Elicitation of utility scores in Canada for immune thrombocytopenia treated with romiplostim or watch and rescue.

OBJECTIVES: The objective of this study was to obtain utilities, or preference-based quality-of-life values, from the Canadian general public, for potential health states experienced by immune thrombocytopenia (ITP) patients receiving either romiplostim (a new thrombopoietin mimetic agent) or 'watch and rescue' therapy. Utilities are needed to conduct a cost-utility analysis of romiplostim for formulary and reimbursement decisions. METHODS: An electronic Time Trade-off (TTO) survey was developed and administered to a sample of the general public in Canada, with 12 distinct health states derived from two randomized clinical trials of romiplostim vs watch and rescue treatment. Two pilot tests assessed interpretability and respondent burden. In the final survey, each subject was administered the TTO for four randomly-selected health states. Descriptive statistics were computed for utility scores, and differences between health states were evaluated with an analysis of variance model. RESULTS: Eight hundred and twenty-one adults completed the TTO survey. Mean age was 36.4 (SD = 15) years; 63% were female. Mean (SD) utility scores ranged from 0.476 (0.271) for the most severe health state (significant bleeding) to 0.633 (0.282) for the least severe health state depicting successful treatment with romiplostim. Statistical significance was found on the mean difference between the most severe health state and five other health states (p < 0.05). After adjusting utilities for matching Canadian demographic parameters, no substantial difference was found between original utility scores and adjusted scores. CONCLUSIONS: This study provides evidence of the Canadian general public's preference for 12 ITP health states pertaining to romiplostim treatment or watch and rescue. This study had a number of limitations, the main ones being the lack of perfect match in demographics between this sample and the Canadian population, as well as the fact that the scenario descriptions were based on both published literature and expert opinion. Despite those limitations, the obtained utility scores may be used in cost-utility models of romiplostim as a treatment for ITP patients in Canada.

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.

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.

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.

Examining the Saskatchewan health drug database for antidepressant use: the case of fluoxetine.

OBJECTIVE: To examine the use of fluoxetine in an adult population in Saskatchewan. METHODS: All adults in the Saskatchewan health care databases who had begun fluoxetine therapy between January 1992 and June 1996 and had not received an antidepressant in the six months before the index fluoxetine prescription were identified. Fluoxetine use for the subsequent six-month period was examined. The rates of completion of six months of fluoxetine, rates of stopping, switching to another serotonin-selective reuptake inhibitor (SSRI) or other class of antidepressant, resumption of fluoxetine, as well as average dosages taken and mean duration of therapy were determined. Rates were summarized as means with standard deviation. RESULTS: Data were obtained for 11,322 subjects, of whom 68.2% were women; 17.4% were 65 years of age or older. The average prescribed daily dose of fluoxetine was 22.5 mg (SD=21.7) and the average duration was 88.1 days (SD=57.2). Only 18.9% of patients filled prescriptions for six months, 7049 (62.3%) stopped fluoxetine at least once for one month or more, and 17.3% were titrated to a higher dose, on average 71 days (SD=44) after the initiation of fluoxetine. The proportion of patients switching to another antidepressant was 13.6% (3.3% to another SSRI, 10.3% to other classes), after a mean of 69 days (SD=51) of fluoxetine treatment. CONCLUSIONS: The authors' data suggest that there is a potential underutilization of fluoxetine in the study population. Further research may be warranted to determine the proportion of depressed patients in this population and to better understand the stop-switch-resume pattern of antidepressant use.

Clinical and economic factors in the treatment of behavioural and psychological symptoms of dementia.

The prevalence of behavioural and psychological symptoms of dementia (BPSD) exceeds 50%. They cause distress to patients and caregivers, increase resource utilisation of various kinds, and form a high risk for accelerated psychiatric care through institutionalisation. Although evidence for current pharmacological treatment is not strong and the construct of BPSD is still not very clear, future aspects of treatment of BPSD may be positive. If we look at overall success rates of the antipsychotics, the traditional antipsychotics have the highest combined success rate of 63.1%, whereas the novel antipsychotics have an overall success rate of 56.1%. Haloperidol is the drug with the highest success rate of 65.4%, although this drug is associated with parkinsonian adverse drug reactions. Newer antipsychotics show promise in treating BPSD, but more convincing evidence (e.g. from randomised clinical trials) is required. We provide an overview of the clinical, epidemiological and economic aspects of BPSD and a review of the available literature on their pharmacological treatment. Although only 1 pharmacoeconomic study has been conducted on BPSD, it seems likely that these manifestations drastically increase the burden of dementia.

