Use of Healthcare Claims Data to Generate Real-World Evidence on Patients With Drug-Resistant Epilepsy: Practical Considerations for Research.

Objectives: Regulatory bodies, health technology assessment agencies, payers, physicians, and other decision-makers increasingly recognize the importance of real-world evidence (RWE) to provide important and relevant insights on treatment patterns, burden/cost of illness, product safety, and long-term and comparative effectiveness. However, RWE generation requires a careful approach to ensure rigorous analysis and interpretation. There are limited examples of comprehensive methodology for the generation of RWE on patients who have undergone neuromodulation for drug-resistant epilepsy (DRE). This is likely due, at least in part, to the many challenges inherent in using real-world data to define DRE, neuromodulation (including type implanted), and related outcomes of interest. We sought to provide recommendations to enable generation of robust RWE that can increase knowledge of "real-world" patients with DRE and help inform the difficult decisions regarding treatment choices and reimbursement for this particularly vulnerable population. Methods: We drew upon our collective decades of experience in RWE generation and relevant disciplines (epidemiology, health economics, and biostatistics) to describe challenges inherent to this therapeutic area and to provide potential solutions thereto within healthcare claims databases. Several examples were provided from our experiences in DRE to further illustrate our recommendations for generation of robust RWE in this therapeutic area. Results: Our recommendations focus on considerations for the selection of an appropriate data source, development of a study timeline, exposure allotment (specifically, neuromodulation implantation for patients with DRE), and ascertainment of relevant outcomes. Conclusions: The need for RWE to inform healthcare decisions has never been greater and continues to grow in importance to regulators, payers, physicians, and other key stakeholders. However, as real-world data sources used to generate RWE are typically generated for reasons other than research, rigorous methodology is required to minimize bias and fully unlock their value.

Patterns of utilization and cost of healthcare services and pharmacotherapy among patients with drug-resistant epilepsy during the two-year period before neurostimulation: A descriptive analysis of the journey to implantation based on analyses of a large United States healthcare claims database.

OBJECTIVE: To conduct a descriptive assessment of patterns of utilization and cost of healthcare services and pharmacotherapies among patients with drug-resistant epilepsy (DRE) before neurostimulator implantation. METHODS: Using a large United States healthcare claims database, we identified all patients with DRE who were implanted with neurostimulators between January 1, 2012, and December 31, 2019. Patients without an epilepsy diagnosis on their implantation date were excluded, as were those without (1) anti-seizure medication (ASM) dispenses within 12 months of implantation date, and (2) continuous enrollment for the 24-month period before this date. Demographic and clinical characteristics were assessed over the two-year period before implantation, as were patterns of utilization and cost of healthcare services and pharmacotherapy. Care was assessed as all-cause or epilepsy-related, with the latter defined as all medical (inpatient and outpatient) care resulting in diagnoses of epilepsy and all ASM dispenses. RESULTS: Eight hundred sixty patients met all selection criteria. Among these patients, comorbidities were common, including depression (27%), anxiety (30%), and learning disabilities (25%). Fifty-nine percent of patients had ≥1 all-cause hospitalizations; 57% had ≥1 epilepsy-related admissions. Patients averaged 8.6 epilepsy-related visits to physicians' offices, including 5.1 neurologist visits. Mean all-cause and epilepsy-related healthcare costs during the pre-implantation period were $123,500 and $91,995, respectively; corresponding median values were $74,567 and $53,029. Median monthly all-cause healthcare costs increased by 138% during the 24-month period (from $1,042 to $2,481 in the month prior to implantation); median epilepsy-related costs, by 290% (from $383 to $1,492). CONCLUSIONS: The two-year period before neurostimulator implantation is a long and costly journey. Estimates likely minimize the burden experienced during this period, given that seizure frequency and severity-and corresponding impacts on quality of life-were unavailable in these data. Further research is needed to understand the clinical, economic, and psychological impact of the time between DRE onset and implantation among qualifying patients.

Impact of Vagus Nerve Stimulation for the Treatment of Drug-resistant Epilepsy on Patterns of Use and Cost of Health Care Services and Pharmacotherapy: Comparisons of the 24-Month Periods Before and After Implantation.

