Showing papers in "PharmacoEconomics in 2004"

Epidemiology and burden of illness of rheumatoid arthritis

Abstract: Rheumatoid arthritis (RA) is a chronic, generally progressive autoimmune disease that causes functional disability, significant pain and joint destruction, and leads to premature mortality. It is estimated to affect between 0.5 and 1.0% of the adult population worldwide, increases in prevalence with age and affects more women than men. The magnitude of the severe long-term economic consequences of RA has been underestimated in the past. Most patients with the disease require continuous treatment to retard or stop progression and to control disease flares. Many also require surgery, such as total hip or knee replacement. In addition to these direct costs, work disability leads to reduced productivity and early retirement, and as a result, substantial indirect costs. The individual and his or her family must cope with the feeling of loss of contribution to society combined with redefined social roles, and the effects of pain, fatigue, low self-esteem, mental distress and depression. A number of countries in North America and Europe have reported a decline in the incidence of RA in recent years, although geographical differences remain that may be associated with genetic, environmental or cultural factors. Nevertheless, patients with RA have not shared the improvements in survival rates seen with other diseases over the last 40 years, and have a mean reduction in life expectancy of between 5 and 10 years. Disease severity, activity and disability are strongly linked to premature mortality in patients with RA. The high direct and indirect costs associated with RA, together with the substantial morbidity and mortality affecting millions of people worldwide, underline the potential benefits of improved treatments for this chronic disease to patients, their families and society.

A review of self-report instruments measuring health-related work productivity: a patient-reported outcomes perspective.

Abstract: Health impairment often leads to work impairment in the form of both absenteeism and presenteeism (i.e. reduced productivity while at work). Several self-report productivity instruments have been designed over the past few years to measure the impact of illness on productivity at work and/or in non-work activities. In a review of the literature we identified six generic subjective instruments - the Endicott Work Productivity Scale, Health and Labor Questionnaire, Health and Work Questionnaire, Health and Work Performance Questionnaire, Work Limitations Questionnaire (WLQ) and the Work Productivity and Activity Impairment Questionnaire (WPAI) - that could theoretically be used in any working population. These instruments were usually validated against other subjective measures (such as health-related QOL). Each productivity instrument has benefits in certain research settings, but the psychometric properties of the WPAI have been assessed most extensively. It was the most frequently used instrument and has also been modified to measure productivity reductions associated with specific diseases (e.g. allergic rhinitis, gastro-oesophageal reflux disease, chronic hand dermatitis). The WLQ has also been tested extensively to measure the general health impact and impact of specific conditions. Two migraine-specific subjective instruments were also identified: the Migraine Disability Assessment questionnaire and the Migraine Work and Productivity Loss Questionnaire, of which the latter was found to have better psychometric properties. Productivity outcomes are useful in that they characterise the impact of an illness in the workplace and show the effect of treatment on productivity. Evidence of psychometric properties and generalisability of different instruments was found to a varying degree. Thus, further research is needed to assess the accuracy and usefulness of individual instruments in certain research settings. Health-related productivity has been increasingly recognised as an important component of the burden of illness associated with a given disease; without it, one cannot reliably assess this burden.

A Review of Health-Related Workplace Productivity Loss Instruments

Abstract: The objective of this review was to identify health-related workplace productivity loss survey instruments, with particular emphasis on those that capture a metric suitable for direct translation into a monetary figure. A literature search using Medline, HealthSTAR, PsycINFO and Econlit databases between 1966 and 2002, and a telephone-administered survey of business leaders and researchers, were conducted to identify health-related workplace productivity measurement survey instruments. This review was conducted from the societal perspective. Each identified instrument was reviewed for the following: (i) reliability; (ii) content validity; (iii) construct validity; (iv) criterion validity; (v) productivity metric(s); (vi) instrument scoring technique; (vii) suitability for direct translation into a monetary figure; (viii) number of items; (ix) mode(s) of administration; and (x) disease state(s) in which it had been tested. Reliability and validity testing have been performed for 8 of the 11 identified surveys. Of the 11 instruments identified, six captured metrics that are suitable for direct translation into a monetary figure. Of those six, one instrument measured absenteeism, while the other five measured both absenteeism and presenteeism. All of the identified instruments except for one were available as paper, self-administered questionnaires and many were available in languages other than English. This review provides a comprehensive overview of the published, peerreviewed survey instruments available to measure health-related workplace productivity loss. As the field of productivity measurement matures, tools may be developed that will allow researchers to accurately calculate lost productivity costs when performing cost-effectiveness and cost-benefit analyses. Using data captured by these instruments, society and healthcare decision makers will be able to make better informed decisions concerning the value of the medications, disease management and health promotion programmes that individuals receive.

A Decision Chart for Assessing and Improving the Transferability of Economic Evaluation Results Between Countries

Abstract: Objective: To develop a user-friendly tool for managing the transfer of economic evaluation results. Methods: Factors that may influence the transfer of health economic study results were systematically identified and the way they impact on transferability was investigated. A transferability decision chart was developed that includes: knock out criteria; a checklist based on the transferability factors; and methods for improving transferability and for assessing the uncertainty of transferred results. This approach was tested on various international cost-effectiveness studies in the areas of interventional cardiology, vaccination and screening. Results: The transfer of study results is possible pending the outcomes of the transferability check and necessary adjustments. Transferability factors can be grouped into areas of methodological, healthcare system and population characteristics. Different levels of effort are required for analysis of factors, ranging from very low (e.g. discount rate) to very high (e.g. practice variation). The impact of differences of most transferability factors can be estimated via the key health economic determinants: capacity utilisation, effectiveness, productivity loss and returns to scale. Depending on the outcomes of the transferability check a correction of the study results for inflation and for differences related to currencies or purchasing power might be sufficient. Otherwise, modelling-based adjustments might be necessary, requiring the (re-)building and sometimes structural modification of the study model. For determination of the most essential adjustments, a univariate sensitivity analysis seems appropriate. If not all relevant study parameters can be substituted with country-specific ones, multivariate or probabilistic sensitivity analysis seems to be a promising way to quantify the uncertainty associated with a transfer. If study results cannot be transferred, the transfer of study models or designs should be investigated as this can significantly save time when conducting a new study. Conclusions: Our transferability decision chart is a transparent and user-friendly tool for assessing and improving the transferability of economic evaluation results. A state of the art description of the methodology in a study, providing detailed components for calculation, is not only essential for determining its transferability but also for improving it via modelling adjustments.

