The effect of nonsteroidal anti-inflammatory drugs on the use of gastroprotective medication in people with arthritis.

OBJECTIVE: To estimate the incidence of gastroprotective medication use among users and nonusers of prescription nonsteroidal anti-inflammatory drugs (NSAIDs) who have arthritis. STUDY DESIGN: A retrospective cohort study. PATIENTS AND METHODS: We used the Protocare Sciences proprietary Managed Care Organization database, which contains data on more than 3 million lives, to identify 57,136 patients given an initial diagnosis of osteoarthritis (OA; International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] codes: 715, 721.0, 721.3, or 721.9) or rheumatoid arthritis (RA; ICD-9-CM codes: 714.0, 714.1, 714.2, or 714.9); the diagnoses were made during inpatient or outpatient medical encounters occurring between October 1, 1993, and September 30, 1997. The duration of therapy was calculated as the sum of the total number of days of receipt of all prescriptions during the year. The prescribed daily dose was determined by multiplying the drug dose by the number of pills dispensed and the dividing the product by the number of days supplied, as noted in the pharmacy records. RESULTS: During the year after NSAID initiation, 27% of people with RA and 12% of those with OA were chronic NSAID users. NSAID users with RA were 4 times as likely as NSAID nonusers with RA to begin using a gastroprotective agent within the first year; NSAID users with OA were twice as likely as nonusers with OA to do so. CONCLUSION: The use of gastroprotective agents during the first year after NSAID initiation for the treatment of arthritis was greater than their use by those who did not take NSAIDs.

A framework for evaluating the clinical consequences of initial therapy with NSAIDs, NSAIDs plus gastroprotective agents, or celecoxib in the treatment of arthritis.

OBJECTIVE: The purpose of this study is to provide a framework for estimating the economic efficiency of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), concomitant gastroprotective agents (GPAs) to reduce the risk of NSAID toxicity, and celecoxib, a specific cyclo-oxygenase-2 inhibitor. Concomitant GPA therapies considered include one of the following: proton pump inhibitors (PPIs) plus NSAIDs, histamine H2 receptor antagonists (H2RAs) plus NSAIDs, misoprostol plus NSAIDs, and a single tablet formulation of diclofenac/misoprostol. DESIGN: The study employs a decision-tree framework to establish probabilities of upper gastrointestinal (GI) adverse events occurring over a 6-month time frame. Celecoxib clinical trial data are used to establish probabilities of upper GI events for celecoxib and NSAIDs, and published literature is used to predict upper GI events for the other concomitant therapies. Upper GI adverse events included in the decision-tree are as follows: GI discomfort, symptomatic ulcer, serious GI complications (with and without death), and anaemia with occult bleeding. MAIN OUTCOME MEASURES AND RESULTS: Clinical probabilities indicate celecoxib has significant tolerability and safety advantages compared with nonselective NSAIDs. Celecoxib also reduces the risk of GI adverse events to a similar or superior degree when compared with reductions observed with NSAIDs with concomitant GPAs. CONCLUSION: Use of celecoxib is expected to significantly reduce the economic costs of GI toxicity and its associated morbidity.

Overview of the arthritis Cost Consequence Evaluation System (ACCES): a pharmacoeconomic model for celecoxib.

Pharmacoeconomic analyses have become useful and essential tools for health care decision makers who increasingly require such analyses prior to placing a drug on a national, regional or hospital formulary. Previous health economic models of non-steroidal anti-inflammatory drugs (NSAIDs) have been restricted to evaluating a narrow range of agents within specific health care delivery systems using medical information derived from homogeneous clinical trial data. This paper summarizes the Arthritis Cost Consequence Evaluation System (ACCES)--a pharmacoeconomic model that has been developed to predict and evaluate the costs and consequences associated with the use of celecoxib in patients with arthritis, compared with other NSAIDs and NSAIDs plus gastroprotective agents. The advantage of this model is that it can be customized to reflect local practice patterns, resource utilization and costs, as well as provide context-specific health economic information to a variety of providers and/or decision makers.

International economic analysis of primary prevention of cardiovascular disease with pravastatin in WOSCOPS. West of Scotland Coronary Prevention Study.

AIMS: The results of the West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated the clinical benefit of using pravastatin for the primary prevention of cardiovascular disease in hypercholesterolaemic men. To inform decision makers, who must also consider costs, this study assesses the economic efficiency of such an intervention in a broad range of countries. METHODS AND RESULTS: A generalized model of cardiovascular disease prevention was used to estimate the cost-effectiveness of primary prevention with pravastatin compared to diet alone. This model follows a cohort of hypercholesterolaemic men over a given period quantifying the effect in terms of the avoidance of cardiovascular disease based on treatment-specific risks derived from WOSCOPS data and extensive record-linkage data on disease-specific survival. Country-specific costs are accounted for by expressing all such parameters in terms of the ratio of monthly treatment to that of managing a myocardial infarction. Over a broad range of inputs the cost-effectiveness ratios remain below $25,000 per life years gained, regardless of country. Subgroups with even better economic efficacy can be defined on the basis of higher baseline risk. CONCLUSIONS: In contrast to some previous reports, this analysis based on trial data demonstrates that pravastatin provides not only an effective means of primary cardiovascular disease prevention, but also an efficient one.

Maternal diabetes status does not influence energy expenditure or physical activity in 5-year-old Pima Indian children.

