Drug Utilization Analysis Research Articles

Geographical epidemiology of antibacterials in the preschool age

BackgroundThematic maps allow a more rapid and immediate reading of the geographical differences in the distribution of data referred to a specific territory. The aim of this study was to show, for the first time, the application of some statistical and cartographic tools in the analysis of drug utilization in the pediatric population of an Italian region, and to assess the intra-regional difference in the antibiotic prescriptions.MethodsTo assess the type of geographic distribution of the prescriptions, the analyses were based on the standardized prevalence rate (z-score) calculated at the local health unit, health district, and municipality levels. Pearson’s coefficient of correlation was used to evaluate the correlation with hospitalization and the Moran’s I index was used to evaluate the existence of spatial autocorrelation. With the use of Getis-Ord’s G statistic, clusters of areas with high and low levels of prevalence were identified and mapped. The probability of receiving at least one prescription of antibacterials during the year for all the children included in the study was evaluated with a logistic regression model.ResultsWith the use of the maps it was possible to see that the prescriptions were not correlated with the health status of the population, but with the tendency of the pediatrician to prescribe drugs. This was also confirmed by the logistic regression model constructed to estimate the probability of receiving at least one prescription of antibacterials considering, as independent variables: age, sex, prevalence of hospitalizations in the district of residence, prescriptive attitude of the pediatrician, sex of the pediatrician, pediatrician’s age group, and duration of the pediatrician’s contract with the local health unit (LHU).ConclusionsThe priority actions to rationalize the use of antibacterials in the preschool age should concentrate on the active participation of the pediatricians in permanent education activities. Moreover, the competent authorities should increasing their efforts to limit unnecessary prescriptions and increase appropriateness of prescribing.RiassuntoIntroduzioneLe mappe tematiche consentono una più rapida ed immediata lettura delle differenze geografiche nella distribuzione di dati riferiti ad un territorio specifico. Lo scopo dello studio è mostrare, per la prima volta, l’applicazione di alcuni strumenti statistici e cartografici, nell’analisi dell’uso dei farmaci nella popolazione pediatrica di una regione italiana e valutare le differenze intra-regionali.MetodiPer valutare il tipo di distribuzione geografica delle prescrizioni, sono stati calcolati i tassi di prevalenza standardizzati (punteggi-z) a livello di ASL, Distretti Sanitari e Comuni. Per valutare la correlazione con le ospedalizzazioni è stato usato il coefficiente di correlazione di Pearson; per valutare l’esistenza di autocorrelazione spaziale è stato usato l’indice I di Moran. Tramite l’uso della statistica G di Getis-Ord sono stati identificati cluster di aree ad alto e basso livello di prevalenza. Infine con un modello di regressione logistica è stata stimata la probabilità di ricevere almeno una prescrizione nel corso dell’anno per tutti i pazienti inclusi nello studio.RisultatiCon l’uso delle mappe è possibile vedere che le prescrizioni non sono correlate con lo stato di salute della popolazione, ma sono correlate con l’attitudine prescrittiva del pediatra. Questo è confermato anche dal modello di regressione logistica costruito per stimare la probabilità di ricevere almeno una prescrizione considerando come variabili indipendenti l’età, il sesso, la prevalenza di ricoveri nel distretto di residenza, l’attitudine prescrittiva del pediatra, la classe di età del pediatra e la durata della convenzione del pediatra con l’Azienda Sanitaria Locale (ASL).ConclusioniGli interventi primari per razionalizzare l’uso degli antibiotici in età prescolare dovrebbero concentrarsi sulla partecipazione attiva dei pediatri in attività di educazione permanente. Inoltre il contenimento delle prescrizioni di ASL e Distretti dovrebbe prevedere un ulteriore controllo da parte delle autorità competenti in merito all’appropriatezza prescrittiva.

Drug utilization according to reason for prescribing: a pharmacoepidemiologic method based on an indication hierarchy

To develop a pharmacoepidemiologic method for drug utilization analysis according to indication, gender, and age by means of register-based information. Statin utilization in 2005 was applied as an example. Following the recommendations for statin therapy, we constructed an indication hierarchy with eight mutually exclusive levels of register markers of cardiovascular disease and diabetes. Danish residents, as of January 1, 1996, were followed at the individual level in nationwide registers with respect to dispensed prescriptions of cardiovascular drugs and antidiabetics (1996-2005) along with discharge diagnoses and surgical procedures (1977-2005). The highest current possible indication level was assigned to all cohort members. Stratified by indication, gender, and age, statin treatment prevalence and incidence were calculated. Statin treatment prevalence was highest among individuals with myocardial infarction and tended to be higher among men with indications in the upper part of the hierarchy, but it was higher among women (especially the elderly) in the lower part of the hierarchy. Treatment incidence rates followed roughly the same pattern. Women with no register marker or primary hypertension accounted for almost 50% of all incident female users; among men, the figure was 35%. The proportion of incident users with ischemic heart disease or myocardial infarction increased with age. The proposed indication hierarchy provided new insight into prescription patterns of statins. The method can be implemented for other drug categories and could be useful for studying trends in drug utilization, differential drug adherence, and cross-national comparisons.

Analysis of drug utilization in department of oncology,Traditional Chinese Medicine Hospital affiliated to Xinjiang Medical University during 2008-2009 by activity-based costing method

Objective:To investigate the situation of drug utilization in department of oncology in Traditional Chinese Medicine Hospital affiliated to Xinjiang Medical University and provide reference for rational use of drugs in clinic.Methods: Variety and consumption sum of drugs used in department of oncology during 2008-2009 were statistically analyzed by activity-based costing(ABC) method.Distribution of category A drugs was determined.Chinese patent medicines and anti-tumor medicines of category A were ranked in order of comsumption sum.Results: The consumption sum of drugs in 2009 was increased by 0.66% compared with that in 2008,while the constituent proportions were not significantly changed.The consumption sum of Chinese patent medicines ranked first in category A,in which the injections were the majority.Anti-tumor drugs ranked the second.The constituent proportions of anti-tumor drugs,immunomodulators,anti-microbials,drugs for circulatory system diseases,analgesics,drugs for respiratory system diseases and hormones in 2009 were increased compared with those in 2008,while the drugs used for digestive diseases,drugs affecting bone metabolism,vitamins and trace element nutrients decreased.The constituent proportion of drugs for blood system diseases did not significantly changed.Conclusion: Some irrational use of drugs exists in department of oncology of this hospital and the management need to be strengthened.

P02-450 - Pharmacoepidemiologic studies on psychiatric drugs use in Serbia

High rate of prescribing of psychiatric drugs causes medical, social and economic consequences.This research was performed by collecting and analysing all the papers published on this matter in Serbia.In former Yugoslavia (of which Serbia was a constitutive republic), during the eighties, a study of benzodiazepines use showed a trend of the increase of their use (17,9 defined daily doses - DDDs in 1983 - 22,3 DDDs in 1988) (Macolic V et al. Benzodiazepines utilization in Yugoslavia 1983–1988. Pharmaca 1990;217–97). Similar trends continued in the nineties. In 1994 diazepam was at the first position on the list of most prescribed drugs (Miljković M. et al. Analysis of Drug Utilization in Serbia During the Years 1996 and 1997. Pharmacoepidemiol Drug Saf 2000;9:59–64.). The analysis of the trend of prescribing of psychiatric drugs in Serbia (2000–2004) shows the increase, with the emphasis on the use of benzodiazepines and antidepressants (Divac N. et al. Trends in consumption of psychiatric drugs in Serbia and Montenegro 2000–2004. Pharmacoepidemiol Drug Saf. 2006;15:835–8.). There are also positive, qualitative changes in the prescribing practice: the increase of the use of SSRI antidepressants and atypical antipsychotics. Specific prescribing habits were noticed: the common practice of polypharmacy in the treatment of psychoses (Divac N. et al. Antipsychotic polypharmacy at the University Psychiatric Hospital in Serbia. Pharmacoepidemiol Drug Saf. 2007;16:1250–1.).Pharmacoepidemiologic methods have found its place in Serbian science. The methodology used in these studies is mostly up-to-date. Main limitation of these studies is the lack of databases.

Drug Utilization and Cost Analysis for Common Skin Diseases in Dermatology OPD of an Indian Tertiary Care Hospital - A Prescription Survey

Introduction: Epidemiology of skin diseases has been studied and evaluated occasionally. In view of high incidence of skin diseases and economic burden that it poses, there is a need to evaluate the present epidemiology and prescribing pattern of skin disorders. Objective: To assess common skin conditions, drug utilization patterns and cost analysis in Dermatology Out patients Department (OPD) of Tertiary Care hospital. Methodology: After taking Ethics committee’s permission, prescriptions of 600 patients attending Dermatology OPD were audited. The prescriptions were analyzed for common skin conditions drug utilization and cost analysis. Results: The common skin conditions found were Pyoderma and Scabies while common classes of drugs prescribed were antiallergics, antifungals and steroids. Drugs prescribed by Generic name were 16.6% and Brand names were 83.4%. It was revealed that 30% of total drugs dispensed from hospital pharmacy and 70% from outside pharmacy. Average hospital and outside pharmacy costs were INR19.40 and INR116.20, respectively. The outside pharmacy cost of prescription (Spearman’s Rho = -0.130, p < 0.01) as well as cost paid by the patients (Spearman’s Rho = 0.408, p < 0.001) had a negative correlation with the socioeconomic score as the drugs were prescribed irrespective of the socioeconomic class. Conclusion: The dermatological prescription analysis gives a message to the prescribing physician to achieve rational and cost effective medical care. The drugs which are made available in the hospital pharmacy should be based on clinical evidence generated from meta-analysis of drug studies, pharmacoepidemiology and pharmacoeconomic studies. There is dire need for physicians training with regards to rational use of drugs and pharmacoeconomics. Hospital should make essential drugs available with continuous monitoring to improve the prescribing pattern. The limitation of this study is that the actual direct costs and indirect costs were not studied. It opens the scope for further study in this area.

Drug Utilization and Cost Analysis for Common Skin Diseases in Dermatology OPD of an Indian Tertiary Care Hospital - A Prescription Survey

Introduction: Epidemiology of skin diseases has been studied and evaluated occasionally. In view of high incidence of skin diseases and economic burden that it poses, there is a need to evaluate the present epidemiology and prescribing pattern of skin disorders. Objective: To assess common skin conditions, drug utilization patterns and cost analysis in Dermatology Out patients Department (OPD) of Tertiary Care hospital. Methodology: After taking Ethics committee’s permission, prescriptions of 600 patients attending Dermatology OPD were audited. The prescriptions were analyzed for common skin conditions drug utilization and cost analysis. Results: The common skin conditions found were Pyoderma and Scabies while common classes of drugs prescribed were antiallergics, antifungals and steroids. Drugs prescribed by Generic name were 16.6% and Brand names were 83.4%. It was revealed that 30% of total drugs dispensed from hospital pharmacy and 70% from outside pharmacy. Average hospital and outside pharmacy costs were INR19.40 and INR116.20, respectively. The outside pharmacy cost of prescription (Spearman’s Rho = -0.130, p < 0.01) as well as cost paid by the patients (Spearman’s Rho = 0.408, p < 0.001) had a negative correlation with the socioeconomic score as the drugs were prescribed irrespective of the socioeconomic class. Conclusion: The dermatological prescription analysis gives a message to the prescribing physician to achieve rational and cost effective medical care. The drugs which are made available in the hospital pharmacy should be based on clinical evidence generated from meta-analysis of drug studies, pharmacoepidemiology and pharmacoeconomic studies. There is dire need for physicians training with regards to rational use of drugs and pharmacoeconomics. Hospital should make essential drugs available with continuous monitoring to improve the prescribing pattern. The limitation of this study is that the actual direct costs and indirect costs were not studied. It opens the scope for further study in this area.

Co-prescription of gastroprotective agents in patients taking non-selective NSAIDs or COX-2 selective inhibitors: analysis of prescriptions

To evaluate the prevalence of co-prescription of GPAs (proton pump inhibitors - PPIs and H2-receptor antagonists) and non-selective NSAIDs or COXIBs in patients registered under the local health authority (LHA) of Bergamo, a city in the north of Italy. A drug utilization analysis was done using the Bergamo prescription Health Services Electronic Database. All patients aged 35 years or older who had received at least one prescription during 2004 for non-selective NSAIDs and/or COXIBs were divided into three groups: occasional, chronic and new users. Among chronic users, 44.8% were treated with non-selective NSAIDs, 11.6% with COXIBs, and 43.6% with both (mixed NSAIDs). For new users, non-selective NSAIDs were prescribed to 82.7%, COXIBs and mixed NSAIDs to 10.8% and 6.5%. PPIs were co-prescribed to 7.1% of COXIB users and 5.8% of non-selective NSAID occasional users. Among chronic users, the figures were 15.6% and 14%. For new users, prescriptions for COXIBs were associated with less use of GPA for patients who received the first and last prescription for NSAIDs and GPAs on the same day, while for patients who became chronic users COXIBs did not reduce the probability of co-prescription of a GPA: the number of co-prescribed medications and antithrombotics or corticosteroids were independent predictors of GPA use. COXIBs seem to be used in patients at high risk of GI toxicity. However, the fear of GI adverse reactions and the uncertain safety profile of COXIBs leads many physicians to boost the gastroprotection by prescribing a PPI.

PDB11 DRUG-USE PATTERNS OF INITIALLY PRESCRIBED INSULIN DETEMIR AND INSULIN GLARGINE IN THE NETHERLANDS;A COMPARATIVE ANALYSIS USING PHARMACY DATA FROM IADB. NL

OBJECTIVES: Newer long-acting insulin analogs have shown to result in several treatment improvements if compared with NPH insulins. Promising results from clinical trials require confirmation from observational settings reflecting potential “real-life” benefits. Therefore, the current study aimed to evaluate trends in prescribing (uptake), treatment adherence, and costs of (newer) insulin analogs (e.g., insulin detemir and insulin glargine). METHODS: A drug-utilization analysis was conducted based on using daily- practice prescription data from IADB.nl (one of the databases available in the Mondri- aan infrastructure), a dispensing database of 50 pharmacies, covering a Dutch population of 500,000. Drug-utilization data were collected for a 7-year period (2000-2007). All patients that received at least one prescription of an insulin analog-defined following the “Anatomical Therapeutical Classification” (ATC) as “A10A”-were included for this study. The prevalence and incidence of insulin use were both presented per 1000 population. Survival analysis was conducted to calculate the persistence on different insulin analogs. RESULTS: Preliminary results show a fast increase in the proportion of patients using the newer long-acting insulin analogs with 7% in 2003 to over 30% in 2006. Among patients initiating these newer insulin analogs, use of insulin glargine is more than two times higher compared to use of insulin detemir (507 vs. 190 starters in 2006). Patients that initiated treatment with long-acting insulin analogs were significantly more adherent to insulin glargine compared to insulin detemir (exact figures will be presented during the presentation). CONCLUSIONS: Current preliminary results show an increase in use of long-acting insulin analogs. Of these analogs, insulin glargine is most often initiated and seems to be well-received by patients. Further results will be presented based on a longer follow-up period including differences in HbAlc level dependent dosing and trends in cost development for insulin analogs over time. Also, the potential feature of “channelling” will be investigated.

Drug use evaluation of tamoxifen focusing on off-label use in a managed care population in Israel.

Policy development to manage new off-label uses of medications is an issue relevant to health policy stakeholders internationally. Retrospective drug utilization analyses may be useful to identify practice trends in the use of drugs for unapproved (off-label) uses. Since drug use evaluations (DUE) are generally performed for expensive medications or when safety concerns warrant increased scrutiny, patterns of off-label use of inexpensive drugs will probably be undetected. Tamoxifen citrate, an estrogen receptor antagonist, is indicated in Israel exclusively for palliative [sic: meaning adjuvant] treatment of breast cancer. This DUE was motivated by observations that tamoxifen may be used off-label for indications without evidence of safety or efficacy. To assess the extent of off-label prescribing of tamoxifen and ascertain what evidence is available supporting the use of the drug for the off-label indications observed. A retrospective DUE of tamoxifen was performed for the 12 months of calendar year 2008 in a 650,000-member HMO in Israel for patients who received at least 1 prescription for tamoxifen. All patients for whom tamoxifen was dispensed in 2008 were identified from pharmacy claims data. The HMO's electronic patient record (EPR) was subsequently queried to identify the diagnoses of patients who received tamoxifen and exclude those patients who had a diagnosis code (ICD-9-CM 174.x or 175.x) for breast cancer. An EPR chart review was also performed to identify and exclude patients who had a diagnosis or treatment of breast cancer that was recorded in free text. For the patients who did not have a diagnosis code or free-text description of breast cancer, the recorded off-label diagnoses and ICD-9-CM codes in the EPR during the visit when tamoxifen was first prescribed were tabulated. A literature search was conducted to collect information supporting the use of tamoxifen for the observed off-label indications. We defined the use as "supported" if studies were found in PubMed, Cochrane database, or Micromedex that supported the clinical decision to use the drug for the off-label indication. 877 patients were treated with tamoxifen in 2008 of whom 826 (94.2%) had a diagnosis of breast cancer, and 51 patients (5.8%) received the drug from 41 physicians in 7 medical specialty categories for 25 different off-label diagnoses. Of these 25 diagnoses, 33 patients (64.7% of 51 patients with off-label use) received tamoxifen for 8 diagnoses that were associated with some evidence to support their off-label use. Malignant neoplasm of ovary (n = 13) and female infertility (n = 13) were the most commonly recorded indications with some evidence to support off-label use. Of the 13 women treated for infertility, 9 (69.2%) had been treated with clomiphene citrate prior to being treated with tamoxifen, suggesting that some physicians may be experimenting with tamoxifen as second-line treatment. Tamoxifen was found to be used off-label in only 5.8% of the patients who received the drug in 2008 in this HMO, and only 18 patients (2.1%) received tamoxifen for a diagnosis that did not have some supporting evidence of efficacy. Since off-label prescribing of tamoxifen was found to be relatively rare, this HMO did not impose a prior authorization requirement for this drug and instead added an edit in the EPR to block off-label prescribing by requiring the physician to register a diagnosis of breast cancer.

