Why does zyvox cost so much

After adjusting for demographic and clinical characteristics, differences in the prescription drug and medical costs remained statistically significant between the fill and reversal groups.

Parameter estimates including exponentiated estimates for ease of interpretation from the GLM for adjusted costs are reported in. The parameter estimate for the reversalvariable was statistically significant, indicating that adjusted costs for members with a reversal were Male sex was associated with a The parameter estimate on preindex healthcare costs was statistically significant, but indicated minimal magnitude.

Parameter estimates for the remaining variables examined were not statistically significant. Results provided upon request were generally similar to those specified in Table 5.

The current study found that Medicare members with an oral linezolid fill had fewer infection-related and day all-cause hospital readmissions than members who reversed their prescriptions and either did not receive any antibiotic or received a different antibiotic following their reversal.

A higher readmission rate, combined with all other types of medical encounters, resulted in higher medical costs during the 30 days after discharge from the initial hospitalization for SSTI or pneumonia. This clearly highlights the need to examine prescription drug costs and benefit design in the context of total healthcare costs. The fill and reversal groups were similar with respect to the vast majority of their demographic and clinical characteristics, suggesting that an economic perspective might have factored in the decision to fill or reverse the linezolid prescription.

If economic factors did indeed influence the decision to fill or reverse the linezolid prescription, then strategies to reduce member out-of-pocket costs eg, benefit design for all health plan members could enable better member access, and in turn, reduce total healthcare costs. As to whether these other antibiotics could be considered alternative therapies to linezolid from a clinical point of view, the specific infection diagnosis and pathogen for each member, along with the specific antibiotic prescription filled postdischarge, would need to be taken into consideration on a case-by-case basis.

An examination of the literature to date regarding the cost-effectiveness of oral linezolid treatment versus comparators indicates that several formal cost-effectiveness analyses have been conducted primarily vs vancomycin , with results suggesting linezolid was cost-effective in each of the analyses, particularly in the cases of shorter hospital length of stays.

One limitation of this study was its focus on members with an inpatient stay, which may not be generalizable to those prescribed oral linezolid in an ambulatory setting. In addition, the length of treatment for oral linezolid or other antibiotic therapies was not evaluated in this study and may have had an impact on postdischarge outcomes.

Furthermore, the distinction between copay and coinsurance was made via visual inspection due to the fact that the medical claims did not contain an indicator for copay or coinsurance. Future work will need to more accurately reflect the distinction between copay and coinsurance. Additionally, limitations common to studies using administrative claims data apply. These include lack of certain information in the database eg, lab results, weight, health behavior information and errors in claims coding.

No causal inference can be ascertained from this study, as it was an observational study using retrospective claims data. Although multivariate regression modeling was used to reduce selection bias and strengthen the causal inference, this approach can only reduce bias caused by measured covariates.

Finally, because this study used data from Humana members only, the results may not be generalized to the general population. However, Humana is a large national health plan with members residing in a broad array of US regions. This study found coinsurance benefit design was linked to higher out-of-pocket costs.

These higher costs were associated with increased rates of reversals, which were associated with higher rates of rehospitalization and adjusted total healthcare costs among Medicare members prescribed oral linezolid after hospital discharge for skin or respiratory infections.

The research concept was approved and plans to publish results were made known prior to commencing the study by the Joint Research Governance Committee of the Humana-Pfizer Research Collaboration, composed of Humana Inc and Pfizer Inc employees. Author Disclosures: Drs Pasquale and Louder report employment with Comprehensive Health Insights, Inc, a wholly owned subsidiary of Humana Inc, who were paid consultants to Pfizer in connection with the development of this manuscript.

Address correspondence to: Margaret K. E-mail: mpasquale humana. Zyvox [full prescribing information]. New York: Pfizer Inc; Accessed August 7, Trends in US hospital admissions for skin and soft tissue infections.

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A chronic disease score from automated pharmacy data. J Clin Epidemiol. A comparison of comorbidity measurements to predict healthcare expenditures. Using generalized linear models to assess medical care costs. Health Serv Outcomes Res Methodol. Costeffectiveness analysis of linezolid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus: complicated skin and skinstructure infection using Bayesian methods for evidence synthesis.

Value Health. Cost-effectiveness of linezolid versus vancomycin in suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany. Cost-effectiveness analysis of linezolid vs. Int J Clin Pract. Cost-effectiveness of linezolid versus vancomycin for hospitalised patients with complicated skin and soft tissue infections in Germany.