PURPOSE: This study examines the impact of vagus nerve stimulation (VNS) as treatment for drug-resistant epilepsy (DRE) on the use and cost of health care services and pharmacotherapy. METHODS: Using a large US health care claims database, we identified all patients with DRE who underwent VNS between January 1, 2012 and December 31, 2019. VNS implantation date was designated as the index date, and patients had to be continuously enrolled for the 24-month period before this date (preindex period). Outcomes included all-cause and epilepsy-related hospitalization, emergency department (ED) visits, and health care costs; health care claims resulting in an epilepsy diagnosis and all claims for antiseizure medications were deemed epilepsy related. Preindex data, except care related to preoperative medical clearance for VNS, were used to estimate multivariate regression models predicting outcomes during the 24-month postindex period (follow-up period). Predicted outcomes during follow-up were then compared with observed values. As a sensitivity analysis, we also replicated all analyses among subgroups defined by comorbid depression. FINDINGS: A total of 659 patients underwent VNS for DRE and met the selection criteria. For the composite outcome of all-cause hospitalizations and ED visits, observed values were 42% lower than expected during the 24-month follow-up period; for the composite outcome of epilepsy-related hospitalizations and ED visits, observed values were 49% lower (P < 0.001 for both). Observed mean total all-cause costs, inclusive of costs of the procedure, were not significantly different than expected costs by month 19 of follow-up; mean total epilepsy-related costs were comparable by month 18. Findings were similar in subgroups with and without depression, although nominally greater differences (observed - expected) were seen in those with comorbid depression. IMPLICATIONS: Our findings suggest that VNS is associated with decreased risk of hospitalization or ED visits (all cause and epilepsy related) during the 2-year period subsequent to implantation and may become cost-neutral within 2 years of implantation (vs continued medical management of DRE without VNS). Although expected outcomes were estimated based on the 24-month period before implantation, the degree to which they approximated what would have happened in the absence of VNS is unknowable. Further research is needed to better understand the extend and duration of the impact of VNS on seizure frequency and severity and health-related quality of life, including its performance among those with and without comorbid depression.

Epidemiology and Economic Outcomes Associated with Timely versus Delayed Receipt of Appropriate Antibiotic Therapy among US Patients Hospitalized for Native Septic Arthritis: A Retrospective Cohort Study.

Timely administration of appropriate antibiotic therapy is associated with better patient outcomes and lower costs of care compared to delayed appropriate therapy, yet initial treatment is often empiric since causal pathogens are typically unknown upon presentation. The challenge for clinicians is balancing selection of adequate coverage treatment regimens, adherence to antimicrobial stewardship principles to deter resistance, and financial constraints. This retrospective cohort study aimed to assess the magnitude and impact of delayed appropriate antibiotic therapy among patients hospitalized with septic arthritis (SA) in the U.S. from 2017 to 2019 using healthcare encounter data. Timely appropriate therapy was defined as the receipt of antibiotic(s) with in vitro activity against identified pathogens within two days of admission; all other patients were assumed to have received delayed appropriate therapy. Of the 517 patients admitted to hospital for SA who met all selection criteria, 26 (5.0%) received delayed appropriate therapy. In inverse-probability-treatment-weighting-adjusted analyses, the receipt of delayed appropriate therapy was associated with an additional 1.1 days of antibiotic therapy, 1.4 days in length of stay, and $3531 in hospital costs (all vs. timely appropriate therapy; all p ≤ 0.02). Timely appropriate therapy was associated with a twofold increased likelihood of antibiotic de-escalation during the SA admission.

Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database.

AIM: Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. MATERIALS AND METHODS: We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. RESULTS: Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. LIMITATIONS: Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. CONCLUSIONS: After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

For some people with epilepsy, medications do not work very well. For these people, other treatment options exist. One such treatment is neurostimulation. There are three types of neurostimulators­vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). All three devices are known to reduce seizures in patients who have tried several medications. However, it is not known how these devices impact the costs of care. We compared the use and costs of medical care over 2 years between patients who got VNS and those who got RNS/DBS. Before comparing the groups, we made sure that they were balanced. Patients who got VNS were less likely than patients who got RNS/DBS to go to the hospital during the follow-up period. Patients who got VNS also had lower healthcare costs than patients who got RNS/DBS during follow-up. These differences were seen for all medical care costs. These differences also were seen in the costs of care for epilepsy. Our results suggest that the use of VNS is associated with fewer hospitalizations than RNS/DBS, and also that use of VNS is associated with lower healthcare costs than RNS/DBS.

