Favorable Assumptions Research Articles

Incompatibility of Model Specifications in Generalized Linear Models

Summary The choice of regression models can vary depending on a study’s objectives and the characteristics of the dataset. Yet it is crucial to recognize that the properties of conditional expectation impose a natural consistency requirement on the formulation of these models. This paper endeavors to demonstrate that, even under the most favorable assumptions concerning the covariates’ structure, inconsistent specifications can arise in generalized linear models, particularly when nonlinear link functions are employed.

What absorbs the early TeV photons of GRB 221009A?

ABSTRACT The tera-electronvolt (TeV) light curve of gamma-ray burst 221009A exhibits an unprecedentedly rapid rise at its start. This phenomenon could be due to the strong absorption of photons and electrons within the emitting region. As the external shock expands outward and the radius increases, the volume of matter also grows, resulting in a gradual reduction of the optical depth for TeV photons. We investigate several potential explanations for the early TeV light curves. We calculate the optical depth for TeV photons, considering both annihilation with lower energy photons in the external shock and their scattering by electrons generated through the cascading of the TeV emission. Even under the favourable assumptions, we have determined that the optical depths for these processes are orders of magnitude too small to explain the observed light curve. Additional sources of absorbers, including electrons in the ejecta or external shock, also do not result in sufficient optical depths. Hence, the cause behind the early peculiar TeV light curve remains unclear.

Was evolution worth it?

The evolutionary process involved the suffering of quadrillions of sentient beings over millions of years. I argue that when we take this into account, then it is likely that when the first humans appeared, the world was already at an enormous axiological deficit, and that even on favorable assumptions about humanity, it is doubtful that we have overturned this deficit or ever will. Even if there’s no such deficit or we can overturn it, it remains the case that everything of value associated with humanity was made possible by our evolutionary history and all that animal suffering. It can seem indecent to regard all that past suffering as having been worth it simply because it was a causal precondition for our existence. But when we consider the realistic alternatives to the way evolution in fact unfolded, there is nevertheless a conditional case for regarding past sentient suffering as a kind of necessary evil.

Characterizing and Mitigating the Impact of Telluric Absorption in Precise Radial Velocities

Precise radial velocity (PRV) surveys are important for the search for Earth analogs around nearby bright stars, which induce a small stellar reflex motion with an RV amplitude of ∼10 cm s−1. Detecting such a small RV signal poses challenges to instrumentation, data analysis, and the precision of astrophysical models to mitigate stellar jitter. In this work, we investigate an important component in the PRV error budget—the spectral contamination from the Earth’s atmosphere (tellurics). We characterize the effects of telluric absorption on the RV precision and quantify its contribution to the RV error budget over time and across a wavelength range of 350 nm–2.5 μm. We use simulated solar spectra with telluric contamination injected, and we extract the RVs using two commonly adopted algorithms: dividing out a telluric model before performing cross-correlation or forward modeling the observed spectrum incorporating a telluric model. We assume various degrees of cleanness in removing the tellurics. We conclude that the RV errors caused by telluric absorption can be suppressed to close to or even below 1–10 cm s−1 in the blue optical region. At red through near-infrared wavelengths, however, the residuals of tellurics can induce an RV error on the meter-per-second level even under the most favorable assumptions for telluric removal, leading to significant systematic noise in the RV time series and periodograms. If the red-optical or near-infrared becomes critical in the mitigation of stellar activity, systematic errors from tellurics can be eliminated with a space mission such as EarthFinder.

Examples of Pathological Dynamics of the Subgradient Method for Lipschitz Path-Differentiable Functions

We show that the vanishing step size subgradient method—widely adopted for machine learning applications—can display rather messy behavior even in the presence of favorable assumptions. We establish that convergence of bounded subgradient sequences may fail even with a Whitney stratifiable objective function satisfying the Kurdyka-Łojasiewicz inequality. Moreover, when the objective function is path-differentiable, we show that various properties all may fail to occur: criticality of the limit points, convergence of the sequence, convergence in values, codimension one of the accumulation set, equality of the accumulation and essential accumulation sets, connectedness of the essential accumulation set, spontaneous slowdown, oscillation compensation, and oscillation perpendicularity to the accumulation set.

