Direct costs of osteoporosis and hip fracture: an analysis for the Mexican healthcare system.

UNLABELLED: This study reports the direct costs related to osteoporosis and hip fractures paid for governmental and private institutions in the Mexican health system and estimates the impact of these entities on Mexico. We conclude that the economic burden due to the direct costs of hip fracture justifies wide-scale prevention programs for osteoporosis (OP). METHODS: To estimate the total direct costs of OP and hip fractures in the Mexican Health care system, a sample of governmental and private institutions were studied. Information was gathered through direct questionnaires in 275 OP patients and 218 hip fracture cases. Additionally, a chart review was conducted and experts' opinions obtained to get accurate protocol scenarios for diagnoses and treatment of OP with no fracture. Microcosting and activity-based costing techniques were used to yield unit costs. RESULTS: The total direct costs for OP and hip fracture were estimated for 2006 based on the projected annual incidence of hip fractures in Mexico. A total of 22,233 hip fracture cases were estimated for 2006 with a total cost to the healthcare system of US$ 97,058,159 for the acute treatment alone ($4,365.50 per case). We found considerable differences in costs and the way the patients were treated across the different health sectors within the country. CONCLUSION: Costs of the acute treatment of hip fractures in Mexico are high and are expected to increase with the predicted increment of life expectancy and the number of elderly in our population.

Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland.

OBJECTIVE: The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes. METHODS: Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results. RESULTS: A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of euro14 000 in Sweden and euro13 600 in Switzerland. CONCLUSION: The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.

[The role of utilities in economic evaluations of healthcare interventions-an introduction]. / Der Gebrauch von Nutzwerten im gesundheitsökonomischen Vergleich von Interventionen bei verschiedenen KrankheitsbildernEine Einführung.

Assessment of strength of preference values (utilities) for patients' own health, or disease states from a societal perspective, is an essential element to economic evaluations of healthcare interventions. This review provides an overview of the different methods used to directly elicit strength of preference values: the standard gamble, time trade-off and rating scale methods. Methods used to derive utilities for patients' health states indirectly, and from a societal perspective are described. Three commonly used questionnaires: Health Utilities Index 3, EQ-5D and SF-6D are briefly commented upon. We also discuss the usefulness of utilities and advantages and disadvantages to be considered when choosing direct or indirect utility elicitation methods.

The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension: a comparative study.

OBJECTIVE: To compare the economic burden to society incurred by patients with RA, OA, or high blood pressure (HBP) in Ontario, Canada. METHODS: Consecutive subjects recruited by 52 rheumatologists (RA) and 76 family physicians (OA and HBP) were interviewed at baseline and 3 months. Information was collected on demographics, health status, and any comorbidities. A detailed, open ended resource utilisation questionnaire inquired about the use of medical and non-medical resources and patient and care giver losses of time and related expenses. Annual costs were derived as recommended by national costing guidelines and converted to American dollars (year 2000). Statistical comparisons were made using ordinary least squares regression on raw and log transformed costs, and generalised linear modelling with adjustment for age, sex, educational attainment, and presence of comorbidities. RESULTS: Baseline and 3 month interviews were completed by 253/292 (86.6%) patients with RA and 473/585 (80.9%) patients with OA and/or HBP. Baseline and total annual disease costs for RA (n = 253), OA and HBP (n = 191), OA (n = 140), and HBP (n = 142), respectively, were $9300, $4900, $5700, and US$3900. Indirect costs related to RA were up to five times higher than indirect costs incurred by patients with OA or HBP, or both. The presence of comorbidities was associated with disease costs for all diagnoses, cancelling out potential effects of age or sex. CONCLUSION: The economic burden incurred by RA significantly exceeds that related to OA and HBP, while differences between patients with a diagnosis of OA without HBP or a diagnosis of HBP alone were non-significant, largely owing to the influence of comorbidities.

Development of a matrix of cost domains in economic evaluation of rheumatoid arthritis.

The aim of our study was to comprehensively review and critically appraise the cost domains used in economic evaluations of the rheumatic diseases and to use this information to propose standardization of cost domains. The literature search identified 210 abstracts, 32 of which included original cost data. The listed cost categories were grouped into 3 major areas: (direct) health care costs, other (direct) disease related costs, and productivity costs (indirect costs). The number of individual cost categories was reduced by considering the following criteria: (1) inclusion of all relevant cost domains; (2) avoidance of double counting; (3) summarizing of related categories under one representative heading; (4) feasibility of level of aggregation. After adjustment for synonymous labeling, 38 cost categories remained. The subsequent development of a classification scheme of cost categories led to a set of 19 separate cost domains including 7 outpatient, 3 inpatient, 6 other disease related, and 3 productivity cost domains. This literature review indicates that cost assessment in economic evaluations in rheumatoid arthritis lacks standardization. A preliminary scheme to categorize cost assessment in rheumatic conditions is presented. The adoption of standards for economic evaluation would greatly facilitate national and international comparisons.