Incidence and Cost of Major Adverse Cardiovascular Events and Major Adverse Limb Events in Patients With Chronic Coronary Artery Disease or Peripheral Artery Disease.

Chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are both associated with elevated risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). The frequency of these events in patients with CAD or PAD, and their corresponding costs, are not well understood. Accordingly, we describe the incidence and cost of both MACE and MALE in patients with CAD or PAD. Using a database that included healthcare claims linked to electronic medical records, we identified patients with evidence of chronic CAD and PAD, respectively, between January 1, 2009, and September 30, 2016. We assessed the occurrence of MACE (defined as myocardial infarction, stroke, or cardiovascular-related death) and MALE (critical limb ischemia, amputation, or peripheral artery disease-related revascularization). A total of 99,730 patients met all selection criteria: 86.0% had CAD, 25.8% had PAD, and 11.8% had both. Mean (±standard deviation) age was 67.7 (±11.5) years and 59.8% were male. During follow-up (mean: 1.8 years), 13.6% experienced MACE or MALE (6.3 per 100 person-years [PYs]), predominantly MACE (9.6% [4.3 per 100 PYs]). Adjusted 1-year healthcare costs were $44,495 greater in patients who experienced MACE or MALE (mean [95% confidence interval]: $64,099 [$33,254 to $123,557] vs $19,604 [$10,175 to $37,771]; p < 0.001). In conclusion, approximately 1 in 7 patients with chronic CAD or PAD experiences additional MACE or MALE within approximately 2 years of follow-up; the relatively high risk and cost of these events highlight the need for new secondary prevention therapies that may improve outcomes in these patients.

Economic burden of hospital admissions for patients with acute bacterial skin and skin structure infections in the United States.

Objectives: We estimated the total US hospital costs associated with acute bacterial skin and skin structure infection (ABSSSI) admissions as well as the admissions that may have been potential candidates for outpatient parenteral antimicrobial therapy (OPAT). Methods: We assessed inpatient admissions for ABSSSI from the Premier database (2011-2014), focusing on all admissions of adults with length of stay (LOS) ≥ 1 days and a primary diagnosis of erysipelas, cellulitis/abscess, or wound infection. We performed a detailed analysis of 2014 admissions for patient, treatment, hospital, and economic characteristic variables. Using published selection criteria, we identified a subset of patients admitted in 2014 who may have been potential candidates for OPAT. Results: We analyzed 277,971 admissions. In 2014, most admissions were for cellulitis without major complications or comorbidities; mean ± SD LOS was 4.0 ± 3.0 days, and total hospital cost per admission was $6400 ± $6874, 54% of which was attributable to room costs. Among 2014 admissions, 14% involved patients with clinical characteristics suggesting that they were consistent with guideline recommendations for exclusive treatment with OPAT. Compared with all admissions in the year, these admissions were of younger patients (aged 50 vs. 55 years), admitted more frequently for cellulitis (90% vs. 70%), with shorter LOS (2.8 ± 1.8 days), and lower mean total hospital cost per admission ($4080 ± $3066). Conclusions: Admissions for ABSSSI impose a substantial cost to US hospitals, with half of costs attributable to room costs. When extrapolated to all US patients admitted to the hospital for ABSSSI during 2014, had OPAT guidelines been universally followed, admissions may have been reduced by 14%, thereby saving US hospitals $161 million.

Cost-effectiveness of a Ceramide-Infused Skin Barrier Versus a Standard Barrier: Findings From a Long-Term Cost-effectiveness Analysis.