Carbonate dissolution cones require more than stemflow funneling from plants

Over geologic timescales, forests have intercepted precipitation and thereby modified the intensity, duration, and spatial patterns of water fluxes to forest soils. Across a range of environmental conditions, persistent focused water flows can dissolve carbonate substrates, and form conical dissolution features—termed “dissolution cones.” These cones generally fill with soils, becoming localized soil (and water) reservoirs occupied by vegetation. A myriad of mechanisms are hypothesized to have formed dissolution cones. Prior work has sought to explain co-located palm trees and modern dissolution cones in tropical unconsolidated carbonates as the result of the chemical action of weakly acidic stemflow funneled by palm canopies down their stems, and into the substrate. Using a geochemical modeling program, PHREEQC, we find that for a range of environmental conditions and favorable assumptions, stemflow is unable to dissolve a benchmark volume of carbonate substrate that typifies tropical dissolution cones. Therefore, dissolution cone formation by abiotic dissolution from stemflow funneling is unlikely to be the chief geomorphic process. Further hypotheses to be tested are discussed.

Cost-effectiveness and potential value of pharmaceutical treatment of nonalcoholic fatty liver disease

Background Nonalcoholic fatty liver disease (NAFLD) is associated with substantial morbidity, mortality, and economic burden. With currently no approved treatment, an effective pharmaceutical intervention for this disease must be both clinically- and cost-effective. Methods A Markov model was constructed to estimate the clinical outcomes, costs, and quality of life impact of a hypothetical pharmaceutical intervention. Lifetime clinical outcomes, life-years, quality-adjusted life-years (QALYs), costs (2020 $US), incremental cost-effectiveness ratios (ICERs), and economically justifiable prices (EJPs) were quantified. Only patients with fibrosis stage F2–F4 were assumed eligible to initiate pharmaceutical treatment. Results Over a mean life expectancy of approximately 21 years in the simulated cohort, drug treatment reduced liver-related mortality by 6.0% (2.7% absolute reduction). Assuming an annual drug cost of $36,000, total discounted medical costs were $574,238 and $120,312 for drug and usual care, respectively, with discounted QALYs estimated to be 9.452 and 9.272 for the two comparators. This yielded an ICER of $2,517,676/QALY gained. The EJP of the drug at an ICER threshold of $150,000/QALY gained was $2,633, a 93% reduction from a base case. Sensitivity analyses suggest that, without a substantial decrease in the drug price, ICERs would exceed $500,000/QALY gained even with the most favorable efficacy assumptions. Conclusions For a pharmaceutical intervention to be considered cost-effective in the NAFLD fibrosis population, the substantial clinical benefit will need to be coupled with a modest annual price. Annual drug costs exceeding $12,000 likely will not provide reasonable value, even with favorable efficacy. More work is needed to estimate the cost-effectiveness of lifestyle modifications.

Toward Secure Localization in Randomly Deployed Wireless Networks

Being able to accurately locate wireless devices, while guaranteeing high-level of security against spoofing attacks, benefits all participants in the localization chain (e.g., end users, network operators, and location service providers). On the one hand, most of existing localization systems are designed for innocuous environments, where no malicious adversaries are present. This makes them highly susceptible to security threats coming from interferers, attacks, or even unintentional errors (malfunctions), and thus, practically futile in hostile settings. On the other hand, existing secure localization solutions make certain (favorable) assumptions regarding the network topology (e.g., that the target device lies within a convex hull formed by reference points), which restrict their applicability. Therefore, this work addresses the problem of target localization in randomly deployed wireless networks in the presence of malicious attackers, whose goal is to manipulate (spoof) the estimation process and disable accurate localization. We propose a low-complex solution based on clustering and weighted central mass to detect attackers, using only the bare minimum of reference points, after which we solve the localization problem by a bisection procedure. The proposed method is studied from both localization accuracy and success in attacker detection point of views, where closed-form expressions for upper and lower bounds on the probability of attacker detection are derived. Its performance is validated through computer simulations, which corroborate the effectiveness of the proposed scheme, outperforming the state-of-the-art methods.

