Reduce Drug Costs Research Articles

PBS/RPBS cost implications of trends and guideline recommendations in the pharmacological management of hypertension in Australia, 1994-1998.

To determine the extent to which "current guidelines" for the management of hypertension are reflected in the prescribing of antihypertensive drugs in Australia over the period 1994-1998, and to examine the cost implications of actual and recommended prescribing patterns. Federal Government and consumer cost estimates modelled on prescribing patterns and guideline recommendations over the period 1994-1998. Prescribing on Federal Government pharmaceutical schemes over the 1994-1998 period. Estimates of Pharmaceutical Benefits Scheme/Repatriation Pharmaceutical Benefits Scheme cost changes in Australian dollar values. The implementation of current guidelines for patients with uncomplicated hypertension taking monotherapy alone could have reduced drug costs by $45-$108 million in 1998. Current prescribing patterns indicate that clinical practice has pre-empted the results from clinical trials of newer, more expensive agents and that clinicians' prescribing patterns do not closely reflect current recommendations.

Alteplase and tenecteplase: Applications in the peripheral circulation

Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator, became the first genetically engineered thrombolytic approved by the Food and Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to AMI, alteplase is currently approved for the treatment of acute ischemic stroke and pulmonary embolism, and we anticipate approval for catheter clearance in late 2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney cellderived urokinase, alteplase has become an alternative agent in peripheral vascular applications. Because few interventionalists had prior experience with the handling and dosage of alteplase, the Advisory Panel to the Soceity of Cardiovascular and Interventional Radiology established practice guidelines for use in noncoronary applications. Emerging clinical experience with contemporary dosing regimens shows a safety and efficacy profile similar to urokinase but with significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified version of alteplase. TNK is the only plasminogen activator available that has shown a significantly enhanced safety profile versus alteplase in AMI. Approved for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life, increased resistance to plasminogen activator inhibitor, and improved fibrin specificity compared with alteplase. Because of its enhanced safety profile, TNK may be a desirable agent for peripheral vascular applications. Initial clinical studies with TNK in acute arterial and venous disease are ongoing. This article outlines the Advisory Panel guidelines for using alteplase and highlights features of tenecteplase.

Impact of a pharmacist on drug costs in a coronary care unit.

The impact of clinical pharmacy services on direct drug costs in a coronary care unit (CCU) was studied. An observational, nonrandomized study was conducted on all patients admitted to the CCU to evaluate the impact of clinical pharmacy services on direct drug costs. Clinical pharmacy services were introduced into the CCU in July 1998. Patient characteristics, mean drug costs per admission, mean drug category costs per admission, and total hospital costs per admission were determined for October 1997 to June 1998 (nonintervention period), July 1998 to March 1999 (intervention period 1), and April 1999 to December 1999 (intervention period 2). The Clini-Trend program was used to estimate the total reduction in drug costs associated with documented pharmacist interventions from January to December 1999. Mean patient age, sex, admitting diagnosis-related group, Medicare case-mix index, ventilator days, length of stay, and number of deaths did not differ significantly among the three study periods. Mean +/- S.D. drug costs per admission for the nonintervention period were $374.05 +/- $75.51. With the introduction of clinical pharmacy services, mean +/- S.D. drug costs per admission were $381.94 +/- $66.16 (p > 0.1 for intervention period 1 compared with the nonintervention period) and $233.74 +/- $84.16 (p = 0.002 for intervention period 2 compared with the nonintervention period). From January to December 1999, 4151 pharmacist interventions were documented. The estimated reduction in drug costs associated with the interventions totaled $372,384. A pharmacist's clinical services in the CCU allowed for significant estimated reductions in total drug costs.