Eur J Health Econ. Cost-effectiveness analysis of linezolid compared with vancomycin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus. Two large, prospective, randomized, double-blind trials demonstrated that linezolid mg every 12 hours was statistically noninferior to fixed-dose vancomycin 1 g twice daily for the treatment of NP [ 13 , 14 ].

In a retrospective combined subgroup analysis of these two trials, researchers found significantly higher survival and clinical cure rates with linezolid treatment compared with vancomycin treatment [ 14 ].

Using post hoc data from the same studies, investigators have reported similar findings in patients with MRSA ventilator-associated pneumonia [ 15 ]. In a recent prospective, randomized, double-blind, controlled, multicenter study, specifically focused on MRSA-confirmed NP, researchers found greater clinical efficacy defined as resolution of signs and symptoms, improved or lack of progression in chest imaging and no additional antibacterial treatment required with linezolid than with adjusted-dose vancomycin [ 16 ].

Linezolid was noninferior and statistically superior to vancomycin in end-of-treatment clinical and in end-of-treatment and end-of-study microbiologic outcomes. All-cause day mortality rates were similar Despite its higher acquisition costs, the overall cost for treating MRSA NP with linezolid may be lower because it is associated with better clinical outcomes compared with vancomycin.

In two cost-effectiveness analyses based on a retrospective decision-analytic modeling approach, investigators found linezolid to be less costly and more efficacious than vancomycin for patients with suspected MRSA NP [ 18 , 19 ]. However, these earlier modeling studies either did not address the use of these agents in the US context [ 18 ] or were focused only on first-line therapy [ 19 ]. Our purpose in this economic analysis was to investigate the economic impact of improved clinical outcomes with linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the United States using a decision tree with a payer perspective and flexibility for real-world clinical conditions.

We conducted a cost-effectiveness analysis of intravenous IV linezolid compared with IV vancomycin for the treatment of MRSA NP in hospitalized adults, which was based on a decision tree modeling approach. The decision tree model was developed to capture first-line and second-line therapy. Because of the short-term window for the clinical management of an NP episode, the model time horizon was up to 4 weeks, which was validated by practicing physicians.

This time horizon spans periods typical for ICU and general ward stays during first-line and second-line treatment [ 18 , 20 , 21 ]. A total payer perspective assuming a per diem basis of payment was considered in the base case analysis, which was comprehensive and comprised all inpatient and outpatient health-care costs antibiotic and medical.

Because this was an economic model in which we used only previously published data to create a hypothetical patient pathway, ethical approval and informed consent were neither applicable nor required. This empiric treatment pathway was not included in the base case analysis. Following confirmation of MRSA NP, the economic model analysis began and patients were placed on first-line treatment vancomycin or linezolid for 10 days Figure 1. We focused on the component of treatment after MRSA confirmation when calculating cost-effectiveness, given the recent clinical trial data available [ 16 ] and because this is an important time point in clinical decision-making for reevaluation of the antibiotic treatment and coverage.

Possible treatment outcomes associated with first-line therapy were 1 treatment success defined as resolution of signs and symptoms of NP, improvement or lack of progression in chest imaging and no additional antibacterial treatment required among survivors , 2 failure due to lack of efficacy among survivors, 3 drug discontinuation due to SAEs and 4 failure due to death Figure 1.

A penalty, described in the section below, was assigned for patients whose treatment failed due to lack of efficacy or was discontinued due to SAEs. Decision model tree. Patients whose first-line treatment succeeded would finish their day treatment duration and exit the model. In cases of any failure of first-line treatment, patients were switched to second-line treatment for example, patients whose first-line treatment with linezolid failed were switched to second-line vancomycin, and vice versa after 7 days, with the second-line treatment lasting 10 days.

The model did not include a third-line treatment, given the lack of published data. Linezolid and vancomycin were the main treatment comparators.

In the base case analysis, we used day treatment duration for the first- and second-line therapies. Data on length of hospital stay, inpatient and outpatient resource use and associated costs, and drug costs were obtained by analysis of the recent clinical trial and published literature Tables 1 and 2 [ 16 , 21 , 23 ].

In cases where a discontinuation due to an SAE or treatment failure occurred, patients were assumed to stay 1. This additional length of stay was determined on the basis of post hoc analysis of recent clinical trial data [ 16 , 21 , 22 ] wherein bivariate analysis was conducted to compare length of stay in patients with or without moderate or severe adverse events and in patients with first-line treatment success versus failure. These values were further validated with expert opinion of the authors who reported the pertinent studies.