The economic burden of allergic rhinitis: A critical evaluation of the literature

Abstract: Although a large number of economic analyses of allergic rhinitis have been published, there are relatively few empirically based studies, particularly outside the US. The majority of these analyses can be classified as burden-of-illness studies. Most estimates of the annual cost of allergic rhinitis range from $US2–5 billion (2003 values). The wide range of estimates can be attributed to differences in identifying patients with allergic rhinitis, differences in cost assignment, limitations associated with available data and difficulties in assigning indirect costs (associated with reduced productivity) of allergic rhinitis. Approximately one-third of burden-of-illness studies include direct and indirect costs of allergic rhinitis, about one-third focus on direct costs only, and the remaining one-third focus exclusively on indirect costs due to reduced productivity. Indirect costs attributable to allergic rhinitis were higher in studies only estimating indirect costs ($US5.5–9.7 billion) than in those estimating both direct and indirect costs ($US1.7–4.3 billion). Although there are many economic evaluations of allergic rhinitis treatments in the published medical literature, very few represent formal cost-effectiveness evaluations that compare the incremental costs and benefits of alternative treatment strategies. Those that are incremental cost-effectiveness analyses have several limitations, including small samples, short study periods and the lack of a standardized measure of effectiveness. To date, the medical literature is lacking a comprehensive economic evaluation of general treatment strategies for allergic rhinitis. In undertaking such an analysis, serious consideration must be given to the study population of interest, the choice of appropriate comparators, the perspective from which the analysis is conducted, the target audience, the changing healthcare marketplace and the selection of a measure of effectiveness that incorporates both positive and negative aspects of treatments for allergic rhinitis. Future work would benefit from the development of a consensus on a summary measure of effectiveness that could be used in cost-effectiveness analyses of therapies for allergic rhinitis as well as additional empirical work to measure the association between severity of disease and its impact on worker productivity.

Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases.

Abstract: Objective: To determine the impact of respiratory syncytial virus (RSV) infection on healthcare resource use and costs in the US from the third-party payer perspective. Design: The study retrospectively analysed cross-sectional medical encounter data from three federally funded databases that comprise nationally representative samples of hospital inpatient stays, physician office visits and visits to hospital outpatient departments and emergency rooms. Methods: Identification of RSV infection-related medical encounters was based on the occurrence of RSV-specific International Classification of Diseases (9th Edition)-Clinical Modification diagnosis codes (079.6, 466.11, 480.1) as principal discharge diagnoses or the assumption that 10–15% of all otitis media visits were due to RSV infection. Outpatient drug costs were estimated based on average wholesale price, and physician fees and test/procedure costs were estimated based on prevailing national fees. Inpatient costs were estimated from total billed charges using a cost-to-charge ratio of 0.53. Results: In 2000, nearly 98% of RSV infection-related hospitalisations occurred in children <5 years old. There were approximately 86 000 hospitalisations, 1.7 million office visits, 402 000 emergency room visits and 236 000 hospital outpatient visits for children <5 years old that were attributable to RSV infection. Total annual direct medical costs for all RSV infection-related hospitalisations ($US394 million) and other medical encounters ($US258 million) for children <5 years old were estimated at $US652 million in 2000. Otitis media was a major cost driver for physician visits. RSV infection-related hospitalisations increased from 1993 to 2000, but average costs per hospitalisation were relatively stable. Conclusion: Treatment of RSV infection-related illness represents a significant healthcare burden in the US. The economic impact of ambulatory care for RSV infection-related illness could be as important as that for RSV infection-related hospitalisation.

Cost-of-illness studies in diabetes mellitus.

Abstract: Several cost-of-illness (COI) studies related to diabetes mellitus have been performed over the last three decades. This review examines the results of these COI studies, identifies the strengths and limitations of the various methods utilised, and suggests future research that will help determine the economic burden of diabetes more accurately. Diabetes imposes a large economic burden on society. The economic cost of diabetes is estimated to be as much as $US100 billion per year in the US alone (1997 values). This estimated cost has increased notably over time, primarily due to price inflation and the increasing prevalence of diabetes. Differing methodologies have significantly influenced the cost estimates and made comparisons between COI studies problematic. For example, early reports tended to rely exclusively on data where diabetes was listed as the primary diagnosis or reason for healthcare use. To better capture the costs associated with diabetes-related complications, later studies have included costs related to diabetes as a secondary or tertiary diagnosis using the attributable risk methodology. Given the types of long-term complications that are associated with diabetes, attempts at capturing these secondary costs are appropriate. However, estimates of attributable risk can be limited by the epidemiological data currently available. The tremendous economic burden of diabetes makes the disease an important clinical and public health problem. In order to formulate an effective response to this problem, it is important to track future economic trends as healthcare delivery, morbidity and mortality patterns evolve. Future research efforts should focus on refining methods to estimate costs, improving the interpretation of study findings, and facilitating comparisons between studies.