Cost assessment instrument in rheumatology: evaluation of applied instrument characteristics.

We compared the major characteristics of internationally applied cost assessment instruments (CAI) in rheumatic conditions. Fifteen utilization questionnaires were identified and assessed using a structured approach. The forms differed considerably with respect to applied characteristics: length (3-113 items), recall period (between 1 week and 1 year), format (2 interview, 13 self-administered), response categories, cost units (physical vs monetary), and cost domains covered. While all included a gross assessment of outpatient and inpatient costs, the level of disaggregation differed. Only a few CAI included an assessment of other direct disease related costs (e.g., home remodeling or home health care services) and out-of-pocket expenditure. Productivity costs were included in all but 2 CAI. Efforts to further standardize the applied CAI should (1) be based on sound psychometric data, (2) define a required core set of cost domains covered, (3) discriminate between generic and relevant disease related cost components, and (4) examine the feasibility of developing international standards for cost data.

Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving disease-modifying anti-rheumatic drugs.

OBJECTIVE: To summarize the evidence on treatment withdrawal rates reported in observational studies and randomized controlled trials (RCTs) of methotrexate (MTX), parenteral gold (GST), sulphasalazine (SSZ) and hydroxychloroquine (HCQ) among patients with rheumatoid arthritis (RA). METHODS: Two independent Medline searches were used to retrieve relevant studies published between 1966 and 1997. Those which disclosed information on the number of patients withdrawing from the drug were retained. Cumulative probabilities of survival on treatment were then computed using actuarial survival estimates, and differences were tested using log-rank, Wilcoxon and Cox proportional hazards tests. RESULTS: A total of 159 studies provided withdrawal information, and the numbers of patients who withdrew, in general or because of inefficacy or toxicity, could be abstracted from 110 studies contributing 142 treatment arms (MTX, 48; GST, 56; SSZ, 22; HCQ, 16). Data for HCQ were available only up to 24 months, but combined percentages of patients estimated to have continued MTX, GST or SSZ, respectively, for 60 months were 36, 23 and 22% when all failures were considered, 75, 73 and 53% when withdrawals due to lack of efficacy alone were considered, and 65, 36 and 48% when only withdrawals due to toxicity were taken into account. The Cox proportional hazards test performed on all withdrawals, after adjusting for year of publication and type of study, revealed that patients remained on MTX significantly longer than they did on the other three agents; however, the patients stayed significantly longer on GST than MTX when withdrawals for inefficacy were analysed separately. No significant differences in withdrawal rates were noted between observational studies and RCTs. CONCLUSION: Patients with RA stay significantly longer on MTX than on other disease-modifying anti-rheumatic drugs. Higher withdrawal rates among those given GST are mainly due to high toxicity, whereas the majority of withdrawals from SSZ and HCQ result from lack of efficacy. Withdrawal rates in observational studies are similar to those reported in RCTs.

Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled trial. Leflunomide Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). METHODS: A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. RESULTS: In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. CONCLUSION: Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states.

Use of grade membership analysis to profile the practice styles of individual physicians in the management of acute low back pain.

The objective of this study was to investigate Grade of Membership analysis (GoM) as a means of profiling the practice styles of individual physicians. GoM uses maximum likelihood techniques to estimate occurrences of management items that define unique practice styles. It also provides statistical estimates (grade of membership coefficients) of how well each individual physician's practice fits the identified styles. Data sources were responses to a mailed survey asking 814 physicians to select from predetermined management options in three scenarios depicting patients with acute low back pain. Four distinct types of practice style were identified: watchful waiting; investigative; guideline based; and physiotherapy focused. Most physicians were characterized by high grades of membership in the two profiles that most closely matched existing guidelines for the management of acute low back pain. GoM successfully identified characteristic practice styles, and the GoM coefficients obtained provided descriptions of individual management approaches. GoM is data driven and less subject to judgment than opinion-based measures of performance. It has several potential applications in identifying physicians for whom some form of intervention would be beneficial.

Pharmacoeconomic evaluation of new treatments: efficacy versus effectiveness studies?