PURPOSE: To assess the cost-effectiveness of a ceramide-infused skin barrier (CIB) versus other skin barriers (standard of care) among patients who have undergone ostomy creation. DESIGN: Cost-effectiveness analysis, based on a decision-analytic model that was estimated using data from the ADVOCATE (A Study Determining Variances in Ostomy Skin Conditions And The Economic Impact) trial, which investigated stoma-related healthcare costs over 12 weeks among patients who recently underwent fecal ostomy, and from other sources. SUBJECTS AND SETTING: Analysis was based on a hypothetical cohort of 1000 patients who recently underwent fecal ostomy; over a 1-year period, 500 patients were assumed to use CIB and 500 were assumed to use standard of care. METHODS: We adapted a previous economic model to estimate expected 1-year costs and outcomes among persons with a new ostomy assumed to use CIB versus standard of care. Outcomes of interest included peristomal skin complications (PSCs) (up to 2 during the 1-year period of interest) and quality-adjusted life days (QALDs); QALDs vary from 1, indicating a day of perfect health to 0, indicating a day with the lowest possible health (deceased). Subjects were assigned QALDs on a daily basis, with the value of the QALD on any given day based on whether the patient was experiencing a PSC. Costs included those related to skin barriers, ostomy accessories, and care of PSCs. The incremental cost-effectiveness of CIB versus standard of care was estimated as the incremental cost per PSC averted and QALD gained, respectively; net monetary benefit of CIB was also estimated. All analyses were run using the perspective of an Australian payer. RESULTS: On a per-patient basis, use of CIB was expected over a 1-year period to result in 0.16 fewer PSCs, an additional 0.35 QALDs, and a savings of A$180 (Australian dollars, US $137) in healthcare costs all versus standard of care. Management with CIB provided a net monetary benefit (calculated as the product of maximum willingness to pay for 1 QALD times additional QALDs with CIB less the incremental cost of CIB) of A$228 (US $174). Probabilistic sensitivity analysis was also completed; it revealed that 97% of model runs resulted in fewer expected PSCs with CIB; 92% of these runs resulted in lower expected costs with CIB. CONCLUSIONS: Findings suggest that the CIB is a cost-effective skin barrier for persons living with an ostomy.

Prostacyclin Use Among Patients with Pulmonary Arterial Hypertension in the United States: A Retrospective Analysis of a Large Health Care Claims Database.

BACKGROUND: Prostacyclins play an important role in the management of pulmonary arterial hypertension (PAH). Intravenous prostacyclin was the first disease-specific treatment for patients with PAH. Subcutaneous and nonparenteral (oral or inhaled) formulations have subsequently become available. However, data are lacking on how these different prostacyclin formulations are being used in clinical practice. OBJECTIVES: To (a) conduct retrospective analyses of a large U.S. health care claims database to describe the characteristics of patients with PAH initiating prostacyclin therapy, and (b) evaluate their treatment patterns, health care resource use, and associated costs. METHODS: Truven Commercial and Medicare databases were used to define annual cohorts of adults with PAH between January 1, 2010, and October 31, 2015. These patients were identified based on claims with ICD-9-CM diagnoses indicative of PAH (codes 416.0 or 416.8) and claims for PAH-specific medications and PAH-related procedures. Patients with evidence of receiving a prostacyclin were identified, and prostacyclin use was categorized as parenteral versus nonparenteral. Health care costs were assessed alternatively employing an all-cause and PAH-related perspective. RESULTS: Of 13,633 adults with identified PAH, 3,006 (22.0%) received a prostacyclin during at least 1 year of the study period, and annual prevalence of prostacyclin use ranged from 19.9% to 22.6%. Across calendar years, the median age of prostacyclin users ranged from 56 to 58 years, and 71.9%-75.8% were female. Among prostacyclin users, parenteral prostacyclin use declined from 63.2% in 2010 to 46.5% in 2015, while use of nonparenteral prostacyclins increased from 39.7% to 56.2% over the same period (both P < 0.001). Few patients (2.7%-4.1%) received both parenteral and nonparenteral formulations in a given calendar year. Among patients using prostacyclins, receipt of other PAH-specific medications increased from 62.1% in 2010 to 79.2% in 2015. Comparing the 6 months preceding the first prostacyclin prescription (any formulation) to the 6 months subsequent, mean overall health care costs rose from $61,243 to $119,283, and PAH-related health care costs increased from $58,815 to $116,661, driven mainly by PAH-specific medications, spending on which increased from $15,053 to $73,705 (all P < 0.001). CONCLUSIONS: While overall use of prostacyclins was relatively constant from 2010 to 2015, our findings revealed a shift from parenteral to nonparenteral formulations, coupled with increased prescribing of PAH-related medications from other drug classes. Further research is needed to better understand how these changes in patterns of prostacyclin use affect levels of health care resource utilization and costs and patients' overall quality of life. DISCLOSURES: This research was funded by Actelion Pharmaceuticals US, a Janssen pharmaceutical company of Johnson & Johnson. Burger has received grant funding from Actelion, Gilead Sciences, and United Therapeutics; personal fees from Actelion and Gilead Sciences; and nonfinancial support from Actelion. Pruett, Lickert, and Drake are employees of Actelion. Pruett and Lickert own shares in Actelion. Berger and Murphy are employees of Evidera, a consultancy that received payment from Actelion to conduct this research. Pruett, Lickert, Berger, and Drake contributed to study conception and participated with Burger in study design. Lickert and Murphy performed the data analyses. Burger, Pruett, Lickert, Murphy, and Drake interpreted the data. All authors participated in manuscript drafting and/or critical revision, approved the final manuscript, and agree to be accountable for all aspects of the work.