The economics of follow-on drug research and development

Abstract: Objectives: The development of so-called ‘me-too’, or ‘follow-on’, drugs by the pharmaceutical industry has been viewed by some as duplicative and wasteful, while others have argued that these drugs often provide needed therapeutic options and inject some price competition into the marketplace. This study examines data on the trends in the speed with which competitive entry has occurred in the pharmaceutical marketplace and the competitive nature of the industry’s development of these drugs. Data and methods: We examined data on the entry rates of drugs in a large number of therapeutic classes over time, as well as detailed survey information on the relative timing of the development of drugs in the classes. Classes were defined according to chemical structure or pharmacologic mode of action and similarity of clinical use. We determined average times to initial and subsequent entry in drug classes by period and examined the timing of development milestones achieved by what have turned out to be follow-on drugs in relation to the development and approval of the first drug in a class to be approved. Results: We found that the period of marketing exclusivity that the breakthrough drug in a new class enjoys has fallen dramatically over time (a median of 10.2 years in the 1970s to 1.2 years for the late 1990s). Approximately one-third of follow-on new drugs received a priority rating from the US FDA. The vast majority of the follow-on drugs for drug classes that were created in the last decade were in clinical development prior to the approval of the class breakthrough drug. Conclusions: The data suggest that entry barriers have fallen over time for new drug introductions. The increased competitiveness of the pharmaceutical marketplace was likely fueled by changes over time on both the supply and demand sides. The development histories of entrants to new drug classes suggest that development races better characterise new drug development than does a model of post hoc imitation. Thus, the usual distinctions drawn between breakthrough and ‘me-too’ drugs may not be very meaningful.

Economic aspects of severe sepsis: a review of intensive care unit costs, cost of illness and cost effectiveness of therapy.

Abstract: Severe sepsis remains both an important clinical challenge and an economic burden in intensive care. An estimated 750,000 cases occur each year in the US alone (300 cases per 100,000 population). Lower numbers are estimated for most European countries (e.g. Germany and Austria: 54-116 cases per year per 100,000). Sepsis patients are generally treated in intensive care units (ICUs) where close supervision and intensive care treatment by a competent team with adequate equipment can be provided. Staffing costs represent from 40% to >60% of the total ICU budget. Because of the high proportion of fixed costs in ICU treatment, the total cost of ICU care is mainly dependent on the length of ICU stay (ICU-LOS). The average total cost per ICU day is estimated at approximately 1200 Euro for countries with a highly developed healthcare system (based on various studies conducted between 1989 and 2001 and converted at 2003 currency rates). Patients with infections and severe sepsis require a prolonged ICU-LOS, resulting in higher costs of treatment compared with other ICU patients. US cost-of-illness studies focusing on direct costs per sepsis patient have yielded estimates of 34,000 Euro, whereas European studies have given lower cost estimates, ranging from 23,000 Euro to 29,000 Euro. Direct costs, however, make up only about 20-30% of the cost of illness of severe sepsis. Indirect costs associated with severe sepsis account for 70-80% of costs and arise mainly from productivity losses due to mortality. Because of increasing healthcare cost pressures worldwide, economic issues have become important for the introduction of new innovations. This is evident when introducing new biotechnology products, such as drotrecogin-alpha (activated protein C), into specific therapy for severe sepsis. Data so far suggest that when drotrecogin-alpha treatment is targeted to those patients most likely to achieve the greatest benefit, the drug is cost effective by the standards of other well accepted life-saving interventions.

Measurement of health-related QOL in diabetes mellitus

Abstract: A number of health-related QOL (HR-QOL) measures specifically designed for people with diabetes mellitus have appeared in the literature. This article provides a selective review of 12 measures that address this important construct. For each included study, a description of the measure and its development phase is provided, followed by discussion of sampling, reliability, validity and appropriateness for selected populations. Measures designed to investigate broad and specific conceptualisations of diabetes-specific QOL are included. For research in which a broad conceptualisation of diabetes-specific QOL is appropriate, the following measures are recommended: Diabetes-39, Diabetes Care Profile (DCP), Diabetes Impact Management Scales (DIMS), Diabetes Quality of Life (DQOL) and the Diabetes-Specific Quality of Life Scale (DSQOLS). For investigation of one or more specific aspects of diabetes-specific QOL, other measures may also be appropriate: single-scale questionnaires such as the Appraisal of Diabetes Scale (ADS) [stressful impact], Audit of Diabetes-Dependent Quality of Life (ADDQoL) [life without diabetes] and the Problem Areas in Diabetes scale (PAID) [diabetes-related distress]; the Diabetes Health Profile (DHP) which focuses on diabetes-related distress, activity and eating behaviour; the Questionnaire on Stress in Patients with Diabetes-Revised (QSDR) which has a primary focus on diabetes-related distress; and the Well-Being Enquiry for Diabetics (WED) which is primarily concerned with the perceptions of patients with diabetes in relation to mental health. Researchers selecting a diabetes-specific QOL measure should also carefully consider the conceptual underpinnings of the available instruments, as there is little uniformity in the definition and conceptualisation of HR-QOL. Based upon participants involved in questionnaire development and validation studies, those questionnaires that appear to be most appropriate for use with a variety of patient populations include the Diabetes-39, DIMS, Diabetes Quality of Life Clinical Trial Questionnaire — Revised (DQLCTQ-R), PAID and the QSD-R. The DCP and DHP appear to be especially relevant measures of HR-QOL for patients with type 2 diabetes, while the DQOL, DSQOLS and WED have clear emphases on concerns of individuals with type 1 diabetes. The length of the DQLCTQ-R may raise concerns about its use among some populations (e.g. older adults). Recommendations for future research include: (i) increasing the diversity of samples used to develop and evaluate existing and new measures in terms of race/ethnicity, age and gender; (ii) examination of the causal relationship between diabetes self-management and QOL using longitudinal designs; (iii) increasing emphasis on the positive aspects of successful chronic illness self-management; and (iv) use of HR-QOL measures to inform empowering relationships between physicians and patients.