Economic evaluation of a new acellular vaccine for pertussis in Canada.

OBJECTIVE: Pertussis is a highly contagious infection affecting mainly children. Acellular pertussis vaccines were recently introduced in Canada based on evidence of improved safety and efficacy over whole cell vaccines, the current standard of care. The following study reports the economic impact of replacing the whole cell vaccine (wP) by a new acellular vaccine (aP) in the Ontario pertussis immunisation programme. DESIGN: For a hypothetical cohort of 100,000 children from birth to the age of 8 years, the costs and consequences of pertussis vaccination with either aP or wP were compared. A decision analytical model was constructed for vaccine delivery, treatment of pertussis cases and vaccine adverse events, with analyses from the viewpoints of the Ontario Ministry of Health and society. MAIN OUTCOME MEASURES AND RESULTS: The main outcomes were expected number of pertussis cases, hospitalisations, and workdays lost by parents. Data on vaccine effectiveness, pertussis incidence, and other parameters used in the model were from published literature. Costs were discounted at 5%, and extensive sensitivity analyses were undertaken. Over 8 years, in a cohort of 100,000 children, the introduction of aP would prevent 10,500 cases of pertussis, avoiding 504 hospital admissions and 73,500 days of work absence. For Ontario, healthcare cost savings over the same period would amount to 275,585 Canadian dollars ($Can), and societal savings to $Can9,752,864

Pharmacotherapies for attention-deficit/hyperactivity disorder: expected-cost analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood neurobehavioral disorder characterized by inattention, hyperactivity, and impulsivity. Prevalence estimates in elementary school children generally range from 3% to 8%. ADHD is frequently treated with psychostimulant medications, which have been shown to improve both cognitive and behavioral outcomes for most children. OBJECTIVE: The goal of this study was to estimate the total expected costs for the treatment and management of school-age children with ADHD using 6 commonly prescribed pharmacotherapies: methylphenidate immediate-release/extended-release (MPH IR/ER), methylphenidate immediate-release (MPH IR), Metadate CD (branded MPH IR/ER), Concerta (branded MPH ER), Ritalin (branded MPH IR), and Adderall (a combination of dextroamphetamine and amphetamine salts). METHODS: A literature review and clinical assessment using a 27-question survey instrument were used to capture information on the clinical characteristics of ADHD, including common treatment regimens, clinical management of patients, pathways of care, and components of care. A meta-analysis provided response rates for 3 commonly used pharmacotherapies: Metadate CD, MPH IR, and Adderall. Information from the clinical assessment and the meta-analysis were used to populate a decision-analytic model to compute total expected cost for each comparator. RESULTS: The average total annual expected cost per patient was $1,487 for Metadate CD, $1,631 for Concerta. $1,792 for MPH IR/ER, $1,845 for MPH IR, $2,080 for Ritalin, and $2,232 for Adderall. CONCLUSIONS: Metadate CD had the lowest total expected cost and Adderall had the highest total expected cost among the ADHD pharmacotherapies evaluated. The differences were attributable to differences in drug-acquisition costs and the need for in-school dosing of twice-daily and thrice-daily medications.

Meta-analysis of the effect of latanoprost and brimonidine on intraocular pressure in the treatment of glaucoma.

OBJECTIVE: The purpose of this study was to indirectly quantify and compare the intraocular pressure (IOP)-lowering effects of latanoprost and brimonidine eye drops at baseline and after 3 and 6 months in the treatment of primary open-angle glaucoma. METHODS: This meta-analysis combined data from all randomized controlled trials comparing the effects on IOP of latanoprost and brimonidine treatment in adults with a baseline IOP > or =20 mm Hg. MEDLINE and EMBASE were searched for reports of the ophthalmic administration of either drug versus the other, placebo, or active therapy. Included studies reported IOP as either means or differences (with SD or SE) and sample sizes. A random-effects model was used to pool data within each drug group. As a proxy for success rates, area under the curve (AUC) was calculated for the proportion of patients having an IOP <20 mm Hg. RESULTS: One hundred fifty-five articles reporting on 158 trials were identified; 147 papers were rejected (141 were not randomized controlled trials, 5 were duplicates, and 1 had nonextractable data), leaving 9 trials from 8 articles. A total of 2152 patients were included in the meta-analysis: 597 received latanoprost, 571 received brimonidine, and the remainder received timolol or betaxolol. Baseline IOPs were similar in patients randomized to latanoprost or brimonidine (25.3 and 24.6 mm Hg, respectively). At 3 months, latanoprost and brimonidine reduced IOP by 8.4 and 6.5 mm Hg, respectively (P = 0.004 latanoprost vs brimonidine), and at 6 months by 8.0 and 6.2 mm Hg, respectively (P = 0.045). AUC was 0.834 and 0.675 at 3 months for latanoprost and brimonidine, respectively, and 0.817 and 0.715 at 6 months, respectively (both, P < 0.001). CONCLUSIONS: This indirect comparison of data from the available randomized clinical trials showed latanoprost to be statistically superior to brimonidine in reducing IOP in adults with primary open-angle glaucoma. Additional long-term, head-to-head comparisons of the efficacy, safety, and cost of latanoprost and brimonidine are needed to support and supplement these findings.