The juxtaposition of economic and clinical evaluation raises new issues in the design of clinical trials. Recent pharmacoeconomic guidelines provide some direction, but do not deal with the appropriate timing of economic evaluations in the drug developmental process. Ideally, pharmacoeconomic data should be available at the time of the regulatory and formulary decision making. Current pivotal phase III trials do not provide these data; they are designed to test safety and efficacy (does the drug work under optimal circumstances?) and not to answer questions about the effectiveness of a drug, the more relevant question for economic analysis (does the drug work in usual care?). The use of more "naturalistic" designs for some phase III randomised trials has been suggested. These so called "effectiveness trials" more closely reflect routine clinical practice. They use a more flexible dosage regimen, and a "usual care" instead of a placebo comparator. Patients randomised are more representative of actual practice and outcomes include quality of life and utility measures. They are more suited to provide the data needed to estimate the real benefit of the treatment in actual care. When costs are applied and compared with these benefits, you can estimate the efficiency of allocating resources to this new drug. Increasing the use of effectiveness trials in phase III would decrease the need for economic modelling.

Function and health-related quality of life: results from a randomized controlled trial of leflunomide versus methotrexate or placebo in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. METHODS: This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. RESULTS: Clinically meaningful and statistically significant (P<0.0001) improvement in measures of function and heath-related quality of life (MHAQ scores, all scales and disability index of the HAQ, weighted top 5 score of the PET, 5 of 8 scales and physical component score of the SF-36, and work productivity) was seen during treatment with leflunomide in comparison with placebo. Methotrexate administration resulted in significant improvements (P<0.05) in comparison with placebo in the MHAQ scores, HAQ disability index, weighted top 5 score of the PET, physical component score of the SF-36, and bodily pain scale. Compared with methotrexate, leflunomide administration resulted in significantly (P<0.01) more improvement in the MHAQ scores, 5 of 8 scales and disability index of the HAQ, weighted top 5 score of the PET, and 2 of 8 scales and physical component score of the SF-36. Improvements in the PET score, SF-36 physical component score, and work productivity correlated with the ACR responder rates of > or =20% and > or =50% improvement. CONCLUSION: Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status.

How Canadian and US rheumatologists treat moderate or aggressive rheumatoid arthritis: a survey.

OBJECTIVE: To determine which second line agents Canadian and US rheumatologists use to treat patients with active rheumatoid arthritis (RA). METHODS: A one page survey was sent by fax or mail to all 263 members of the Canadian Rheumatology Association and 320 members of the American College of Rheumatology (10% random sample weighted by region) known to practice adult rheumatology. The survey asked for first and second treatment preferences in patients with (1) aggressive RA; (2) moderate RA; and (3) aggressive RA failing a trial of methotrexate (MTX) 25 mg. RESULTS: Altogether 231 (87.8%) Canadian and 230 (71.7%) US rheumatologists responded, and 214 responses in each survey were analyzable. In aggressive RA. MTX was the drug of first choice of most Canadian (68.7%) and US (78.5%) rheumatologists. Intramuscular gold was a drug of first choice for 14.5 and 1.9% of Canadians and Americans, respectively. 93.9% of Canadian and 90.2% of US respondents preferred single agents for the treatment of moderate RA. Among US rheumatologists. no clear leader emerged as a single agent alternative for the management of aggressive RA unresponsive to MTX. Most said they would use combination (38.3%) or triple (23.8%) therapy involving MTX plus sulfasalazine and/or hydroxychloroquine. 52.3% of Canadians preferred single agent therapy, with 34.6% choosing gold as an alternative to MTX. CONCLUSION: Canadian and US rheumatologists preferred MTX for the treatment of aggressive RA. Canadian rheumatologists saw a small but significant role for intramuscular gold. No single agent emerged as a clear alternative to MTX among US rheumatologists.

A review of cost-effectiveness analyses in rheumatology and related disciplines.

A MEDLINE search of the 1996 and 1997 literature yielded two reviews of the methodology of cost-effectiveness analyses (CEAs) in the field of rheumatology and eight original CEAs evaluating slow-acting antirheumatic agents (two studies), total hip arthroplasty for patients with osteoarthritis (one study), educational intervention for patients with fibromyalgia (one study), interventions for patients with low back pain (three studies), and hormone replacement therapy for women with osteoporosis (one study). Most CEAs relied on modelling of data that were assembled from various sources; however, in one CEA a cost-effectiveness comparison was based on data collected prospectively within a randomized clinical trial. Extensive sensitivity analyses were conducted by a majority of the studies. The CEAs of slow-acting antirheumatic agents provided results that were difficult to interpret given extensive modelling and reliance on expert estimates. Only one CEA was supported by an industry grant. Most of the studies were of high quality and met current methodologic requirements, including the use of discounting, sensitivity analysis, and incremental analysis. However, the major shortcoming of these recent studies continues to be the use of estimated costs instead of prospectively measured resource utilization data presented in terms of separate physical units.

The cost-effectiveness of misoprostol in preventing serious gastrointestinal events associated with the use of nonsteroidal antiinflammatory drugs.

