsCompared with SSM, other strategies increased TB case detection by >6%; Truenat POC increased LE by ~0.3 years with ICER $210/YLS (Table 1). Compared with Xpert, Truenat DMC decreased LE and cost, but Truenat POC improved LE by 0.05 years and was cost-effective. In multi-way sensitivity analysis at 5 years horizon, Truenat POC, at 89% diagnostic sensitivity and linkage to care >86%, was cost-effective and sometimes cost-saving compared with Xpert (Figure 1). The cost-effectiveness of Truenat, relative to Xpert, depended on the interplay of sensitivity and linkage to care. Public-sector implementation of Truenat POC increased healthcare expenditures by $360 million compared with full scale-up of Xpert (Figure 2). Treatment costs, not diagnostic test costs, accounted for most of the difference. ConclusionWhen used at the point of care, Truenat for TB diagnosis should improve linkage to care, increase LE, and be cost-effective compared with SSM or Xpert and, thus, should be more widely utilized in India.Disclosures All authors: No reported disclosures.

Tsunami evacuation simulation using geographic information systems for homecare recipients depending on electric devices.

Tsunamis cause direct damage to property and destroy infrastructure. In addition, power outages can lead to death, especially for patients who rely on medical equipment requiring a power supply. Recently, Nankai Trough Earthquakes have been predicted, and much effort has been put into developing countermeasures in Japan. Kochi City on Shikoku Island is expected to suffer in the event of a large tsunami. The present study identifies individuals living in Kochi who need evacuation assistance and depend on electrical medical devices, simulates evacuation behavior and inundation during a tsunami using a geographic information system (GIS), and considers the usefulness of such a GIS. We asked caregivers, including visiting nurses, to introduce us to homecare recipients who rely on a ventilator, an endotracheal suction device, or other medical devices requiring electric power. We received introductions to 52 homecare recipients. Using a GIS, we plotted the area of predicted inundation and the locations of homecare recipients, nursing stations, and welfare evacuation shelters. We predicted evacuation routes, and then analyzed the time difference between the time required for evacuation and tsunami arrival at a welfare evacuation shelter. To measure the effects of the main parameters, we conducted both one-way and multi-way sensitivity analysis. In the event of a tsunami, eight of the homecare recipients living in the forecasted inundation areas in Kochi may face delayed evacuation. Among homecare recipients facing a high possibility of escape delay, 95.2% lived more than 1,800 m from the nearest welfare evacuation shelter. We found that individual evacuation behavior can be simulated by specifying the residence of a homecare recipient and the evacuation route using a GIS.

Potential Mortality Reduction with Optimal Usage of Sacubitril/Valsartan Therapy for the Treatment of Heart Failure in Chile

PARADIGM-HF, a phase III trial conducted in patients with heart failure (HF), showed that sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor for treatment of HF with reduced ejection fraction (HFrEF), provided incremental cardiovascular and overall survival benefit versus enalapril. This analysis aims to quantify the number of potential all-cause deaths that could be avoided with optimal usage of sacubitril/valsartan in the treatment of HFrEF in Chile. Data from the Instituto Nacional de Estadísticas was used to identify patients with heart failure for whom sacubitril/valsartan would be indicated, and a literature review was conducted to determine the prevalence of HF, the proportion of those NYHA Class II-IV and finally, the proportion of patients with HFrEF. The number needed to treat (NNT) to avoid one death, standardized to 12 months, was derived from the PARADIGM-HF trial. The potential number of deaths prevented or postponed as a result of sacubitril/valsartan treatment was estimated along with multi-way sensitivity analysis. The main outcome measure was all-cause mortality. The 2017 population (≥ 20 years) in Chile was estimated at 13,413,474 and the estimated prevalence of HF was 2%. The percentage of patients diagnosed with HF in Chile was 80%. Of these, 75% were classified as NYHA Class II-IV, 48% of whom had HFrEF. This equated to 77,262 patients for whom sacubitril/valsartan may be indicated. The absolute reduction in mortality in PARADIGM-HF was 2.8% over an average follow-up time of 27 months with a NNT standardized to 12 months of 80.3. Thus, optimal usage of sacubitril/valsartan therapy was estimated to prevent 962 deaths each year. The findings from this analysis suggest that a substantial number of deaths could potentially be prevented by optimal implementation of sacubitril/valsartan therapy. Thus, implementation of sacubitril/valsartan into routine clinical practice may substantially improve clinical outcomes in HFrEF patients in Chile.

Bubble continuous positive airway pressure in the treatment of severe paediatric pneumonia in Malawi: a cost-effectiveness analysis

ObjectivesPneumonia is the largest infectious cause of death in children under 5 years globally, and limited resource settings bear an overwhelming proportion of this disease burden. Bubble continuous positive airway...

Cost comparison of initial lobectomy versus fine-needle aspiration for diagnostic workup of thyroid nodules in children

BackgroundThough uncommon in children, pediatric thyroid nodules carry a higher risk of malignancy than adult nodules. While fine-needle aspiration (FNA) has been well established as the initial diagnostic test in adults, it has been more slowly adopted in children. The purpose of this study was to examine the comparative cost of FNA versus initial diagnostic lobectomy (DL) in the pediatric patient with an ultrasound-confirmed thyroid nodule. MethodsA decision tree model was created using an adolescent with an asymptomatic thyroid nodule as the reference case. Probabilities were defined based on review of the pediatric and adult literature. Costs were determined from previous literature and the publicly available Medicare physician fee schedule. Tornado plot and sensitivity analyses were performed to assess sources of cost variation. ResultsUsing decision analysis, FNA was less costly than DL with an estimated cost of $2529 vs. $5680. Tornado analysis demonstrated that the probability of an initial indeterminate FNA result contributed most to cost variation. On sensitivity analysis, when probability of an indeterminate FNA result was increased to 35%, the maximum value found in the literature, FNA remained less costly. In Monte Carlo simulation set to 10,000 iterations, FNA was superior to DL in 74% of cases. ConclusionsIn this theoretical model based on available literature and costs, FNA is less costly than DL for initial diagnostic workup of thyroid nodules in children. Securing resources to offer FNA in the work-up of thyroid nodules may be financially beneficial to hospitals and patients. Level of evidenceLevel 1 cost effectiveness study - using reasonable costs and alternatives used in study with values obtained from many studies, study used multi-way sensitivity analysis.

Cost-effectiveness of HIV and syphilis antenatal screening: a modelling study

ObjectivesThe WHO called for the elimination of maternal-to-child transmission (MTCT) of HIV and syphilis, a harmonised approach for the improvement of health outcomes for mothers and children. Testing early in...

European Union-28: An annualised cost-of-illness model for venous thromboembolism.

Annual costs for venous thromboembolism (VTE) have been defined within the United States (US) demonstrating a large opportunity for cost savings. Costs for the European Union-28 (EU-28) have never been defined. A literature search was conducted to evaluate EU-28 cost sources. Median costs were defined for each cost input and costs were inflated to 2014 Euros (€) in the study country and adjusted for Purchasing Power Parity between EU countries. Adjusted costs were used to populate previously published cost-models based on adult incidence-based events. In the base model, annual expenditures for total, hospital-associated, preventable, and indirect costs were €1.5-2.2 billion, €1.0-1.5 billion, €0.5-1.1 billion and €0.2-0.3 billion, respectively (indirect costs: 12 % of expenditures). In the long-term attack rate model, total, hospital-associated, preventable, and indirect costs were €1.8-3.3 billion, €1.2-2.4 billion, €0.6-1.8 billion and €0.2-0.7 billion (indirect costs: 13 % of expenditures). In the multiway sensitivity analysis, annual expenditures for total, hospital-associated, preventable, and indirect costs were €3.0-8.5 billion, €2.2-6.2 billion, €1.1-4.6 billion and €0.5-1.4 billion (indirect costs: 22 % of expenditures). When the value of a premature life-lost increased slightly, aggregate costs rose considerably since these costs are higher than the direct medical costs. When evaluating the models aggregately for costs, the results suggests total, hospital-associated, preventable, and indirect costs ranging from €1.5-13.2 billion, €1.0-9.7 billion, €0.5-7.3 billion and €0.2-6.1 billion, respectively. Our study demonstrates that VTE costs have a large financial impact upon the EU-28's healthcare systems and that significant savings could be realised if better preventive measures are applied.

COST-EFFECTIVENESS ANALYSIS OF HERPES ZOSTER VACCINATION IN ITALIAN ELDERLY PERSONS.

Herpes zoster (HZ) is characterized by a painful skin rash. Its main complication is postherpetic neuralgia (PHN), pain persisting or occurring after the rash onset. HZ treatment aims to reduce acute pain, impede the onset complications, and disease progression. The aim of this study was to assess the cost-effectiveness of HZ vaccination compared with no vaccination strategy, within the Italian context. The natural history of HZ and PHN was mapped through a Markov model with lifetime horizon. A population of patients aged between 60 and 79 years was hypothesized. Third party payer (Italian National Health Service, I-NHS) and societal perspectives were adopted. Data were derived from literature. The incremental cost-effectiveness ratio of the vaccination equaled EUR 11,943 per quality-adjusted life-year (QALY) under the I-NHS perspective and EUR 11,248 per QALY under the societal perspective. Considering a cost-effectiveness threshold of EUR 30,000/QALY, the multi-way sensitivity analysis showed that vaccination is cost-effective regardless of the perspective adopted, in 99 percent of simulations.

