A modeled economic evaluation comparing atomoxetine with stimulant therapy in the treatment of children with attention-deficit/hyperactivity disorder in the United Kingdom.

OBJECTIVE: To estimate the cost-effectiveness of atomoxetine for children with attention-deficity/hyperactivity disorder (ADHD) in the United Kingdom compared with current alternatives. METHODS: An economic model with Markov processes was developed to estimate the costs and benefits of atomoxetine versus other current ADHD treatment options. The model evaluated atomoxetine in five patient subgroups according to treatment history and the existence of comorbidities precluding stimulant medication. The incremental cost per quality-adjusted life-year (QALY) was calculated for atomoxetine treatment algorithms compared with comparator algorithms. The Markov process incorporated 18 health states, representing a range of outcomes across all treatment options included in the algorithms. Utility values were derived from a survey of 83 parents of children with ADHD. The effectiveness and safety aspects of the treatment options were based on a thorough review of controlled clinical trials and other clinical literature, and validated by international experts. Costs and outcomes were estimated using Monte Carlo simulation over a 1-year duration, with costs estimated from the perspective of the National Health Service in England and Wales. RESULTS: For stimulant-naive patients, the incremental cost per QALY gained for the atomoxetine algorithm compared with immediate-release methylphenidate hydrochloride (MPH) was pound 15,224 ( pound 13,241 compared with extended-release MPH). In the stimulant-exposed populations, the incremental cost per QALY for the atomoxetine algorithm was between pound 14,169 and pound 15,878. For patients contraindicated for stimulant therapies, the incremental cost per QALY was pound 11,523 and pound 12,370 for stimulant-naive and stimulant-exposed populations, respectively. CONCLUSION: The economic evaluation showed atomoxetine is an effective alternative across a range of ADHD populations and offers value-for-money in the treatment of ADHD.

Classifying patients by antipsychotic adherence patterns using latent class analysis: characteristics of nonadherent groups in the California Medicaid (Medi-Cal) program.

OBJECTIVES: This study identifies latent classes defined by varying degrees of adherence to antipsychotic drug therapy and examines the sociodemographic, clinical, and resource utilization correlates associated with membership in each adherence class. DATA AND METHODS: Patient-level data were drawn from the 1994 to 2003, 100%-sample California Medicaid fee-for-service paid claims data for patients with schizophrenia (N = 36,195). The date of the first antipsychotic medication filled after January 1, 1999 was then used to divide each patient's data into a 6-month preindex (baseline) and a 12-month postindex (follow-up) period. Three categorical adherence indicators-a dichotomous variable of medication possession ratio greater than 0.80, the number of antipsychotic treatment attempts, and time to a change in antipsychotic medications-and two covariates-a categorical variable of duration of therapy and a dichotomous variable of polypharmacy-were used in the latent class model. RESULTS: A three-class model returned the lowest values for all the information criteria and was therefore interpreted as follows: The prevalence rates of the latent classes were 1) 14.8% for the adherent; 2) 20.7% for the partially adherent; and 3) 64.5% for the nonadherent. Membership in the nonadherent class was associated with minority ethnicity, being female, eligibility due to welfare status, prior hospitalizations, and a higher number of prior treatment episodes. Membership in the partially adherent class was associated with higher use of outpatient care, higher rates of depot antipsychotic drug use, and polypharmacy. CONCLUSION: Multiple indicators of adherence to antipsychotic medication can be used to define classes of adherence that are associated with patient characteristics and distinct patterns of prior health-care use.

Open-label olanzapine treatment in bipolar I disorder: clinical and work functional outcomes.

OBJECTIVES: The objective of this study was to describe clinical and work functional outcomes associated with 6-month open-label olanzapine treatment for bipolar I disorder. METHODS: The study consisted of 249 patients entering a 6-month open label phase after 12 weeks of acute double-blind haloperidol or olanzapine treatment. Baseline for analysis was defined as the beginning of open-label treatment. The clinical outcomes were symptomatic remission defined by a Y-MRS total score < or = 12 and a HAM-D total score < or = 8 at the end of 6 months of treatment. The work functional outcomes included work functional scores, the proportion of patients who reported to 'work' as employee, volunteers, students, or house workers and the proportion of patients who specifically reported to 'work for pay'. RESULTS: A total of 240 patients reported work functional outcomes post open-label baseline. Among them, 15.4% patients moved into a 'work group' from a 'no-work group' at baseline, while 7.1% did the opposite (p = 0.0065) and 13.3% reported an improvement to 'work for pay' status from a 'not working for pay' status at baseline, while there was 4.2% of worsening in employment status (p = 0.0007). Overall, improvement in the work functional score was found at all post-baseline time points, beginning at month two (p = 0.003). LIMITATIONS: Results of this study need to be confirmed by double-blind randomized controlled studies. There was a lack of detailed information on work functioning from the questionnaire. CONCLUSIONS: Open-label olanzapine treatment for 6 months was associated with improvements in work functional outcomes in patients with bipolar disorder.

