Ganciclovir evaluation in AIDS patients with cytomegalovirus retinitis: a European study of treatment patterns and resource utilization.

OBJECTIVE: To describe the treatment patterns for intravenous ganciclovir induction and maintenance therapy in AIDS patients with cytomegalovirus (CMV) retinitis in five European countries and to investigate the anticipated impact of oral ganciclovir on resource utilization during maintenance. DESIGN: Study was a retrospective analysis based on a prospective randomized clinical trial (AV1034) comparing the efficacy of oral versus intravenous ganciclovir in CMV retinitis maintenance therapy. Resource utilization patterns for ganciclovir induction and maintenance, retinitis progression and management and treatment of adverse events were based on clinical trial data and interviews with local experts involved in treatment of patients with CMV retinitis. RESULTS: Oral ganciclovir maintenance was effective, although associated with a faster time to progression, compared to intravenous ganciclovir. There was considerable variation in the treatment patterns for induction with intravenous ganciclovir in the different countries. Most inductions were achieved with a central intravenous line, also used in subsequent intravenous maintenance therapy, usually performed on an outpatient or day care inpatient basis. Intravenous maintenance therapy was identified as a large resource utilization which would decrease considerably with the introduction of oral ganciclovir. In addition, decreased incidence of adverse side effects with oral ganciclovir would also lead to decreased resource use. CONCLUSIONS: Introduction of oral ganciclovir is expected to lead to significant reduction in resource use and may avoid the need for central line placement. This, and the lower incidence of adverse side effects, normally associated with intravenous ganciclovir, are also expected to lead to improvement in the patient's quality of life.

Methodological approaches to pharmaco-economics.

Due to the increased need for cost-containment policies, most decision makers are facing the issue of the efficiency of health care strategies. In this context, economic evaluation becomes a major instrument. However, the credibility of economic data depends on a number of methodological steps: selection of strategy of economic evaluation (cost/effectiveness, cost/benefit, generation of economic hypotheses, study design (cross-sectional, prospective, naturalistic), data collection (data-base, physicians), data analysis (costing, statistics). In this respect, the conduct of proper economic evaluation relies on a combination of expertise in clinical epidemiology as well as in health economics.

Measuring sensitivity in pharmacoeconomic studies. An integration of point-sensitivity and range-sensitivity.

The level of uncertainty with regard to the outcomes of pharmacoeconomic studies cannot be completely covered by the statistical methods routinely employed to handle uncertainty in clinical research. Sensitivity analysis is the most common methodology to deal with the extra uncertainty associated with pharmacoeconomics, and has also been incorporated in recent guidelines on healthcare evaluation. However, the execution of a sensitivity analysis and the interpretation of its results have not yet been standardised, which may lead to subjectivity and consequently weaken the value of economic evaluations. This article presents a method of dealing more systematically with uncertainty and eliminating potential bias in sensitivity analysis, with regard to the measurement of sensitivity and the comparison of the degree of sensitivity between variables. An assessment of the disadvantages of using slope as a measure of sensitivity leads to 2 types of sensitivity analyses (point-sensitivity and range-sensitivity), which are integrated into one method for the measurement of sensitivity.

A Markov process analysis comparing the cost effectiveness of maintenance therapy with citalopram versus standard therapy in major depression.

The objective of this study was to demonstrate the cost effectiveness of long term maintenance treatment with citalopram versus standard therapy (defined as short term antidepressant treatment) in patients with major depression in Germany. We chose doxepin, amitriptyline and trimipramine as standard therapy because these drugs are the leading antidepressants in that country. A Markov process analysis was used to model health status and economic outcomes as they accrued over a 1-year follow-up period. The main outcome measures were time without depression, direct costs and indirect costs (work days lost). All costs were in 1993 Deutsche marks. The clinical data were obtained from the published literature and US clinical practice guidelines; the associated unit costs of the medical resources used were derived from official German tariff lists. The results show that, compared with standard therapy, long-term maintenance treatment with citalopram is associated with a mean increase in time without depression of 7.9% (8.2 vs 7.6 months). The total costs of maintenance treatment with citalopram were substantially lower than with standard therapy (DM7985 vs DM11,948 per patient per year. In addition, both the direct and indirect costs of maintenance treatment with citalopram (DM3764 vs DM4221 per patient, respectively) were lower than with standard therapy (DM4577 vs DM7371 per patient, respectively). In conclusion, the study demonstrates that one year's maintenance treatment with citalopram is both more effective and less costly than standard therapy in the treatment of patients with major depression.

