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The impact of a pharmacist-managed dosage form conversion service on ciprofloxacin usage at a major Canadian… Ho, Bradley P; Lau, Tim T; Balen, Robert M; Naumann, Terryn L; Jewesson, Peter J Jun 29, 2005

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ralssBioMed CentBMC Health Services ResearchOpen AcceResearch articleThe impact of a pharmacist-managed dosage form conversion service on ciprofloxacin usage at a major Canadian teaching hospital: a pre- and post-intervention studyBradley P Ho1, Tim TY Lau*1,2, Robert M Balen1,2, Terryn L Naumann1,2 and Peter J Jewesson2Address: 1Pharmaceutical Sciences Clinical Services Unit, Vancouver General Hospital, Vancouver Coastal Health, 855 West 12th. Avenue, Vancouver, BC, Canada, V5Z 1M9 and 2Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, Canada, V6T 1Z3Email: Bradley P Ho - Bradley.Ho@vch.ca; Tim TY Lau* - Tim.Lau@vch.ca; Robert M Balen - Robert.Balen@vch.ca; Terryn L Naumann - Terryn.Naumann@vch.ca; Peter J Jewesson - pjj@interchange.ubc.ca* Corresponding author    AbstractBackground: Despite cost containment efforts, parenteral (IV) ciprofloxacin appears to be overutilized at VancouverGeneral Hospital. In November 2003, the Pharmacist-managed intravenous to oral (IV-PO) Dosage Form ConversionService was implemented, enabling autonomous pharmacist-initiated dosage form conversion for ciprofloxacin. Thisstudy evaluates characteristics of ciprofloxacin use prior to and following implementation of this conversion service.Methods: This was a single-centre, two-phase (pre/post), unblinded study. Phase I occurred between November 12,2002 and November 11, 2003 (365 days), and Phase II between November 12, 2003 and March 11, 2004 (120 days). Allpatients receiving ciprofloxacin IV during these periods were reviewed. The primary endpoint was IV:PO ciprofloxacinuse ratio. Secondary endpoints were total number of ciprofloxacin doses, proportion of inappropriate IV ciprofloxacindoses, cost of therapy between phases, and estimated cost avoidance with the intervention.Results: Two hundred ciprofloxacin IV treatment courses were evaluated (100 per phase). The IV:PO ciprofloxacin useratio was 3.03 (Phase I) vs. 3.48 (Phase II). Total number of doses and ratio of IV to total doses across phases were similar(p = 0.2830). IV-PO ciprofloxacin conversion occurred in 27/100 (27%) of IV courses in Phase I and 23/100 (23%) in PhaseII. Proportion of inappropriate ciprofloxacin IV doses decreased between Phases I and II (244/521 (47%) vs. 201/554(36%) (p = 0.0005), respectively). Furthermore, the proportion of pharmacist-preventable inappropriate ciprofloxacin IVdoses was reduced between Phases I and II (114/244 (47%) vs. 65/201 (32%) (p = 0.0026). Proportional cost avoidanceassociated with total inappropriate IV use was $7,172/$16,517 (43%) (in Canadian dollars) in Phase I vs. $6,012/$17,919(34%) in Phase II (p = 0.001). Similarly, proportional cost avoidance associated with pharmacist-preventable inappropriateIV doses was reduced from $3,367/$16,517 (20%) in Phase I to $1,975/$17,919 (11%) in Phase II (p = 0.001).Conclusion: While overall utilization of ciprofloxacin remained unchanged and the proportion of IV to total doses wasstable during the study period, the proportion of inappropriate IV doses and its associated costs appear to have declinedsubsequent to implementation of a Pharmacist-managed IV-PO Dosage Form Conversion Service. Such a program maybe a beneficial adjunct in facilitating appropriate and cost-effective usage of ciprofloxacin.Published: 29 June 2005BMC Health Services Research 2005, 5:48 doi:10.1186/1472-6963-5-48Received: 07 March 2005Accepted: 29 June 2005This article is available from: http://www.biomedcentral.com/1472-6963/5/48© 2005 Ho et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 8(page number not for citation purposes)BMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48BackgroundThe annual drug expenditures at Vancouver Hospital areapproximately $13 million (in Canadian dollars). At theVancouver General Hospital (VGH) site, anti-infectivesaccounted for an expenditure of $3.39 million or 25% ofthe 2002–03 fiscal year total drug costs. Ciprofloxacinranked third among all drugs