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The American Journal of Managed Care September 2013
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Out-of-Pocket Costs and Prescription Reversals With Oral Linezolid
Margaret K. Pasquale, PhD; Anthony M. Louder, PhD, RPh; Michael C. Deminski, MS, RPh; Richard B. Chambers, MSPH; and Seema Haider, MSc
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Out-of-Pocket Costs and Prescription Reversals With Oral Linezolid

Margaret K. Pasquale, PhD; Anthony M. Louder, PhD, RPh; Michael C. Deminski, MS, RPh; Richard B. Chambers, MSPH; and Seema Haider, MSc
Associations between out-of-pocket costs and prescription reversals, as well as impact of reversals on rehospitalizations and healthcare costs, were examined among patients prescribed oral linezolid.
As shown in Table 2, infection-related (complicated or uncomplicated SSTI or pneumonia) rehospitalizations were 14 percentage points higher (P <.0001) and all-cause rehospitalizations were 10 percentage points higher (P = .0027) in the reversal group versus the fill group. For each type of infection (complicated or uncomplicated SSTI, pneumonia, or both SSTI  and pneumonia), no significant difference was detected between the fill and reversal groups. When grouping prescription fill versus reversal groups by the percentage readmitted for the same infection as the one diagnosed at initial hospitalization, a higher percentage of the reversal group was hospitalized for the same infection: 20% reversal group versus 9% fill group (P <.0001) for complicated or uncomplicated SSTI and 3% reversal group versus 1% fill group (P = .0268) for pneumonia.

Unadjusted postindex prescription drug, medical, and total healthcare costs are reported in Table 3. Whereas postindex prescription drug costs were significantly lower for members with a reversal (P <.0001), postindex medical costs were  significantly higher for these members (P = .0013) compared with members with a fill. The combined total unadjusted healthcare costs were not statistically different between the 2 groups (P = .1853).

Adjusted prescription drug, medical, and total healthcare costs are reported in Table 4. After adjusting for demographic and clinical characteristics, differences in the prescription drug and medical costs remained statistically significant between the fill and reversal groups. Notably, with adjustment, the difference in total healthcare costs between the fill and reversal groups became statistically significant (P = .0349),  with the mean healthcare cost for the reversal group being $1280.93 higher than that for the fill group.

Parameter estimates (including exponentiated estimates for ease of interpretation) from the GLM for adjusted costs are reported in Table 5. The parameter estimate for the reversalvariable was statistically significant, indicating that adjusted costs for members with a reversal were 19.4% higher than those for members with a fill (P = .0349). Male sex was associated with a 20.1% increase in adjusted costs (P = .0027), and an incremental point increase in the RxRisk-V score was associated with a 4.8% increase in adjusted costs (P <.0001). The parameter estimate on preindex healthcare costs was statistically significant, but indicated minimal magnitude. Theparameter estimate for members whose out-of-pocket costs were more than $100 was associated with lower adjusted total healthcare costs (P = .0080). Parameter estimates for the remaining variables examined were not statistically significant.

Several sensitivity analyses further explored the GLM results by varying cutoffs for the out-of-pocket cost categorical variable (above and below $60, above and below $125), as well as including an interaction term between the reversal term and out-of-pocket-cost term. 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 30-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. Whereas treatment with oral linezolid was associated with higher postindex prescription drug costs, higher prescription drug costs were offset by lower medical costs for the fill group, resulting in total healthcare costs that were $1280.93 lower for the fill group versus the reversal group. 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. Consistent with this interpretation is the significantly higher distribution of low-income subsidy/dual-eligibility status among members with a fill versus members with a reversal (42% vs 10%, respectively). Low-income subsidy/dual-eligible members are more likely to fill the prescription for oral linezolid as it is probable they will have low or no out-of-pocket costs. 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.

Among members who reversed their prescriptions for oral linezolid, 27% went untreated and 73% filled prescriptions for alternative antibiotics in the 30 days after discharge. 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.16-20 As pathogens, disease states, additional indications for existing comparators, and emerging new comparators change the clinical and economic landscape of the treatments for SSTIs and pneumonia over time, additional research including cost-effectiveness analyses will need to be conducted.

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.

Author Affiliations: From Comprehensive Health Insights, Inc, (MKP, AML), Louisville, KY; Pfizer Global Biopharmaceuticals (MCD), Pfizer Inc (RBC), New York, NY; Pfizer Inc (SH), Groton, CT.

Funding Source: This research project was funded jointly by Humana Inc and Pfizer Inc. 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. Mr Deminski, Mr Chambers, and Ms Haider report employment with Pfizer Inc, as well as stock ownership in the company.

Authorship Information: Concept and design (MKP, AML, MCD, RBC, SH); acquisition of data (AML); analysis and interpretation of data (MKP, AML, MCD, RBC, SH); drafting of the manuscript (MKP, MCD, SH); critical revision of the manuscript for important intellectual content (MKP, MCD, RBC, SH); statistical analysis (AML, RBC); obtaining funding (SH); administrative, technical, or logistic support (MKP); and supervision (SH).

Address correspondence to: Margaret K. Pasquale, PhD, Principal Researcher, Comprehensive Health Insights, Inc, 325 W Main St, WFP6W, Louisville, KY 40202. E-mail:
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