Use of concomitant medication with antipsychotic treatment in outpatients with schizophrenia: results from the European Schizophrenia Outpatients Health Outcomes (SOHO) study.

Use of concomitant medications with antipsychotic agents in the treatment of schizophrenia is common but lacks a clear scientific rationale. We evaluated concomitant medication usage during the first 6 months of the prospective, observational, European Schizophrenia Outpatient Health Outcomes (SOHO) study, examining its frequency, variation according to type of antipsychotic drug used, and impact on treatment tolerability. We also determined factors that were associated with concomitant medication use. The use of concomitant medications differed greatly among the countries participating in the SOHO study. The presence of depressive symptoms and being female were associated with the use of concomitant antidepressants. Certain antipsychotics were associated with less use of concomitant medications: significantly fewer olanzapine-, quetiapine- and clozapine-treated patients used concomitant anticholinergics or anxiolytics/hypnotics. Patients using concomitant medications had an increased incidence of sexually related side effects and extrapyramidal side effects (EPS) at 6 months follow-up compared with patients not using concomitant medications. The results should be interpreted conservatively due to the observational design of SOHO.

Pharmacological treatment and other predictors of treatment outcomes in previously untreated patients with schizophrenia: results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study.

The present study aimed to compare health outcomes and tolerability according to antipsychotic medication (olanzapine, risperidone or an oral typical antipsychotic) after 6 months of treatment in a group of 919 schizophrenic patients who had never previously been treated with antipsychotics. Demographic and clinical predictors of outcome were also identified. Data were extracted from the Schizophrenia Outpatient Health Outcomes (SOHO) study, a prospective, observational study of schizophrenia treatment in 10 European countries. Patients who initiated olanzapine were more likely to have a clinical response than those in the risperidone cohort, and had a greater improvement in quality of life than patients in the risperidone or typical antipsychotic cohorts. High negative and depression symptom scores at baseline and the presence of extrapyramidal symptoms at baseline predicted a worse clinical response, whereas hostile behaviour, paid employment and substance abuse predicted a better clinical outcome. The olanzapine cohort gained more weight than patients in the risperidone cohort, but no significant difference in weight gain was observed between olanzapine and the oral typical antipsychotic cohort. The results should be interpreted conservatively due to the observational study design.

Health state utilities for childhood attention-deficit/hyperactivity disorder based on parent preferences in the United kingdom.

OBJECTIVES: The purpose of this study was to use standard gamble (SG) utility interviews to assess parent preferences for health states of childhood attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in August 2003 in London, England. Parents (N=83) of children diagnosed with ADHD completed SG utility interviews, rating their child's current health and 14 hypothetical health states describing untreated ADHD and ADHD treated with a nonstimulant, immediate-release stimulant, or extended-release stimulant. Raw temporary utilities ranging from 0 (worst health) to 1 (best health) were adjusted to a chronic utility scale ranging from 0 (death) to 1 (best health) using a linear transformation. Parents rated the severity of their children's ADHD symptoms using the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS) and their children's health-related quality of life using the EuroQol EQ-5D. RESULTS: Raw and adjusted SG ratings of hypothetical health states ranged from 0.63-0.90 and 0.88-0.96, respectively. Parents' raw SG scores of their child's current health state (mean=0.72) were significantly correlated with inattentive, hyperactive, and overall ADHD symptoms (r=-0.25, -0.27, -0.27; P <0.05) and the EQ-5D visual analogue scale (r=0.26; P <0.05). CONCLUSION: This UK-based study suggests that parent SG interviews are a valid method for obtaining utilities for child ADHD-related health states. The utilities obtained in this study would be appropriate for use in a cost-utility analysis evaluating the costs and benefits of childhood ADHD treatments in the United Kingdom.

Costs of bipolar disorder.

