Prioritizing comparative-effectiveness research topics via stakeholder involvement: an application in COPD.

A major priority for funding agencies and researchers involved in comparative-effectiveness research (CER) is to ensure that research questions will produce findings that are relevant and feasible to implement. In this article, we describe a process for involving experts and stakeholders in identifying and prioritizing CER studies, as illustrated by our experience in chronic obstructive pulmonary disease (COPD).

Clinical and economic burden of fractures in patients with renal osteodystrophy.

UNLABELLED: Renal osteodystrophy is a key cause of fractures in patients with chronic kidney disease (CKD). AIMS: This article reviews the clinical and economic burden of fractures and explores the types of studies that need to be conducted in order to fully understand the impact of fractures in renal osteodystrophy. We also discuss the role that active vitamin D compounds and calcimimetics play in treating secondary hyperparathyroidism. MATERIALS AND METHODS: Medline was searched for relevant articles on renal osteodystrophy and fractures. RESULTS: CKD-related fractures are the source of significant morbidity and costs. Extensive osteoporosis research has been utilized to guide fracture prevention and improve disease management, but further costs and outcomes analyses are needed for renal osteodystrophy. Recent research regarding newer, present-day treatment paradigms has suggested that distinct cost savings and improved patient outcomes are possible. CONCLUSIONS: In order to realize such economic and human benefits, the medical community must first have sufficient pathologic, pharmacoeconomic and epidemiologic data to properly understand, manage and prevent renal osteodystrophy and fractures.

Low molecular weight heparin versus unfractionated heparin in the colonoscopy peri-procedure period: a cost modeling study.

OBJECTIVE: The aim of this study was to compare the economic outcomes of peri-procedure anticoagulation approaches for elective colonoscopy. METHODS: Decision analysis was used to model the economic outcomes of five peri-procedure anticoagulation options: outpatient low molecular weight heparin (LMWH), inpatient unfractionated heparin infusion (UFHi), continuous warfarin (with probability of a repeat procedure using LMWH or UFHi), and discontinuation of anticoagulation therapy. The model's base-case scenario assumed drug therapy options for high-risk patients were equally effective in preventing a thromboembolic event (0.1% risk), with a higher probability for the no anticoagulation strategy (0.4%); event costs were based on published data and adjusted to 1997 dollars. Drug costs reflected 1997 average wholesale price. Medical costs for other variables were estimated based on local hospital charges. Indirect costs were not considered. Risk probabilities and LMWH drug cost were tested in sensitivity analysis. RESULTS: In the base-case scenario, costs for the options evaluated were $1436/patient, $1792/patient, $1848/patient, $2629/patient, and $5196/patient for no anticoagulation, continuous warfarin/repeat LMWH, LMWH as outpatient, continuous warfarin/repeat UFHi, and UFHi as inpatient respectively ($1997). Discontinuing anticoagulation was the least costly approach but involved the greatest thromboembolic risk. The cost of continued warfarin anticoagulation/repeat LMWH was minimally less than the LMWH option, but assumes 25% of patients would require a second procedure. The traditional approach (UFHi) requires an extended hospitalization and is the most costly option. Varying risk category or LMWH cost in sensitivity analysis had a negligible impact on overall costs. CONCLUSION: Within the model's assumptions, LMWH offers a novel, convenient, and economical solution to the problem of peri-procedure anticoagulation for elective colonoscopy.

Methods to assess the economic outcomes of clinical pharmacy services.

Studies that demonstrate the clinical and economic burden of drug misadventures have been published. The economic burden of drug misadventures likely exceeds $100 billion annually in the United States alone. Clinical pharmacy services (CPS) have been shown to reduce negative clinical outcomes and costs of drug therapy. Pharmacy practitioners and pharmacy managers need to demonstrate the impact of CPS at the local level and present the value to financial decision-makers to gain support for implementation, continuation, and/or expansion of those services. The basic model of an economic evaluation includes measurement of both costs and consequences of a service and of an alternative for comparison. Strategies for economic assessments include the generalization from previously published literature, use of modeling techniques, and measurement of actual costs and consequences of an existing service. Guidelines for conducting an economic assessment are widely available. Pharmacy practitioners and managers should use these methods of assessing economic outcomes of CPS and, at the same time, develop relationships and skills to effectively communicate the value of those services so as to ensure long-term success.

Impact of Parkinson's disease and its pharmacologic treatment on quality of life and economic outcomes.