Children of women who have diabetes during pregnancy are more likely to become obese by early adulthood than those of women with normal glucose tolerance during pregnancy. Obesity can result from either excess food intake, low levels of energy expenditure or both. In our study, we tested whether maternal diabetes status influences total energy expenditure (TEE by doubly labelled water), resting metabolic rate (RMR by ventilated hood) and physical activity level (PAL = TEE/RMR and assessed by activity questionnaire). Measurements were taken in 88 5-year-old Pima Indian children, 24 children of women with diabetes (2-h plasma glucose > or = 11.1 mmol/l) diagnosed before or during pregnancy and 64 children of women with normal glucose tolerance (2-h plasma glucose < 7.8 mmol/l during pregnancy and no prior history of abnormal glucose tolerance). Although birth weight was higher in children of diabetic than of nondiabetic women (mean +/- SD; 3.8 +/- 0.6 vs 3.5 +/- 0.4 kg, p < 0.03), there were no differences in weight (26.4 +/- 6.9 vs 24.2 +/- 5.6 kg) or per cent body fat (18O dilution; 33 +/- 8 vs 31 +/- 8%) between the groups at 5 years of age. There was no difference in TEE (6508 +/- 1109 vs 6175 +/- 942 kJ/d) or in RMR (4674 +/- 786 vs 4483 +/- 603 kJ/d) expressed as absolute values or after adjustment for weight and sex (TEE) or fat-free mass, fat mass, and sex (RMR). Physical activity level was also similar between the groups (1.40 +/- 0.12 vs 1.38 +/- 0.12). These results suggest that maternal diabetes status does not influence energy expenditure in the children by 5 years of age. Thus the greater obesity seen at older ages in the children of women with diabetes could be due to excess energy intake. Alternatively, if energy expenditure does have a role in the aetiology of obesity in these children, perhaps it does so only in older children.

Strategies for the management of hypercholesterolaemia: a systematic review of the cost-effectiveness literature.

OBJECTIVE: To review research addressing the management of cholesterol in the prevention of coronary heart disease in order to assess the cost-effectiveness of such interventions. METHODS: A systematic review of economic evaluations identified through searches of MEDLINE and the Social Sciences Citation Index revealed 38 studies addressing the cost-effectiveness of cholesterol management. They were distinguished according to screening approaches, dietary advice and drug treatment. Most studies were not associated directly with clinical trial results, but adopted economic modelling approaches. RESULTS: Whilst there is general agreement among the majority of analyses, studies of cholesterol management concerned with screening strategies were extremely sensitive to changes in their assumptions; so much so that only a limited emphasis may be placed on specific cost-effectiveness ratios and the conclusions drawn from them. All studies considered direct costs, though many were limited to drug costs. The cost-effectiveness of primary prevention by cholesterol-lowering drugs is highly variable, depending on age at initiation of treatment and cardiovascular risk profile. Pharmacological intervention is least cost-effective in the young and the elderly. The cost-effectiveness of cholesterol-reducing agents improves when they are targeted at those at high risk. HMG-CoA reductase inhibitors are generally more effective and more cost-effective at reducing cholesterol-related coronary events than other medications. CONCLUSION: The methods and economic data upon which these studies are based need to be improved if robust policy conclusions are to be formulated.

The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin.

OBJECTIVE: To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia. DESIGN: Economic benefit analysis based on data from the West of Scotland coronary prevention study. Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated. Scottish record linkage data provided disease specific survival. Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotland coronary prevention study. SUBJECTS: Men with hypercholesterolaemia similar to the subjects in the West of Scotland coronary prevention study. MAIN OUTCOME: Cost consequences, the number of transitions from health to cardiovascular disease prevented, the number needed to start treatment, and cost per life year gained. RESULTS: If 10,000 of these men started taking pravastatin, 318 of them would not make the transition from health to cardiovascular disease (number needed to treat, 31.4), at a net discounted cost of 20m Pounds over 5 years. These benefits imply an undiscounted gain of 2,460 years of life, and thus 8121 Pounds per life year gained, or 20,375 Pounds per life year gained if benefits are discounted. Restriction to the 40% of men at highest risk reduces the number needed to treat to 22.5 (5601 Pounds per life year gained (undiscounted) and 13,995 Pounds per life year gained (discounted)). CONCLUSIONS: In subjects without evidence of prior myocardial infarction but who have hypercholesterolaemia, the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups.

Is paclitaxel and cisplatin a cost-effective first-line therapy for advance ovarian carcinoma?

BACKGROUND: Paclitaxel and cisplatin use for the treatment of advanced ovarian carcinoma (AOC) has been shown to increase median survival duration. An evaluation was performed on the economic consequences of treating AOC patients with combined paclitaxel and cisplatin chemotherapy compared with current usual care, i.e., combined cyclophosphamide and cisplatin chemotherapy. METHODS: Linear modeling techniques combined with retrospective chart analysis were used to predict the clinical progression and treatment of AOC patients until death. Cost-effectiveness analysis comparing paclitaxel and cisplatin and usual care was performed from a simplified Ministry of Health perspective. RESULTS: Assuming a 50% increase in survival for paclitaxel and cisplatin patients, an assumption supported by recent clinical trial data, this treatment showed an average lifetime cost per patient of $50,054 Cdn compared with a cost of $36,837 Cdn for usual care. The incremental cost of the paclitaxel and cisplatin treatment over the usual treatment was $20,355 Cdn per life year gained. These results withstood extensive sensitivity analyses. CONCLUSIONS: Paclitaxel, in combination with cisplatin, appears to be a cost-effective first-line treatment for AOC. A moderate increase in incremental cost compares favorably with other life-saving strategies currently in use. As more data become available for the use of paclitaxel, this pilot study will provide a basis for more extensive economic evaluation of paclitaxel.

Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens.

The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin-to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to-creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional-hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections.