Impact of carbapenem resistance on clinical and economic outcomes among patients with Acinetobacter baumannii infection in Colombia.

Acinetobacter baumannii is a major cause of healthcare-associated infection, often affecting critically ill patients. The purpose of the study was to examine the associations of carbapenem resistance with mortality, length of hospital stay and hospital costs among patients infected with A. baumannii in intensive-care units (ICUs) in Colombia. A prospective, multicentre cohort study was conducted among 165 patients with A. baumannii infection admitted to ICUs between April 2006 and April 2010. Patients with carbapenem-resistant A. baumannii had higher risk of 30-day mortality than patients with carbapenem-susceptible A. baumannii in the univariate analysis (unadjusted hazard ratio = 2.12; 95% CI 1.14-3.95; p 0.018). However, carbapenem resistance was not significantly associated with risk of mortality (adjusted hazard ratio = 1.45; 95% CI 0.74-2.87; p 0.28) after adjusting for APACHE II score and other confounding factors. We did not find a significant difference in length of stay in ICU after the onset of infection between the two groups in the multivariate analysis (adjusted mean = 13.1 days versus 10.5 days; p 0.14). The average total cost of hospitalization among patients with carbapenem-resistant A. baumannii was significantly higher than that among patients with carbapenem-susceptible A. baumannii in the multivariate analysis (adjusted cost; US$ 11 359 versus US$ 7049; p <0.001). Carbapenem resistance was not significantly associated with mortality, though we are unable to rule out an increased risk due to the limited sample size. Carbapenem resistance was associated with an additional cost of hospitalization.

Composite endpoints in trials of type-2 diabetes.

Composite endpoints (CEPs) are being used more frequently as outcomes for trials of drugs in type-2 diabetes. We reviewed the literature to determine how CEPs have been used to date in trials of drugs for type-2 diabetes. A systematic search was undertaken on Medline, Embase and Cochrane databases and Clinicaltrials.gov for randomized controlled trials of currently marketed agents including SGLT-2 inhibitors (dapagliflozin), GLP-1 agonists (exenatide, liraglutide) and DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin and vildagliptin). CEPs used were identified as well as numbers and percentages of patients achieving each. Thirty-six studies were identified that reported results on ≥1 CEP; 15 different CEPs were reported (7 with 2 components, 8 with 3 components). All CEPs addressed goals recommended by the American Diabetes Association (ADA). All included HbA1c<7%; other endpoints measured weight, blood pressure and hypoglycaemic events. Results were obtained for CEPs from 6 months to 2 years. Rates of achieving CEPs decreased with increasing numbers of components and outcomes assessed. CEPs are becoming used as indicators of clinical outcomes in type-2 diabetes trials, but are still not common. More research is required to identify optimal CEPs. Standardization of outcomes and their reporting is needed.

Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: systematic review and meta-analysis.

Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. Controversy exists as to whether antimicrobial resistance increases the risk of mortality. We conducted a systematic review and meta-analysis to examine this association. We searched MEDLINE and EMBASE databases up to May 2013 to identify studies comparing mortality in patients with carbapenem-resistant A. baumannii (CRAB) vs. carbapenem-susceptible A. baumannii (CSAB). A random-effects model was used to pool Odds Ratios (OR). Heterogeneity was examined using I(2). We included 16 observational studies. There were 850 reported deaths (33%) among the 2546 patients. Patients with CRAB had a significantly higher risk of mortality than patients with CSAB in the pooled analysis of crude effect estimates (crude OR = 2.22; 95% CI = 1.66, 2.98), although substantial heterogeneity was evident (heterogeneity I(2) = 55%). The association remained significant in the pooled adjusted OR of 10 studies. Studies reported that patients with CRAB compared to patients with CSAB were more likely to have severe underlying illness and also to receive inappropriate empirical antimicrobial treatment, which increases the risk of mortality. Our study suggests that carbapenem resistance may increase the risk of mortality in patients with A. baumannii infection. However, cautious interpretation is required because of the residual confounding factors and inadequate sample size in most studies.

Haemoglobin A1c levels and subsequent cardiovascular disease in persons without diabetes: a meta-analysis of prospective cohorts.

AIMS/HYPOTHESIS: The aim of this meta-analysis was to determine the relationship between HbA(1c) levels and subsequent cardiovascular outcomes in individuals without diabetes. METHODS: We searched Medline, Embase and Scopus from initiation of the study until the end of 2009. One reviewer searched and another verified findings. Data were extracted by one reviewer and verified by another. We accepted prospective studies in any language reporting three or more quartiles for HbA(1c) levels. Within quartiles, authors must have presented both numbers of patient-years at risk and cardiovascular outcomes. Outcomes per person-time at risk were regressed on average HbA(1c) values using Poisson regression. We pooled ß coefficients using Cochran's semi-weighted (inverse variance) random-effects model. Study quality was assessed using the Downs-Black scale. RESULTS: We investigated 16 datasets (nine for total cardiovascular events and seven for death) from five papers with 44,158 patients (44% men) over 404,899 patient-years of follow-up. There were 1,366 cardiovascular deaths (3.1%; 3.37/1,000 person-years) and 2,142 cardiovascular events (4.9%; 5.29/1,000 person-years). The overall meta-analytic ß coefficients were 0.720 (95% CI 0.307-1.133) and 0.757 (95% CI 0.382-1.132) for cardiac death and events, respectively. Compared with the baseline value of 0.0427, an HbA(1c) level of 0.05 was associated with a relative risk for cardiovascular death of 1.13 (95% CI 1.05-1.21), a 0.06 value with 1.34 (95% CI 1.13-1.58), and a 0.07 HbA(1c) with relative risk 1.58 (95% CI 1.22-2.06). Results for total cardiovascular events were similar. The average study quality was 0.7 (70%). CONCLUSIONS/INTERPRETATION: We conclude that HbA(1c) was significantly associated with cardiovascular events and deaths in persons without diabetes.

Comparison of SSRIs and SNRIs in major depressive disorder: a meta-analysis of head-to-head randomized clinical trials.

CONTEXT: Controversy exists whether serotonin-norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVE: To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure. DATA SOURCES: Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007. STUDY SELECTION: Included studies were those head-to-head randomized trials comparing remission (HAMD-17 0.05). The OR (under ITT) was 1.27 (1.06-1.52 95% CI) favoring SNRIs. Meta-analytic remission rates were 48.5 +/- 3.2% and 41.9 +/- 4.2% for SNRIs and SSRIs, respectively. The meta-analytic difference in remission rates between drugs was 5.7% (P = 0.007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3.2% difference, P < 0.001). Dropout rates due to LoE were non-significant between studied groups (P > 0.05). CONCLUSIONS: Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.

Adverse effects of antidepressant use in pregnancy: an evaluation of fetal growth and preterm birth.

OBJECTIVE: To compare the rates of low birth weight, preterm delivery and small for gestational age (SGA), in pregnancy outcomes among women who were exposed and nonexposed to antidepressants during pregnancy. METHODS: At The Motherisk Program, we analyzed pregnancy outcomes of 1,243 women in our database who took various antidepressants during their pregnancy. Nine hundred and twenty-eight of these women and 928 nonexposed women who delivered a live born infant were matched for age, (+/-2 years), smoking and alcohol use and specific pregnancy outcomes were compared between the two groups. RESULTS: There were 82 (8.8%) preterm deliveries in the antidepressant group and 50 (5.4%) in the comparison group. OR: 1.7 (95% CI: 1.18-2.45). There were 89 (9.6%) in the antidepressant group and 76 (8.2%) in the comparison group who delivered babies evaluated as SGA; OR: 1.19 (95% CI: 0.86-1.64). The mean birth weight in the antidepressant group was 3,449+/-591 g and 3,455+/-515 g in the comparison group (P=.8). CONCLUSION: The use of antidepressants in pregnancy appears to be associated with a small, but statistically significant increased rate in the incidence of preterm births, confirming results from several other studies. It is difficult to ascertain whether this small increased rate of preterm births is confounded by depression, antidepressants, or both. However, we did not find a statistically significant difference in the incidence of SGA or lower birth weight. This information adds to limited data available in the literature regarding these outcomes following the use of antidepressants in pregnancy.

Effect of selected antihypertensives, antidiabetics, statins and diuretics on adjunctive medical treatment of glaucoma: a population based study.

BACKGROUND: The prevalence of open angle glaucoma increases with age, with many patients also receiving medications for non-ocular systemic diseases. Little is known about how systemic medications impact on the need for adjunctive therapy with prostaglandin analogues (PGA). OBJECTIVES: To evaluate whether systemic medications for hypertension, cholesterol, or glucose influence the need for adjunctive intraocular pressure (IOP) lowering medications in patients using PGAs. METHODS: Pharmaceutical records from the Québec prescription database provided a sample of patients receiving prescriptions for bimatoprost, latanoprost, or travoprost, from which subjects receiving > or =1 prescription for antihypertensives, antidiabetics. diuretics, and statins were identified. Chi-square tests compared proportions using PGAs to those using PGAs + adjunctive therapy, based on the use or non-use of systemic medications; a logistic regression was performed post hoc to adjust for gender and age. RESULTS: Of the 8548 evaluated patients (all using PGAs); 2934 (34.3%) took none of the studied systemic drugs. For the 5614 patients taking systemic medications, significantly fewer (p < 0.001) required an additional IOP lowering medication if taking a systemic antihypertensive medication. The use of a statin or a diabetic medication, alone or in combination, in addition to a PGA, made no significant difference in the need for adjunct glaucoma therapy. Individual drugs associated with significantly less utilization of adjunctive glaucoma medications were calcium-channel blockers, angiotensin-converting enzyme (ACE), and combination antihypertensive therapies. DISCUSSION: A profound association between systemic antihypertensive use and a reduced need for adjunct topical IOP lowering medications in patients using the same prostaglandin analogue for at least one year was found. LIMITATIONS: The use of a prescription claims database without patient compliance or patient outcomes may not reflect actual patient medication use. In addition, these findings may not be applicable to all patients initiating prostaglandin analogues. CONCLUSIONS: In this real-world population-based evaluation, a significant association exists between using systemic antihypertensive medications and reduced use of adjunctive IOP lowering therapies. These results confirm findings from previous studies suggesting an IOP lowering effect with systemic agents or some synergy with topical therapies.

The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events.

OBJECTIVE: To evaluate the safety of biological treatments for rheumatoid arthritis (RA) using results from randomised controlled trials (RCT). METHODS: The literature was searched to December 2007 for RCT evaluating inhibitors of tumour necrosis factor alpha (anti-TNF) for RA. Safety data were abstracted and risk estimates were calculated using three approaches, meta-analysis with and without adjustment for exposure and simple exposure-adjusted pooling. RESULTS: Eighteen randomised trials involving 8808 RA subjects were included. Treatment with recommended doses of anti-TNF found no increase in the odds of death (odds ratio (OR) 1.39; 95% CI 0.74 to 2.62), serious adverse events (OR 1.11; 95% CI 0.94 to 1.32), serious infection (OR 1.21; 95% CI 0.89 to 1.63), lymphoma (OR 1.26; 95% CI 0.52 to 3.06), non-melanoma skin cancers (OR 1.27; 95% CI 0.67 to 2.42) or the composite endpoint of non-cutaneous cancers plus melanomas (OR 1.31; 95% CI 0.69 to 2.48) when evaluated using the unadjusted meta-analytic method. Risk estimates were similar with the other methods. For subjects who received two to three times the recommended doses of anti-TNF the risk of serious infection was increased with the unadjusted meta-analytic and pooled analysis, (OR 2.07; 95% CI 1.31 to 3.26) and (risk ratio (RR) 1.83; 95% CI 1.18 to 2.85), respectively, but not increased in the exposure-adjusted meta-analysis (RR 1.99; 95% CI 0.90 to 4.37). Meta-regression identified that the risk of serious infection with anti-TNF therapy decreases with increasing trial duration (p = 0.035). CONCLUSION: Meta-analytic and exposure-adjusted pooled analyses on over 8800 RA subjects in RCT treated over an average of 0.8 years did not identify an increased risk of serious adverse events with recommended doses. High-dose anti-TNF therapy was associated with a twofold increase in the risk of serious infections.

Existence and severity of nausea and vomiting in pregnancy (NVP) with different partners.

Nausea and vomiting in pregnancy (NVP) is a widespread condition which may impact on the quality of life. Our objective was to understand the role of the placenta, which is mostly made up of fetal cells, in NVP. We examined the relationship between NVP and different partners in the same women. If a paternal contribution to placental function affects NVP, this could shed light on the genetics of the most common condition in pregnancy. We assessed nausea and vomiting in two groups of 100 women counselled by the Motherisk Program in Toronto, using a score from 1 (none) to 5 (severe with hyperemesis). The first group had >/=2 pregnancies with the same partner; the second had >/=2 pregnancies with >/=2 partners. Scores were averaged across pregnancies, partners and overall. Regression was used to separate numbers of pregnancies and partners. The 100 women having one partner reported an average score of 3.1 in their 261 pregnancies, which was similar to the score of 3.0 in 319 multi-partner pregnancies (p = 0.508). There was a positive (but weak) correlation between gravidity and NVP score (Spearman's rho = 0.21, p < 0.001) but not between partner and score. There was a linear increase in scores from 2.7 in the first pregnancy, to 4.0 in the tenth (rho = 0.948, p < 0.01). After controlling for number of pregnancies, number of partners was not associated with NVP scores (p = 0.302). NVP severity tends to increase with each successive pregnancy. Different partners have no impact on NVP severity.

Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis.

Prenatal supplementation of folic acid has been shown to decrease the risk of several congenital malformations. Several studies have recently suggested a potential protective effect of folic acid on certain pediatric cancers. The protective role of prenatal multivitamins has not been elucidated. We conducted a systematic review and meta-analysis to assess the potential protective effect of prenatal multivitamins on several pediatric cancers. Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases were searched for studies published in all languages from 1960 to July 2005 on multivitamin supplementation and pediatric cancers. References from all articles collected were reviewed for additional articles. Two blinded independent reviewers assessed the articles for inclusion and exclusion. Rates of cancers in women supplemented with multivitamins were compared with unsupplemented women using a random effects model. Sixty-one articles were identified in the initial search, of which, seven articles met the inclusion criteria. There was an apparent protective effect for leukemia (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.50-0.74), pediatric brain tumors (OR=0.73, 95% CI=0.60-0.88) and neuroblastoma (OR=0.53, 95% CI=0.42-0.68). In conclusion, maternal ingestion of prenatal multivitamins is associated with a decreased risk for pediatric brain tumors, neuroblastoma, and leukemia. Presently, it is not known which constituent(s) among the multivitamins confer this protective effect.

Cost-effectiveness of treprostinil versus epoprostenol in patients with pulmonary arterial hypertension: a Canadian analysis.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with substantial morbidity and mortality, exerting a tremendous health and economic impact on patients. In the present study, an economic evaluation of patients with PAH treated with either treprostinil or epoprostenol was performed. METHODS: A cost-minimization analysis (a cost-effectiveness subtype) was performed under the assumption that treprostinil and epoprostenol were clinically equivalent. Two cohorts of 60 patients, treated with treprostinil or epoprostenol, were evaluated over three years by using a dynamic spreadsheet model. The evaluation included both the provincial ministries of health and societal perspectives. Resource valuation data for drugs, medical supplies, consultations, and surgical and diagnostic procedures were obtained from standard lists. Costs of hospitalizations and adverse events were derived from published sources. Additional outpatient costs were considered equivalent and, therefore, were excluded from the analysis. Costs are presented in 2003 Canadian dollars discounted at 3%. Sensitivity analyses were performed testing all uncertainties in the model. RESULTS: In the base-case analysis (over three years), treatment with treprostinil resulted in an expected savings of 2,610,642 US dollars and 2,781,438 US dollars from the ministries of health and societal perspectives, respectively. On a per-patient level, treatment with treprostinil resulted in an average annual savings of 14,504 US dollars and 15,452 US dollars, respectively. The greatest savings with treprostinil came from reduced hospitalizations. Multivariate sensitivity analyses estimated cost savings in greater than 99% of scenarios. CONCLUSIONS: By initiating and continuing treprostinil treatment over a three-year period, the economic burden associated with PAH may be reduced compared with epoprostenol treatment.

Cost-minimization analysis of treprostinil vs. epoprostenol as an alternate to oral therapy non-responders for the treatment of pulmonary arterial hypertension.

INTRODUCTION: Idiopathic pulmonary arterial hypertension (IPAH) is associated with substantial morbidity and mortality. Treprostinil was compared to epoprostenol for the economic impact of treating IPAH patients who failed or were not candidates for bosentan. METHODS: The model was a cost-minimization analysis, assuming clinical equivalence was achieved by proper dosing of both drugs, in terms of survival and surrogate measures. Two theoretical cohorts of 270 patients were treated with subcutaneous treprostinil and intravenous epoprostenol, and were evaluated over 3 years using a spreadsheet model. Annual survival rates were estimated for the cohorts so that at endpoint 114 (42%) patients survived in both groups. The model utilized resource valuation data for medication and supply costs from Medicare; hospital, consultation, surgical, and diagnostic procedural fees from North Carolina hospitals; and costs to treat adverse events from published sources. Costs were obtained from standard lists and were presented as 2003 US dollars, discounted at 3%. Sensitivity analyses were performed testing all model uncertainties. RESULTS: In the base case analysis, treprostinil demonstrated savings of 22,701 US dollars and 37,433 US dollars per patient over 1- and 3-year time horizons, respectively. The greatest savings came from reduced or minimal hospitalizations attributed to the dose titration and treatment of adverse events, such as sepsis, associated with epoprostenol and its delivery system. Probabilistic sensitivity analyses resulted in average 3-year cost-savings of 41,051 US dollars (Standard Deviation = 13,902 US dollars) per patient. CONCLUSIONS: By initiating and continuing treatment with treprostinil over a 3-year period, the economic burden associated with IPAH may be reduced compared to treatment with epoprostenol. The greatest saving with treprostinil was attributed to decreased sepsis.

Cost effectiveness of duloxetine compared with venlafaxine-XR in the treatment of major depressive disorder.

PURPOSE: To determine the cost effectiveness of duloxetine, a new serotonin norepinephrine reuptake inhibitor, when compared with venlafaxine-XR in treating major depressive disorder. METHODS: A cost effectiveness analysis, using a decision tree modelled outpatient treatment over 6 months. Analytic perspectives were those of society (all direct and indirect costs) and the Ministry of Health of Ontario (MoH) as payer for all direct costs. Rates of success and dropouts were obtained from a meta-analysis of randomized placebo-controlled trials. Costs were taken from standard lists, adjusted to 2005 Canadian dollars; discounting was not applied. One-way sensitivity analyses were performed on monthly acquisition costs and success rates; Monte-Carlo analysis examined all parameters over 10000 iterations. RESULTS: From both perspectives, outcomes all numerically favoured venlafaxine-XR (Expected success = 53% and 57%; symptom-free days [SFDs] = 52.72 and 57.03 for duloxetine and venlafaxine-XR, respectively). Total expected costs/patient treated were, Can dollar 7081 and Can dollar 6551 (MoH), Can dollar 20987 and Can dollar 19 997 (societal perspective), for duloxetine and venlafaxine-XR, respectively. Expected costs/SFD were Can dollar134 and Can dollar 115 (MoH) and Can dollar 398 and Can dollar 351 (societal viewpoint) for duloxetine and venlafaxine-XR, respectively. Although results were sensitive to changes in success rate within the 95% CI, Monte-Carlo analyses using the ICER (incremental cost effectiveness ratio) as outcome found venlafaxine-XR was dominant in approximately 78% of scenarios in both perspectives. CONCLUSIONS: Differences in pharmacoeconomic outcomes found were modest, but in all cases, favoured venlafaxine-XR over duloxetine. Therefore, a possible advantage may exist at the population level in the treatment of major depressive disorder in Canada. Ultimately, a head to head study of the two drugs would be needed to confirm these findings.

Use of antidepressants by pregnant women: evaluation of perception of risk, efficacy of evidence based counseling and determinants of decision making.