The impact of Parkinson's disease (PD) and its pharmacologic treatment on health-related quality of life (HRQL) and economic outcomes is reviewed. PD is a chronic and progressive neurologic disorder characterized by specific motor deficits resulting from the degeneration of dopaminergic neurons in the substantia nigra. The cardinal symptoms are tremor, rigidity, bradykinesia, and loss of postural reflexes. PD markedly reduces HRQL and places an economic burden on society of up to $25 billion per year. Patients' inability to move freely and to perform everyday tasks restricts their independence and leads to increased reliance on caregivers and assistive devices. Emotional and psychosocial well-being is also negatively affected. As the disease progresses, the response to levodopa typically decreases and various motor complications develop; these are difficult to treat and result in further declines in HRQL. The economic costs of PD include both direct health care costs (for drugs, physician services, and hospitalization) and indirect costs (for lost worker productivity). Economic analyses of PD and its treatments can help guide effective allocation of health care resources. Various antiparkinsonian agents and formulations, such as extended-release levodopa-carbidopa and pramipexole, have been found to be cost-effective relative to other agents. The newest antiparkinsonian drugs, cathechol-O-methyltransferase inhibitors, also have the potential to improve HRQL and economic outcomes, although more study is needed to confirm this. The total impact of PD and its treatment can be fully appreciated only when HRQL and economic outcomes, in addition to clinical outcomes, are examined.

Clinical and cost comparison of ibutilide and direct-current cardioversion for atrial fibrillation and flutter.

The clinical effectiveness and cost to convert recent-onset atrial fibrillation or flutter to sinus after 3 to 4 weeks of anticoagulation with intravenous ibutilide was compared with direct-current cardioversion. The low success rate with ibutilide made direct-current cardioversion the more clinical and cost-effective method to restore sinus rhythm.

Re-engineering: an opportunity to advance clinical practice in a community hospital.

A hospital pharmacy's efforts to advance clinical pharmacy practice and reduce pharmacy costs as part of a hospitalwide re-engineering program are described. In 1995, a 321-bed community hospital in Wisconsin undertook a three-year re-engineering program aimed at reducing operating expenses, primarily labor costs. The pharmacy department focused its efforts within the program on improving the efficiency of product-related functions, mainly through automation, and redeploying staff to value-added clinical functions. This involved installation of a hospitalwide pneumatic-tube system, use of unit-based automated medication dispensing devices, and implementation of a dedicated clinical pharmacy services program. Implementation of this program was to occur incrementally, with the first 12 months to be used primarily in developing a service model, initiating a staff-development program, and hiring additional clinical staff. Services added under the program included i.v. to oral conversion, dosage adjustments for patients with renal impairment, advanced patient counseling, development of care plans, and rounds in all areas of the hospital. After the first full year of implementation of the program, a cost-benefit analysis was undertaken; costs were composed primarily of pharmacists' salaries and benefits, and benefits were composed primarily of drug cost savings. A benefit to cost ratio of 2.61:1 and a net saving of $217,551 were calculated. The introduction of clinical pharmacy services as part of a hospitalwide re-engineering program was associated with a positive benefit to cost ratio and a substantial net cost saving.

Characteristics associated with ability to prevent adverse drug reactions in hospitalized patients.

We conducted a retrospective analysis to identify characteristics of preventable adverse drug reactions (ADRs). We reviewed reports on 612 ADRs occurring in hospitalized patients over 4 years, identified by the hospital's spontaneous ADR reporting program, and classified the events as potentially preventable or not preventable. Characteristics related to ADR preventability in the univariate analysis were the patient's clinical service, organ system involved in the ADR, class of drug causing the ADR, relationship to dosage, type of ADR, and probability that the reaction was due to the drug. Among these, relationship to dosage (p<0.001) and type of ADR (p<0.001) appeared to be most strongly related to preventability. In a multivariate analysis, preventable ADRs were associated with dosing (OR 3.82, 95% CI 2.42-6.03) and previous allergy to the drug (OR 3.46, 95% CI 1.01-11.88). An ADR that was classified as an allergic (OR 0.50, 95% CI 0.27-0.94) or idiosyncratic reaction (OR 0.44, 95% CI 0.28-0.71) was unlikely to be considered preventable. Preventable ADRs in hospitalized patients are likely to be dosage related or to occur among patients allergic to the specific agent.

Economic considerations in the treatment and management of Alzheimer's disease.

Cost issues and formal economic evaluations of treatment for Alzheimer's disease (AD) are reviewed. The annual cost of AD in the United States is estimated to be $100 billion. Each case of AD is associated with total costs of up to $195,000, with a substantial portion of this attributable to lost patient and caregiver productivity and to family out-of-pocket expenses. Only a few studies have evaluated the economic impact of therapeutic interventions in AD. In one study of tacrine, dosages greater than 80 mg/day significantly delayed nursing-home placement. In another study, treatment that improved cognitive deficits significantly reduced the time spent by caregivers, an outcome that is also associated with reduced indirect costs. A decision-analytic model that incorporated the progressive nature of AD demonstrated an average cost saving of $9250 for each patient started on tacrine at the time of diagnosis. This saving was attributed to the delay in nursing-home placement. Other studies have described a mathematical model that considers the relationship between cognitive performance and the cost of illness; it can be used to obtain an initial estimate of the economic benefit of new AD treatments. The available economic studies indicate that, when used appropriately, cholinesterase inhibitors improve outcomes and reduce costs for patients with mild to moderate AD.