Economic evaluation of donepezil for the treatment of Alzheimer's disease in Canada.

BACKGROUND: Donepezil is a new drug recently approved in the United States and Canada for the treatment of Alzheimer's disease (AD). We estimated the cost-effectiveness of donepezil 5 mg daily as an adjunct to usual care in the management of persons with mild-to-moderate AD defined as a Mini-Mental Health State Examination (MMSE) score in the range 10 to 26. METHODS: Treatment effect data as MMSE change-over-baseline scores were obtained from a 30-week placebo-controlled trial of donepezil. MMSE scores beyond observed trial data were estimated using a Markov model with 10 cycles of 24 weeks based on the placebo MMSE progression observed in the trial. Data from AD subjects in the Canadian Study of Health and Aging were used to estimate costs of nursing home care, community services, medications, and caregiver time as a function of MMSE score. A clinic-based cohort study from Alberta was used to estimate the distribution of AD patients by MMSE score presenting for treatment. The effectiveness measure for the economic model was expected time (over 5 years) spent with nonsevere AD (MMSE > or = 10). RESULTS: Over 5 years of treatment, donepezil is predicted to reduce health care costs by CA$929 per patient but increase caregiver time costs by CA$48 per patient for an overall cost saving to society of CA$882 per patient. Patients not receiving donepezil are predicted to spend 2.21 years of the 5 years in nonsevere AD compared with 2.41 years for treated patients (a gain of just over 2 months). Sensitivity analysis reveals that cost savings per patient increase if more AD patients are assumed to survive to 5 years; however, if donepezil treatment continues when patients' MMSE score falls below 10, the incremental cost is higher for treatment at CA$1554 per patient. CONCLUSION: Based on the limited available data, our model predicts that the use of donepezil for mild-to-moderate AD in Canada is associated with lower 5-year costs and less time spent with severe AD when compared with the alternative of usual care with no donepezil therapy. As more reliable long-term data become available, these predictions should be confirmed and/or updated.

The Canadian experience with risperidone for the treatment of schizophrenia: an overview.

OBJECTIVE: To summarize published data to date by Canadian authors and from Canadian sources on risperidone, a novel neuroleptic indicated in the management of schizophrenia and related psychotic disorders. It was introduced in Canada in 1993. DATA SOURCES: A MEDLINE search was performed using "risperidone" as a keyword. Three Canadian journals were also searched manually. STUDY SELECTION: Articles published between January 1991 and June 1996 by Canadian authors or involving Canadian patients. DATA EXTRACTION: Retrieved articles were categorized according to data on efficacy, safety, resource use/economics and other miscellaneous aspects. Articles were abstracted and summarized. Some non-Canadian sources were used for comparison. DATA SYNTHESIS: The initial Canadian multicentre trial found resperidone (6 mg daily) to be superior to haloperidol (20 mg daily) in reducing positive and negative symptoms, with fewer extrapyramidal side effects (EPS). Various case reports have extended both the clinical use and safety profile of risperidone, while neuro-imaging studies have tried to clarify its mechanism of action. Economic studies suggest substantial cost benefits due to prevention of hospitalization as well as improvement in quality of life. CONCLUSIONS: Canadian research has contributed considerably to the current knowledge regarding risperidone. Future studies, both controlled and naturalistic, will need to focus on comparisons with the various new compounds now available.

Relation between severity of Alzheimer's disease and costs of caring.