Implementing Protocol-Based Therapy of Continuous Neuromuscular Blockade Provides Cost Minimization

Objective: To compare empiric and protocol-based therapies of neuromuscular blockade in terms of cost and control of paralysis. Methods: Data were prospectively collected for nine months before and five months after a protocol was implemented in the 24-bed medical/surgical/neurologic intensive care unit as a physician-initiated, doublesided medication order form. Pancuronium was the preferred agent and vecuronium was an alternative for patients with renal dysfunction, hepatic dysfunction, or hemodynamic instability. Results: Twenty-nine empiric-therapy patients and 17 protocol-based therapy patients were comparatively evaluated. Length of stay in the intensive care unit and duration of neuromuscular blockade were similar between groups. Protocol adherence rate was 76.5%. Protocol-based therapy increased the hourly dose of pancuronium (0.29 ± 0.37 mg vs. 0.02 ± 0.10 mg; p < 0.005) and reduced the mean hourly cost of neuromuscular blockade compared with empiric therapy ($5.11 ± 4.76 Canadian [CDN] vs. $9.03 ± 7.03 CDN; p < 0.05). Vecuronium use did not change, but rocuronium and atracurium were not given after protocol implementation. The proportion of recorded train-of-four measurements representing adequate neuromuscular blockade increased (52.3% vs. 32.7%; p < 0.05) with protocol-based therapy. Conclusions: Compliance with a neuromuscular blocking protocol reduces drug costs and improves control of neuromuscular blockade.

A Multi-professional Taught Course in Primary Care Therapeutics: Description and Evaluation

Aim: To describe and present an evaluation of a taught certificate course in therapeutics for primary care professionals. Design: A questionnaire study of the course participants analysed qualitatively and quantitatively. Subjects and setting: Students attending four primary care therapeutics courses held in east London and North Essex. Outcome measures: Participation and pass rates, participants comments and measures of course effectiveness in fulfilling participants aims. Results: 44 pharmacists, 48 GPs, and eight nurses attended the courses. They attended 91% of the sessions, 83% of assignments were submitted and 83% of students were awarded a certificate in primary care therapeutics. The course appears to be effective in satisfying most of the participants’ aims particularly “general interest” and promoting professional and inter-professional development; it was less successful in fulfilling specific objectives such as the development of formularies, becoming a trainer, participating in prescribing reviews and in reducing drug costs. Conclusions: Community pharmacists, general practitioners and senior primary care nurses have much to gain from being educated together in an activelearning environment. This programme meets the demand for courses of intermediate length and difficulty within primary health care. There is the possibility that such courses will enhance inter-disciplinary working and encourage rational prescribing.

Economic Evaluation of Drug Resistance Genotyping for the Adaptation of Treatment in HIV-Infected Patients in the VIRADAPT Study

Background: Costs of antiretroviral therapy for HIV-infected patients have increased at a time when most countries are attempting to contain health care costs. Part of this increase results from HIV drug resistance associated with virologic failure and a subsequent shift to more complex and costly therapies. Genotypic guided treatment is associated with better virologic outcome. However, it is not yet known whether it will be cost effective. Methods: We present here an economic evaluation based on the results from the VIRADAPT study, a prospective, open-label, randomized trial comparing patients assigned to standard of care (n = 43), versus genotypic guided treatment (n = 64) for 6 months. Total follow-up for the extended trial was 1 year. Costs were computed from the viewpoint of the health care system. Hospitalization data were retrieved from the VIRADAPT study case report forms, costs were estimated from the cost of the corresponding diagnosis-related groups derived from the French national cost data base: these were actual costs and not charges. Data on the volume of tests prescribed, drugs, and clinic visits were retrieved from the VIRADAPT study database. The unit costs of tests and clinic visits were determined using the French national Social Security reimbursement price; costing of drugs used were based upon purchase price by either retail pharmacies or hospitals. Genotyping using TruGene HIV-1 assay was estimated at $500 per test from manufacturer’s data (all figures in this paper are expressed in U.S. dollars). Results: Total mean (standard deviation) yearly costs per patients were $20,412 (±$10,129) in the standard of care group and $18,484 (±$9,652) in the genotyping group (p = .35). Drug costs represented 55% of total costs. There was a trend toward a decrease in drug costs in the genotyping arm (p = .07), the greatest reduction being in the decreased use of protease inhibitors in the genotyping arm. The additional expense of genotyping appeared to be offset by the savings obtained in drug costs. Conclusion: In our study, the cost of drug resistance testing is offset by a reduced use of protease inhibitors and their attendant costs. Although not reaching statistical significance, this trend in the reduction of drug costs and drug use presents a great interest for future trials.

Association between medication supplies and healthcare costs in older adults from an urban healthcare system.

The amount of medication dispensed to older adults for the treatment of chronic disease must be balanced carefully. Insufficient medication supplies lead to inadequate treatment of chronic disease, whereas excessive supplies represent wasted resources and the potential for toxicity. We used an electronic medical record system to determine the distribution of medications supplied to older urban adults and to examine the correlations of these distributions with healthcare costs and use. A cross-sectional study using data acquired over 3 years (1994-1996). A tax-supported urban public healthcare system consisting of a 300-bed hospital, an emergency department, and a network of community-based ambulatory care centers. Patients were >60 years of age and had at least one prescription refill and at least two ambulatory visits or one hospitalization during the 3-year period. Focusing on 12 major categories of drugs used to treat chronic diseases, we determined the amounts and direct costs of these medications dispensed to older adult patients. Amounts of medications that were needed by patients to medicate themselves adequately were compared with the medication supply actually dispensed considering all sources of care (primary, emergency, and inpatient). We calculated the excess drug costs attributable to oversupply of medication (>120% of the amount needed) and the drug cost reduction caused by undersupply of medication (<80% of the amount needed). We also compared total healthcare use and costs for patients who had an oversupply, an undersupply, or an appropriate supply of their medications. The cohort comprised 4164 patients with a mean age of 71 +/- 7 (SD) who received a mean of 3 +/- 2 (SD) drugs for chronic conditions. There were 668 patients (16%) who received <80% of the supply needed, 1556 patients (37%) who received between 80 and 120% of the supply needed, and 1940 patients (47%) who received >120% of the supply needed. The total direct cost of targeted medications for 3 years was $1.96 million or, on average, $654,000 annually. During the 3-year period, patients receiving >120% of their needed medications had excess direct medication costs of $279,084 or $144 per patient, whereas patients receiving <80% of drugs needed had reduced medication costs of $423,438 or $634 per patient. Multivariable analyses revealed that both under- and over-supplies of medication were associated with a greater likelihood of emergency department visits and hospital admissions. More than one-half of the older adults in our study have under- or over-supplies of medications for the treatment of their chronic diseases. Such inappropriate supplies of medications are associated with healthcare utilization and costs.

Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients.

This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients. Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n = 48), paroxetine (n = 48) or sertraline (n = 39). A global efficacy evaluation was made at baseline and after 6-9 months. Antidepressant drug costs before and after TDM were estimated. Eight samples were excluded due to technical problems or noncompliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%. The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

HIV-1 Drug Resistance Testing: Health Outcomes Issues

The cost of care for HIV-infected individuals, as for all chronically ill patients, is of increasing concern to healthcare providers and payers due to increasingly limited healthcare resources. Antiretroviral (ARV) drug therapy may cost in excess of 15000 Euros per year, yet evidence shows that total cost-of-care declines are due to decreased hospitalizations and clinic utilization [1–3]. Mostly these costs have been determined in aggregate for patient care and are only now being analysed for the various stages of disease. The majority of direct costs are for drugs and in-patient care, with diagnostics accounting for <5% of total costs (even in a clinical trial setting [4]). While the majority of patients in clinical practice are successfully suppressed below the limit of detection, many patients fail (as defined as a viral load above the limit of detection) within the medium to short term (1–2 years). Recent research has revealed that costs may rise by over 250 Euros per month after an episode of virological failure [5] and that each subsequent failure is more expensive. These preliminary data suggest there is an economic incentive to avoid ARV failure. Knowledge of viral resistance patterns in an individual may increase the ability of healthcare providers to select a successful and durable drug combination, and thus reduce ARV failure rates. However, from a budget perspective, the declining mortality rate in HIV disease means that the total cost of care for an HIV-infected population is rising rapidly. Thus, introduction of any additional tests or therapeutic agents that are priced higher than those already on the market is viewed with deep aversion by healthcare payers. It is therefore important to assess the impact of resistance testing on patients’ quality of life to inform decisions on the use of these tests in HIV disease. There are currently limited data available as to the actual effects of HIV-1 genotyping upon the total cost of patient care, and these data are only available for ARV-experienced patients, or from modelling studies based on these data. The only prospective economic study to date (based on the VIRADAPT study [6]) failed to show a statistically significant difference in the cost of care between patients who received genotyping and those who received standard-of-care. However, the study did show a trend (P=0.06) toward reduced costs, mainly through reduced drug costs and hospitalization costs [7]. Furthermore, it is possible that the use of a

Evaluation of a computer-based decision support system for treatment of hypertension with drugs: retrospective, nonintervention testing of cost and guideline adherence.

To evaluate a computerized decision support system (DSS) for drug treatment of hypertension, regarding quality, safety, and cost compared to actual antihypertensive drug treatment. The medical profiles of 338 hypertensive patients treated with drugs against hypertension were processed by the DSS. The drug treatment proposed by the system was then compared to actual treatment given by their physician. Four health centres in the county of Västerbotten, in Sweden. A list of hypertensive patients was extracted from the computerized medical records of each health centre and every fifth patient's medical profile was assessed by the system. None. Drug used, drug used in relation to certain major diseases such as diabetes mellitus, asthma, ischaemic heart disease (IHD), and previous myocardial infarction. Adherence to hypertension guidelines, safety, and cost. The DSS suggested significantly more thiazides and significantly fewer calcium antagonists than the physicians had prescribed, with a total cost reduction of 33-40%, depending on doses chosen. The DSS drug profile was more adherent to guidelines in patients with major complicating diseases, suggesting an improvement in treatment quality for these patients by the DSS. The DSS which fully implements current guidelines may improve the quality of antihypertensive treatment, concurrently leading to a considerable reduction in drug costs.

Reducing drug costs of a Medicare-risk population.

Reducing drug costs of a Medicare-risk population.

A Cost Comparison of Methohexital and Propofol for Ambulatory Anesthesia

Methohexital is eliminated more rapidly than thiopental, and early recovery compares favorably with propofol.We designed this study to evaluate the recovery profile when methohexital was used as an alternative to propofol for the induction of anesthesia before either sevoflurane or desflurane in combination with nitrous oxide. One hundred twenty patients were assigned randomly to one of four anesthetic groups: (I) methohexitaldesflurane, (II) methohexital-sevoflurane, (III) propofoldesflurane, or (IV) propofol-sevoflurane. Recovery times after the anesthetic drugs, as well as the perioperative side effect profiles, were similar in all four groups. A cost-minimization analysis revealed that methohexital was less costly for the induction of anesthesia. At the fresh gas flow rates used during this study, the costs of the volatile anesthetics for maintenance of anesthesia did not differ among the four groups. However, at low flow rates (<or=to1 L/min), the methohexital-desflurane group would have been the least expensive anesthetic technique. In conclusion, methohexital is a cost-effective alternative to propofol for the induction of anesthesia in the ambulatory setting. At low fresh gas flow rates, the methohexital-desflurane combination was the most cost-effective for the induction and maintenance of general anesthesia. Implications: Using methohexital as an alternative to propofol for the induction of anesthesia for ambulatory surgery seems to reduce drug costs. When fresh gas flow rates <or=to1 L/min are used, the combination of methohexital for the induction and desflurane for maintenance may be the most cost-effective general anesthetic technique for ambulatory surgery. (Anesth Analg 1999;89:311-6)

Cost reduction and outcome improvement in the intensive care unit.

Decreasing reimbursement provided by third-party payors necessitates reduction of costs for providing critical care services. If academic medical centers are to remain viable, methods must be instituted that allow cost reduction through practice change. We used short cycle improvement methodology to rapidly achieve these goals. Short cycle improvement methodology involves identifying the areas for improvement, defining a mechanism to evaluate outcome, initiating an improvement plan on a small number of patients, and repeating the cycle with new adjustments based on outcome. Baseline data on areas for improvement was prospectively collected, and protocols to initiate change were developed and tested by short improvement cycles. Outcomes were evaluated, protocols were modified, and another cycle was performed. This methodology was continued until the desired goals had been achieved. To adjust outcomes for severity of illness, Acute Physiology and Chronic Health Evaluation II methodology was used. Using this methodology, we focused on three areas for improvement. Standing orders for laboratory studies, electrocardiograms, and chest x-ray films were eliminated. Protocols were developed for the appropriate use of sedation, analgesics, and neuromuscular blocking agents. Finally, a protocol for weaning from mechanical ventilation was developed to allow respiratory therapists to proceed through the weaning process, which was ordered by a physician. Laboratory tests were reduced by 65% (from 510 to 180 tests per day) with an annual cost savings of $21,593. Chest x-ray reduction of 56% resulted in an annual savings of $3,941. There was a 75% reduction in cost of neuromuscular blocking agents. The use of neuromuscular blocking agents resulted in a 75% reduction in drug costs. Ventilator hours were reduced by 35% from 140 to 90 hours. The average length of overall intensive care unit stay was reduced by 1.5 days (5.0 to 3.5 days). The cost per patient day decreased with an annualized cost savings of 4% per patient day. Unexpected outcomes included a reduction in intensive care unit days from 54 days at baseline to 7 days at the 6-month interval. The infection rates for blood stream infections, urinary tract infections, and nosocomial pneumonia were reduced. Using national nosocomial infection data, these rates represented a reduction from the fiftieth percentile to the twenty-fifth percentile for all measured indicators. Acute Physiology and Chronic Health Evaluation II scores were 19.54 at baseline and increased to 21.2 (p = 0.001) at the 6-month interval. Mortality rates were 16.7% at baseline and were 17.6% (p = 0.89) at the 6-month interval. We concluded that utilization of short cycle improvement methodology provided an ongoing method for reducing costs of critical care services in our patient population with no change in mortality.

Comparative efficacy and tolerability of low-dose pravastatin versus lovastatin in patients with hypercholesterolemia

Background The HMG CoA reductase inhibitors have quickly become the most widely prescribed family of agents for the treatment of patients with elevated low-density lipoprotein (LDL) cholesterol. The incidence of side effects with these agents increases as the dose increases within the recommended dosage range. A lower dosage presumably would have a lower incidence of adverse effects. In addition, lower doses should translate into reduced drug costs. Methods and Results We compared the efficacy of 10 mg of pravastatin and 10 mg of lovastatin in a randomized, crossover design trial among 30 patients with hypercholesterolemia. At baseline, their total cholesterol and LDL cholesterol levels were 249.0 ± 27.3 and 185.1 ± 25.5 mg/dL. After 4 weeks of treatment with lovastatin, the total cholesterol and LDL cholesterol levels fell to 202.8 ± 29.6 and 141.0 ± 25.3 mg/dL, decreases of 19% and 24%, respectively. Four weeks of pravastatin treatment resulted in levels of 212.6 ± 30.8 and 150.5 ± 25.5 mg/dL, or 15% and 19%, respectively. Conclusions There were highly significant changes in total cholesterol and LDL cholesterol levels with each agent and no differences in effect between the 2 agents. In 13 (43%) of the 30 patients, LDL levels were reduced to ≤130 mg/dL with one of the agents. Both agents were generally well tolerated, with no clinically important change in liver function tests or creatinine kinase levels. (Am Heart J 1999;137:458-62.)

Dialysis Graft Declotting with Very Low Dose Urokinase: Is it Feasible to Use “Less and Wait?”

"Lyse and wait" dialysis graft declotting is simple and effective, but the minimum necessary dose of urokinase is unknown. The efficacy of the technique with very low dose urokinase is evaluated. Twenty-one grafts in 17 patients were declotted with use of the lyse and wait technique, but with 5,000-15,000 U of urokinase initially. Graft angiography was performed when an interventional suite was available. Declotting was completed in the manner chosen by the individual operator. Angiograms, interventional radiology records, and dialysis records were reviewed. Technical and clinical success were achieved in 95% of cases. Mean initial urokinase dose was 6,667 U. Initial angiography was performed at a mean 86 minutes. Two cases required second 5,000-U boluses to achieve complete graft thrombolysis. In all other cases, complete or near complete graft thrombolysis was observed with the initial very low dose. No bleeding, arterial embolic, or pulmonary embolic complications were observed. Doses of urokinase as low as 5,000 U are effective for lyse and wait declotting. A substantial reduction in drug costs can be expected with the "less and wait" modification. Bleeding risk may also be reduced.

Using information systems to measure and improve quality

Information systems (IS) are increasingly important for measuring and improving quality. In this paper, we describe our integrated delivery system's plan for and experiences with measuring and improving quality using IS. Our belief is that for quality measurement to be practical, it must be integrated with the routine provision of care and whenever possible should be done using IS. Thus, at one hospital, we now perform almost all quality measurement using IS. We are also building a clinical data warehouse, which will serve as a repository for quality information across the network. However, IS are not only useful for measuring care, but also represent powerful tools for improving care using decision support. Specific areas in which we have already seen significant benefit include reducing the unnecessary use of laboratory testing, reporting important abnormalities to key providers rapidly, prevention and detection of adverse drug events, initiatives to change prescribing patterns to reduce drug costs and making critical pathways available to providers. Our next major effort will be introduce computerized guidelines on a more widespread basis, which will be challenging. However, the advent of managed care in the US has produced strong incentives to provide high quality care at low cost and our perspective is that only with better IS than exist today will this be possible without compromising quality. Such systems make feasible implementation of quality measurement, care improvement and cost reduction initiatives on a scale which could not previously be considered.

Pharmacotherapeutic circles. Results of an 18-month peer-review prescribing-improvement programme for general practitioners.

To assess the effectiveness of the pharmacotherapeutic circle (PTC), a general practitioner (GP) prescribing-improvement programme to enhance prescribing quality and reduce drug costs. Combined pre- and post-intervention time-series design using an internal comparison of subgroups and an external comparative control. Small discussion groups meeting 8 times over 18 months. 79 GPs exceeding the mean drug costs/patient of all Hessian physicians by > or = 40%; 10 moderators. Peer-review feedback of prescription patterns based on guidelines targeting 3 suboptimal prescribing areas: drug prescriptions lacking evidence-based efficacy (target A); presumptive prescribing habits (target B); and underprescribing of new, effective therapies (target C). Significant decreases in prescription rates for target A drugs were recorded for varicose vein medications (p = 0.006), peripheral vasodilators (p = 0.0001) and topical antirheumatics (p = 0.0145), but not for prokinetics/enzymes/digestives. Prescribing of target B drugs such as benzodiazepines and nonsteroidal anti-inflammatory drugs declined markedly (p = 0.0019 and 0.0014, respectively). Target C drug prescriptions such as for opioids and proton pump inhibitors were not significantly increased. Highly significant reductions in prescription costs were observed for target A and B drugs, irrespective of whether GPs were stratified into high, medium or low prescribers. When mean prescribing costs for PTC participants were compared with those of a control group comprising 8000 GPs over a 21-month period, PTC GPs decreased their costs by 2%, whereas drug costs for all Hessian physicians rose by 10%. PTCs appear to be an effective method to optimise the quality of drug prescribing and reduce drug costs.

Clinical Problems with Generic Antiepileptic Drugs

Objective: In the treatment of epilepsy, as in all areas of drug therapy, generic formulations are becoming more important as pressure to reduce drug costs increases. In clinical practice, the interchangeability of reference and generic preparations is often assumed. However, in individual patients with a narrow therapeutic range, switching to another formulation of an antiepileptic agent with low water solubility and nonlinear pharmacokinetics may lead to breakthrough seizures or toxicity The purpose of this study was to examine the bioequivalence and clinical effects after switch of equal daily dosages of two commercially available sustained-release preparations of carbamazepine (CBZ). Patients and Study Design: This was a nonblinded intra-individual trial in 14 patients aged 18 to 52 years with focal epilepsy who had been receiving mono-therapy with the reference preparation of sustained-release carbamazepine (mean dosage 1985 mg/day given twice daily) for at least 35 days. After a minimum of 3 further days, the reference preparation (denoted CBZ-R) was immediately replaced by an identical dosage of the generic preparation (denoted CBZ-G). Under steady-state conditions, for each preparation we determined area under the serum concentration-time curve (AUC), maximum serum concentration (Cmax), minimum serum concentration (Cmin) and peak-trough fluctuation (PTF) of carbamazepine and carbamazepine 10,11-epoxide. Results: One patient dropped out because of intolerable adverse effects with CBZ-G. For carbamazepine, the data for the remaining 13 patients, expressed as CBZ-G/CBZ-R, were: AUC 111.5% [90% confidence interval (CI) 105.6-117.8%]; PTF 90.9% (90% CI 73.4-112.8%); Cmax110.1% (90% CI 100.4-117.0%). These data indicate a higher bioavailability for CBZ-G. For carbamazepine 10,11-epoxide, about 20% higher average concentrations were measured with CBZ-G. Applying the usual inclusion rule [90% CI within the range 80 to 125% (AUC) or 70to 143% (PTF and Cmax) of the reference preparation], the two formulations can be considered as bioequivalent. In contrast, we observed marked adverse effects, such as dizziness, nausea, ataxia, diplopia and nystagmus, in eight of the remaining 13 patients after switching to CBZ-G. Conclusions: Proof of bioequivalence between reference and generic preparations of antiepileptic drugs does not mean that they are freely interchangeable. Generic formulations with proven bioequivalence to branded preparations can be used, for example, at the beginning of treatment or in poorly controlled patients with serum concentrations in the mid range. The results demonstrate that the usual rules for bioequivalence and the range of acceptability for preparations of carbamazepine are problematic.

Effects of a low-cost protocol on outcome and cost in a group practice setting

Study Objective: To investigate, in a group practice setting, the effects of combining information about drug costs with adoption of a voluntary low-cost protocol. Design: Prospective before-and-after intervention comparison study. Setting: Private practice anesthesiology group (certified registered nurse-anesthetists and anesthesiologists) of a large midwestern for-profit hospital. Measurements and Main Results: Clinical outcome and anesthesia-related drug cost were examined for coronary artery bypass grafts (CABG), laparoscopic cholecystectomy (LC), and lumbar laminectomy (LL). There were no restrictions on the use of any drug if warranted by the patient’s condition. 135 consecutive prospective (P) cases performed by the anesthesiology group after the intervention were retrospectively matched by surgery type and surgeon to cases done 9 months prior to the protocol to form the retrospective control group (R) resulting in a total sample of 270 subjects. Significant cost reductions were seen in LC-(57%), LL-(42%), and CABG-(37%). The largest cost reductions were opioids (78%), induction drugs (50%), and muscle relaxants (41%). There were no differences in pain, nausea, or hypertension scores between the P and R groups, but there were minor differences in recovery room, oxygen therapy, and dismissal times between the R and P groups of LC and LL patients. There were no differences in anesthetic outcome for CABG patients between the P and R groups. A follow-up survey completed 4 months after the study demonstrated that muscle relaxant costs and fresh gas flow rates and costs had returned to preintervention levels, while opioid and induction drug savings were maintained. Conclusions: A private practice anesthesia group that followed a voluntary protocol could significantly reduce drug costs with little change in clinical outcome. However, the savings may not be completely maintained after the monitoring period.

Low-flow sevoflurane reduces anaesthesia costs

T he rapid uptake and elimination of volatile anaesthetics such as sevoflurane means that these agents are convenient for induction and maintenance of general anaesthesia in adults and children. In the current economic climate, strategies to reduce drug costs associated with anaesthesia are becoming increasingly important. The amount of volatile agent used, and therefore the cost of the anaesthetic procedure, is directly proportional to the rate of fresh gas flow used during the surgical procedure. Consequently, reducing the rate of flow is a simple way to reduce the cost of anaesthesia, as long as other risks (e.g. haemodynamic) are managed. Several presentations focused on the cost implications of reduced flow sevoflurane administration at the International Anaesthesia Research Society 72nd Clinical and Scientific Congress [ Orlando, US; March 1998 ].