Differential costs of treatment of depression with SSRIs.

Although the field of economic analysis of mental health care is still in development, several issues are now well established. For example, it is generally accepted that the treatment costs for depression are significant, with estimates for the US ranging up to US$43·7 billion. This includes only US$12·4 billion for the costs of treating the patients with depression; the remaining costs are from lost working days, lost income due to suicides, and lost productivity. The high risk of recurrence and chronicity also leads to high direct health care costs. In particular, the frequent and long hospitalizations required for severe depression have an enormous impact in economic terms. The other main costs are related to drug and psychotherapy, and the treatment of side-effects, which are particularly pronounced with the tricyclic antidepressants. Preliminary analyses indicate that the differential tolerability of the current selective serotonin reuptake inhibitors (SSRIs) can also give rise to differences in total costs of treatment. Thus, it can be hypothesized that the relatively favourable side-effect profile of the SSRI fluvoxamine may have positive economic consequences, especially as it is one of the lower priced drugs in this class. Further research based on primary data is needed to substantiate these benefits.

Absorption enhancement of rectally infused cefoxitin sodium by medium-chain fatty acids in conscious rats: concentration-effect relationship.

The objective of this study was to assess the relative absorption promoting potency in terms of concentration-effect relationships of the medium-chain fatty acids hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid in conscious rats, using cefoxitin sodium as the rectally delivered model compound. Rectal uptake of cefoxitin, which was absorbed to a limited extent without enhancer (30 +/- 25%), proved to be significantly enhanced by 2.0 M sodium hexanoate, 0.69 M sodium octanoate, and 0.22 M sodium decanoate, resulting in mean bioavailabilities of 102 +/- 24, 68 +/- 25, and 68 +/- 10%, respectively. Thus, increasing fatty acid chain length results in increased enhancing potency from hexanoic acid to decanoic acid. However, using dodecanoate a statistically significant effect could not be reached, because of its limited aqueous solubility. Optimal chain length for absorption enhancement by medium-chain fatty acids is probably determined by interplay of intrinsic effects on mucosal permeability and solubility of the medium-chain fatty acid.

Economic analysis of antibiotic regimens used in the treatment pharyngitis: a prospective comparison of azithromycin versus roxithromycin.

The economic impacts in terms of cost and effectiveness (speed of resolution of symptoms) of 3- and 5-day courses of azithromycin and a 10-day course of roxithromycin were compared in a randomized, open study in patients with symptoms suggestive of beta-haemolytic streptococcal pharyngitis. Direct medical costs and absence from work were recorded and symptom scores and compliance were used to assess the effectiveness of therapies. Although no differences between treatment groups in terms of overall clinical response rates were detected 2 and 4 weeks after the start of treatment, more rapid resolution of symptoms was achieved with 3- and 5-day courses of azithromycin than with a 10-day course of roxithromycin. There was also a significant reduction in the time absent from work in the azithromycin treatment groups. The total costs of care over the 4-week evaluation period were lower for the 3- and 5-day azithromycin courses (US$193.60 and US$195.30 respectively) than for roxithromycin (US$202.10). The major cost components were absence from work (58.6%), visits to the physician (15.3%) and utilization of antibiotics (14.9%). Compliance was significantly better (P < 0.01) in patients prescribed azithromycin for 3 and 5 days (58.0% and 42.9% respectively) than in those who received roxithromycin (20.3%) and a significantly longer symptom-free period (P < 0.01) was reported in azithromycin- compared with roxithromycin-treated patients. These findings support the hypothesis that a 3- or 5-day course of azithromycin is as effective as a 10 day course of roxithromycin in the treatment of patients with pharyngitis and is associated with lower costs. Furthermore, azithromycin is associated with faster resolution of symptoms and improved patient compliance.