This study is primarily a cost-effectiveness analysis and not a cost—utility analysis, because the treatment effect of interest is drug efficacy that is, proportion of patients successfully treated , instead of quality-adjusted life years QALYs or life-years LYs. The latter two outcomes QALYs and Lys were not considered ideal for this analysis and hence are not reported, because the model uses a short-term duration and the trial data used for this model suggest equal mortality rates between linezolid and vancomycin [ 16 ].

The key result outcomes of this analysis, which are reported in the Results section, are total costs and effectiveness proportion for the two treatments, total cost per successfully treated patient for each treatment calculated as ratio of total costs and total effectiveness and incremental cost-effectiveness ratio ICER , calculated as the difference in costs between treatments divided by the difference in the proportion of successfully treated patients receiving linezolid versus vancomycin.

Every patient received treatment as long as they were hospitalized, and all patients were on IV therapy during their hospital stay. In the absence of published data for second-line treatment, the clinical inputs for second-line treatment were the same as those used for first-line treatment [ 18 ]. Because we used the day mortality rates reported in the clinical trial [ 16 ], which represented total mortality and included deaths associated with first-line and second-line treatment, mortality occurred only at the end of first-line treatment to avoid overestimation attributable to double-counting.

Because the first-line mortality rates did not statistically differ between linezolid and vancomycin in the clinical trial, these rates were considered the same in the model. Patients whose second-line treatment failed and those who had SAEs were deemed to have completed the duration of therapy because no third-line therapy was available. Alternatively, if the treatment duration was 14 days, then the ICU stay would be 10 days and the remaining 4 days would be in the general ward.

Univariate one-way sensitivity analysis was conducted to assess the impact of model uncertainties and the robustness of our analysis. Key model parameters were varied individually within the predefined sensitivity ranges Tables 2 and 3 , and ICERs were recorded.

A published source was used for ranges whenever possible. The results are presented in the form of a tornado diagram, with the variables stacked in decreasing order of impact on the ICER. A probabilistic sensitivity analysis PSA was also performed, wherein all parameters were varied simultaneously within their range using 10, second-order Monte Carlo simulations.

The expected proportions of successfully treated patients were General ward costs were higher with vancomycin compared with linezolid, because, even though the length of stay in the hospital was comparable between treatments, there was a higher percentage of patients for whom vancomycin failed as first-line therapy and thus were transitioned to second-line treatment and had an associated longer general ward stay.

Moreover, the higher percentage of vancomycin-treated patients requiring second-line therapy may have led to marginally higher costs for additional physician visits and laboratory work. The results of one-way sensitivity analysis as seen in the Tornado diagram in Figure 2 demonstrated variables that had the greatest impact on the model results.

These ICERs can be considered greater than the acceptable willingness-to-pay WTP threshold, making vancomycin the cost-effective option. There is no clearly defined WTP threshold for successful treatment of one patient, and hence different WTP values were tested in the PSA cost-effectiveness acceptability curve. A cost-effectiveness acceptability curve generated from a PSA is presented in Figure 3.

This plot displays the percentages for linezolid being more cost-effective compared to vancomycin at the different WTP thresholds. Linezolid had a One-way sensitivity analyses of key parameters Tornado diagram.

Cost-effectiveness acceptability curve of linezolid versus vancomycin. This economic decision tree analysis is the first, to our knowledge, to mirror real-world clinical conditions by allowing for a switch of therapy if needed that is, it models first- and second-line treatment and allowed us to assess the impact of varying treatment parameters, including treatment duration.

To our knowledge, no other published studies of NP have researchers accounted for these factors from a US health-care payer perspective. Our results with this model show that linezolid is a cost-effective alternative to vancomycin for the treatment of MRSA-confirmed NP, owing primarily to the higher clinical response rate of linezolid-treated patients compared with vancomycin-treated patients. The higher acquisition cost of linezolid was offset by lower costs of treatment failure and SAEs, as well as fewer days spent in the hospital, when we accounted for combined first-line and second-line therapies.

Only direct medical costs were included in the model, with a distinction made between inpatient and outpatient costs. For NP, inpatient costs accounted for the largest proportion of overall costs. Linezolid was a more cost-effective treatment option in the majority of one-way sensitivity analyses vancomycin was cost-effective only under two scenarios: low ICU stay and high vancomycin efficacy rate and under varying WTP thresholds in PSA.