Forced, Balanced, Axisymmetric Shallow Water Model for Understanding Short-Term Tropical Cyclone Intensity and Wind Structure Changes

A minimal modeling system for understanding tropical cyclone intensity and wind structure changes is introduced: Shallow Water Axisymmetric Model for Intensity (SWAMI). The forced, balanced, axisymmetric shallow water equations are reduced to a canonical potential vorticity (PV) production and inversion problem, whereby PV is produced through a mass sink (related to the diabatic heating) and inverted through a PV/absolute–angular–momentum invertibility principle. Because the invertibility principle is nonlinear, a Newton–Krylov method is used to iteratively obtain a numerical solution to the discrete problem. Two versions of the model are described: a physical radius version which neglects radial PV advection (SWAMI-r) and a potential radius version that naturally includes the advection in the quasi-Lagrangian coordinate (SWAMI-R). In idealized numerical simulations, SWAMI-R produces a thinner and more intense PV ring than SWAMI-r, demonstrating the role of axisymmetric radial PV advection in eyewall evolution. SWAMI-R always has lower intensification rates than SWAMI-r because the reduction in PV footprint effect dominates the peak magnitude increase effect. SWAMI-r is next demonstrated as a potentially useful short-term wind structure forecasting tool using the newly added FLIGHT+ Dataset azimuthal means for initialization and forcing on three example cases: a slowly intensifying event, a rapid intensification event, and a secondary wind maximum formation event. Then, SWAMI-r is evaluated using 63 intensifying cases. Even though the model is minimal, it is shown to have some skill in short-term intensity prediction, highlighting the known critical roles of the relationship between the radial structures of the vortex inertial stability and diabatic heating rate. Because of the simplicity of the models, SWAMI simulations are completed in seconds. Therefore, they may be of some use for hurricane nowcasting to short-term (less than 24 h) intensity and structure forecasting. Due to its favorable assumptions for tropical cyclone intensification, a potential use of SWAMI is a reasonable short-term upper-bound intensity forecast if the storm intensifies.

Energetics of polymeric carbon monoxide.

The transformation of carbon monoxide (CO) from a molecular liquid to a polymeric solid under isothermal compression at room temperature is investigated using first principles theory. We report structural and thermodynamic properties from ambient density up to 2.45 g/cc obtained using density functional theory molecular dynamics simulations, including hybrid exchange corrections. The theoretical results are compared with newly obtained polymeric CO samples, synthesized in a large volume press. The explosive performance of polymeric CO is predicted and discussed. Under most favorable assumptions, it is found to be comparable to trinitrotoluene.

Cost-Effectiveness of Ribociclib for Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer.

PurposeRibociclib has provided significant improvements in progression-free survival (PFS) and overall survival (OS) of postmenopausal patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). However, given the high cost of ribociclib, its value must be evaluated based on cost-effectiveness. Thus, we aimed to explore the cost-effectiveness of ribociclib for postmenopausal patients with HR-positive and HER2-negative ABC.MethodsA comprehensive Markov model was developed to estimate the cost-effectiveness of ribociclib plus fulvestrant versus placebo plus fulvestrant as first-line treatment for HR-positive, HER2-negative ABC. Variables were estimated based on data from the randomized Phase III MONALEESA-3 trial. Ten-year values were estimated for quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Direct treatment costs were estimated from the perspective of a United States payer. One-way and probabilistic sensitivity analyses were conducted to confirm the model’s robustness.ResultsRibociclib plus fulvestrant increased the treatment cost by $382,172 and provided 0.47 QALYs, relative to fulvestrant alone, which corresponded to an ICER of $813,132 per QALY. Sensitivity analyses revealed that ribociclib was unlikely to be cost-effective even under the most favorable assumptions. When the cost of ribociclib was <$1,384, there was a >50% chance of cost-effectiveness at a willingness-to-pay threshold of $150,000/QALY. Subgroup analyses also confirmed that ribociclib was not cost-effective.ConclusionAt current drug prices in the United States, ribociclib is unlikely to be cost-effective for treating postmenopausal patients with HR-positive HER2-negative ABC. Despite the clinical benefits of ribociclib, its cost would need to decrease to provide more favorable economic outcomes.