BACKGROUND: Data from the Canadian Study of Health and Aging (CSHA) were used to examine the relation between severity of Alzheimer's disease, as measured by the Mini-Mental State Examination (MMSE), and costs of caring. METHODS: The CSHA was a community-based survey of the prevalence of dementia, including subtypes such as Alzheimer's disease, among elderly Canadians. Survey subjects with a diagnosis of possible or probable Alzheimer's disease were grouped into disease severity levels of mild (MMSE score 21-26), mild to moderate (MMSE score 15-20), moderate (MMSE score 10-14) and severe (MMSE score below 10). Components of care available from the CSHA were use of nursing home care, use of medications, use of community support services by caregivers and unpaid caregiver time. Costs were calculated from a societal perspective and are expressed in 1996 Canadian dollars. RESULTS: The annual societal cost of care per patient increased significantly with severity of Alzheimer's disease. The cost per patient was estimated to be $9451 for mild disease, $16,054 for mild to moderate disease, $25,724 for moderate disease and $36,794 for severe disease. Institutionalization was the largest component of cost, accounting for as much as 84% of the cost for people with severe disease. For subjects living in the community, unpaid caregiver time and use of community services were the greatest components of cost and increased with disease severity. INTERPRETATION: The societal cost of care of Alzheimer's disease increases drastically with increasing disease severity. Institutionalization is responsible for the largest cost component.

Meta-Analyses of Cisapride, Omeprazole and Ranitidine in the Treatment of GORD: Implications for Treating Patient Subgroups.

OBJECTIVE: Meta-analyses of efficacy results reported in trials of the pharmacological treatment of gastro-oesophageal reflux disease (GORD) with cisapride, omeprazole or ranitidine were performed using randomised, double-blind studies identified by a Medline search covering the years 1984 to 1995. RESULTS: The overall order of efficacy following 12 weeks of acute treatment was omeprazole 40 mg/day (95% cured) > ranitidine 600 mg/day (81% cured) > cisapride 40 mg/day or ranitidine 300 mg/day (approximately 60% cured). However, important differences emerged regarding efficacy in mild versus severe GORD, and in the frequency of relapse. In mild GORD, the cure rate with cisapride 40 mg/day was greater than the cure rate with ranitidine 300 mg/day (56 vs 38%, respectively), and the cure rate with cisapride 80 mg/day was similar to the cure rate with omeprazole 20 mg/day (82 vs 75%, respectively). In severe GORD, the cure rate with cisapride 80 mg/day was half that of omeprazole 20 mg/day (43 vs 87%, respectively) and comparable with that of ranitidine 300 mg/day (50%). Among patients treated acutely with omeprazole, 6-month relapse rates were 17% with omeprazole 20 mg/day maintenance therapy, but 76 to 80% without maintenance therapy. Among patients treated acutely with cisapride, 6-month relapse rates were 33% with 20 mg/day maintenance therapy and only 40% without maintenance therapy, which compare favourably with those following 6 months' maintenance therapy with ranitidine 300 mg/day (49%). CONCLUSION: These results indicate that omeprazole is clearly the treatment of choice for severe GORD, suggest that cisapride may be the treatment of choice for mild GORD, and indicate that either of these two treatments is superior to ranitidine for the prevention of relapse. Further comparative clinical studies are needed, designed specifically to delineate the most appropriate drug therapy for various subgroups of GORD patients.

Quality assessment of economic evaluations published in PharmacoEconomics. The first four years (1992 to 1995).

Our objective was to assess the quality of reporting of original economic research articles in PharmacoEconomics from inception to the end of 1995, in order to identify areas of strength and weakness, and analyse trends over time. Each regular issue of the journal was examined for original economic evaluations. Accepted articles were categorised by study type and by year of publication. A previously developed 13-item quality-scoring checklist was applied. The maximum possible score that an article could be assigned was 4.0. Quality scores were analysed over time and by study type. 54 articles were identified for analysis. Mean overall score (OS) ranged from a minimum of 1.80 to a maximum of 3.75, with a mean OS of 3.01 [standard deviation (SD) = 0.47]. The item with the highest mean score was the 'definition of study aim' (mean OS = 3.46, SD = 0.69). The item with the lowest score was 'ethical problems discussed and identified' (mean OS = 1.44, SD = 0.92). Only 4 items on the checklist had mean scores lower than 3.0. No significant time trend was apparent for OS (R2 = 0.002). Cost-benefit (mean OS = 3.25, SD = 0.85, n = 5), cost-effectiveness (mean OS = 3.11, SD = 0.97, n = 27), and cost-utility (mean OS = 3.29, SD = 0.93, n = 6) analyses had mean scores significantly higher than cost-analysis/cost-of-illness studies (mean OS = 2.51, SD = 1.14, n = 8). The mean OS for cost-minimisation studies was 2.74 (SD = 0.49, n = 8). Despite some weaknesses in particular aspects of economic evaluations published in PharmacoEconomics, we conclude that the journal has offered publications with acceptable overall quality and adequate methodology.

Pharmacoeconomic analysis of venlafaxine in the treatment of major depressive disorder.

We conducted a cost-effectiveness analysis of acute major depressive disorder (MDD) using serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine), selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, sertraline, paroxetine), or tricyclic antidepressants (TCAs; amitriptyline, imipramine, desipramine, nortriptyline). A decision-tree model over 6 months was constructed using an expert panel. The analytic perspective was that of the Ontario Ministry of Health as payor for all direct costs, which were derived from standard lists and included the cost of the drug as well as those for medical care, laboratory services, hospitalisation and managing adverse events. Success and dropout rates were determined from a meta-analysis of published randomised controlled trials. Medline, Embase, and International Pharmaceutical Abstracts were searched from 1984 to 1996, as were references from retrieved articles and reviews. Inpatients and outpatients were analysed separately. SSRIs were used as backup therapy for patients receiving venlafaxine and TCAs, and SNRIs were used as backup therapy for patients receiving SSRIs. Pharmacoeconomic outcomes were expected cost per success, expected cost per symptom free day (SFD), and incremental cost per success and per SFD. The meta-analysis identified 56 treatment arms from 36 randomised controlled trials involving 2953 patients (2380 outpatients and 573 inpatients). SNRIs had the highest success rates. The respective costs (in 1996 $Can; $Can1 = $US0.74) for outpatients and inpatients are given below. The expected costs per success were $6044 and $17,234 for venlafaxine, $6634 and $20,874 for SSRIs, and $9035 and $20,459 for TCAs in outpatients and inpatients, respectively. The respective expected costs per SFD were $45.92 and $127.31 for venlafaxine, $51.64 and $157.04 for SSRIs, and $70.71 and $152.43 for TCAs. Venlafaxine was dominant for all incremental pharmacoeconomic analyses. Sensitivity analyses indicated that the results were robust for outpatients but somewhat sensitive for inpatients. In conclusion, venlafaxine is a cost-effective drug for the treatment of MDD in adult outpatients and inpatients.

Drug-related mortality in Canada (1984-1994).

OBJECTIVE: To examine drug-related deaths due to adverse drug reactions between 1984 and 1994. DATA SOURCE: Voluntary reports of deaths due to adverse events as reported to the Adverse Drug Reaction Monitoring Program, Drugs Directorate, Health Protection Branch, Health Canada. METHODS: Drugs were classified according to the Anatomical, Therapeutic, Chemical (ATC) coding system. Descriptive statistics were utilized. RESULTS: One thousand four hundred and seventeen drug-related deaths were reported (700 male, 685 female, 32 unknown). The mean+/-SD age of patients was 54.6+/-21.7 years (range 1 month-97 years). In total, 2131 medications were implicated as suspect drugs (1.5+/-1.0, range 1-7). The most commonly reported categories of suspect drugs were the nervous system agents (50.6%), followed by cardiovascular system agents (9.0%), general antiinfectives for systemic use (8.8%) and musculoskeletal system agents (8.3%). One thousand and eighty-six deaths were classified as non-suicides. For non-suicide deaths, the most commonly reported suspect drugs were classified as nervous system agents (37.9%), followed by general antiinfectives for systemic use (12.3%), musculoskeletal system (11.5%) and cardiovascular system agents (10.2%). Three hundred and thirty-one (23.3%) reports were identified as suicides. For suicides, the most commonly reported suspect drugs were the nervous system agents (81.1%), followed by the respiratory system agents (8.5%) and the cardiovascular system agents (6.0%). CONCLUSION: Nervous system agents, musculoskeletal medications and general antiinfectives for systemic use figured prominently in deaths reported to HPB between 1984 and 1994.

Quality assessment of pharmacoeconomic abstracts of original research articles in selected journals.