Length of ICU stay and clinical efficacy rate appeared to be the most sensitive variables in one-way analysis, with the greatest impact on the ICER. This was expected, especially with regard to the length of ICU stay, because ICU stay per diem is very expensive in the United States and the cost of ICU stay accounts for the largest proportion of total treatment cost. Our results are consistent with those reported in two previous cost-effectiveness analyses in which investigators found therapy initiated with linezolid to be less costly and more efficacious than vancomycin for patients with suspected MRSA NP [ 18 , 19 ].

Mullins et al. In a German cost-effectiveness analysis [ 18 ], the researchers used a decision-analytic model based on previously published clinical data [ 14 ] and found higher clinical cure and survival rates with linezolid, but at a small incremental cost compared with vancomycin, resulting in acceptable ICERs of cost per death avoided and cost per patient cured [ 18 ].

From a clinical standpoint, they demonstrated that linezolid had better efficacy than vancomycin for the treatment of MRSA NP on the basis of trial data specifically in MRSA-confirmed patients , with fewer patients requiring a switch to second-line therapy.

Costs, therefore, were not considered in patients who did not have MRSA infection. In clinical practice, initiation with empiric antibiotic treatment is started as soon as MRSA is suspected, and antibiotic treatment success and the related costs of empiric therapy are determined by how well MRSA is predicted and by the proportion of patients with MRSA in the treated population.

Our present analysis therefore does not include the costs of initial empiric therapy and the harm that comes from 1 not covering MSSA by using only MRSA coverage, 2 choosing vancomycin and the possibility of renal toxicity developing in a patient without MRSA and 3 not starting empiric therapy with either drug and having a delay in starting appropriate therapy until after culture results have been confirmed.

Although we did not address these clinical aspects in our model, they are relevant and important and should be explored in future studies. Vancomycin has been the mainstay generic for decades; however, challenges with tissue penetration at the site of infection, therapeutic drug monitoring and increased risk for renal dysfunction in NP patients makes the use of this agent more difficult in critically ill patients.

In the economic analysis presented here, we used the recent and only clinical trial data specifically designed to evaluate clinical success in the treatment of patients with MRSA NP [ 16 ]. To date, linezolid is the only agent to have proven better clinical success rates in NP than vancomycin in a MRSA-only population. Linezolid is sold as ZYVOX and is under patent in the United States until the end of ; thus, use of this agent may increase further with the introduction of generic versions.

However, there is another oxazolidinone drug for nosocomial pneumonia currently under development, tedizolid, in ongoing phase III trials. A newer glycopeptide, telavancin, became available in late for gram positive NP, and while the phase III trials included MRSA patients, the studies were not specifically designed to examine clinical success in the MRSA-only population. Our study has limitations. Further, because the Wunderink trial enrolled US patients, the results may not be applicable to scenarios outside the United States.

The model included only first-line and second-line treatments, not potential later treatment options. However, this is consistent with other published models [ 18 ] and is justifiable because the majority of the resources used and outcomes witnessed were within the first two lines of therapy. In the model, we estimated direct costs only and did not include indirect costs related to lost productivity incurred as a result of the length of hospital stay, convalescence or early mortality.

In addition, mortality rates were not statistically different in the clinical trial; thus, a cost per LY saved calculation was less relevant, given that the trial was never designed to show a difference in mortality. In fact, patients could have received up to 2 days of vancomycin before being randomized to the study drugs; thus, patients doing poorly on vancomycin would have been less likely to be enrolled in the study, where the chance of being randomized to vancomycin was 50— However, we think that successful treatment is a clinically important efficacy measure for NP, and hence it can be argued to be relevant for this model.

Cost savings with linezolid were derived largely from lower treatment failure rates, fewer days of hospitalization and lower incidence of renal failure. We found our findings to be consistent in sensitivity analyses. In future analyses, researchers should use other country costs and resource-use data to test result generalizability and could model the empiric treatment phase before MRSA confirmation.

Higher drug costs for linezolid are offset by lower overall medical costs due to fewer treatment failures and fewer serious adverse events, such as renal failure, as well as fewer days spent in the hospital, when accounting for combined first-line and second-line therapies. PubMed Google Scholar. Infect Control Hosp Epidemiol.

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