SCENARIOS FOR THE DEPLOYMENT OF CARBON CAPTURE AND STORAGE IN THE POWER SECTOR IN A PORTFOLIO OF MITIGATION OPTIONS

Using the MIT Economic Projection and Policy Analysis (EPPA) model, we explore factors influencing carbon capture and storage (CCS) deployment in power generation and its role in mitigating carbon emissions. We find that in the 2∘C scenario with EPPA’s base-case technology cost and performance assumptions, CCS plays an important role in the second half of the century: by 2100 CCS is applied to almost 40% of world electricity production, with a third coming from coal with CCS and the other two-thirds from gas with CCS. Results on CCS deployment depend on the assumed fraction of carbon captured in CCS power plants, as emissions constraints get tighter and the carbon price rises. Adding options for higher capture fractions or offsetting uncaptured emissions leads to greater deployment of CCS than in the 2∘C base case. We provide a sensitivity analysis by making favorable assumptions for CCS, nuclear and renewables. We also explore regional differences in the deployment of CCS. We find that US and Europe mostly rely on gas CCS, whereas China relies on coal CCS and India pursues both options. We also assess how these projections align with assessment of CO2 storage potential, and find that storage potential is larger than storage demand at both global and regional scales. Ultimately, we find that under stringent mitigation scenarios, the power sector relies on a mix of technological options, and the conditions that favor a particular mix of technologies differ by region.

Composite optimization for robust rank one bilinear sensing

Abstract We consider the task of recovering a pair of vectors from a set of rank one bilinear measurements, possibly corrupted by noise. Most notably, the problem of robust blind deconvolution can be modeled in this way. We consider a natural nonsmooth formulation of the rank one bilinear sensing problem and show that its moduli of weak convexity, sharpness and Lipschitz continuity are all dimension independent, under favorable statistical assumptions. This phenomenon persists even when up to half of the measurements are corrupted by noise. Consequently, standard algorithms, such as the subgradient and prox-linear methods, converge at a rapid dimension-independent rate when initialized within a constant relative error of the solution. We complete the paper with a new initialization strategy, complementing the local search algorithms. The initialization procedure is both provably efficient and robust to outlying measurements. Numerical experiments, on both simulated and real data, illustrate the developed theory and methods.

Cost utility analysis of tisagenlecleucel vs salvage chemotherapy in the treatment of relapsed/refractory diffuse large B-cell lymphoma from Singapore’s healthcare system perspective

Background Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) have limited treatment options and poor prognoses. Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy has shown early promise in improving survival outcomes, but at a high upfront cost. This study evaluated the cost-effectiveness of tisagenlecleucel versus salvage chemotherapy for treating patients with r/r DLBCL who have failed at least 2 lines of systemic therapies. Methods A hybrid decision tree and three-state partitioned survival model (progression-free (PF), progressive disease and death) was developed from the Singapore healthcare payer perspective. Survival curves from JULIET trial and CORAL-1 extension study were extrapolated beyond trial period over a 15-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions for both arms. Health state utilities were retrieved from the literature, and direct costs were sourced from public healthcare institutions in Singapore. One-way probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. Results Compared with salvage chemotherapy, tisagenlecleucel was associated with a base-case incremental cost-effectiveness ratio (ICER) US$508,530 (S$686,516) per quality adjusted life year (QALY) gained and US$320,200 (S$432,269) per life year (LY) gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon, PF utility and cost of tisagenlecleucel. Scenario analyses confirmed that the ICERs remained high under favorable assumptions and substantial price reduction was required to reduce the ICER. Conclusions Our analysis showed tisagenlecleucel use in r/r DLBCL patients who failed at least 2 prior lines of systemic therapies was associated with exceedingly high ICER, which is unlikely to represent good use of healthcare resources. Comparative clinical evidence from the ongoing trials might provide more insight into future evaluations.

Weighing the potential late benefits versus early hazard associated with bioresorbable vascular scaffolds in percutaneous coronary interventions: a Markov decision analytic model.