The role of cost-effectiveness analysis in the era of pharmacogenomics

Abstract: The broad availability of genetic information and technologies heralds an era when practitioners will utilise genomic testing to individualise patients' care. Pharmacogenomics uses a spectrum of approaches to explore the association of genetic variation with drug efficacy or toxicity. Investigators have described a broad array of genetic polymorphisms that confer inter-individual differences in drug response. Pharmacogenomics offers the potential to improve drug effectiveness, reduce adverse drug reactions and provide cost-effective care. However, it has had little impact on current clinical practice and the economic implications of pharmacogenomics remain unclear. Assessing the incremental cost effectiveness of a pharmacogenomic strategy involves examination of factors associated with the genotype of interest, the genomic test, the disease state and the treatment. A pharmacogenomic strategy is likely to be cost effective when: (i) the polymorphism under consideration is prevalent in the population and has a high degree of penetrance; (ii) genetic testing is highly sensitive and specific, and less costly alternative tests that could be used to individualise therapy are not readily available; (iii) the disease state involves outcomes with significant morbidity or mortality if left untreated; and (iv) the treatment involves significant outcomes and/or costs that can be impacted by genotype-individualised therapy. We foresee pharmacogenomic applications being particularly relevant for drugs: with a narrow therapeutic index or a high degree of variability in inter-individual response; where there are limitations in current methods for monitoring their adverse effects and treatment responses; and where there are few alternative treatment options. Because of the characteristics of chemotherapeutic agents and the severity of clinical outcomes in cancer, oncology appears to be one of the most appropriate disease areas for the application of pharmacogenomics. We have developed a framework which can assist researchers, pharmacists, physicians, and policy makers in evaluating the implications of specific strategies, and identifying when formal cost-effectiveness analyses should be conducted to quantitatively evaluate the benefits of pharmacogenomics.

Patient-reported outcomes and their role in the assessment of rheumatoid arthritis

Abstract: Patients with rheumatoid arthritis (RA) face considerable physical, social and emotional disabilities. In this chronic disease, for which a cure is not yet available, improving patients' health-related quality of life (HRQoL) is of the utmost concern, particularly as the use of long-term and potentially toxic therapy increases. Early HRQoL outcome measures in RA focused on physical functioning, but the social and emotional aspects of the disease are now increasingly important. Thus, several generic and RA-specific HRQoL instruments have been developed, but no one tool covers all areas of HRQoL that affect the patient with RA. For this reason, a combination of generic and disease-specific tools is currently recommended for RA clinical trials.

Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy

Abstract: Introduction and Objective: The National Cholesterol Education Program recommends regular physician follow-up and lipid testing to promote adherence with lipidlowering medications. The objective of this study was to determine whether lipid tests and physician visits after treatment initiation are indeed associated with adherence to statin therapy. Subjects and Methods: A retrospective cohort study was conducted among 19 422 enrolees in a US managed care plan who initiated treatment with a statin between October 1999 and August 2001. Computerised pharmacy, medical and laboratory records were used to study the patterns and predictors of adherence with lipid-lowering therapy for up to 3 years. Adherence was assessed in 3-month intervals with patients considered ‘adherent’ if ≥80% of days were covered by lipid-lowering therapy. Results: In the first 3 months, 40% of patients had follow-up lipid tests and only 21% had dyslipidaemia visits (14% had both). Those receiving such care were substantially more likely to be adherent in subsequent intervals. Compared with those without follow-up, the relative odds of adherence were 1.42 and 1.27 for patients with one or more lipid test and one or more dyslipidaemia visit, respectively (95% confidence intervals [CI] 1.33, 1.50 and 1.16, 1.39). Patients who received a followup visit and lipid test were 45% more likely to be adherent (95% CI 1.34, 1.55). Similar associations were observed when lipid tests and dyslipidaemia visits occurred later in therapy. Conclusion: Early and frequent follow-up by physicians — especially lipid testing — was associated with improved adherence to lipid-lowering therapy. A randomised prospective study is needed to determine whether this relationship is causal.

The economics of follow-on drug research and development: trends in entry rates and the timing of development.

Abstract: Objectives: The development of so-called ‘me-too’, or ‘follow-on’, drugs by the pharmaceutical industry has been viewed by some as duplicative and wasteful, while others have argued that these drugs often provide needed therapeutic options and inject some price competition into the marketplace. This study examines data on the trends in the speed with which competitive entry has occurred in the pharmaceutical marketplace and the competitive nature of the industry’s development of these drugs. Data and methods: We examined data on the entry rates of drugs in a large number of therapeutic classes over time, as well as detailed survey information on the relative timing of the development of drugs in the classes. Classes were defined according to chemical structure or pharmacologic mode of action and similarity of clinical use. We determined average times to initial and subsequent entry in drug classes by period and examined the timing of development milestones achieved by what have turned out to be follow-on drugs in relation to the development and approval of the first drug in a class to be approved. Results: We found that the period of marketing exclusivity that the breakthrough drug in a new class enjoys has fallen dramatically over time (a median of 10.2 years in the 1970s to 1.2 years for the late 1990s). Approximately one-third of follow-on new drugs received a priority rating from the US FDA. The vast majority of the follow-on drugs for drug classes that were created in the last decade were in clinical development prior to the approval of the class breakthrough drug. Conclusions: The data suggest that entry barriers have fallen over time for new drug

The Measurement of Contingent Valuation for Health Economics

Abstract: In health economics, contingent valuation is a method that elicits an individual's monetary valuations of health programmes or health states. This article reviews the theory and conduct of contingent valuation studies, with suggestions for improving the future measurement of contingent valuation for health economics applications. Contingent valuation questions can be targeted to any of the following groups: the general population, to value health insurance premiums for programmes; users of a health programme, to value the associated programme costs; or individuals with a disease, to evaluate health states. The questions can be framed to ask individuals how much they would pay to obtain positive changes in health status or avoid negative changes in health status ('willingness to pay'; WTP) or how much they would need to be paid to compensate for a decrease in health status or for foregoing an improvement in heath status ('willingness to accept'; WTA). In general WTP questions yield more accurate and precise valuations than WTA questions. Payment card techniques, with follow-up bidding using direct interviews with visual aids, are well suited for small contingent valuation studies. Several biases may be operative when assessing contingent valuation, including biases in the way participants are selected, the way in which the questions are posed, the way in which individuals interpret probabilities and value gains relative to losses, and the way in which missing or extreme responses are interpreted. An important aspect of all contingent valuation studies is an assessment of respondents' understanding of the evaluation method and the valuation task. Contingent valuation studies should measure the potential influence of biases, the validity of contingent valuation tests as measures of QOL, and the reliability and responsiveness of responses. Future research should address equity concerns associated with using contingent valuation and explore contingent valuation as a measure of utility for health states, particularly those that are minor or temporary.