Cost Shifting and Timeliness of Drug Formulary Decisions in Atlantic Canada

Our objectives were to investigate the timeliness of formulary decision-making in Atlantic Canada, including the Common Drug Review (CDR) process and the adoption of positive CDR recommendations by Atlantic Canadian provincial public drug plans, and to determine the degree of cost shifting to private payers. Dates of formulary listing decisions from Atlantic Canadian provincial drug plan formularies and utilization analyses from Medavie Blue Cross were used to calculate the timeliness of decisions and cost shifting from public payers to a private payer. The median time period between the issuance of a positive CDR recommendation and the addition of a drug to an Atlantic Canadian provincial drug plan was 26.7 weeks (σ=19.1). Cost shifting to employer-sponsored health plans provided by Medavie Blue Cross was minimal. There is significant variation in the timing of provincial drug formulary listings among the four Atlantic Canadian provinces and the uptake of CDR recommendations. Atlantic Canadian provincial governments should support the mandate of the CDR by aiming for a more timely consideration of recommendations.

Cost Effectiveness of Angiotensin Receptor Blocker Monotherapy in Patients with Hypertension in the Netherlands

Health gains and related cost savings achieved by optimizing treatment in hypertensive patients is highly important. The aim of this study was to evaluate the costs and cost effectiveness of treatment with angiotensin II receptor antagonists (angiotensin II receptor blockers [ARBs]) in patients with essential hypertension and to compare within-trial with real-life dosing of ARBs. Cost effectiveness was estimated based on a published clinical trial comparing the BP-lowering effects of olmesartan, losartan, valsartan, and irbesartan. BP lowering after 8 weeks of treatment was entered into the Framingham risk functions to estimate cardiovascular complications after 1 and 5 years, using an international health economics model that was adapted to the Netherlands. Dutch costs (2006 values) and complications derived from the model were discounted at 4% and 1.5%, respectively, and cost effectiveness was expressed in net costs per cardiovascular complication averted. In a drug-utilization study, pharmacy dispensing records were used to evaluate differences between within-trial and daily-practice dosing and related costs for treatment in the Netherlands. After 8 weeks, the trial-based analysis showed that treatment with olmesartan versus losartan, valsartan, and irbesartan resulted in a significantly larger decrease in BP (11.5 vs 8.2, 7.9 and 9.9 mmHg [p < 0.05], respectively) and consequently more complications averted. Cost effectiveness for olmesartan, losartan, valsartan, and irbesartan was estimated at euro39,100, euro77,100, euro70,700, and euro50,900 per cardiovascular complication averted, respectively. The incremental cost-effectiveness analysis indicated the most favorable cost-effectiveness outcome for olmesartan, with lower costs and less cardiovascular complications for olmesartan compared with the other three ARBs. The drug-utilization analysis showed that the dosing followed within clinical trials was not found in daily practice. On average, losartan, valsartan, and irbesartan were administered at doses above those used in clinical trials, whereas olmesartan was dosed lower than in clinical trials, resulting in relatively lower costs. Based on the exact trial data, olmesartan was estimated to be the most favorable option of the four ARBs based on within-trial decreases in BP levels after 8 weeks and in terms of cost-effectiveness for this particular Dutch setting. However, for definite conclusions to be drawn, this hypothesis-generating study requires confirmation from further prospective studies comparing ARBs based on comparable BP control and including hard endpoints.

Results of a retrospective database analysis of drug utilization and costs for treatment of chronic hepatitis B virus infection in the Northern Netherlands between 2000 and 2006

Objectives: The main aims of this work were to describe patterns of medication use in the treatment of chronic hepatitis B virus (HBV) infection in patients in the northern part of the Netherlands and to compare these practices with established guidelines. In addition, the duration of use and the costs of these treatments were investigated. Methods: We selected subjects from the University of Groningen's IADB.nl database; by 2006, the database provided information about drug utilization from 55 community pharmacies in the northern Netherlands and included a population of 528,911 individuals, of which 49% were male. Eligible subjects had received ≥1 prescription for drugs used to treat chronic HBV infection (ie, lamivudine, pegylated interferon-α2a, pegylated interferon-α2b, adefovir, tenofovir, and entecavir) between the years 2000 and 2006. The annual prevalence and cumulative incidence of HBV treatment per 1000 people covered in the database were calculated and stratified by sex. Kaplan-Meier survival analysis was used to analyze the duration of use. Drug costs in the treatment were calculated for all patients or per patient, and by drugs used per subperiod (2000–2003 and 2004–2006). Treatments for hepatitis C virus and HIV were excluded from the analyses. Results: From the database, we identified 59 patients (46 male, 13 female), aged 25 to 60 years, who received ≥1 prescription for a medication to treat chronic HBV infection between 2000 and 2006. The overall prevalence of people using chronic treatments for HBV was between 0.03 and 0.06 per 1000 during the years of the study. The cumulative incidence of treatment was ∼0.01 per 1000 per year (ranging from a high of 0.021 in 2000 to a low of 0.009 in 2006). When stratified by sex, there were more male than female subjects who received medications for HBV. Lamivudine was the most commonly prescribed drug, followed by adefovir and pegylated interferon-α2b. In 2000 and 2001, lamivudine was the only medication prescribed for the treatment of chronic HBV. From 2002 to 2006, the prescription rate for lamivudine dropped from 90% to 61%. In contrast, the prescription rate for adefovir increased from 4% in 2003 to 36% in 2006. Pegylated interferon-α2b remained stable at 8% to 11% between 2002 and 2006. Twenty-five percent of patients had stopped HBV treatment by the end of 1 year. Fifty-five percent had stopped by 3 years. Seventy-seven percent of patients received their first HBV prescription from a medical specialist. Per patient, the cost of drug therapy was highest with adefovir. From 2004 to 2006, the cost of adefovir therapy accounted for 49% of total expenditures for the treatment of chronic HBV (equivalent to €128,037; as of January 2010, €1.00 = US $1.43). The second and third most expensive drugs were tenofovir and pegylated interferon-α2b (€33,700 and €33,250, respectively). Costs incurred per patient increased over the years of the study period. Conclusions: The overall prevalence and cumulative incidence of patients with treatments for chronic HBV were relatively low in the northern part of the Netherlands between 2000 and 2006. The prescribing and utilization patterns were in agreement with international and Dutch guidelines. Given the low numbers of prescriptions, the costs also remained relatively low.

The Impact of Primary Prophylaxis for Cryptococcosis on Fluconazole Resistance in Candida Species

To the Editor: Primary anticryptococcal prophylaxis in advanced HIV infection is generally not recommended, given no evidence for improved survival, associated excess costs, and the potential risk for emerging drug resistance.1 In Thailand, however, the prevalence of cryptococcosis is high, primary fluconazole prophylaxis has been associated with reduced invasive fungal infections and mortality, and primary cryptococcal prophylaxis is recommended in national HIV treatment guidelines.2,3 Although primary prophylaxis has not been shown to select for fluconazole resistance among patients who subsequently developed cryptococcal meningitis,4 the impact of primary anticryptococcal prophylaxis on the emergence of fluconazole resistance in Candida species among patients with HIV infection has not been evaluated. Thammasart University is a 450-bed tertiary care referral hospital in central Thailand. Infectious diseases consultative services and care formally began in January 2003, with an annual increase in the number of HIV-related admissions from the year 2002 (N = 125) to the year 2006 (N = 405). Most HIV-related admissions were for the evaluation of fever; 45% of cases had CD4 counts <100 cells/μL.5 Since 2003, primary anticryptococcal prophylaxis has been routinely prescribed to patients with advanced HIV infection (CD4 counts <100 cells/μL), as recommended by the Thai National HIV Treatment Guideline.3 We conducted a drug utilization and antimicrobial resistance correlation analysis of inpatient antifungal consumption and the prevalence of fluconazole-resistant Candida spp. among hospitalized adults with HIV infection for the calendar years 2002 to 2006. The rate of inpatients' antifungal use was recorded as the total number of grams of drug, converted into defined daily doses (DDDs) per 1000 patient-days, in accordance with the recommendations of the World Health Organization.6 Oral and parenteral drug expenditures were included for analysis. Antimicrobial susceptibility patterns of Candida spp., and the proportion of resistant isolates, were derived from existing data in the Microbiology Department. Correlations between antifungal consumption and resistance were assessed by Pearson correlation analyses. There was an incremental increase in oral fluconazole consumption (from 6 to 35 DDDs per 1000 patient-days) during the years 2002 to 2006, whereas the consumption of oral itraconazole and other parenteral antifungal agents (eg, fluconazole, amphotericin B) remained unchanged (Table 1). Notably, 86% of oral fluconazole prescriptions were for primary anticryptococcal prophylaxis, and 36% of the patients prescribed oral fluconazole had CD4 counts >100 cells/μL for at least 6 months. During the same 5-year period that the prevalence of fluconazole-resistant Candida spp. increased from 2% to 33%, detection of Candida albicans significantly declined from 95% to 54% (see Table 1). A significant correlation between oral fluconazole consumption and fluconazole-resistant Candida spp. (r = 0.71, P < 0.001) was noted. No correlation was evident for fluconazole-resistant Candida spp. and other antifungal drugs.TABLE 1: Antifungal Consumptions and Incidence of Inpatient Candida spp. From Year 2002 Through 2006Our study findings have significant implications for clinical and laboratory practices. The incremental increase in oral fluconazole consumption was temporally attributed to the national HIV prevention policy for opportunistic infections. Notably, this increase in fluconazole use correlated with increased fluconazole-resistant Candida spp. Our findings suggest that systematic surveillance for fluconazole-resistant Candida spp. is judicious in countries where primary anticryptococcal prophylaxis is given to persons with advanced HIV infection. In addition, our findings imply potential benefit from interventions that minimize inappropriate antifungal use in developing countries. Focused educational interventions aimed at improving guideline compliance with prophylaxis against opportunistic infections are needed. Anucha Apisarnthanarak, MD* Linda M. Mundy, MD† *Division of Infectious Diseases Thammasart University Hospital Pratumthani, Thailand †Saint Louis University School of Public Health Saint Louis, MO

An Informatics Approach to Assess Pediatric Pharmacotherapy: Design and Implementation of a Hospital Drug Utilization System

Drug utilization in the inpatient setting can provide a mechanism to assess drug prescribing trends, efficiency, and cost-effectiveness of hospital formularies and examine subpopulations for which prescribing habits may be different. Such data can be used to correlate trends with time-dependent or seasonal changes in clinical event rates or the introduction of new pharmaceuticals. It is now possible to provide a robust, dynamic analysis of drug utilization in a large pediatric inpatient setting through the creation of a Web-based hospital drug utilization system that retrieves source data from our accounting database. The production implementation provides a dynamic and historical account of drug utilization at the authors' institution. The existing application can easily be extended to accommodate a multi-institution environment. The creation of a national or even global drug utilization network would facilitate the examination of geographical and/or socioeconomic influences in drug utilization and prescribing practices in general.

When gatekeepers meet the sentinel: the impact of a prior authorization requirement for cefuroxime on the prescribing behaviour of community‐based physicians

Prior authorization (PA), the requirement of physicians to obtain pre-approval as a prerequisite for coverage, may decrease drug utilization via a 'sentinel effect', a decrease in utilization caused by external review of prescribing. The purpose of this study was to assess the affect a PA restriction had on the utilization patterns of cefuroxime tablets in a managed care organization (MCO) in Israel. Physician prescribing patterns were evaluated by conducting a retrospective drug utilization analysis. Data were derived from the electronic patient records of the MCO studied. All prescriptions for solid state antibiotics for patients diagnosed with an infectious disease written during three parallel 3-month segments, before, during and after a PA restriction for cefuroxime was enforced, were included. Frequency and proportion of antibiotic prescriptions for cefuroxime tablets, distribution of infectious diseases treated with cefuroxime, and the request rejection rate when PA was required were calculated. Prescriptions for cefuroxime declined from 5538 prescriptions (8.0% of eligible antibiotic prescriptions, 95% CI 7.8, 8.2) in the initial period to 1036 (1.2%, 95% CI 1.1, 1.3) during the PA period, rising to 3961 (4.3%, 95% CI 4.2, 4.4) in the post-PA period. Changes in the distribution of diseases treated with cefuroxime during the PA stage tended to regress after revocation to those observed in the pre-PA period. The rejection rate was found to be 8.5% (95% CI=6.9, 10.1). The implementation of a prior authorization requirement for cefuroxime tablets markedly reduced the use of this drug, probably due to a 'sentinel effect'.

Impact of clinical pharmacology on health care: Serbian experience

Dear Sirs, During the recent 7th Congress of the European Association for Clinical Pharmacology and Therapeutics, held in Poznan, Poland, serious concerns were expressed by leading invited speakers on the future of clinical pharmacology as a discipline [1]. Their joint conclusion was that clinical pharmacologists in the majority of developed European countries are less and less involved in health care [2]. ‘‘It is the retreat from the bedside into the laboratory that is responsible’’ for the discipline’s decline, one of the speakers said ominously [3]. However, this trend is not taking place in all European countries. In some Eastern European countries, clinical pharmacology is still very much a patientbased discipline, with a significant impact on health care. It is that impact that keeps the discipline alive and prosperous, as can be seen from the Serbian experience. The status and impact of clinical pharmacology on health care in Serbia was investigated in two ways: by field survey and by questionnaire. In the field survey, 38 hospitals and health centers (two tertiary health care hospitals, three mixed tertiary/secondary health care hospitals, and 33 health centers, each consisting of a secondary care hospital plus a primary health care facility) were visited twice during the years 2002 to 2005, and the anonymous questionnaire was sent to 78 available clinical pharmacologists (out of 90 registered) from November 2004 to January 2005. While the field survey confirmed that the tertiary care and the mixed tertiary/secondary care hospitals had three to four clinical pharmacologists each, and four health centers had one clinical pharmacologist each, the questionnaire showed that 50% of the respondents (60 clinical pharmacologists) worked in the health care system, half of them as full-time employees. Both the field survey and the questionnaire indicated that the following services were given by clinical pharmacologists in the Serbian health care system: drug/patient problem consultations, drug information, chairing of drug and therapeutics committees, intensive monitoring of adverse drug effects, therapeutic drug monitoring, formulation of hospital drug policies, auditing of prescribing practice, design of postmarketing studies, continuing medical education, predispensing control of prescribing, and drug utilization analyses. The scope of health care services given by clinical pharmacologists was the largest in the two tertiary care hospitals with independent departments of clinical pharmacology. There is a growing trend in the number of services given, as can be seen from the data from the Center for Clinical and Experimental Pharmacology, Clinical Center ‘‘Kragujevac,’’ for a 10-year period (Fig. 1). Due to good organization of work within the departments, the drug management process in both hospitals was advanced (active drug and therapeutics committees, more than 60 local guidelines adopted), and the availability of all necessary drugs was achieved within the limits of modest drug budgets. Both hospitals had drug formularies completely agreed upon by other clinicians that yet were not far from the World Health Organization’s essential drugs model list (for instance, Clinical Center ‘‘Kragujevac’’ had 338 different drug entities and 584 formulations in total, with 6.08 euros spent for drugs per one bed-day in 2004; the available budget for 2004 was 5.94 euros per one bed-day). With predispensing control of prescribing (in Clinical Center ‘‘Kragujevac,’’ errors were found in about 12% of prescriptions, and drug dispensing was corrected appropriately), continuing medical education, and auditing of prescribing practice, clinical pharmacologists in these S. M. Jankovic (&) AE D. R. Milovanovic University of Kragujevac and Center for Clinical & Experimental Pharmacology, Clinical Center ‘‘Kragujevac’’, Kragujevac, Serbia & Montenegro

Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost

The objective of this study was to evaluate the impact of medication adherence on healthcare utilization and cost for 4 chronic conditions that are major drivers of drug spending: diabetes, hypertension, hypercholesterolemia, and congestive heart failure. The authors conducted a retrospective cohort observation of patients who were continuously enrolled in medical and prescription benefit plans from June 1997 through May 1999. Patients were identified for disease-specific analysis based on claims for outpatient, emergency room, or inpatient services during the first 12 months of the study. Using an integrated analysis of administrative claims data, medical and drug utilization were measured during the 12-month period after patient identification. Medication adherence was defined by days' supply of maintenance medications for each condition. The study consisted of a population-based sample of 137,277 patients under age 65. Disease-related and all-cause medical costs, drug costs, and hospitalization risk were measured. Using regression analysis, these measures were modeled at varying levels of medication adherence. For diabetes and hypercholesterolemia, a high level of medication adherence was associated with lower disease-related medical costs. For these conditions, higher medication costs were more than offset by medical cost reductions, producing a net reduction in overall healthcare costs. For diabetes, hypercholesterolemia, and hypertension, cost offsets were observed for all-cause medical costs at high levels of medication adherence. For all 4 conditions, hospitalization rates were significantly lower for patients with high medication adherence. For some chronic conditions, increased drug utilization can provide a net economic return when it is driven by improved adherence with guidelines-based therapy.

Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: Comparative analysis of drug utilization, costs, and hematologic response

A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (approximately US$9800 or approximately 8300) with epoetin alfa and SEK85,285 (approximately US$11,000 or approximately 9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81% and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.

Physician Adherence to Recommendations for Duration of Empiric Antibiotic Treatment for Uncomplicated Urinary Tract Infection in Women: A National Drug Utilization Analysis

Physician Adherence to Recommendations for Duration of Empiric Antibiotic Treatment for Uncomplicated Urinary Tract Infection in Women: A National Drug Utilization Analysis

Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money.

Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines. To evaluate the economic consequences of longer than recommended durations of antibiotic therapy in the empiric treatment of uncomplicated UTI in women. Data were derived from the electronic records of one of the four health maintenance organizations in Israel. The sample included all women aged 18-75 years who were diagnosed with acute cystitis or UTI from January 2001 to June 2002 and were empirically treated with antibiotics. Of the 7738 patients identified, 1138 received nitrofurantoin and 1054 ofloxacin. The excess expenditure accrued due to longer than recommended therapy with these drugs was evaluated. The rate of adherence was 22.23% for nitrofurantoin (95% CI=19.81%, 24.65%), and 4.08% for ofloxacin (95% CI=2.88%, 5.28%). The average excess expenditure per case was 5.78 USD (US Dollar) with ofloxacin and 3.43 USD with nitrofurantoin, resulting in an annual loss to the health maintenance organizations of approximately 19,000 USD. When extrapolated to the national population of 6.5 million, the loss due to inappropriate treatment of adult women is 190,000 USD. The lack of adherence to national and international guidelines with regard to the recommended duration of antibiotic treatment of UTI in women resulted in a significant and avoidable waste of health system resources. This study suggests that drug utilization analyses that concentrate solely on the choice of drug may be overlooking important information.