Economic considerations in Alzheimer's disease.

Alzheimer's disease (AD) is the third most expensive disease in the United States, costing society approximately $100 billion each year. It is one of the most prevalent illnesses in the elderly population, and with the aging of society, will become even more significant. Costs associated with AD include direct medical costs such as nursing home care, direct nonmedical costs such as in-home day care, and indirect costs such as lost patient and caregiver productivity. Medical treatment may have economic benefits by slowing the rate of cognitive decline, delaying institutionalization, reducing caregiver hours, and improving quality of life. Pharmacoeconomic evaluations have shown positive results regarding the effect of drug therapy on nursing home placement, cognition, and caregiver time.

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in the treatment of patients with hypercholesterolemia: a meta-analysis of clinical trials.

Recent studies have documented the long-term impact of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mortality and morbidity related to coronary heart disease, establishing the link between lowering cholesterol levels and reducing cardiac events. Our study was a comparative literature review and meta-analysis of the efficacy of four HMG-CoA reductase inhibitors-fluvastatin, lovastatin, pravastatin, and simvastatin-used in the treatment of patients with hypercholesterolemia. The data sources for our meta-analysis of the efficacy of these cholesterol-lowering agents were 52 randomized, double-masked clinical trials with at least 25 patients per treatment arm. The results showed all four agents to be effective in reducing blood cholesterol levels. We computed summary efficacy estimates for all published dose strengths for the four agents. Fluvastatin 20 mg/d reduced low-density lipoprotein cholesterol (LDL-C) levels by 21.0% and total cholesterol (total-C) levels by 16.4%; fluvastatin 40 mg/d reduced these levels by 23.1% and 17.7%, respectively. Lovastatin 20 mg/d reduced LDL-C levels by 24.9% and total-C levels by 17.7%; lovastatin 80 mg/d reduced these levels by 39.8% and 29.2%, respectively. Pravastatin 10 mg/d reduced LDL-C levels by 19.3% and total-C levels by 14.0%; pravastatin 80 mg/d reduced these levels by 37.7% and 28.7%, respectively. Simvastatin 2.5 mg/d reduced LDL-C levels by 22.9% and total-C levels by 15.7%; simvastatin 40 mg/d reduced these levels by 40.7% and 29.7%, respectively. The results of our meta-analysis can be used in conjunction with treatment objectives and comparative cost-effectiveness data for these agents to decide appropriate therapeutic alternatives for individual patients.

Economic evaluations of clinical pharmacy services--1988-1995. The Publications Committee of the American College of Clinical Pharmacy.

The objectives of this effort were to summarize and critique original economic assessments of clinical pharmacy services published from 1988-1995, and to make recommendations for future work in this area. A literature search was conducted to identify articles that were than blinded and randomly assigned to reviewers to confirm inclusion, abstract information, and assess the quality of study design. The 104 articles fell into four main categories based on type of service described: disease state management (4%), general pharmacotherapeutic monitoring (36%), pharmacokinetic monitoring services (13%), and targeted drug programs (47%). Articles were categorized by type of evaluation; 35% were considered outcome analyses, 32% outcome descriptions, and 18% full economic analyses. A majority (89%) of the studies reviewed described positive financial benefits from the clinical services evaluated; however, many (68%) did not include the input costs of providing the clinical service as part of the evaluation. Studies that were well conducted were most likely to demonstrate positive results. Commonly, results were expressed as net savings or costs avoided for a given time period or per patient. Seven studies expressed results as a benefit:cost ratio (these ranged from 1.08:1 to 75.84:1, mean 16.70:1). Overall this body of literature contains a wealth of information pertinent to the value of the clinical practice of pharmacy. Future economic evaluations of clinical pharmacy services should incorporate sound study design and evaluate practice in alternative settings.

Pharmacoeconomic analysis of stress ulcer prophylaxis for critically ill patients.