Reconciliation of economic concerns and health policy: illustration of an equity adjustment procedure using proportional shortfall.

Abstract: Economic evaluations have become an important and much used tool in aiding decision makers in deciding on reimbursement or implementation of new healthcare technologies. Nevertheless, the impact of economic evaluations on reimbursement decisions has been modest; results of economic evaluations do not have a good record in predicting funding decisions. This is usually explained in terms of fairness; there is increasing awareness that valuations of QALYs may differ when the QALYs accrue to different patients. The problem, however, is that these equity concerns often remain implicit, and therefore frustrate explicitness and transparency in evidence-based decision making. It has been suggested that a so-called equity adjustment procedure may (partially) solve this problem. Typically this would involve the application of so-called equity weights, which can be used to recalculate the value of QALY gains for different patients. This paper explores such an equity adjustment procedure, using the equity concept of proportional shortfall. Proportional shortfall assumes that measurement of inequalities in health should concentrate on the fraction of QALYs that people lose relative to their remaining life expectancy, and not on the absolute number of QALYs lost or gained. It is the ratio of QALYs lost over the QALYs remaining. This equity concept combines elements of two popular but conflicting notions of equity: fair innings and severity-of-illness. We applied the concept of proportional shortfall to ten conditions and tentatively explored how an equity adjustment procedure using proportional shortfall might affect priority setting. Our equity adjustment procedure lowered the cost-effectiveness threshold when a condition was relatively mild. Because the proportional shortfall caused by the ten conditions differed considerably, the equity-adjustment procedure discriminated strongly between the ten conditions, and this experiment provided a good opportunity to explore the impact of equity adjustment for healthcare reimbursement decisions. In conclusion, our results suggest that equity can be measured and that integration of equity concerns into an economic evaluation improves the fit between economic models and reimbursement decisions. It is recommended that cost-effectiveness driven health policy systems consider equity adjustments.

Economic Implications of Treatment-Resistant Depression Among Employees

Abstract: Background: Conservative estimates indicate between 10% and 20% of all individuals with major depressive disorders (MDDs) fail to respond to conventional antidepressant therapies. Amongst those with MDD, individuals with treatment-resistant depression (TRD) have been found to be frequent users of healthcare services and to incur significantly greater costs than those without TRD. Given the prevalence of the disorder, it is understandable that MDDs are responsible for a significant amount of both direct and indirect healthcare costs. Objective: To provide empirical findings for employees likely to have TRD based on analysis of employer claims data, in the context of previous research. Methods: We conducted a claims data analysis of employees of a large national (US) employer. The data source consisted of medical, pharmaceutical and disability claims from a Fortune 100 manufacturer for the years 1996–1998 (total beneficiaries <100 000). The employee sample included individuals with medical or disability claims for MDDs (n = 1692). A treatment pattern algorithm was applied to classify MDD patients into TRD-likely (n = 180) and TRD-unlikely groups. Treated prevalence of select comorbid conditions and the patient costs (direct and indirect) from the employer perspective by condition were compared among TRD-likely and TRD-unlikely employees, and with a 10% random sample of the overall employee population for 1998. Results: The average annual cost of employees considered TRD-likely was $US14 490 per employee, while the cost for depressed but TRD-unlikely employees was $US6665 per employee, and $US4043 for the employee from the random sample. TRD beneficiaries used more than twice as many medical services compared with TRD-unlikely patients, and incurred significantly greater work loss costs. Conclusion: TRD has gained increasing recognition due to both the clinical challenges and economic burdens associated with the condition. TRD imposes a significant economic burden on an employer. TRD-likely employees are more likely to be treated for selected comorbid conditions and have higher medical and work loss costs across all conditions.

Psychometric Validation of the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) French version: in a population of patients treated for ocular hypertension and glaucoma.

Abstract: Objective: Physicians need reliable, valid and sensitive questionnaires to assess QOL related to glaucoma or ocular hypertension. This article presents the psychometric properties of the French version of the National Eye Institute Visual Function Questionnaire — 25 (NEI VFQ-25). Methods: A mail survey was sent to 20 000 households. The survey identified 581 residents with glaucoma or ocular hypertension. Of these a random sample (n = 204) took part in a telephone survey during which the NEI VFQ-25 was completed by eligible patients (those taking at least one topical treatment for glaucoma or ocular hypertension on the day of the interview). Multi-trait analysis was performed to assess the construct validity of the questionnaire. Internal consistency reliability was assessed using Cronbach’s α and the average inter-item correlation. Known groups validity was assessed by comparing patients grouped by duration of glaucoma, adjusted for age and gender. Results: One hundred and seventy-three patients participated in the survey. Analysis of convergent validity showed that all of the items in each scale correlated above 0.40 with their own scale except for the ‘driving’ scale. The success rate of the discriminant validity ranged from 57.1% to 100% except for the ‘driving’ scale, which was 7.1%. Cronbach’s α coefficients were all above 0.70 except the ‘driving’ score. Participants with glaucoma for less than 20 years consistently had better ‘global’, ‘near vision’, ‘distant vision’, ‘driving’, ’social function’ and ‘peripheral vision’ scores than those with disease of 20+ years duration, indicating better QOL in patients with a shorter disease duration. Conclusion: The NEI VFQ-25 is a validated instrument to measure vision-targeted QOL in French populations with glaucoma.

Transferability of economic evaluation results.