OBJECTIVE: To assess and compare the quality of pharmacoeconomic abstracts of cost-minimization analyses, cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses of original research articles in selected medical, pharmacy, and health economics journals. METHODS: MEDLINE was used to identify articles in selected medical, pharmacy, and health economics journals using the MeSH word "economic" and text words "cost" and "pharmacoeconomic"; the journal PharmacoEconomics was searched manually. All retrieved abstracts were evaluated. Original, comparative (at least one drug comparator) research articles (1990-1994) reporting both costs and clinical outcomes were included in the quality analysis. Abstract quality was assessed as a percentage by using a checklist with 29 objective criteria. Group consensus produced interrater reliability greater than 0.8. RESULTS: One thousand two published abstracts labeled with the above key words were identified. Of these, 951 were excluded from quality assessment because they were not original research (18%), were not pharmacoeconomic research (47%), lacked a drug comparator (35%), or did not report a clinical outcome (0.5%). Thus, the quality of 51 (5% of the total) remaining abstracts was assessed. Overall scores were 56% in 1990 and 58% in 1994 (p = 0.094). Medical articles scored highest (61.5%; n = 25), pharmacy articles were next (54.3%; n = 5), and health economics articles were lowest (53.4%; n = 21) (p = 0.091); structured abstracts scored significantly higher (62.5%; n = 20) than unstructured (53.3%; n = 31) (p = 0.003). CONCLUSIONS: Abstract quality was generally poor, with no significant change in quality over time. Medical journals scored highest, probably because they use structured abstracts. Guidelines for structured pharmacoeconomic abstracts may assist in improving quality.

Sensitivity analysis in health economic and pharmacoeconomic studies. An appraisal of the literature.

The objective of this study was to analyse the extent of reporting of sensitivity analyses in the health economics, medical and pharmacy literature between journal types and over time. 90 articles were chosen from each of the bodies of literature on health economics, medicine and pharmacy. MEDLINE, EMBASE and International Pharmaceutical Abstracts were searched for English-language economic studies published between 1989 and 1993. The studies chosen for inclusion had to be original articles published in one of the selected journals between January 1989 and December 1993, involving a comparison between drugs, treatments or services, and evaluating both costs and outcomes. 123 articles initially met these criteria; however, 16 were inappropriate, 17 were randomised out, leaving 90 studies (73%) that were used (30 from each literature group). Data were extracted independently by 5 raters using a validated checklist. Inter-rater reliability was assessed by calculating kappa. 53 of the 90 articles (59%) conducted sensitivity analyses. 39 (74%) stated explicitly that a sensitivity analysis was being performed; this was noted in the Methods section of 35 papers (67%). 80% of health economics journals, 70% of medical journals and 20% of pharmacy journals conducted sensitivity analyses. Despite the fact that all published pharmacoeconomic guidelines suggest the use of sensitivity analysis, only 59% of studies between 1989 and 1993 did so. Improvement is required, especially in the pharmacy literature. No time trends in the conduct of sensitivity analyses were detected. However, the sample may not have been sufficient to detect such trends. Pharmacoeconomic guidelines should provide more details on preferred methods of sensitivity analysis and on desired parameters.

Quality assessment of economic evaluations in selected pharmacy, medical, and health economics journals.

OBJECTIVE: To assess and compare the quality of economic studies in selected pharmacy, medical, and health economics journals. DATA SOURCES: DICP The Annals of Pharmacotherapy, American Journal of Hospital Pharmacy, Hospital Pharmacy, New England Journal of Medicine, Medical Care, Journal of the American Medical Association, PharmacoEconomics, International Journal of Technology Assessment in Health Care, and Journal of Health Economics using MEDLINE, EMBASE, and International Pharmaceutical Abstracts. Search terms included "economic," "cost," and "cost analysis." STUDY SELECTION: Reviewers appraised abstracts to identify original research published during 1989-1993 comparing costs and outcomes between drugs, treatments, and/or services. Initially, 123 articles met criteria; 16 were inappropriate, 17 were randomized out, and 90 (73%) were used (30/group). DATA EXTRACTION: Quality was assessed using a 13-item checklist. Interrater reliability was 0.91 (p < 0.05) for 9 raters, test-retest reliability was 0.94 (p < 0.001). DATA SYNTHESIS: A 2-way ANOVA, with overall quality scores as a dependent variable with journal type and year as independent variables, was significant (F = 2.79, p = 0.002, r2 = 0.34), with no significant interaction (F = 0.71, p = 0.68) or time effect (F = 0.70, p = 0.60). Journal types differed; pharmacy journals scored significantly lower (chi 2 = 53.89, df = 2, p < 0.001). Items rated adequate (i.e., correct or acceptable) increased over time (chi 2 = 21.18, df = 4, p < 0.001). Ethical issues and study perspective most needed improvement. CONCLUSIONS: Article quality for all journal types increased over time nonsignificantly; health economics journals scored highest, then medical journals, with pharmacy journals significantly lower (and having the highest standard deviation). We recommend that authors and reviewers pay closer attention to study perspective and ethical implications.