Use of poly-L-lactic acid-based bioresorbable scaffolds (BRS) has been associated with increased risk of device thrombosis during the first 3 years after implantation as compared to metallic everolimus-eluting stents (EES). The long-term performance of BRS relative to EES remains unknown. We used a Markov decision analysis model to evaluate the effectiveness of BRS vs. EES over a lifetime horizon. In addition to one-way sensitivity analyses of key variables, we evaluated the impact of optimal implantation technique and limiting procedures to larger vessels (>2.6 mm in diameter) on model results. Assuming no risk of target lesion revascularization for BRS after 3 years, we found a small increment in quality-adjusted life expectancy (QALE) of 0.02 with the use of BRS relative to EES, with benefit being observed after 21.8 years. Optimal implantation technique and limiting to larger vessels resulted in larger gains in QALE (0.08 and 0.06, respectively) with BRS and shorter times to equipoise (6.7 and 8.3 years, respectively). Model results were highly sensitive to variations in the relative risk of stent thrombosis (BRS vs. EES). Based on currently available data, it would take approximately 21.8 years for the presumed late benefits of current BRS relative to EES to overcome the early hazard associated with their use under favorable assumptions. Optimal implantation technique and limiting procedures to larger vessels improved BRS performance and reduced time to equipoise. Eliminating the higher BRS thrombosis risk is necessary in developing future generations of BRS as an acceptable alternative to EES.

Clusters in the Function of Strenghtening the Competitiveness of Agricultural Sector – A Review of the Southern and Eastern Serbia Region

The current scope and structure of agricultural production, its high extensiveness, oscillation, low productivity, and inefficient organization of production and traffic flows are factors that limit domestic producers and exporters in reaching the competitiveness on the international market of alimentary products. With the aim of faster and more active inclusion of domestic agricultural products in the world trends of marketing and contemporary agrarian technologies, the accent of the research of this paper was the choice of optimal competitive procedures in the market, through clusters. Clusters represent a form of regional inter-organizational connectedness of enterprises from connected businesses with a unique interest to promote the competitive position of organization within the cluster, branches of economy and appropriate national economies through exchange of experiences and knowledge, sharing resources and joining of research-scientific and other supporting activities (Porter). However, even though clusters have an undisputed importance in strengthening of competitiveness, innovativeness and export of agricultural sector, when it comes to the agriculture in Serbia, and especially in the region of Sothern and Eastern Serbia, a major problem for their development is a rural ambience, characterized by the lack of favorable assumptions for their development. That is why in practice the condition is far from desirable. Numerous practical, institutional and normative problems, doubts and questions are present, which need to be resolved on the move in order for the agricultural clusters to achieve expected effects. The concept of clusters is being wrongly interpreted, so that, instead of being an important strategic lever of promoting the competitiveness, the cluster is being used and misused as a cover for various interests of individuals, local community, even state institutions. The competitive advantage of economy (and agriculture within it), regional development, as well as cluster development, cannot be achieved on their own. They must be directed and mutually supportive processes. Moreover, the government of Serbia with their working bodies must assume a much more operative role in providing adequate institutional environment for clusters, by creating supportive policies, social and legal basis which create a favorable climate for this kind of inter-organizational relationships. Also, with the aim of promoting rural development and networking in the agriculture of the region, the state must be much more pronounced in the certain phases of agricultural cluster development; apart from coordinating, control mechanisms must also be established, in order for one good concept not to be misused and compromised in practice, which is something cluster agents point out to. The state can achieve this through projects that are specifically targeted at agricultural clusters. This must be done on all levels of state structure, from the level of republic to region and local communities. Especially local communities should have more understanding for the processes of association in their respective regions, as the examples from more developed economies show that the successful clusterization of economy is best achieved with a “bottom up” approach.

Retaining Privileged Information for Multi-Task Learning.

Knowledge transfer has been of great interest in current machine learning research, as many have speculated its importance in modeling the human ability to rapidly generalize learned models to new scenarios. Particularly in cases where training samples are limited, knowledge transfer shows improvement on both the learning speed and generalization performance of related tasks. Recently, Learning Using Privileged Information (LUPI) has presented a new direction in knowledge transfer by modeling the transfer of prior knowledge as a Teacher-Student interaction process. Under LUPI, a Teacher model uses Privileged Information (PI) that is only available at training time to improve the sample complexity required to train a Student learner for a given task. In this work, we present a LUPI formulation that allows privileged information to be retained in a multi-task learning setting. We propose a novel feature matching algorithm that projects samples from the original feature space and the privilege information space into a joint latent space in a way that informs similarity between training samples. Our experiments show that useful knowledge from PI is maintained in the latent space and greatly improves the sample efficiency of other related learning tasks. We also provide an analysis of sample complexity of the proposed LUPI method, which under some favorable assumptions can achieve a greater sample efficiency than brute force methods.

