The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gaucher disease.

The effect of enzyme replacement therapy (ERT) on bone crisis and bone pain was investigated in patients with Gaucher disease (GD) type 1 followed over 4 years. Data from the International Collaborative Gaucher Group Gaucher Registry were used. Only patients with bone crisis and/or bone pain data for 1 year prior to ERT, and for each of 3 years after the start of ERT, were included. Bone crises were reported in 17% of patients during the year before starting ERT. The frequencies of bone crises decreased to 5%, <1% and 3% for 1, 2, and 3 years after initiation of treatment, respectively (p < 0.0001). Bone pain followed a similar pattern of response. Bone pain was reported in 49% of patients the year before treatment and decreased to 30% in the first year, 29% in the second year, and 30% in the third year of ERT (p < 0.0001). ERT is associated with a reduction in bone crisis and bone pain in patients with GD type 1 . This study shows that significant improvements in symptoms of skeletal disease are achievable clinical outcomes and treatment goals in GD type 1.

An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia.

OBJECTIVE: To examine treatment costs of community-acquired pneumonia (CAP) in adult outpatients given oral (p.o.) levofloxacin or cefuroxime axetil as initial therapy. STUDY DESIGN: Patients with a primary diagnosis of CAP were enrolled in a multicenter, prospective, randomized, open-label, active-controlled Phase III clinical trial. Both inpatients and outpatients were assigned to 1 of 2 treatment groups: (1) intravenous (i.v.) or p.o. levofloxacin; or (2) i.v. ceftriaxone and/or p.o. cefuroxime axetil. METHODS: To make legitimate and meaningful cost comparisons between similar types of patients receiving drugs via the same route of administration (i.e., orally), this outpatient economic study examined the resource utilization of the 211 patients enrolled as outpatients who received oral formulations as initial treatment (levofloxacin, 103 patients; cefuroxime axetil, 108 patients). Resource utilization data and clinical trial data were collected concurrently. To generate cost estimates, Medicare cost estimates for resources were multiplied by the resource units used by patients in each treatment arm. RESULTS: Cost estimates indicated a total cost difference that favored the levofloxacin group (base case: $169; sensitivity analysis: $223 [P = .008]). The results for the base case were not significant (P = .094). In addition, within the cost categories, there was a statistically significant study drug cost differential favoring levofloxacin ($86; P = .0001 for both the base case and sensitivity analysis). CONCLUSION: Oral levofloxacin is less costly than oral cefuroxime axetil in the outpatient treatment of adults with CAP.

Determinants of antidepressant treatment outcome.

OBJECTIVE: To understand the determinants of the outcome of an episode of major depression, including factors that affect receipt of guideline-consistent care and their subsequent effect on treatment outcomes, particularly relapse or recurrence. Results of previous studies are generalized to a population typical of depressed individuals in the United States, i.e., a cohort of antidepressant users with employer-provided health benefits. STUDY DESIGN: A quasi-experimental design was used to assess the determinants of the outcome of an episode of major depression. Healthcare utilization-based measures of treatment characteristics and outcomes were used. PATIENTS AND METHODS: The final analytical file for this study contained data on 2917 patients who had an antidepressant prescription associated with an indicator of a depressive disorder. We identified relapse or recurrence of depression by (1) a new episode of antidepressant therapy, (2) suicide attempt, (3) psychiatric hospitalization, (4) mental health-related emergency department visits, or (5) electroconvulsive therapy. Antidepressant use patterns were used to construct a measure for adherence to treatment guidelines. Multivariate Cox proportional hazard and logit regression models were used to predict relapse/recurrence and adherence with treatment guidelines, respectively, for each patient. RESULTS: Factors that affect relapse/recurrence include comorbidities, demographics, and adherence to treatment guidelines. Factors that affect adherence to treatment guidelines include choice of initial antidepressant drug, comorbidities, psychotherapy, and frequency of physician visits. CONCLUSIONS: Adherence to treatment guidelines was associated with a significant reduction in the likelihood of relapse or recurrence of depression. Choice of initial antidepressant drug affects adherence to treatment guidelines.

Olanzapine versus risperidone. A prospective comparison of clinical and economic outcomes in schizophrenia.

OBJECTIVE: To compare the clinical and economic outcomes associated with olanzapine and risperidone treatment for schizophrenia. DESIGN AND SETTING: An international, multicentre, double-blind, prospective study. To facilitate economic comparisons, our sample was restricted to patients enrolled in US sites. 150 patients with a Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder were randomised to therapy with either olanzapine 10 to 20 mg/day (n = 75) or risperidone 4 to 12 mg/day (n = 75) for a maximum of 28 weeks. In addition to tolerability and efficacy assessments, use of health services was assessed at baseline and prospectively, at 8-week intervals and at study completion. Clinically important response, defined as a 40% improvement in the Positive and Negative Syndrome Scale total score, maintenance of response and rates of treatment-emergent extrapyramidal symptoms were compared between groups. Direct medical costs were estimated by assigning standardised prices to resource units. Median total, inpatient/outpatient service and medication acquisition costs were compared between treatment groups. MAIN OUTCOME MEASURES AND RESULTS: The mean modal dosages for the olanzapine and risperidone treatment groups were 17.7 +/- 3.4 mg/day and 7.9 +/- 3.2 mg/day, respectively. Olanzapine-treated patients were more likely to maintain response compared with risperidone-treated patients (p = 0.048). In addition, a smaller proportion of olanzapine-treated patients required anticholinergic therapy compared with risperidone-treated patients (25.3 vs 45.3%; p = 0.016). Total per patient medical costs over the study interval were $US2843 (1997 values) [36%] lower in the olanzapine treatment group than in the risperidone treatment group (p = 0.342). Medication costs were significantly higher for olanzapine-treated patients ($US2513 vs $US1581; p < 0.001), but this difference was offset by a reduction of $US3774 (52%) in inpatient/outpatient service costs for olanzapine-treated patients in comparison with risperidone-treated patients ($US3516 vs $US7291, p = 0.083). Median cost findings were consistent with results observed using other robust measures of central tendency and provide conservative estimates of potential savings that may be obtained from olanzapine therapy. CONCLUSIONS: In this study, olanzapine-treated patients experienced clinical improvements that translated into savings in costs of care for both inpatient and outpatient services. These savings offset the difference in medication acquisition cost between olanzapine and risperidone.