Timing of elective delivery in gastroschisis: a decision and cost-effectiveness analysis.

To determine the most cost-effective timing of delivery in pregnancies complicated by gastroschisis, using a decision-analytic model. We created a decision-analytic model to compare planned delivery at 35, 36, 37, 38 and 39 weeks' gestation. Outcomes considered were stillbirth, death within 1 year of birth and respiratory distress syndrome (RDS). Probability estimates of events (stillbirth, complex gastroschisis and RDS for each gestational age at delivery and risk of death with simple and complex gastroschisis), utilities and costs assigned to the outcomes were obtained from the published literature. Cost analysis was assessed from a societal perspective, using a willingness-to-pay threshold of $100,000 per surviving infant. Outcomes and costs were considered throughout 1 year of postnatal life. Multiway sensitivity analysis was performed to address uncertainties in baseline assumptions. In the base-case analysis, delivery at 38 weeks' gestation was the most cost-effective strategy. Planned delivery at 35 weeks was associated with the fewest stillbirths and deaths within 1 year of delivery, owing largely to a lower ongoing risk of stillbirth. In Monte Carlo simulation when every variable was varied over its entire range, delivery at 38 weeks was cost-effective compared to delivery at 39 weeks in 76% of trials and delivery at 37 weeks was cost-effective in 69% of trials. Delivery at 38 weeks resulted in three additional cases of RDS for every 100 stillbirths or deaths within 1 year that were prevented. For pregnancies complicated by gastroschisis, the most cost-effective timing of delivery is at 38 weeks. Few additional cases of RDS are caused for every one stillbirth or death within 1 year that was prevented with delivery at 37-38 weeks compared with at 39 weeks.

Modeling of novel diagnostic strategies for active tuberculosis - a systematic review: current practices and recommendations.

IntroductionThe field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB.MethodsPubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts.Results & DiscussionFrom 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4), key determinants of diagnostic delay (n = 5), operational context (n = 5), and the pre-diagnostic infectious period (n = 1). The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7), and alternative nucleic acid amplification tests (NAATs) (n = 4). Most (n = 16) of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER).ConclusionAlthough models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical models. Further models are needed that address a wider array of diagnostic and epidemiological settings, that explore the inherent uncertainty of models and that include additional epidemiological data on transmission implications of false-negative diagnosis and the pre-diagnostic period.

Cost‐Effectiveness of Total Knee Replacement: A Prospective Cohort Study

Total knee replacement (TKR) rates have significantly increased in the past decade. While the procedure itself might be costly, the cost-effectiveness and potential offset costs from patient and societal benefits have not been clearly established. The objective of this study was to perform an economic evaluation of TKR in patients with knee osteoarthritis (OA). We conducted a 6-month prospective cohort study of 212 patients with knee OA who underwent TKR at a single hospital in Houston, Texas. We included patient-level data from hospital billing databases and the patients' self-reported direct and indirect costs. The clinical outcome measure was pain and function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire; we used the minimum clinically important difference (MCID; ≥20-point change) and the WOMAC 20% (WOMAC20), 50% (WOMAC50), and 70% (WOMAC70) relative improvement criteria. Incremental cost-effectiveness ratios were estimated using direct and indirect costs and WOMAC improvement. A societal perspective was used and multiple sensitivity analyses were performed to assess the robustness of the principal analysis. The total incremental cost per TKR was $20,133. The incremental cost-effectiveness ratios (ICERs) for improvement at 6 months were $33,345, $25,255, $35,274, and $56,908 for the MCID, WOMAC20, WOMAC50, and WOMAC70, respectively. Best- and worst-case scenario sensitivity analyses did not have a significant impact on the ICERs. Patient time lost was the most influential variable in the multiway sensitivity analysis. TKR is an effective intervention in reducing pain and improving functional status among patients with knee OA and is cost effective at both low and high levels of improvement.

Cost Analysis of Youth Violence Prevention

Effective violence interventions are not widely implemented, and there is little information about the cost of violence interventions. Our goal is to report the cost of a brief intervention delivered in the emergency department that reduces violence among 14- to 18-year-olds. Primary outcomes were total costs of implementation and the cost per violent event or violence consequence averted. We used primary and secondary data sources to derive the costs to implement a brief motivational interviewing intervention and to identify the number of self-reported violent events (eg, severe peer aggression, peer victimization) or violence consequences averted. One-way and multi-way sensitivity analyses were performed. Total fixed and variable annual costs were estimated at $71,784. If implemented, 4208 violent events or consequences could be prevented, costing $17.06 per event or consequence averted. Multi-way sensitivity analysis accounting for variable intervention efficacy and different cost estimates resulted in a range of $3.63 to $54.96 per event or consequence averted. Our estimates show that the cost to prevent an episode of youth violence or its consequences is less than the cost of placing an intravenous line and should not present a significant barrier to implementation.

Is there a role for elective neck dissection with salvage laryngectomy? A decision‐analysis model

Elective neck dissection for the clinically negative neck is often a matter of debate. A decision-analysis model that was published in 1994 established the widely accepted principle that neck dissection is warranted when the risk for occult metastases is higher than 20%. The aim of the present study was to build a specific and up-to-date decision-analysis model to determine the need for elective neck dissection during salvage laryngectomy after chemoradiation failure and to identify the variables that effect the decision. Decision-analysis model. A decision-analysis model was performed to compare the outcome of patients after salvage total laryngectomy with and without an elective neck dissection. Probabilities and expected utilities were derived from available literature to construct the model. Monte Carlo simulation and sensitivity analysis were used to calculate our models' outcomes and to identify the variables that influence the model most, respectively. When calculating our model results with published data, we found that elective neck dissection is not warranted during salvage total laryngectomy. Optimal decision was found to be sensitive by two variables: 1) the probability for cure with neck dissection, and 2) the probability for regional-only recurrence after salvage laryngectomy without neck dissection. In multiway sensitivity analysis, only when cure rate with neck dissection exceeded 82%, adding neck dissection was the preferred decision. In practice, cure rates for patients after salvage total laryngectomy are around 50% to 65%. Based on our decision-analysis model, we do not recommend routine elective neck dissection during salvage total laryngectomy after failure of chemoradiation.

Could Early Antiretroviral Therapy Entail More Risks than Benefits in Sub-Saharan African HIV-Infected Adults? A Model-Based Analysis

Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of CD4⁺ T-cell count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4⁺ T-cell counts. We used a simulation model to compare ART initiation upon entry to care ('immediate ART') to initiation at CD4⁺ T-cell count ≤ 350 cells/μl ('WHO 2010 ART') in African adults with CD4⁺ T-cell counts >500 cells/μl. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. The 15-year mortality was 56.7% for WHO 2010 ART and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was >1.0/100 person-years, the rate of withdrawal from care was >1.2-fold higher or the rate of ART failure due to poor adherence was >4.3-fold higher on immediate than on WHO 2010 ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100 person-years) were combined with rates of withdrawal from care >1.1-fold higher and rates of treatment failure >2.1-fold higher on immediate than on WHO 2010 ART. In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4⁺ T-cell counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be crucial.

Pharmaco-economic analysis of direct medical costs of metastatic colorectal cancer therapy with XELOX or modified FOLFOX-6 regimens: Implications for health-care utilization in Australia

The objective of this economic evaluation, which was based on patients from two randomized controlled clinical trials (NO16966 and NO16967), was to compare direct medical costs to the Australian health-care system of capecitabine plus oxaliplatin (XELOX) and bolus and/or infusional 5-fluorouracil (5-FU) plus folinic acid combined with oxaliplatin (modified [m] FOLFOX-6) in first-line and second-line treatment of advanced or metastatic colorectal cancer (mCRC). Direct medical costs were estimated for five treatment settings from a public and private hospital. The costs included in evaluation were for drug acquisition, preparation (oxaliplatin, bolus and infusional 5-FU), administration and wastage. The cost of drug acquisition was calculated based on dosage data and the mean number of treatment cycles from the pivotal studies NO16966 and NO16967. There were no costs associated with preparing capecitabine and leucovorin. An oncology grouping and costing study was performed to determine the relevant administration costs associated with central venous access devices, their placement, maintenance and removal (for oxaliplatin administration) and the continuous infusion of 5-FU via a continuous ambulatory delivery device pump or infuser. This economic evaluation has shown that treating mCRC patients with XELOX in the first and second-line settings results in average cost savings of $9110 and $7113, respectively, compared with mFOLFOX-6. A multi-way sensitivity analysis demonstrated that the use of XELOX remained cost-saving from an Australian government health budget perspective. The use of XELOX, compared with mFOLFOX-6, for the treatment of mCRC is cost-saving in the Australian government health budget.