Clinical and economic consequences of post-operative infections following major elective surgery in U.S. hospitals.

BACKGROUND: The incidence and consequences of post-operative infections in patients undergoing major elective surgery is not well understood. METHODS: Using a large U.S. healthcare claims database, we identified all patients who underwent major elective surgery between January 1, 2007, and December 31, 2009. For each such patient, date of the first-noted surgery during this period was designated as the index date. Patients who developed infections within 30 d of their index date were matched to those who did not using propensity score matching. We compared hospital readmissions, mortality, and total healthcare cost during the 30-d period following index date between patients who developed post-operative infections versus those who did not. RESULTS: A total of 327,618 patients met all selection criteria. At 30 d following major elective surgery, 10.9% of patients had evidence of post-operative infections, 39% of which occurred during the index admission. In propensity-matched analyses, patients with post-operative infections were about five times as likely to be readmitted to hospital (11.3% vs. 2.1%) and more than twice as likely to die (0.8% vs. 0.3%) in the 30-d period following surgery; their average total healthcare cost was $8,417 higher ($29,229 vs. $20,812) (all comparisons, p<0.01). CONCLUSION: Approximately one in 10 patients undergoing major elective surgery develop post-operative infections by day 30. Post-operative infections are associated with significantly worse clinical outcomes and higher total healthcare cost.

Can dialysis patients be accurately identified using healthcare claims data?

BACKGROUND: While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis - especially peritoneal dialysis (PD) and hemodialysis (HD) - in these data is unknown. METHODS: The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient's first dialysis-related claim ("index encounter"), we attempted to designate each study subject as either a "PD patient" or "HD patient." Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients' medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients' medical records as the "gold standard." RESULTS: We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high - 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review. CONCLUSIONS: While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD.

Initial treatment failure in non-ICU community-acquired pneumonia: risk factors and association with length of stay, total hospital charges, and mortality.

OBJECTIVES: To identify risk factors for initial treatment failure in patients with community-acquired pneumonia (CAP) in non-intensive care unit (non-ICU) settings, and to characterize the association between initial treatment failure and length of stay, total hospital charges, and mortality. METHODS: Retrospective cohort study. Using data from >100 US hospitals, this study identified all adults (age ≥18 years) hospitalized for pneumonia between January 1, 2000 and June 30, 2009 who began antibiotic therapy within 24 h of admission and were treated for at least 48 h if alive; patients admitted to intensive care within the first 24 h in hospital were excluded. Initial therapy was defined as all parenteral antibiotics administered within the first 24 h in hospital. Treatment failure was assessed based on subsequent receipt of new antibiotic(s), excluding agents of similar/narrower spectrum and those begun at discharge. Multivariate logistic regression was used to identify risk factors for treatment failure, and multivariate linear and logistic regression to compare length of stay, total hospital charges, and in-hospital mortality between patients experiencing initial treatment failure and those who did not. RESULTS: Among 32,324 patients with non-ICU CAP, 4695 (14.6%) experienced initial treatment failure, most often within 72 h of hospital admission. Significant predictors of initial treatment failure included malnourishment (OR = 1.87; 95% CI = 1.60-2.18), receipt of vasoactive medications within 24 h of admission (1.51 [1.17-1.94]), and renal failure (1.45 [1.32-1.59]). Treatment failure was associated with higher case fatality (8.5% vs 3.3%), longer hospital stays (mean [SD] = 10.1 [8.1] days vs 4.9 [3.3] days), and higher total hospital charges ($37,602 [$71,876] vs $14,371 [$21,633]) (all comparisons, p < 0.01). Study limitations include possible inclusion of patients with healthcare-associated pneumonia (HCAP) in the study sample, our focus on the 40 most commonly used antibiotic regimens, and indirect measurement of treatment failure. CONCLUSIONS: Approximately one in seven non-ICU CAP patients experience failure of initial antibiotic therapy. Risk of failure is higher for patients with significant comorbidities and/or severe infections. Non-ICU patients who experience initial treatment failure have significantly longer hospital stays, higher total hospital charges, and higher rates of mortality.

Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Little is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH) impacts patterns of healthcare utilization and costs. METHODS: Using a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8) who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the "index date," and claims data were compiled for all study subjects for 6 months prior to their index date ("pretreatment") and 6 months thereafter ("follow-up"); patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects. RESULTS: A total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD) age was 52 (10) years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p<0.01) and the percentage of patients hospitalized (from 35% to 29%; p=0.01). The mean cost of all PAH-related medication was $7139 during pretreatment and $14,095 during follow-up (sildenafil cost during follow-up= $5236); exclusive of PAH-related medications, however, total healthcare costs decreased modestly (from $30,104 to $27,605) (p<0.01 for all comparisons). CONCLUSIONS: The cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

Change in healthcare utilization and costs following initiation of benzodiazepine therapy for long-term treatment of generalized anxiety disorder: a retrospective cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepine anxiolytics are used in the US to treat generalized anxiety disorder (GAD). While benzodiazepines typically provide rapid symptomatic relief, long-term use is not recommended due to risks of dependency, sedation, falls, and accidents. METHODS: Using a US health insurance database, we identified all persons with GAD (ICD-9-CM diagnosis code 300.02) who began a long-term course of treatment (≥ 90 days) with a benzodiazepine anxiolytic between 1/1/2003 and 12/31/2007, We compared healthcare utilization and costs over the six-month periods preceding and following the date of treatment initiation ("pretreatment" and "post-treatment", respectively), and focused attention on accident-related encounters (e.g., for treatment of fractures) and care received for other reasons possibly related benzodiazepine use (e.g., sedation, dizziness). RESULTS: A total of 866 patients met all study entry criteria; 25% of patients began treatment on an add-on basis (i.e., adjunctive to escitalopram, paroxetine, sertraline, or venlafaxine), while 75% of patients did not receive concomitant therapy. Mean total healthcare costs increased by $2334 between the pretreatment and post-treatment periods (from $4637 [SD=$9840] to $6971 [$17,002]; p<0.01); costs of accident-related encounters and other care that was possibly related to use of benzodiazepines increased by an average of $1099 ($1757 [$7656] vs $2856 [$14,836]; p=0.03). CONCLUSIONS: Healthcare costs increase in patients with GAD beginning long-term (≥ 90 days) treatment with a benzodiazepine anxiolytic; a substantial proportion of this increase is attributable to care associated with accidents and other known sequelae of long-term benzodiazepine use.

Utilization and cost in clinical practice of darbepoetin alfa and epoetin alfa for anemia concomitant with chemotherapy.