OBJECTIVE: To reexamine the cost-effectiveness of misoprostol, using data from a recently published placebo-controlled trial of misoprostol in > 8,000 patients with rheumatoid arthritis (RA) taking nonsteroidal antiinflammatory drugs (the Misoprostol Ulcer Complications Outcome Safety Assessment [MUCOSA] study). METHODS: Actual clinical events and the rates of endoscopies and upper gastrointestinal (GI) radiographic series, hospitalizations, and surgery for these events were derived from the MUCOSA study and used in a decision analysis. Estimates of costs for the management of these events were derived from the Ontario Case Cost Project database and published economic evaluations; costs were adjusted to 1994 Canadian dollars. Incremental cost-effectiveness (from the viewpoint of the provincial health care plan in Canada) was calculated for the original trial population (risk of a serious GI complication 1%) and for the subsets of patients with medium (3%) and high (6%) risk. RESULTS: For the original study population, averting 1 serious GI complication by prescribing misoprostol would cost an additional $94,766 (Canadian; range $60,286-137,146). For patients with previous peptic ulcer disease (medium risk), the cost would be $14,943 (range $10,912-32,157), and for patients with previous peptic ulcer disease and age > 75 (high risk), the cost would be $4,101 (range $-220 to $18,146). CONCLUSION: Prescribing misoprostol for all patients with RA who are > or =52 years old costs $94,766 for each additional GI event averted. However, when patients at higher risk are specifically selected, the cost per averted GI complication is markedly reduced. These results, based on actual serious event rates and actual data on endoscopies and upper GI series, hospitalizations, and surgeries, provide a better estimate of the true cost-effectiveness of misoprostol than previous analyses based on endoscopic data and modeling of all resource utilizations.

A summary of economic evaluations published in the field of rheumatology and related disciplines.

INTRODUCTION: The relationship between the effectiveness of health care interventions and their costs is of increasing interest. The goal of the present study was to summarize the economic evaluations (EEs) published in the field of rheumatology and related disciplines, and to focus in particular on methodologic issues. METHODS: MEDLINE was searched in order to identify all relevant EEs published between 1966 and February 1995. Titles and abstracts of 1,435 articles were retrieved and independently reviewed by 2 assessors. Overall, 63 articles were identified by either assessor as being definite or possible full EEs (defined as an analysis comparing 2 or more strategies involving the assessment of both costs and consequences), and were assessed independently. RESULTS: Thirty-six articles were determined to be full EEs (33 cost-effectiveness and 3 cost-utility analyses). Most were published in the periods 1984-1990 (31%) and 1991-1995 (61%). Main areas covered were methods of prevention (44%), treatment (31%), and treatment-prevention (22%). Disorders most frequently studied were osteoarthritis (36%), osteoporosis (22%), and rheumatoid arthritis (14%). Direct and indirect costs were measured or estimated in 100% and 28% of the EEs, respectively. The viewpoint of the analysis was stated explicitly in 12 studies (33%). Incremental and sensitivity analyses were presented in 17 (47%) and 23 (64%), respectively. Inadequate use of economic terms was also documented. CONCLUSION: The EE articles reviewed adhered partially to basic analytic methods. Economic evaluations in the field of rheumatology need to be improved to comply with current standards for the evaluation of health care interventions.

Osteoarthritis of the hip and knee and mechanical occupational exposure--a systematic overview of the evidence.

OBJECTIVE: To clarify examine the epidemiologic evidence linking work related exposure to osteoarthritis (OA) of the hip and knee. METHODS: We investigated MEDLINE and EMBASE 1966-1994 with search terms of osteoarthritis, osteoarthrosis, arthrosis; risk factors, exposure; occupational diseases, agricultural workers' diseases, work. From 123 original studies on risk factors for OA, 17 studies were identified as providing a comparison group and relating the presence or absence of radiologically diagnosed OA to occupational factors. The quality of the methodology of each study was evaluated independently by 4 reviewers using a standardized protocol. RESULTS: Common methodological problems were encountered in areas such as representatives, recall of exposure, and evaluation of exposure and outcome. These problems often made a cause-effect relationship difficult to interpret. However, 7 of the 17 studies met our criteria for good methodological quality. A critical analysis of their results led to the following conclusions: (1) A consistently positive relationship exists between work involving knee bending and knee OA in men (range of odds ratio: 1.4-6). (2) The evidence suggesting a relationship between knee OA and occupational exposure in women is inconclusive. (3) A consistently positive but weak relationship exists between work related exposure (i.e., farming in particular) and hip OA in men. We felt we could not conclude with confidence that this relationship is strong due to the potential biases that exist in each of these studies. (4) No study attempted to investigate occupational exposure and hip OA in women. CONCLUSION: Studies suggest a strong positive relationship between work related knee bending exposure and knee OA. The evidence between work related exposure, farming in particular, and hip OA is consistently positive but weak.