Eradicating Poverty by the Year 2030: Implications for Income Inequality, Population Policies, Food Prices (and Faster Growth?)

Abstract The paper examines whether the planned eradication of poverty to the year 2030 part of the Sustainable Development Goals strategy is compatible with the trends expected over the next 15 years in key economic variables such as GDP growth, population growth, income inequality and food prices. To do so, the paper develops a comparative-static, poverty-accounting model that allows to simulate to 2030 the impact on SDG1 (poverty eradication) of favorable future improvements equal to best results recorded for such variables during the last 30 years. Numerous model simulations show that – even under the most favorable assumptions – between 14 and 16 countries (mainly from Africa) out of the 78 analyzed will not reach the SDG1 target. Policy suggestions on how to improve on such results are presented at the end of the paper.

Cost-effectiveness analysis of asymptomatic peripheral artery disease screening with the ABI test.

Screening for asymptomatic peripheral artery disease (aPAD) with the ankle-brachial index (ABI) test is hypothesized to reduce disease progression and cardiovascular (CV) events by identifying individuals who may benefit from early initiation of medical therapy. Using a Markov model, we evaluated the cost effectiveness of initiating medical therapy (e.g. statin and ACE-inhibitor) after a positive ankle-brachial index (ABI) screen in 65-year-old patients. We modeled progression to symptomatic PAD (sPAD) and CV events with and without ABI screening, evaluating differences in costs and quality-adjusted life years (QALYs). The cost of the ABI test, physician visit, new medication, CV events, and interventions for sPAD were incorporated in the model. We performed sensitivity analysis on model variables with uncertainty. Our model found an incremental cost of US $338 and an incremental QALY of 0.00380 with one-time ABI screening, resulting in an incremental cost-effectiveness ratio (ICER) of $88,758/QALY over a 35-year period. The variables with the largest effects in the ICER were aPAD disease prevalence, cost of monthly medication after a positive screen and 2-year medication adherence rates. Screening high-risk populations, such as tobacco users, where the prevalence of PAD may be 2.5 times higher, decreases the ICER to $24,092/QALY. Our analysis indicates the cost effectiveness of one-time screening for aPAD depends on prevalence, medication costs, and adherence to therapies for CV disease risk reduction. Screening in higher-risk populations under favorable assumptions about medication adherence results in the most favorable cost effectiveness, but limitations in the primary data preclude definitive assessment of cost effectiveness.

Cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel as a first-line treatment for HER-2 positive metastatic breast cancer

ABSTRACTObjective: To provide perspective for the National Health Insurance Bureau (NHIB), we determined the cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel (TDP) versus trastuzumab and docetaxel (TD) as a first-line treatment for HER-2 positive metastatic breast cancer.Methods: We used a Markov model to simulate cost-effectiveness, disease progression, and survival, based on clinical data and transition probabilities extracted from the CLEOPATRA study. Direct medical costs were acquired from the NHIB claims database.The utilities in health state were based on a recent cost-effectiveness study on trastuzumab and pertuzumab. Outcomes included quality-adjusted life-years (QALYs), costs in New Taiwan dollars (NT$), and the incremental cost-effectiveness ratio (ICER). We performed one-way deterministic and probabilistic sensitivity analyses to assess the impact of specific parameters on the model.Results: Modeled median survival was 39.1 months for TD and 50.1 months for TDP. The ICER was NT$18,999,687 (US$593,741) per QALY gained. The sensitivity analyses indicated that TDP could be cost-effective under favorable assumptions; TDP had a 68% chance of being cost-effective, if TDP costs could be reduced with 10% in the stable disease state.Conclusion: Our model predicted that TDP would be cost-effective as a first-line treatment for HER-2 positive metastatic breast cancer, but only under favorable drug cost assumptions.