The objective of this study was to evaluate the economic outcomes of drug options for stress ulcer prophylaxis in critically ill and/or intensive care unit patients. Decision analytic modelling was used to compare the costs of stress ulcer prophylaxis and possible clinical outcomes [acute upper gastrointestinal bleeding (AUGB) and nosocomial pneumonia]. The regimens evaluated were: antacids, histamine H2 receptor antagonists (H2RAs), sucralfate and no prophylaxis. The results of published studies were pooled to determine the expected probability of AUGB and nosocomial pneumonia following stress ulcer prophylaxis with each of the agents under study. The costs of stress ulcer prophylaxis, treatment of AUGB and treatment of nosocomial pneumonia were identified from various sources. Sucralfate was the least costly agent for stress ulcer prophylaxis. The average net costs per patient for sucralfate, antacids, no prophylaxis and H2RAs were $US1457, $US1737, $US2268, and $US2638 to $US2712, respectively (1994 dollars). No prophylaxis was found to be less costly than giving H2RAs. Sucralfate and antacids, which induced net savings of $US7373 and $US4321 per case of AUGB averted, respectively, were more cost effective than H2RAs. Sensitivity and threshold analyses revealed that the results were constant over a wide range of cost and probability values. Break-even analysis suggested that sucralfate was the optimal agent for stress ulcer prophylaxis unless the acquisition cost of a prophylactic course of sucralfate was > $US304.05 per patient. At that point, antacids become the optimal agent. Based on this analysis, sucralfate may be the most cost-effective agent for stress ulcer prophylaxis in critically ill or intensive care patients.

Estimating the rate of adverse drug reactions with capture-recapture analysis.

The capture-recapture technique used to estimate the number of ADRs at UICMC may offer institutions and health systems a way to better identify and address the occurrence of ADRs.

Control charts to monitor rates of adverse drug reactions.

We describe the use of control charts in monitoring rates of adverse drug reactions. Adverse drug reactions are recognized as important outcomes of patient care and are specifically associated with the process of medication use. The systematic monitoring of adverse drug reactions may allow one to identify opportunities to improve this process. Reported adverse drug reactions from 36 consecutive months at a university hospital were analyzed. The mean rate of adverse drug reaction reporting was 1.65% (denominator of patient admissions) and the 3 sigma upper and lower control limits were 3.22% and 0.08%, respectively. The mean rate of preventable adverse drug reactions was 21.25% (denominator of total reported adverse drug reactions) and the 3 sigma upper and lower control limits were 73.54% and < 0%, respectively. The experience described in this report suggests that monitoring adverse drug reactions using control charts, facilitates identification of trends in reporting and the actual incidence of adverse drug reactions, and allows identification of opportunities to improve the systems and processes of medication use.

National survey of once-daily dosing of aminoglycoside antibiotics.

To evaluate the scope of once-daily dosing of intravenous aminoglycoside antibiotics, a questionnaire was designed and mailed to a random sample of pharmacy directors at 500 acute care hospitals in the United States. The response rate was 68.4%. Nineteen percent of the respondents reported use of once-daily dosing of aminoglycosides. Affiliation with a pharmacy residency program and the presence of a pharmacokinetic consultation service by the pharmacy department were associated with this practice (p < 0.05). No other statistically significant differences were found. Reported indications, contraindications, and dosing were consistent with those found in the literature. The profession of pharmacy, as demonstrated by pharmacy residency programs and pharmacokinetic consultation services, appears to have been instrumental in implementing this method of dosing aminoglycosides.

Meta-analysis of controlled trials of drug therapy in mild chronic asthma: the role of inhaled corticosteroids.

OBJECTIVE: To determine the role of inhaled corticosteroids in the treatment of mild chronic asthma. SOURCE OF STUDIES: Searches of MEDLINE and Index Medicus for English language literature dealing with asthma and inhaled corticosteroids. DESIGN: All retrieved articles were subjected to predetermined criteria for inclusion in the meta-analysis. Inclusion criteria centered around randomized, double-blind studies reporting objective clinical endpoint(s) for subjects with mild chronic asthma who were treated for more than seven days. Studies that were included were not allowed to have any predetermined exclusion criteria. RESULTS: The literature search identified 129 articles, of which 41 satisfied some but not all of the criteria for inclusion. Five articles met all the criteria and were subjected to meta-analysis. The total number of subjects was 141. Peak expiratory flow rate (PEFR) was used as the objective endpoint for effect size calculation. Subjecting these five studies to quality review revealed a range of 0.607-0.741, with 1 as the highest attainable quality and 0 the lowest. Reported results for the different studies were found to be homogenous, thus allowing for the calculation of overall effect size. Inclusion of children in some of the studies added variance to the reported studies, but not to the point at which studies would be considered heterogenous. Effect sizes ranged between 0.41 and 0.89, and the overall weighted average effect size for PEFR was 0.59, with the calculated 95 percent confidence interval at 0.32 to 0.84. A tabulated display of binomial effect size for included trials provided ranges of success rates for treatment versus control values. Results of the studies were judged robust, as 92 studies reporting no significant effects are needed to turn the finding of the meta-analysis insignificant. CONCLUSIONS: Based on the results of the meta-analysis, the existing literature suggests a role for inhaled corticosteroids in the treatment of mild chronic asthma.