by cost and was the secondhighest annual expenditure within the anti-infective drugclass at $646,000. In addition, ciprofloxacin expendituresincreased 5% from the previous year. Of the 39,147 cipro-floxacin doses administered in the 2002–03 fiscal year,18,297 doses (47%) were given intravenously (IV).Ciprofloxacin is a fluoroquinolone antibacterial that isprimarily active against aerobic gram-negative bacterialinfections [1]. It can be administered via the IV and oral(PO) routes. Concentrations similar to those achievedwith the IV formulation are possible when administeringciprofloxacin orally, as it is highly bioavailable [2,3]. Thedaily drug cost (including material and labour costs fordispensing, preparation, and administration) of a typicalciprofloxacin 400 mg IV regimen administered twice dailyis $72.62 [4]. Conversely, the daily drug cost of an equiv-alent ciprofloxacin 500 mg PO regimen given twice dailyis $8.48, or 12% of the IV regimen [4].In an effort to optimize use and minimize drug expendi-tures, ciprofloxacin has been designated a reserved anti-microbial drug (RAD) at our institution and has beenincluded in the existing intravenous to oral (IV-PO) Step-down Program since 1992 [5]. Under this initiative, theuse of the PO formulation of ciprofloxacin has been pro-moted at our institution through the means of newsletters[6], chart talkers and notes [7,8], and direct pharmacist-physician interactions. Other drugs included in this pro-gram are cefuroxime, cefixime, clindamycin, fluconazole,levofloxacin, and metronidazole.Despite these cost containment efforts, there is some evi-dence to suggest that the IV formulation of these drugsmay not be optimally utilized. Previous investigations byothers and ourselves have shown that the IV formulationis often initiated when the PO formulation can be used [9-13]. Of equal importance, conversion to the PO formula-tion does not appear to be undertaken in a timely manner[6,10,11,13,14]. This results in unnecessary medicationcosts, IV drug administration expenses, and potentialexposure to adverse events associated with IV therapy (e.g.pain at injection site, phlebitis, and line infections).Various authors have described criteria-based medicationdosage form conversion programs in the literature[8,10,11,13,15-24]. Some institutions have implementeddosage forms in accordance with established criteria (i.e.clinical stability of the patient, ability to tolerate PO med-ications, and lack of drug interactions that may impairdrug absorption from the gastrointestinal tract)[10,17,18,23,24]. The anticipated benefit of a pharmacist-managed conversion program is that delays in IV-PO con-version will be reduced if a pharmacist can avoid therequirement of conferring with the initiating physicianbefore commencing a dosage form change. These serviceshave demonstrated that cost savings can be achievedwhen pharmacists are directly responsible for changingthe route of administration for selected medications [24].In November 2003, the Pharmacist-managed IV-PO Dos-age Form Conversion Service was approved at VGH by theAntibiotic Use Subcommittee (AUS), Drugs and Thera-peutics Committee (D&TC), and the Medical AdvisoryCommittee (MAC). Several antimicrobial agents wereincluded in this service; namely, ciprofloxacin, clindamy-cin, co-trimoxazole, fluconazole, levofloxacin, metroni-dazole, acyclovir, ampicillin, cefazolin, cefuroxime,penicillin G, ceftriaxone, imipenem-cilastatin, cloxacillin,erythromycin, and ticarcillin-clavulanate [25].Our hypothesis was that ciprofloxacin IV was overutilizedat VGH and that a more cost-effective use of this dosageform was possible with the implementation of a Pharma-cist-managed IV-PO Dosage Form Conversion Service.Accordingly, this study was conducted to assess the impactof this service on the relative utilization of the IV versusPO dosage form of ciprofloxacin. To our knowledge, thereare no published reports involving an assessment of theimpact of a Pharmacist-managed IV-PO Dosage FormConversion Service on ciprofloxacin usage characteristicsat a major Canadian teaching hospital.MethodsLiterature reviewA literature search of the Medline, EMBASE and IPA data-bases, as well as a bibliographic review from the cited arti-cles was performed to