Bipolar disorder is a chronic affective disorder that causes significant economic burden to patients, families and society. It has a lifetime prevalence of approximately 1.3%. Bipolar disorder is characterised by recurrent mania or hypomania and depressive episodes that cause impairments in functioning and health-related quality of life. Patients require acute and maintenance therapy delivered via inpatient and outpatient treatment. Patients with bipolar disorder often have contact with the social welfare and legal systems; bipolar disorder impairs occupational functioning and may lead to premature mortality through suicide. This review examines the symptomatology of bipolar disorder and identifies those features that make it difficult and costly to treat. Methods for assessing direct and indirect costs are reviewed. We report on comprehensive cost studies as well as administrative claims data and program evaluations. The majority of data is drawn from studies conducted in the US; however, we discuss European studies when appropriate. Only two comprehensive cost-of-illness studies on bipolar disorder, one prevalence-based and one incidence-based, have been reported. There are, however, several comprehensive cost-of-illness studies measuring economic burden of affective disorders including bipolar disorder. Estimates of total costs of affective disorders in the US range from $US30.4-43.7 billion (1990 values). In the prevalence-based cost-of-illness study on bipolar disorder, total annual costs were estimated at $US45.2 billion (1991 values). In the incidence-based study, lifetime costs were estimated at $US24 billion. Although there have been recent advances in pharmacotherapy and outpatient therapy, hospitalisation still accounts for a substantial portion of the direct costs. A variety of outpatient services are increasingly important for the care of patients with bipolar disorder and costs in this area continue to grow. Indirect costs due to morbidity and premature mortality comprise a large portion of the cost of illness. Lost workdays or inability to work due to the disease cause high morbidity costs. Intangible costs such as family burden and impaired health-related quality of life are common, although it has proved difficult to attach monetary values to these costs.

Frequency of hospitalisations and inpatient care costs of manic episodes: in patients with bipolar I disorder in France.

BACKGROUND: Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment. However, very few recent studies have investigated the economic burden of the disease. OBJECTIVE: To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France. METHOD: A cost-of-illness study was conducted based on available data using a hospital payer perspective. The lifetime prevalence of manic episodes was estimated from published epidemiological data using a random-effects meta-analysis. Data were obtained by a computerised literature search using the main scientific and medical databases. Additional epidemiological references were identified from published studies and textbooks. Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital. Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris, France for the year 1999. RESULTS: Extrapolating from international data on the average prevalence of bipolar I disorder, the proportion of rapid cycling patients and the average cycle duration, we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265,000 in France. Based on hospital data in Paris, the proportion of manic episodes that require hospitalisation was estimated to be around 63%. The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs (Euro 3 billion) [1999 values]. CONCLUSION: Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France. As the lifetime prevalence of bipolar I disorder may be as high as 3% among adults, further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France.

Cost and utilization of healthcare services for hip and knee replacement.

OBJECTIVE: Describe resource utilization and costs for total hip replacement (THR) and total knee replacement (TKR) for the 90 days before hospitalization for surgery, the hospital event, and the 90 and 360 days after hospitalization for surgery with emphasis on 90 days after hospitalization. METHODS: A large insurance database was used to identify outpatient and summarized hospital resource use and payments (insurer perspective) for THR and TKR. A second large US database provided hospital details (charge description master level) of inpatient services, costs, and charges (hospital perspective) for a different sample of THR and TKR patients. Included patients were ≥45 years old, had no hospitalization record within 1 year before surgery, and THR length of stay (LOS) of 2-8 days or TKR LOS 2-6 days. RESULTS: There were 22 618 THR and 50 686 TKR patients in the insurance database and 81 635 THR and 158 990 TKR in the hospital database. Average age was ∼66 years for THR and TKR patients. Median LOS was 4 days (both surgeries). Hospital costs (hospital perspective) were $17 588 in US dollars (USD) and $16 267 (USD) for THR and TKR, respectively. Reimbursement for hospital services (insurer perspective) were $22 967 (USD) and $21 583 (USD) for THR and TKR, respectively. In 90 days post-surgery, THR and TKR total payments were $3827 (USD) and $4237 (USD), respectively. Payments for the first 90 days post-surgery were 57.5% of the 360-day post-period for THR-related payments and 59.9% for TKR-related payments. CONCLUSION: Payers considering use of episode-of-care payment models for THR and TKR may wish to concentrate efforts on the 90 days post-discharge. LIMITATIONS: While this study used large samples of subjects, generalisability of the results may be limited since the samples were not randomized samples of THR and TKR patients. It is noteworthy that patients in the hospital sample are not the same as those in the insurer sample. Selection of hip-related and knee-related procedures and associated costs was based on qualitative review. Payers may use different billing codes or aggregate costs differently.

Treatment patterns and resource utilization and costs among patients with pulmonary arterial hypertension in the United States.

