The risks and costs of multiple-generic substitution of topiramate.

OBJECTIVE: To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ). METHODS: Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis. RESULTS: In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420). CONCLUSION: Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Economic burden of pneumonia in an employed population.

OBJECTIVE: To estimate the overall economic burden of pneumonia from an employer perspective. METHODS: The annual, per capita cost of pneumonia was determined for beneficiaries of a major employer by analyzing medical, pharmaceutical, and disability claims data. The incremental costs of 4036 patients with a diagnosis of pneumonia identified in a health claims database of a national Fortune 100 company were compared with a 10% random sample of beneficiaries in the employer overall population. RESULTS: Total annual, per capita, employer costs were approximately 5 times higher for patients with pneumonia ($11 544) than among typical beneficiaries in the employer overall population ($2368). The increases in costs were for all components (eg, medical care, prescription drug, disability, and particularly for inpatient services). A small proportion (10%) of pneumonia patients (almost all of whom were hospitalized) accounted for most (59%) of the costs. CONCLUSIONS: Patients with pneumonia present an important financial burden to employers. These patients use more medical care services, particularly inpatient services, than the average beneficiary in the employer overall population. In addition to direct health care costs related to medical utilization and the use of prescription drugs, indirect costs due to disability and absenteeism also contribute to the high cost of pneumonia to an employer.

Assessing the economic impact of psychiatric disorders: where to begin?

Over the past decade, psychiatric disorders have increasingly been regarded as serious public health concerns, with debilitating symptoms as well as high social and economic costs to patients, caregivers, third party payers and society. In this article, we review findings from recent research on psychiatric disorders, while providing a framework for assessing their pharmacoeconomic impact. In particular, we consider the prevalence of psychiatric disorders, their far-reaching impacts, and their associated treatment patterns. These categories present a starting point for analysing the pharmacoeconomic consequences of psychiatric disorders and underlie an expert opinion in this context

The effects of chronic medical conditions on work loss and work cutback.

Although work performance has become an important outcome in cost-of-illness studies, little is known about the comparative effects of different commonly occurring chronic conditions on work impairment in general population samples. Such data are presented here from a large-scale nationally representative general population survey. The data are from the MacArthur Foundation Midlife Development in the United States (MIDUS) survey, a nationally representative telephone-mail survey of 3032 respondents in the age range of 25 to 74 years. The 2074 survey respondents in the age range of 25 to 54 years are the focus of the current report. The data collection included a chronic-conditions checklist and questions about how many days out of the past 30 each respondent was either totally unable to work or perform normal activities because of health problems (work-loss days) or had to cut back on these activities because of health problems (work-cutback days). Regression analysis was used to estimate the effects of conditions on work impairments, controlling for sociodemographics. At least one illness-related work-loss or work-cutback day in the past 30 days was reported by 22.4% of respondents, with a monthly average of 6.7 such days among those with any work impairment. This is equivalent to an annualized national estimate of over 2.5 billion work-impairment days in the age range of the sample. Cancer is associated with by far the highest reported prevalence of any impairment (66.2%) and the highest conditional number of impairment days in the past 30 (16.4 days). Other conditions associated with high odds of any impairment include ulcers, major depression, and panic disorder, whereas other conditions associated with a large conditional number of impairment days include heart disease and high blood pressure. Comorbidities involving combinations of arthritis, ulcers, mental disorders, and substance dependence are associated with higher impairments than expected on the basis of an additive model. The effects of conditions do not differ systematically across subsamples defined on the basis of age, sex, education, or employment status. The enormous magnitude of the work impairment associated with chronic conditions and the economic advantages of interventions for ill workers that reduce work impairments should be factored into employer cost-benefit calculations of expanding health insurance coverage. Given the enormous work impairment associated with cancer and the fact that the vast majority of employed people who are diagnosed with cancer stay in the workforce through at least part of their course of treatment, interventions aimed at reducing the workplace costs of this illness should be a priority.

Depression and work productivity: the comparative costs of treatment versus nontreatment.

This article discusses the impact of depression on work productivity and the potential for improved work performance associated with effective treatment. We undertook a review of the literature by means of a computer search using the following key terms: cost of illness, work loss, sickness absence, productivity, performance, and disability. Published works were considered in four categories: (1) naturalistic cross-sectional studies that found greater self-reported work impairment among depressed workers; (2) naturalistic longitudinal studies that found a synchrony of change between depression and work impairment; (3) uncontrolled treatment studies that found reduced work impairment with successful treatment; and (4) controlled trials that usually, but not always, found greater reduction in work impairment among treated patients. Observational data suggest that productivity gains following effective depression treatment could far exceed direct treatment costs. Randomized effectiveness trials are needed before we can conclude definitively that depression treatment results in productivity improvements sufficient to offset direct treatment costs.

Impact of illness and its treatment on workplace costs: regulatory and measurement issues.