Abstract: ds on many others that can hardly be controlled. If Physicians take their decisions about the managethis is the case, every economic evaluation should be ment and use of health technologies based on scienrepeated in each setting where it is to be applied. tific knowledge as well as on their own experience. This would mean an enormous effort and, most During the last century, clinical trials have become likely, the practical paralysation of health decisions more common and have constituted the best apif efficiency criteria must be considered. proach to demonstrate the outcomes of health techThe concept of transferability appeared at the nologies. Most of the clinical trials are performed horizon as a bridge to facilitate the accumulation of under special (ideal) conditions that control for general knowledge and to avoid repeatedly starting many parameters. Clinicians have access to the refrom zero. However, this concept has to be defined sults of the trials, frequently carried out in a few and its many issues must be analysed prior to applicountries, and believe that by applying the same cation. In this issue of PharmacoEconomics, Welte technologies to their patients they will achieve simiet al.[1] elaborate and propose a guide for assessing lar results. Significant departures from those entry the transferability of economic evaluations. They requirements to the clinical trials usually change argue with three real-world examples that by investhealth outcomes; the concept of effectiveness being a small effort on an economic evaluation, its comes relevant at this point. Recently, and thanks to results can also be transferred to other settings and information technology, many records from the used in the decision-making process. This paper is application of such technologies in real world condiwelcome; it will certainly be quoted many times in tions are available (Cochrane Library, for instance). the near future and will constitute a milestone in the Consequently physicians can learn about the applispread of economic evaluation studies and their use cation of technologies in different settings, and idenin health decision making. tify those which seem to be more appropriate (more Fernando Antoñanzas effective) for their patients and health systems.

Economic impact of migraine and other episodic headaches in France: data from the GRIM2000 study.

Abstract: Background: Migraine is a prevalent and incapacitating condition that affects individuals in the prime of their productive life, thus generating an economic burden for both society and healthcare systems. The direct annual healthcare costs of migraine in France were assessed over 10 years ago, and the current study updates these figures. Objective: The objective of this study was to determine the economic cost (primarily direct costs) of migraine and other episodic headache in France based on a general population survey of headache, the GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). Design: From a representative general population sample of 10 585 individuals aged ≥15 years in France in 1999, 1486 individuals experiencing headaches were identified and interviewed regarding healthcare resource consumption in the previous 6 months. By applying unit costs to the resource data, costings (in 1999 values) were determined for physician consultations, hospitalisation, medication use and diagnostic/laboratory tests, and evaluated from a healthcare system perspective. Information on absenteeism and lost productivity was derived from the Migraine Disability Assessment Score (MIDAS) questionnaire. Results: The prevalence of migraine (including migrainous disorder) was determined to be 17%. Total annual direct healthcare costs were estimated to be €128 per individual with migraine in 1999, corresponding to €1044 million when extrapolated to all individuals experiencing migraine and aged ≥15 years. Around two-thirds of this cost accrued to the social security system (€698 million; €85 per individual). The total annual direct cost of other forms of episodic headache was much lower at €28 per individual (social security cost €18); with a prevalence of 9.2%, the annual national direct cost for other forms of episodic headache totalled €124 million. The principal cost element was physician consultations. However, it was found that many individuals had never consulted a physician for their headaches, and self-medication contributed substantially to the medication costs (the second greatest cost factor for migraine). The cost per individual rose steeply with increasing severity of headache. Conclusion: The direct healthcare costs of migraine do not seem to have risen significantly over the past decade. A small minority of individuals with more severe headaches consume most of the healthcare resources devoted to migraine, while most individuals generate relatively low direct costs. The total annual direct costs in France for migraine are almost 10-fold higher than those of other episodic headache.

Psychometric and Utility-Based Measures of Health Status of Asthmatic Patients with Different Disease Control Level

Abstract: Objective: To explore the relationship between asthma control level and healthrelated QOL (HR-QOL), and to understand the role of various psychometric and utility-based methods in studying this relationship. Methods: Two hundred and twenty-eight consecutive adult outpatients and inpatients at four sites participated in the study. Physicians identified the level of disease control according to the Global Initiative for Asthma (GINA) classification system. Patients filled in three different HR-QOL questionnaires (EuroQol 5-D [EQ-5D], Short-Form 36-item health survey [SF-36], and St George’s Respiratory Questionnaire [SGRQ]) and a direct time trade-off question. The Short Form- 6D (SF-6D) was used to derive utility values from SF-36 data. Results: All patient-reported evaluation methods could discriminate between patients with different disease control levels, and both generic and diseasespecific instruments strongly correlated to each other. The magnitude of differences in HR-QOL between groups with different disease control levels was clinically meaningful. All three HR-QOL measures reflected a relationship between disease control level and HR-QOL, but the actual pattern of the relationship depended on the instrument used. Utilities gained from the EQ-5D index, compared with the SF-6D index, had higher values in the patient group with the best disease control and lower values in the patient group with poor disease control. Conclusions: When choosing an instrument to measure the health status of asthmatic patients in clinical studies, the severity range of the study population should be considered. Researchers might prefer to use the EQ-5D in asthma patients with severe disease or poor disease control and the SF-6D in patients with mild disease or good disease control.

The generation gap: Differences between children and adults pertinent to economic evaluations of health interventions

Abstract: Differences between children and adults have both technical and ethical implications for the design, interpretation and employment of economic analyses of health-related programmes. Even though policy makers increasingly turn to economic analyses to inform decisions about resource allocation, pertinent child-adult differences have received fragmented discussion in leading methodological references. Key areas warranting attention include: the ways in which a child's distinctive biology modifies the cost and effectiveness of healthcare interventions; challenges in assessing utilities for infants and young children given their limited but developing cognitive capacity; how a child's age, dependency and disability affect the selection of the appropriate time horizon and scope of the analysis; whether a child's non-wage earning productivity should be incorporated into analyses, and if so, what metric to use; what principles of equity policy makers should employ in using economic evaluations to choose between child- and adult-focused interventions; and whether special protective measures should be introduced to secure the rights and interests of children who cannot advocate for themselves.