OBJECTIVE: To explore treatment patterns and resource utilization and cost for subjects with pulmonary arterial hypertension (PAH). RESEARCH DESIGN: Retrospective claims database analysis of 706 patients with PAH enrolled in a large, geographically diverse US managed-care organization. RESULTS: In the final sample of PAH patients treated with bosentan (n=251) or sildenafil (n=455), average age was 57 years, 86% of patients were commercially insured, and 52% of patients were male. Gender distribution varied significantly across subgroups, with a lower proportion of males in the bosentan (30%) subgroup compared with the sildenafil group (64%) (p<0.001). Average baseline Charlson comorbidity score was 2.4. Average numbers of fills per month were 0.8 and 0.4 for bosentan and sildenafil patients, respectively (p<0.001). Over 80% of patients received only one PAH treatment in the first 90 days following the index date, with 28% of bosentan and 13% of sildenafil patients receiving combination therapy (p<0.001). Over one-third of bosentan patients and one-quarter of sildenafil patients experienced a dose increase in the follow-up period (p=0.009). Sixteen percent of sildenafil patients experienced a dose decrease in the follow-up period, while a smaller proportion of patients receiving bosentan (4%) experienced a dose decrease (p<0.001). On average, number of PAH-related per subject per month (PSPM) inpatient stays and emergency department visits and PSPM length of inpatient stays were statistically similar between the subgroups. PAH-related PSPM healthcare costs were high for both subgroups, with average monthly costs of $5,332 and $3,632 among bosentan and sildenafil patients, respectively (p=0.003). Differences in total costs were driven mainly by differences in pharmacy expenditures. CONCLUSIONS: Of the oral agents approved for treating PAH at the time of this study, sildenafil was most commonly prescribed as index therapy and was also associated with the lowest costs, largely due to significantly lower pharmacy costs. This study is characterized by limitations inherent to claims database analyses, such as the potential for coding errors and lack of information on whether a drug was taken as prescribed. Furthermore, PAH severity (WHO functional class) was not assessed.

Direct and indirect costs of non-vertebral fracture patients with osteoporosis in the US.

Osteoporosis is a condition marked by low bone mineral density and the deterioration of bone tissue. One of the main clinical and economic consequences of osteoporosis is skeletal fractures. To assess the healthcare and work loss costs of US patients with non-vertebral (NV) osteoporotic fractures. Privately insured (aged 18-64 years) and Medicare (aged >/=65 years) patients with osteoporosis (ICD-9-CM code: 733.0x) were identified during 1999-2006 using two claims databases. Patients with an NV fracture (femur, pelvis, lower leg, upper arm, forearm, rib or hip) were matched randomly on age, sex, employment status and geographic region to controls with osteoporosis and no fractures. Patient characteristics and annual healthcare costs were assessed over the year following the index fracture for privately insured (n = 4764) and Medicare (n = 48 742) beneficiaries (Medicare drug costs were estimated using multivariable models). Indirect (i.e. work loss) costs were calculated for a subset of privately insured, employed patients with available disability data (n = 1148). All costs were reported in $US, year 2006 values. In Medicare, mean incremental healthcare costs per NV fracture patient were $US13 387 ($US22 466 vs $US9079; p < 0.05). The most expensive patients had index fractures of the hip, multiple sites and femur (incremental costs of $US25 519, $US20 137 and $US19 403, respectively). Patients with NV non-hip (NVNH) fractures had incremental healthcare costs of $US7868 per patient ($US16 704 vs $US8836; p < 0.05). Aggregate annual incremental healthcare costs of NVNH patients in the Medicare research sample (n = 35 933) were $US282.7 million compared with $US204.1 million for hip fracture patients (n = 7997). Among the privately insured, mean incremental healthcare costs per NV fracture patient were $US5961 ($US11 636 vs $US5675; p < 0.05). The most expensive patients had index fractures of the hip, multiple sites and pelvis (incremental costs of $US13 801, $US9642 and $US8164, respectively). Annual incremental healthcare costs per NVNH patient were $US5381 ($US11 090 vs $US5709; p < 0.05). Aggregate annual incremental healthcare costs of NVNH patients in the privately insured sample (n = 4478) were $US24.1 million compared with $US3.5 million for hip fracture patients (n = 255). Mean incremental work loss costs per NV fracture employee were $US1956 ($US4349 vs $US2393; p < 0.05). Among patients with available disability data, work loss accounted for 29.5% of total costs per NV fracture employee. The cost burden of NV fracture patients to payers is substantial. Although hip fracture patients were more costly per patient in both Medicare and privately insured samples, NVNH fracture patients still had substantial incremental costs. Because NVNH patients accounted for a larger proportion of the fracture population, they were associated with greater aggregate incremental healthcare costs than hip fracture patients.