BACKGROUND: The World Health Organization predicts that by 2012, depression will be the number one disease in the world. Thus, many women who become pregnant will require treatment with antidepressants. We are aware that women and their health care providers remain hesitant to prescribe and take these drugs during pregnancy, despite evidence of the relative safety. OBJECTIVES: 1) To determine perception of risk of antidepressant drugs by pregnant women with depression, 2) to determine the efficacy of evidence-based counseling, and 3) to identify determinants that influence women in their decision making regarding the continuation/discontinuation of antidepressants during pregnancy. METHODS: Women who called The Motherisk Program requesting information about the safety of an antidepressant during pregnancy were compared with two other groups: 1) Women who called about antibiotic use (i.e., non-teratogenic drugs used short-term) and 2) women who called about gastric medications (i.e., non-teratogenic drugs used long-term). Their perception of risk was measured before and after evidenced-based information was given and determinants of decision making was also evaluated. RESULTS: We recruited 100 women taking antidepressants during pregnancy and 100 in each comparison group. Despite receiving evidence-based reassuring information, 15% of antidepressant users, compared to 4% using gastric drugs and 1% using antibiotics, chose to discontinue their medication. The main determinants of decision making were based on: information received prior to calling Motherisk, family and friends advice, the internet, sequence of advice given and if a women was undecided at the time of call. CONCLUSIONS: Women continue to fear taking antidepressants during pregnancy, more so than non psychiatric drugs, however, evidence based counseling can lower this fear, although not totally. Deciding whether to continue to take a medication or not during pregnancy, is a complex decision for women and their healthcare providers to make.

Cost of severe haemophilia in Toronto.

Our objective was to determine costs and trends in treating boys with severe haemophilia A before our centre routinely used prophylaxis. One reviewer extracted data from patient charts to determine resource consumption for 17 boys with severe haemophilia A from 1978 to 1998 at Toronto's Hospital for Sick Children. Resources included factor concentrate, doctors and health care professionals (physiotherapists/social workers), tests (laboratory, radiological and diagnostic) and hospitalizations. Subgroup analysis on those patients infected with HIV and/or hepatitis were also performed. Costs in Canadian Dollars were taken from standard lists and discounted at 3%. Total average cost (range) 62 292 dollars (3339-121 738) per year patient(-1); the largest fraction, 59 910 dollars (3103-119 480), 96.2% was accounted for by factor VIII. Hospitalizations accounted for 1832 dollars (0-5217) per patient year(-1) including drugs, nursing care and stay. Doctor and health care professionals visits averaged 252 dollars (36-462) and 72 dollars (0-175) per patient year(-1), laboratory and other tests cost 201 dollars (22-377) and 26 dollars (2-60) per patient year(-1), respectively. The average number of bleeds was 12.9 (2.0-22.0) per patient year(-1), decreasing since 1977 by 0.68 per patient year(-1) (R(2) = 0.56). Hospitalizations averaged 0.22 (0-4) per patient year(-1), lasting 2.3 days. From 1984, hospitalizations decreased by 0.025 patient(-1) year(-1) (R(2) = 0.76). Concurrently, the average treatment costs increased by 5456 dollars patient(-1) year(-1) (R(2) = 0.81). Clotting factor concentrate cost per patient increased by 5521 dollars year(-1) (R(2) = 0.82). Patients with virally transmitted diseases had considerable higher costs. The cost per year was substantial. Costs increased with virally transmitted diseases. Number of bleeds and hospitalizations over the period of study decreased and costs increased because of factor use in secondary prophylaxis.

Pharmacoeconomic evaluation of clozapine in treatment-resistant schizophrenia: a cost-utility analysis.

The high costs and efficacy of clozapine warrant a systematic pharmacoeconomic evaluation to assess its relative cost-utility compared with that of older antipsychotic therapies. An economic analysis of clozapine consisted of a meta-analysis and a cost-utility analysis. Clozapine was compared with haloperidol and chlorpromazine. An incidence-based deterministic decision analysis was used to model the management of chronic schizophrenia over one year. Probabilities of clinical outcomes were obtained from a random effects, single arm meta-analysis. Utility weights were evaluated in a cohort of patients by using a standard gamble methodology. A government payer perspective was adopted for this analysis. Clozapine was the dominant therapy in this analysis because it was associated with the lowest overall expected cost and highest expected number of quality-adjusted life years (QALYs). Compared with chlorpromazine, clozapine might save $38,879/year while producing 0.04 more QALYs. This analysis was limited in that studies were of short duration, the sample size for health utility analysis was small and the analysis was based on a model. Clozapine appears to be a very cost effective therapy in patients with treatment-resistant schizophrenia compared with haloperidol and chlorpromazine.