BACKGROUND: In 2005, the mean weekly dose ratio of epoetin alfa (EA) to darbepoetin alfa (DA) in clinical practice was estimated to be ∼400 to 1. In 2006, a 500-µg dose and new dosing schedule was approved for DA in the United States. In 2007, the warnings and dosing/administration sections were modified for both agents. All of these factors may have changed the way that physicians use EA and DA. Previous studies of the use of erythropoiesis-stimulating agents (ESAs) in patients with anemia concomitant with chemotherapy may thus not reflect current clinical practice. OBJECTIVE: The goal of this study was to examine the use and costs of ESAs in clinical practice in patients with anemia concomitant with chemotherapy. METHODS: Using 2 large US health care claims databases, all adults (aged ≥18 years) were identified who received ESAs in 2008 and had evidence of receipt of chemotherapy ≤42 days before initial ESA receipt (ie, the index date). Episodes of care were defined as beginning on the index date and ending on the date of the last ESA claim that was followed by a ≥42-day gap without any receipt of ESAs, to which was added an assumed duration of clinical benefit (in days) based on the ESA and corresponding dose received. DA- and EA-treated patients were matched using propensity scoring. The mean weekly dose and cost of DA and EA during episodes of care was calculated using all information from relevant claims noted during such episodes. Each database was analyzed separately. RESULTS: In the first database, 475 patients with DA episodes of care were matched to an equal number of patients with EA episodes; in the second database, there were 424 matched pairs. In the first database, the mean (95% CI) weekly dose was 37,444 U (35,942 U-39,001 U) during EA episodes and 110 µg (108 µg-113 µg) during DA episodes; the mean weekly EA/DA dose ratio was 340 to 1. In the second database, the mean (95% CI) weekly dose was 37,047 U (35,944 U-38,175 U) during EA episodes and 121 µg (117 µg-125 µg) during DA episodes; the mean weekly EA/DA dose ratio was 306 to 1. CONCLUSIONS: The mean weekly EA/DA dose ratio during episodes of ESA care has declined in patients with anemia concomitant with chemotherapy, due at least in part to the availability and use of a new dose/dosing schedule for DA without similar changes for EA.

Resource utilization and costs before and after total joint arthroplasty.

BACKGROUND: The purpose of this study was to compare pre- and post-surgical healthcare costs in commercially insured total joint arthroplasty (TJA) patients with osteoarthritis (OA) in the United States (U.S.). METHODS: Using a large healthcare claims database, we identified patients over age 39 with hip or knee OA who underwent unilateral primary TJA (hip or knee) between 1/1/2006 and 9/30/2007. Utilization of healthcare services and costs were aggregated into three periods: 12 months "pre-surgery," 91 days "peri-operative," and 3 to 15 month "follow-up," Mean total pre-surgery costs were compared with follow-up costs using Wilcoxon signed-rank test. RESULTS: 14,912 patients met inclusion criteria for the study. The mean total number of outpatient visits declined from pre-surgery to follow-up (18.0 visits vs 17.1), while the percentage of patients hospitalized increased (from 7.5% to 9.8%) (both p < 0.01). Mean total costs during the follow-up period were 18% higher than during pre-surgery ($11,043 vs. $9,632, p < 0.01), largely due to an increase in the costs of inpatient care associated with hospital readmissions ($3,300 vs. $1,817, p < 0.01). Pharmacotherapy costs were similar for both periods ($2013 [follow-up] vs. $1922 [pre-surgery], p = 0.33); outpatient care costs were slightly lower in the follow-up period ($4338 vs. $4571, p < 0.01). Mean total costs for the peri-operative period were $36,553. CONCLUSIONS: Mean total utilization of outpatient healthcare services declined slightly in the first year following TJA (exclusive of the peri-operative period), while mean total healthcare costs increased during the same time period, largely due to increased costs associated with hospital readmissions. Further study is necessary to determine whether healthcare costs decrease in subsequent years.

Adherence with migraine prophylaxis in clinical practice.

OBJECTIVE: To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice. METHODS: Using a large US health insurance claims database (calendar years 2003 to 2005), we identified all patients with migraine who began prophylaxis with selected antidepressants, antiepileptic drugs, or beta blockers ("study agents"). Patients not continuously enrolled for 6 months prior to start of prophylaxis ("pretreatment") and for 6 months subsequently ("follow-up") were excluded. Treatment cohorts were constituted based on the type of prophylaxis received. Adherence with migraine prophylaxis was examined by type of agent received using medication possession ratios (MPRs), defined as total days with medication divided by total follow-up days. MPR < 0.80 was considered indicative of nonadherence. RESULTS: A total of 4,634 patients met all entry criteria and received antidepressants (n = 1,803), antiepileptics (n = 1,896), or beta blockers (n = 935) on their index date. Over the next 6 months, the mean (SD) number of prescriptions for study agents was 2.7 (1.9) for antidepressants, 2.9 (2.0) for antiepileptics, and 2.8 (2.0) for beta blockers, totaling 91.0 (71.4), 98.7 (75.6), and 96.7 (73.0) therapy-days, respectively. Mean MPR at 6 months was 0.48 for antidepressants, 0.51 for antiepileptics, and 0.51 for beta blockers. By the end of the follow-up, 73.4%, 70.2%, and 67.6% of patients who initiated migraine prophylaxis with antidepressants, antiepileptics, and beta blockers, respectively, were designated nonadherent (ie, MPR < 0.80). CONCLUSION: Our findings suggest that many patients who begin migraine prophylaxis with antidepressants, antiepileptics, or beta blockers are no longer taking these medications at 6 months.

Healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder: a retrospective cohort study.

BACKGROUND: Patterns of healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder (GAD) have not been well characterized. METHODS: Using a large US health insurance database, we identified all patients with evidence of GAD (ICD-9-CM diagnosis code 300.02) who initiated pharmacotherapy with medications commonly used to treat GAD (eg, selective serotonin reuptake inhibitors [SSRIs], venlafaxine, benzodiazepines) between 1/1/2003 and 12/31/2007. We examined healthcare utilization and costs over the 12-month periods preceding and following date of initial receipt of such therapy ("pretreatment" and "follow-up", respectively). Patients with incomplete data were excluded. RESULTS: A total of 10,275 patients met all study inclusion criteria. Forty-eight percent of patients received SSRIs; 34%, benzodiazepines; and 6%, venlafaxine. SSRIs and venlafaxine were about three times more likely to be used on a long-term basis (> 90 days) than benzodiazepines (p < 0.01). In general, levels of healthcare utilization were higher during follow-up than pretreatment. Mean (SD) total healthcare costs increased from $4812 ($10,006) during pretreatment to $7182 ($22,041) during follow-up (p < 0.01); costs of GAD-related pharmacotherapy during follow-up were $420 ($485). CONCLUSIONS: More than one-half of patients initiating pharmacotherapy for GAD receive either SSRIs or venlafaxine. Levels of healthcare utilization and costs are greater in the year following initiation of therapy than in the immediately preceding one.

Direct and indirect economic costs among private-sector employees with osteoarthritis.

OBJECTIVE: To estimate direct and indirect economic costs among private-sector employees with osteoarthritis (OA). METHODS: Using a large US employer benefits database, we identified all employees with evidence of OA during calendar year 2007, and compared their costs of health care and work loss to age-and-sex-matched employees without evidence of OA in that year. RESULTS: Private-sector employees with OA (n = 2399) averaged 62.9 days of absenteeism versus 36.7 days among matched comparators (n = 2399) (P < 0.01). Mean total direct costs among these persons were $17,751 and $5057, respectively (P < 0.01); 34% of health care costs among persons with OA arose from medical encounters with listed diagnoses of OA. Mean total indirect costs were two-fold higher among persons with OA ($5002 versus $2120 for those without OA; P < 0.01). CONCLUSIONS: Private-sector employees with OA have higher direct and indirect costs than those without this condition.

Patterns of pharmacotherapy and health care utilization and costs prior to total hip or total knee replacement in patients with osteoarthritis.

OBJECTIVE: To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). METHODS: Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with <2 years of complete data prior to TKR or THR were excluded, as were those with evidence of other conditions for which TKR or THR may be performed (e.g., rheumatoid arthritis). We then examined patterns of health care utilization and costs over the 2-year period preceding surgery. RESULTS: A total of 16,527 patients met all study entry criteria. Their mean ± SD age was 56.6 ± 6.1 years, and 56% of them were women. In the 2 years preceding surgery, 55% of patients received prescription nonsteroidal antiinflammatory drugs, 58% received opioids, and 50% received injections of corticosteroids. The numbers of patients receiving these drugs increased steadily during the presurgery period. The mean ± SD total health care costs in the 2 years preceding surgery were $19,466 ± 29,869, of which outpatient care, inpatient care, and pharmacotherapy represented 45%, 20%, and 20%, respectively. Costs increased from $2,094 in the eighth calendar quarter prior to surgery to $3,100 in the final quarter. CONCLUSION: Patients with OA who undergo THR or TKR have relatively high levels of use of pain-related pharmacotherapy and high total health care costs in the 2-year period preceding surgery. Levels of utilization and cost increase as the date of surgery approaches.