Changes in perceived health and functioning as a cost-effectiveness measure for olanzapine versus haloperidol treatment of schizophrenia.

We utilize data from a large, double-blind, randomized clinical trial of treatment for schizophrenia to compare the effect of therapy with the second generation antipsychotic olanzapine versus therapy with the conventional agent haloperidol on the perceived functioning and well-being of patients over 1 year as measured by the Medical Outcome Study Short Form (SF-36). We also compare the total cost of care between the treatment groups over 1 year and combine cost and functional outcomes information to estimate the incremental cost-effectiveness of both therapies in this sample. Over 1 year of therapy, patients receiving olanzapine experienced a mean of 5.75 units greater improvement than did haloperidol-treated patients on the physical health and functioning factor of the SF-36 and 1.66 units greater improvement on the mental health and functioning factor. The mean annual total cost of care, including the cost of medication therapies, was $9386.87 less for olanzapine-treated patients than for haloperidol-treated patients. The incremental cost-effectiveness ratio for olanzapine versus haloperidol treatment indicated a savings of $1632.50 per unit of improvement in the SF-36 physical health and functioning score and a savings of $5654.74 per unit of improvement in the mental health and functioning composite. Improvements in perceived health and functioning were also associated with reduction in hospital costs in the full sample. These findings suggest that patient-centered measures of functioning such as the SF-36 are an important component of the evaluation of the cost-effectiveness of novel treatments for schizophrenia.

At what price significance? The effect of price estimates on statistical inference in economic evaluation.

Because data on resource utilization are now collected in many comparative trials of health interventions, statistical analysis of between-group differences in mean costs has become common. Statistical analyses of costs are generally performed conditional on a set of resource prices (or unit costs), thereby suppressing any uncertainty associated with those price estimates. Results presented here demonstrate that varying price estimates can have a non-negligible effect on statistical inference regarding between-group cost differences. Depending on the relative prices used in an analysis, between-group differences in total costs per patient may be either statistically significant or insignificant, regardless of whether differences in utilization of the underlying resources are statistically significant. These results highlight the importance of recognizing that evaluations based on patient-level economic data may be sensitive to assumptions regarding the values of unobserved variables, such as the relative prices of resources. Traditional methods of sensitivity analysis remain a valuable tool for analysing the implications of uncertainty around estimates of those unobserved variables.

Driver age and traffic citations resulting from motor vehicle collisions.

This paper is an initial effort to examine whether driver age is related to the likelihood of receiving a traffic citation as a consequence of a crash. All crashes involving two motor vehicles in Wisconsin, 1991 were examined; additional information on any injuries resulting from a crash were obtained from hospital discharge records. Controlling for a variety of driver, vehicle and crash-related factors, these data suggest that the likelihood of receiving a citation is an increasing function of driver age.

Older drivers and risk to other road users.

This paper examines the degree to which older drivers impose an "excess" risk of death or injury serious enough to require hospitalization on other road users; that is, the amount of risk older drivers impose on others above and beyond the amount imposed by drivers who are not yet old. A data set linking crash information from police accident reports to hospital discharge data in Wisconsin, 1991, was used to analyze excess risk associated with older drivers in two ways. First, the difference in the rate of serious injuries to other road users per 100 million driver age-group miles was used to estimate the total number of serious injuries resulting from the excess risk imposed on others by older drivers. Second, statistical models were used to infer the association between driver age and crash severity while conditioning on a variety of crash-specific information. Drivers aged 65-74 did not appear to impose excess risk of either deaths or injuries requiring hospitalization in either the aggregate or individual level analyses. Drivers aged 75 and over are associated with increased injuries to others, although the actual number is very small; the individual crash-level analysis suggests that a non-trivial part of the excess risk found in the aggregate analysis is a product of confounding.

Methodological issues in testing the hypothesis of risk compensation.

The hypothesis of risk compensation implies that persons experiencing a real or perceived change in the riskiness of an activity will alter their consumption of that activity to obtain a preferred combination of risk and reward. In evaluating whether individuals display compensating behavior in response to safety interventions, not all persons subject to the intervention will necessarily display compensating behavior, even if the hypothesis is correct: the hypothesis has testable implications only for the subset of persons subject to the intervention who perceive that their risk has changed. This paper argues that methodologies that include persons for whom the hypothesis has no testable implications (against a null hypothesis of no compensation effect) result in estimates of the compensation effect and test statistics which are biased towards zero. Previously published data on motor-vehicle-related injuries to cyclists and pedestrians in Britain before and after a mandatory safety-belt-use law went into effect were used to infer the size of this bias. In these data, the inclusion of persons for whom the hypothesis of risk compensation has no testable implications appears to have resulted in estimates of a risk-compensation effect which are too small by about half. This work suggests that the British data are consistent with a risk-compensation effect of 7-13 percent, and raises important methodological issues in testing the hypothesis of risk compensation.