Are the economics of pharmaceutical research and development changing?: productivity, patents and political pressures.

Abstract: Pharmaceutical research and development (R&D) competition in the 1980s and 1990s was characterised by rising R&D expenditures, favourable returns to innovators and the introduction of many new classes of drugs with high social benefits. However, in the past 3 years, the number of new drug introductions has been well below the historical trend, while the cost per new drug continues to increase. In addition to lagging R&D productivity, the industry has been characterised by other economic and policy uncertainties. These include a wave of early patent challenges and growing political pressure to contain pharmaceutical expenditures. This paper examines the consequences of these developments.

Changing health environment: The challenge to demonstrate cost-effectiveness of new compounds

Abstract: With the development and introduction of costly new technologies and restrictive drug budgets, health economic evaluation has gained increasing importance. Health economic evaluation is now mandatory as part of reimbursement decisions in many countries. Cost-effectiveness analysis, which relates to a defined alternative and indication, and for a specific patient group and specific perspective, is the preferred health economic analysis used to make valued judgements about the efficiency of a new treatment. The costs of the new treatment are assessed relative to its potential benefits in terms of improved health, measured as increased survival and impact on quality of life. The cost per quality-adjusted life-year (QALY), an index combining quality of life and length of life, facilitates comparisons between treatments for different diseases. Governments are increasingly using QALYas an outcome measure in economic evaluation. The QALY provides an estimate, which is then used to make a decision dependent on the willingness to pay for the treatment, based on a certain threshold value. Current thresholds, usually in the range of approximately US$50 000 a year (comparable with the annual cost of renal dialysis), vary between different countries. However, these thresholds are not absolute limits; choices about the allocation of healthcare resources are also influenced by other factors, including considerations of equity and the severity of the disease.

The economic implications of non-adherence after renal transplantation.

Abstract: Background: The economic impact of therapeutic non-adherence in chronic diseases has rarely been examined using qualitative standards for economic evaluation. This study illustrates the impact of non-adherence on the cost utility of renal transplantation versus haemodialysis from the societal perspective and examines the scope for adherence-enhancing interventions. Methods: Long-term costs and outcomes in adherent and non-adherent renal transplant patients were simulated in a Markov model. The cost (euros, year 2000 values) and outcome data that were imputed in the model were derived from a prospective study in renal transplantation candidates performed in 2002. Probabilities of adverse events, graft rejection, graft loss and death in adherent and non-adherent renal transplant patients were derived from literature. Results: Compared with dialysis, renal transplantation offers a better outcome in both adherent and non-adherent patients. Lifetime costs after transplantation in the adherent patient group are higher than lifetime dialysis costs and lifetime costs in the non-adherent patient group, mainly because adherent patients live longer after transplantation. Long-term outcomes after transplantation are better for adherent than for non-adherent patients. The mean cost per QALY gained in adherent patients relative to non-adherent patients was €35 021 per QALY (95% CI 26 959, 46 620). Conclusion: Compared with established healthcare interventions, such as haemodialysis, renal transplantation can be considered a cost-effective therapy for patients with end-stage renal disease, even if patients are non-adherent after transplantation. The low incremental cost per QALY calculated in this model for adherent renal transplant patients, suggests there may be scope for adherenceenhancing interventions (provided that such interventions with a sufficiently high effectiveness exist or can be developed). As the findings are based on simulated long-term costs and outcomes, they should not be considered as precise estimates of the impact of non-adherence. This study is rather meant as an illustration of how non-adherence may impact on the results of cost-effectiveness analyses.

Cost effectiveness of peginterferon α-2a plus ribavirin versus interferon α-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis C

Abstract: Introduction: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon α-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon α-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon α-2a plus ribavirin is worth the incremental cost. Methods: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon α-2a plus ribavirin or interferon α-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon α-2a plus ribavirin and interferon α-2b plus ribavirin used to populate the model were 46% and 36% for patients infected with HCV genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs were in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service. Results: In patients infected with HCV genotype 1, peginterferon α-2a plus ribavirin increased life-years (LYs) by 0.78 years and QALYs by 0.67 years, compared with interferon α-2b and ribavirin. The incremental cost per LY and QALY gained was €9433 and €10 894, respectively. In patients infected with HCV non-1 genotypes, peginterferon α-2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with interferon α-2b plus ribavirin. The incremental cost per LY and QALY gained was €3261 and €3766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was €6811 per LY gained and €7865 per QALY gained. Conclusion: Our model suggests that peginterferon α-2a plus ribavirin is cost effective compared with conventional interferon α-2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.

Current lipid management and low cholesterol goal attainment in common daily practice in Spain. The REALITY Study.

Abstract: Objective: To evaluate prescribing patterns of lipid-lowering drugs used in management of patients at risk of coronary heart disease (CHD) in usual clinical practice in Spain and to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among CHD and CHD equivalent patients (<100 mg/dL) and non-CHD patients with two or more risk factors (<130 mg/dL) who were prescribed lipid-lowering drugs. Methods: Cohort study with retrospective chart review at 23 primary care centres and 16 lipid treatment centres across Spain (59% primary care; 41% outpatient lipid centres). Physicians consecutively identified eligible patients. Adults (aged.18 years) with CHD/CHD equivalent or two or more major risk factors prior to first prescription of lipid-lowering drugs were eligible. Medical records were reviewed by physicians to collect patient characteristics, baseline and follow-up laboratory values and lipid-lowering drug treatment data. Results: 619 patients (45.5% CHD and CHD equivalent patients and 54.5% non-CHD with two or more major risk factors) were included in the study with an average study follow-up of 3.6 years. Mean age was 60.1 years (SD 10.2), and 47.8% were female. Mean baseline LDL-C was 178 mg/dL (SD 45.0) for the CHD/CHD equivalent patients and 191 mg/dL (SD 56.95) for patients with two or more risk factors. Statins were the initial lipid-lowering drugs in 90.2% of patients; 52.5% of patients were initiated on low-dose (simvastatin 10mg or lower potency) statins. Overall 20.2% of CHD/CHD equivalent and 31.4% of patients with two or more risk factors attained LDL-C goal during the study period; of patients not attaining goal, 28.7% required an additional LDL-C reduction of >30% to attain goal. In a logistic regression model for goal attainment, CHD/CHD equivalent patients (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.31, 0.72) and patients with baseline LDL-C >190 mg/dL (OR 0.53; 95% CI 0.35, 0.80) were least likely to reach cholesterol goal when compared with patients having baseline LDL-C >100 mg/dL and <130 mg/dL. Conclusion: Only 12.9% of patients attained LDL-C goal on their initial lipid-lowering drugs, and an additional 13.4% achieved goal after a change in their lipid-lowering therapy, resulting in 73.7% of patients not attaining goal after at least 3 years of follow-up, after initiation of lipid-lowering therapy. Patients who would gain the most from aggressive lipid lowering (CHD patients and patients with high baseline LDL-C) were least likely to achieve goal. More effective lipid management is needed to help these patients lower their cholesterol to goal levels or even lower.

Assessing the value of antipsychotics for treating schizophrenia: the importance of evaluating and interpreting the clinical significance of individual service costs.

Abstract: Schizophrenia is a serious and complex disorder, with treatment requiring a large number and wide range of health and social service resources. This paper addresses one challenge for assessing the direct costs of antipsychotic treatments — that of interpreting both cost and effectiveness implications of specific components of service use. Information collected on direct component costs has frequently been analysed and reported only in total. Results of several published studies provide evidence that the total direct medical costs associated with atypical antipsychotics appear to be at least equivalent to, and in some cases lower than, those associated with conventional agents. An important implication of this cost-equivalency finding is that treatment involving higher medication costs have led to offsets in certain medical service costs. Results from several studies demonstrate a shift of cost components, primarily from more expensive inpatient to less expensive outpatient care. Although the common inpatient versus outpatient dichotomy is useful, the complexities of schizophrenia and the heterogeneity of outpatient service provision are likely to warrant greater specificity. Published schizophrenia treatment guidelines can assist researchers to more fully understand and meaningfully interpret the possible relationship of antipsychotic effectiveness to the use of particular outpatient services. Because the disease requires comprehensive and continuous care, outpatient treatment costs may be better conceptualised as baseline or expectable costs necessary in the maintenance phase of treatment. Lack of expectable costs may represent poor patient outcomes and increased intangible costs. In contrast, reductions in acute outpatient service costs may provide important markers of treatment effectiveness. A small number of studies have examined the use of crisis services, but additional work is needed to differentiate treatments vis-a-vis the need for intensive (acute) interventions. The assessment and clinical interpretation of individual cost components may offer an important opportunity to build upon initial results focusing on total costs and tailor analyses to the complexities of the disorder and the treatment process. Research able to incorporate clinical acumen into cost analyses will enhance the ability of healthcare policy makers to make informed decisions regarding the value of different antipsychotic medications for the treatment of schizophrenia.

Pharmacoeconomic implications of new therapies in sepsis.

Abstract: Severe sepsis is a major healthcare problem, characterised by a high incidence, mortality and cost. New breakthroughs in treatment are quite diverse, including: (i) more effective regimens for generic, inexpensive broad anti-inflammatory agents (corticosteroids); (ii) a recombinant protein (drotrecogin-alfa [activated]); and (iii) a protocol-based treatment approach (early goal-directed therapy). Economic analyses of new sepsis agents should adopt the societal perspective, which requires prolonging the time horizon beyond that currently typically studied in sepsis trials, so that patient-centred outcomes can be more fully captured. Sepsis affects a very diverse group of patients, and if findings are to be generalisable, careful attention must be paid to study entry criteria and differences in effects and costs across different patient subgroups. Existing care patterns for sepsis are also quite diverse, with the consequence that the incremental effects on costs and outcomes could vary widely by practice pattern, again affecting generalisability. Furthermore, many sepsis patients receive multiple other therapies, which together with therapies under study may have varied and unintended, potentially costly or dangerous adverse effects, which could have a large influence on cost-effectiveness estimates. Finally, there are a number of large yet potentially hidden costs of sepsis, such as the long-term costs of managing patients who develop sepsis or the costs of introducing different interventions into clinical practice. Such costs must also be addressed in economic analyses. The search for new anti-sepsis strategies remains vigourous and exciting. We recommend wider incorporation of economic analyses into the study of potential new therapies, with appropriate attention to the caveats discussed above. Clinical demand to use new agents must be balanced against the economic consequences of their use.

The burden of coronary, cerebrovascular and peripheral arterial disease

Abstract: Atherothrombosis is a potentially life-threatening generalised disease process that affects the coronary, cerebral and peripheral vasculature, with clinical manifestations including myocardial infarction, ischaemic stroke and peripheral arterial disease. Atherothrombosis represents a massive clinical and economic burden to healthcare, annually accounting for at least 22% of all deaths globally. Moreover, the prevalence of atherothrombotic disease is increasing as a result of increased longevity resulting in a larger cohort of older individuals. Stroke in particular is a major burden, and is the primary cause of adult disability, the second most important cause of dementia, and the third leading cause of death in industrialised countries. Atherothrombosis is also associated with a poor prognosis, significantly reducing life expectancy in the 60-year-old patient by 8–12 years depending on the vascular event. Moreover, this already shortened life expectancy is further and substantially reduced in patients with more than one atherothrombotic event. The economic burden of atherothrombosis is significant, particularly given its increasing prevalence, with the United States spending over US$300 billion on it. There is thus a need for effective intervention to prevent or reduce mortality and morbidity. Evidence-based medicine using economics, clinical trials data, outcomes research, epidemiology and risk stratification are necessary to target treatment effectively to patients at greatest risk, in an attempt to reduce the burden of atherothrombotic disease.