In an attempt to document a broader spectrum of the benefits of their pharmaceutical products, drug companies increasingly seek to include productivity claims in their promotional campaigns. We describe the existing regulatory framework of the Food and Drug Administration (FDA) for considering productivity claims, distinguishing between the traditional "substantial evidence" standard and the "competent and reliable scientific evidence" standard. But the notion of competent and reliable scientific evidence may itself be problematic, even when it is the appropriate regulatory standard, because there exists no consistent measurement approach across diseases, workplaces, jobs, and worker capabilities that is widely accepted in this emerging area of health outcomes research. We examine the various measurement approaches that have been used to quantify the impact of illness and its treatment on workplace productivity, and we describe some of the shortcomings associated with each alternative. This discussion highlights the possible difficulties faced by the FDA in reviewing productivity-based promotional claims. Finally, we suggest possible strategies for furthering this field of investigation.

Cost of depression: current assessment and future directions.

Depression is a common psychiatric disorder affecting approximately 17 million Americans each year and resulting in a significant economic burden, estimated at $43-$53 billion in 1990. The cost burden of depression extends beyond the direct cost of treatment, to include the costs of lost productivity, both while at work and days absent from work, as well as lost earnings due to increased mortality and the impacts experienced by a patient's caregivers. This range of costs is discussed, in the context of the prevalence and impacts of depression and detailing the cost components of depression. We highlight that existing estimates of the cost of depression are underestimates and we conclude with areas for future research.

Direct and indirect costs of rheumatoid arthritis to an employer.

This study is among the first to estimate the overall economic burden of rheumatoid arthritis (RA) from an employer perspective. The annual, per capita cost of RA was determined for beneficiaries of a major employer by analyzing medical, pharmaceutical, and disability claims data. The incremental costs related to RA were determined by matching RA patients to a case-control group of individuals with no recorded RA treatment. The utilization of health care services as well as the rate of disability among RA patients was substantially higher than among the controls. For example, annual, per capita employer expenditures for RA employees with disability were almost 3 times those for their controls ($17,822 vs $6131, respectively). Treatment to address not only the severity but also the progression of RA may substantially reduce overall employer expenditures for this disease.

Using healthcare claims data for outcomes research and pharmacoeconomic analyses.

Healthcare claims data are a practical complement to data from randomised controlled trials (RCTs) for evaluating health outcomes in non-experimental settings and for generalising results to a broader population. Claims data are a relatively inexpensive way to obtain useful information about patient demographics, as well as healthcare resources used for specific medical conditions and procedures from large numbers of patients over extended periods of time. With claims data, it is possible to identify patients who meet specific medical or sociodemographic criteria, estimate their costs, define episodes of medical care, and measure outcomes more globally than is possible with RCT data. Statistical methods exist to address some of the inherent issues with claims data due to their limited clinical detail. We also identify extensions of claims data to productivity issues, the use of centralised claims data such as in Canada, and the application of new statistical methods to outcomes research literature such as sample selection correction methods.

Depression in the workplace: effects on short-term disability.

We analyzed data from two national surveys to estimate the short-term work disability associated with thirty-day major depression. Depressed workers were found to have between 1.5 and 3.2 more short-term work-disability days in a thirty-day period than other workers had, with a salary-equivalent productivity loss averaging between $182 and $395. These workplace costs are nearly as large as the direct costs of successful depression treatment, which suggests that encouraging depressed workers to obtain treatment might be cost-effective for some employers.

The economic burden of anxiety disorders in the 1990s.

BACKGROUND: We assess the annual economic burden of anxiety disorders in the United States from a societal perspective. METHOD: Using data from the National Comorbidity Study, we applied multivariate regression techniques to calculate the costs associated with anxiety disorders, after adjusting for demographic characteristics and the presence of comorbid psychiatric conditions. Based on additional data, in part from a large managed care organization, we estimated a human capital model of the societal cost of anxiety disorders. RESULTS: We estimated the annual cost of anxiety disorders to be approximately $42.3 billion in 1990 in the United States, or $1542 per sufferer. This comprises $23.0 billion (or 54% of the total cost) in nonpsychiatric medical treatment costs, S13.3 billion (31%) in psychiatric treatment costs, $4.1 billion (10%) in indirect workplace costs, $1.2 billion (3%) in mortality costs, and $0.8 billion (2%) in prescription pharmaceutical costs. Of the $256 in workplace costs per anxious worker, 88% is attributable to lost productivity while at work as opposed to absenteeism. Posttraumatic stress disorder and panic disorder are the anxiety disorders found to have the highest rates of service use. Other than simple phobia, all anxiety disorders analyzed are associated with impairment in workplace performance. CONCLUSION: Anxiety disorders impose a substantial cost on society, much of which may be avoidable with more widespread awareness, recognition, and appropriate early intervention.

Pharmacoeconomics and health policy. Current applications and prospects for the future.