retrieve references pertaining topharmacy-managed IV-PO conversion programs. Addi-tional references were obtained through the St. Paul'sHospital and Lions' Gate Hospital pharmacy depart-ments, as these local institutions had established pharma-cist-managed conversion services [18,23]. Theinformation collected was used to formulate a policy andprocedure for the Pharmacist-managed IV-PO ConversionService at our institution. This document was approved bythe AUS, D&TC, and MAC, and a hospital-wide servicewas implemented.Study designPage 2 of 8(page number not for citation purposes)modified IV-PO conversion programs in which pharma-cists are given the authority and responsibility to changeThis was a single-centre, 2-phase (pre/post), unblindedstudy to assess the impact of a hospital-approvedBMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48intervention aimed at improving the utilization of cipro-floxacin dosage forms. Phase I (365 days; November 12,2002 to November 11, 2003) was designed to characterizeciprofloxacin usage patterns under the existing IV-POStep-down Program. Phase II (120 days; November 12,2003 to March 11, 2004) was designed to characterize theimpact of the new Pharmacist-managed Dosage FormConversion Service (implemented on November 12,2003) on the relative utilization of the ciprofloxacin IVand PO dosage forms.The primary endpoint was the relative utilization of IVand PO ciprofloxacin by dose (IV:PO ciprofloxacin useratio). The secondary endpoints were the overall utiliza-tion of ciprofloxacin (by dose), the proportion of total IVdoses considered to be inappropriate, and relative IV andPO total and treatment course acquisition costs betweenthe two phases. Potential cost avoidance associated withthe intervention was estimated from the data.InterventionPrior to the implementation of the program, pharmacistswere educated on the approved conversion servicethrough in-house presentations. A newsletter was distrib-uted to all medical staff detailing the program [25].Decentralized clinical pharmacists on the medical wardswere expected to conduct target drug report reviews 5 daysper week to identify inpatients who had been prescribedciprofloxacin IV. Health records were then reviewed, andpatients assessed to determine if IV-PO conversion criteriawere met. A patient was eligible for IV-PO dosage formconversion after 48 hours of IV therapy if he/she 1) con-tinued to need an antibiotic; 2) was clinically stable; 3)was capable of tolerating the PO dosage form; and 4) hadno factors present that would adversely affect PO bioavail-ability (e.g. gastrointestinal abnormalities or drug interac-tions). Pharmacists could consult the Infectious Diseasesservice or Infectious Diseases Pharmacist at anytime withany questions regarding IV-PO conversion eligibility.For patients who met the conversion criteria, the pharma-cist would write the order for the PO regimen in the Phy-sician's Orders section of the health record. If thepharmacist wanted to convert the patient to PO cipro-floxacin prior to 48 hours of IV therapy, they would firstconfer with the physician. In collaboration with thehealthcare team, the pharmacist would monitor thepatient for clinical progress and medication tolerability,and could convert the patient back to IV therapy asrequired.A randomly selected convenience sample of 200 cipro-impact of this new intervention. These courses were iden-tified using computerized pharmacy records and a ran-dom sample was undertaken using a computer-generatednumber list.All patients who were ordered ciprofloxacin IV wereincluded in the sample collection. Patients were excludedif they did not receive any doses of ciprofloxacin IV, iftheir ciprofloxacin IV treatment course did not occurwithin the pre-specified phase to which they were rand-omized, or if their charts were unavailable from theHealth Records department at VGH as of July 14, 2004.Charts were reviewed to gather demographic data, cipro-floxacin utilization information, inappropriate IV doses,and pharmacist-preventable IV doses of ciprofloxacin.Data collection and analysisData was collected by one investigator and entered intostatistical analysis software (SPSS© Version 11.0). Anytreatment course that this investigator considered to havefour or more inappropriately administered ciprofloxacinIV doses was reviewed in collaboration with the coordi-nating investigator to ensure accuracy of interpretation.Inferential statistics were performed. A two-sample Stu-dent's t-test was used for parametric data, the Mann-Whit-ney test was used for non-parametric data, and the Fisher'sExact and Chi-square tests were used for proportionalanalyses.DefinitionsFor the purposes of this study, a ciprofloxacin IV dose wasconsidered "inappropriate" when the patient met the cri-teria for use of the PO dosage form. A ciprofloxacin IVdose was considered "pharmacist-preventable" if the dosewas administered when the patient met the criteria for useof the PO dosage form and the decentralized clinical phar-macist was considered to have had the opportunity tointervene (i.e. Monday to Friday between 08:00 and 16:00hours, excluding statutory holidays). The inappropriateIV-PO ciprofloxacin acquisition cost was the differentialcost between the IV and the PO dosage form at currentcontract prices multiplied by the number of inappropriateIV doses administered.ResultsTwo hundred and fifteen health records of patients whowere prescribed ciprofloxacin IV during the study periodwere reviewed. Of these, seven patients were excluded, asthe ciprofloxacin IV treatment courses were not com-pleted within the pre-specified treatment phase. Sixpatients were excluded, as no IV ciprofloxacin doses werePage 3 of 8(page number not for citation purposes)floxacin IV treatment courses (100 treatment courses perphase) was considered to be adequate to determine theactually received. Health records were not accessible at thetime of the study for the remaining two patients.BMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48Accordingly, 200 treatment courses for 200 patients (100per phase) were included for analysis. This represented a4% (100/2411 treatment courses) sampling rate for PhaseI and a 10% (100/994 treatment courses) sampling ratefor Phase II.Patient demographics are presented in Table 1. Patientsreceiving ciprofloxacin IV were equally distributed by gen-der, typically in their sixth/seventh decade of life with anaverage duration of hospital stay of approximately twoweeks. Treatment courses were initiated in both surgicaland medical service areas for a wide variety of infectiousindications. There were no significant differences betweenthe two phases in terms of age, gender, renal function,length of stay, and medical service area to which thepatients were assigned. Most patients (75% in Phase I,78% in Phase II) received IV ciprofloxacin in combinationwith one or more antibiotics.Of the 200 ciprofloxacin IV courses reviewed, the totalnumber of doses and the ratio of IV to total doses acrossphases were similar (p = 0.2830) (Figure 1). The IV:POciprofloxacin use ratio was 3.03 in Phase I vs. 3.48 inPhase II.Ciprofloxacin treatment characteristics are described inTable 2. No significant differences were observed betweenthe initial ciprofloxacin dosing strengths (p = 1.00), theinitial dosing frequencies (p = 0.55), and the number ofIV-PO conversions per treatment course (p = 0.73). IV-POciprofloxacin conversion occurred in 27/100 (27%) of IVtreatment courses in Phase I and 23/100 (23%) of coursesin Phase II (Table 2). The number of IV-PO conversionsthat were subsequently reversed to IV was 2 cases in PhaseI and 3 cases in Phase II. Chart documentation of a phar-macist-initiated IV-PO conversion was recorded in 3/27(11%) episodes in Phase I and 4/23 (17%) episodes inTable 1: Patient demographicsPhase I Nov. 12, 02 to Nov. 11, 03 (365 days)Phase II Nov. 12, 03 to Mar. 11, 04 (120 days)No. of patients 100 100No. of treatment courses 100 100Age (yr), median (range) 57 (17–93) 63 (16–91)Gender, NMale 45 50SCr1 (µmol/L), median (range) 84 (40–541) 89 (35–641)Length of Stay (d), mean (range) 12 (1–84) 17 (1–165)Service Area, NGeneral Surgery 31 30Medicine 22 11Emergency 15 11Intensive Care Unit 7 8Urology 3 12Other 222 283Indication, NOff-label indications4 38 35Intra-abdominal infection 18 15Respiratory tract infection 15 16Urinary tract infection 15 15Other 145 1961Serum creatinine closest to start of ciprofloxacin IV treatment.2 Other service areas: Thoracic, Respiratory, Spine, Hematology/BMT, Transplant, Cardiothoracic Surgery, Neurosciences Intensive Care Unit, Cardiology, Day Bed Unit, Same Day Admit Unit, Pre-admission Clinic, Trauma Special Care Unit, Neurosciences, Family Practice, Orthopedics, Vascular, and Gynecology.3 Other service areas: Thoracic, Spine, Hematology/BMT, Transplant, Cardiology, Day Bed Unit, Same Day Admit Unit, Neurosciences, Family Practice, Vascular, Gynecology, Palliative Care, and Trauma.4Off-label indications refer to those not approved on the manufacturer's drug monograph.5Other indications: Empiric therapy in febrile neutropenia, skin and soft tissue, and septicemia.6 Other indications: Empiric therapy in febrile neutropenia, skin and soft tissue, septicemia, and infectious diarrhea.Page 4 of 8(page number not for citation purposes)Phase II. There was no difference between phases withrespect to the median number of ciprofloxacin dosesBMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48administered and the median costs associated with eachtreatment course (Table 2).For those patients who met the criteria for the use of anoral dosage form, 59/100 (59%) received one or moreinappropriate doses of ciprofloxacin IV in Phase I com-pared to 61/100 (61%) in Phase II. There was a significantdecrease in the proportion of inappropriate ciprofloxacinIV doses between phases (244/521 (47%) in Phase I vs.201/554 (36%) in Phase II (p = 0.0005) (Figure 2). Fur-thermore, there was a significant reduction in the propor-tion of pharmacist-preventable inappropriateciprofloxacin IV doses between Phase I and Phase II (114/244 (47%) vs. 65/201 (32%) (p = 0.0026) (Figure 2).Phase II. Ciprofloxacin IV accounted for $16,517 (97%)of total ciprofloxacin costs in Phase I and $17,919 (98%)of these costs in Phase II (Figure 3). The proportional costavoidance associated with inappropriate use of IV cipro-floxacin was $7,172/$16,517 (43%) in Phase I comparedto $6,012/$17,919 (34%) in Phase II (p = 0.001). Theproportional pharmacist-preventable cost avoidance asso-ciated with inappropriate IV ciprofloxacin use wasreduced from $3,367/$16,517 (20%) in Phase I to$1,975/$17,919 (11%) in Phase II (p = 0.001).DiscussionThe purpose of this study was to assess the relative utiliza-tion of the IV and PO dosage form of ciprofloxacinsubsequent to the implementation of the Pharmacist-managed Dosage Form Conversion Service. We did notaim to assess the appropriateness of ciprofloxacin usagefor specific indications.Overall, the IV:PO ratio of ciprofloxacin usage remainedsimilar between the two phases, and the total number ofciprofloxacin doses did not change significantly. Initially,it was anticipated that implementation of the conversionservice would reduce the IV:PO ratio, however, there werenumerous variables that may have affected this endpoint.We were also interested in evaluating whether the numberof inappropriate IV doses and pharmacist-preventableinappropriate IV doses could be reduced. Our resultsshowed a 23% relative reduction in the proportion ofinappropriate ciprofloxacin IV doses and a 32% relativereduction in the incidence of pharmacist-preventableinappropriate ciprofloxacin IV doses subsequent to theintervention.A possible explanation for the decline in the inappropri-ate and pharmacist-preventable inappropriate cipro-floxacin IV doses was the drive to reduce hospitalexpenditures at our institution at the time this programwas implemented. There was an increased awareness andemphasis for cost-effective prescribing. The conversionservice was an adjunct to the cost savings initiatives andwas readily adapted to our established practice.VGH has had a pre-existing IV-PO Step-Down Programsince 1992. In a previous study at our institution in 1992,the rate of patients eligible for IV-PO conversion was 52%,which is similar to the 59% observed in Phase I of ourpresent study [6]. The rate of IV-PO conversions in 1992was also comparable to our baseline in Phase I (34% vs.27%, respectively). This suggests that the interventions ofour IV-PO Step-down Program have remained relativelyconstant since 1992. With an effective IV-PO Step-downProgram in place, it is possible that the magnitude ofTotal number of ciprofloxacin dosesFigure 1Total number of ciprofloxacin doses. p = 0.2830 for ratio of IV to total number of ciprofloxacin doses between phases.5215541721590100200300400500600700800Phase I Phase IINumberofDosesTotal IV Total POPage 5 of 8(page number not for citation purposes)The total cost of IV and PO ciprofloxacin for the treatmentcourses reviewed was $16,993 in Phase I and $18,332 inchange associated with the implementation of the conver-sion service may have been blunted.BMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48Pharmacist-initiated IV-PO conversion was documentedin the health record in 4 cases in Phase I and 3 cases inPhase II. This low incidence of documentation may beattributed to the activities of the decentralized clinicalpharmacists who attend patient care rounds and interactdirectly with physicians, so that orders are written duringrounds for IV-PO conversion. Greater awareness of otherhealth care professionals on the bioavailability of PO cip-rofloxacin may also have resulted in the earlier usage ofthe PO dosage form.Total costs of ciprofloxacin therapy were similar betweenthe two phases. This was expected, as the conversionservice would not alter the indications for ciprofloxacinuse. However, the costs associated with inappropriate cip-rofloxacin IV therapy and pharmacist-preventable inap-propriate ciprofloxacin IV therapy declined from Phase Ito II, which may be attributed to the increased interven-tions of the clinical pharmacists and the improved aware-ness for PO therapy post intervention.Following implementation of the conversion service, 12%(65/554) of ciprofloxacin doses deemed inappropriateand preventable by pharmacists were still administered.Ideally, all of these doses should have been avoided. Onefull working day (excluding weekends and statutory holi-days) was allotted as the time required for clinical phar-macists to assess these patients. This delay in IV-POthe new service, as pharmacists may not yet have beencomfortable exercising a dosage form conversion autono-mously. The retrospective assessment for appropriatenessby the investigator may also differ from that of the clinicalpharmacist. It would be beneficial to obtain an internalassessment to discover the barriers associated with theprogram. Of course, it would be preferable to educate themedical staff to initiate PO regimens where indicated andavoid the use of the IV formulation.Several limitations exist with this study. The retrospective,pre/post, unblinded design precludes the formulation ofany direct causal relationships between the implementa-tion of the conversion service and the subsequent reduc-tion in inappropriate ciprofloxacin IV doses. The samplesize of convenience may not have achieved the powerrequired to detect a difference. In addition, the samplingrate was relatively low at 4.1% (100/2411 ciprofloxacin IVcourses) in Phase I and 10.1% (100/994) in Phase II, andthus may not truly represent the characteristics of our pop-ulation. Time restrictions resulted in differences in sam-pling periods between Phase I (365 days) and Phase II(120 days), which may affect the representation of cipro-floxacin IV treatment courses throughout the year. How-ever, this should not directly influence the proportion ofinappropriate and pharmacist-preventable inappropriateciprofloxacin IV treatment doses. The assessment of thisservice was over a relatively short period, and so may notTable 2: Ciprofloxacin treatment course characteristicsPhase I Phase II P valueTreatment regimen characteristicsDosing Strength 1.00200 mg IV 6 6400 mg IV 94 94Dosing Frequency 0.55Once 17 22Once daily 5 3Twice Daily 78 75IV to PO Conversion Rate (% by treatment course) 27 23 0.73Ciprofloxacin doses/treatment course, median (range) 5 (1–33) 5 (1–44) 0.55IV, median (range) 3 (1–33) 4 (1–25) 0.29Inappropriate IV, mean (range) 2.4 (0–26) 2.0 (0–9) 0.33Inappropriate & pharmacist-preventable IV, mean (range) 1.1 (0–24) 0.6 (0–6) 0.14PO, mean (range) 1.7 (0–26) 1.6 (0–26) 0.83Treatment course acquisition costs ($)Ciprofloxacin, median (range) 99 (17–1089) 132 (17–825) 0.32IV, median (range) 99 (17–1089) 132 (17–825) 0.28Inappropriate IV, mean (range) 72 (0–790) 60 (0–274) 0.39Inappropriate & pharmacist-preventable IV, mean (range) 34 (0–729) 20 (0–182) 0.17Page 6 of 8(page number not for citation purposes)conversion may be explained