The use of pharmacoeconomic tools has grown dramatically in the past decade as provision of healthcare throughout the industrialised world has required increased cost consciousness. However, pharmacoeconomic analysis has not yet been fully exploited as a conceptual underpinning for public or private health policy decisions. Pharmacoeconomics is likely to become an increasingly important basis for health policy decisions as a number of significant dynamics evolve in the marketplace, including: (i) consumers acting on their growing access to information and becoming more actively involved in treatment decisions; (ii) payers, providers and patients deepening their interaction and overcoming their traditional (narrow) focus on either costs or benefits alone; and (iii) manufacturers being challenged by other healthcare constituencies as sponsors of cost-based outcomes studies.

Workplace performance effects from chronic depression and its treatment.

Utilizing data from a clinical trial and an econometric model incorporating the impact of a medical intervention and regression to the mean, we present evidence supporting the hypotheses that for chronically depressed individuals: (i) the level of perceived at-work performance is negatively related to the severity of depressive status; and (ii) a reduction in depressive severity improves the patient's perceived work performance. Improvement in work performance is rapid, with about two-thirds of the change occurring already by week 4. Those patients having the greatest work improvement are those with both relatively low baseline work performance and the least severity of baseline depression.

Improvement in subjective work performance after treatment of chronic depression: some preliminary results. Chronic Depression Study Group.

We analyzed the relationship between depression and patient-assessed or clinician-rated work performance among chronically depressed patients followed for 12 weeks in a large clinical trial. The data were collected in a double-blind design comparing sertraline, a selective serotonin reuptake inhibitor, with imipramine, a tricyclic antidepressant, in 12 academic centers nationwide. Incorporating work-related questions from a portfolio of rating scales used to assess depression, we constructed several measures of work performance, assessed at baseline and at Week 12 of the clinical investigation, and examined how they changed with improvement in depressive symptoms. As depressive symptoms subsided following treatment, patients reported substantial improvement in our measures of work performance. Eighty-six percent of the cohort reported some improvement from base-line to Week 12. The extent of improvement in work performance correlates highly with improvement in the depressive symptoms measured on the Hamilton Rating Scale for Depression. Treatment of depression with antidepressant medications resulted in substantial improvement in subjective work performance among the patients studied.

Consolidation and restructuring: the next step in managed care.

Rising expenditures on health care in the U.S. have been facilitated by the fundamental problems of asymmetric information and insurance-induced moral hazard. If managed care is to succeed, it must take both into account through strategies such as information-based consumer education and provider risk-sharing. Because larger networks offer significant advantages in implementing such strategies, hospital mergers, physician-hospital alliances, and economies of scale are major trends in the evolution of managed care.

The economic burden of depression in 1990.

BACKGROUND: We estimate in dollar terms the economic burden of depression in the United States on an annual basis. METHOD: Using a human capital approach, we develop prevalence-based estimates of three major cost-of-illness categories: (1) direct costs of medical, psychiatric, and pharmacologic care; (2) mortality costs arising from depression-related suicides; and (3) morbidity costs associated with depression in the workplace. With respect to the latter category, we extend traditional cost-of-illness research to include not only the costs arising from excess absenteeism of depressed workers, but also the reductions in their productive capacity while at work during episodes of the illness. RESULTS: We estimate that the annual costs of depression in the United States total approximately $43.7 billion. Of this total, $12.4 billion-28%-is attributable to direct costs, $7.5 billion-17%-comprises mortality costs, and $23.8 billion-55%-is derived from the two morbidity cost categories. CONCLUSION: Depression imposes significant annual costs on society. Because there are many important categories of cost that have yet to be estimated, the true burden of this illness may be even greater than is implied by our estimate. Future research on the total costs of depression may include attention to the comorbidity costs of this illness with a variety of other diseases, reductions in the quality of life experienced by sufferers, and added out-of-pocket costs resulting from the effects of this illness, including those related to household services. Finally, it may be useful to estimate the additional costs associated with expanding the definition of depression to include individuals who suffer from only some of the symptoms of this illness.

Depression: a neglected major illness.

BACKGROUND: To illustrate the burden depression imposes on society, we present estimates of the annual costs of depression--$44 billion--as well as the number of individuals it affects per year--almost 11 million. Although these estimates point to depression as a major illness, this study examines why it is not generally considered as such by the medical and public health communities or by society at large. METHOD: We develop a framework that compares depression with major illnesses such as coronary heart disease, cancer, and AIDS by highlighting salient characteristics of each illness. This comparative illness framework considers the costs, prevalence, distribution of sufferers, mortality, recognition, and treatability of each disease. This comparison underscores many of the similarities and differences among the illnesses examined. RESULTS: Because depression often is not properly recognized and begins to affect many people at a relatively early age, it exacts costs over a longer period of time and in a more subtle manner than other major illnesses. It also imposes a particularly heavy burden on employers in the form of higher workplace costs. CONCLUSION: We conclude that, because of the potential for successful treatment, increased attempts to reach untreated sufferers of depression appear to be warranted. Employers as a group have a particular incentive to invest in the recognition and treatment of this widespread problem, in order to reduce the substantial costs it imposes upon them each year.