in part by having our datacollection period immediately after the introduction oftruly reflect the long-term impact of this program.BMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48As with any unblinded study of this type, the potential forinvestigator assessment bias existed. As the evaluation ofdose appropriateness was undertaken sequentially acrossphases, potential bias may have been introduced as theinvestigator gained experience during the process. Tominimize this bias, charts were reviewed by a senior inves-tigator when greater than four inappropriate and pharma-cist-preventable inappropriate ciprofloxacin IV doses wereidentified by the junior investigator. A 100% concordanceexisted between the assessments made by the junior andsenior investigators.In the context of drug use optimization and cost minimi-appropriate, cost-effective therapy. This service can beused in conjunction with other established methodsincluding newsletters [6], chart talkers, notes [7,8], anddirect pharmacist-physician interactions. To further pro-mote antimicrobial use appropriateness, strategies aimedat affecting prescribing behaviour may be employed.These include individual physician prescribing feedback,multidisciplinary inservices in collaboration with infec-tious diseases physicians, and prescriber educationthrough academic detailing.ConclusionNumber of total, inappropriate, and pharmacist-preventable inappropriate IV ciprofloxacin dosesFigu  2Number of total, inappropriate, and pharmacist-pre-ventable inappropriate IV ciprofloxacin doses. p = 0.0005 for difference in the proportions of inappropriate IV ciprofloxacin doses between phases. p = 0.0026 for differ-ence in the proportions of pharmacist-preventable inappro-priate IV ciprofloxacin doses between phases.521554244201114650100200300400500600NumberofDosesTotal IVTotal inappropriate IVTotal inappropriate pharmacist-preventable IVPhase IIPhase ICosts associated with total, inappropriate, and pharmacist-preventable inappropriate IV ci rofloxacin dosesFigure 3Costs associated with total, inappropriate, and phar-macist-preventable inappropriate IV ciprofloxacin doses. p = 0.001 for difference in potential cost avoidance of inappropriate IV ciprofloxacin doses between phases. p = 0.001 for difference in potential cost avoidance of pharma-cist-preventable inappropriate IV ciprofloxacin doses between phases.$16,517$17,919$7,172$6,012$3,367$1,975$-$2,000$4,000$6,000$8,000$10,000$12,000$14,000$16,000$18,000$20,000CostCost of total IVCost of inappropriate IVCost of inappropriate pharmacist-preventable IVPhase I Phase IIPage 7 of 8(page number not for citation purposes)zation, implementation of a Pharmacist-managed IV-PODosage Form Conversion Service may be used to facilitateIn summary, the overall utilization of ciprofloxacin seemsto have remained unchanged and the proportion of IV toPublish with BioMed Central   and  every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime."Sir Paul Nurse, Cancer Research UKYour research papers will be:available free of charge to the entire biomedical communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Central BMC Health Services Research 2005, 5:48 http://www.biomedcentral.com/1472-6963/5/48total doses appears stable. However, the proportion ofinappropriate IV doses and its associated costs appear tohave declined subsequent to the implementation of aPharmacist-managed IV-PO Dosage Form ConversionService. Such a program may be a beneficial adjunct infacilitating appropriate and cost-effective usage ofciprofloxacin.Competing interestsThe author(s) declare that they have no competinginterests.Authors' contributionsBPH participated in the design of the study, performeddata collection and analyses, and drafted the manuscript.TTYL participated in the design and coordination of thestudy, performed data and statistical analyses, and draftedand revised the manuscript. RMB participated in thedesign of the study, developed the analytical database,and revised the manuscript. TLN participated in thedesign of the study and revision of the manuscript. PJJconceived the study, participated in its design, performeddata and statistical analyses, and drafted and revised themanuscript. 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