ORIGINAL RESEARCH ARTICLE
`
`Pharmacoeconomics 2002; 20 (8): 529-536
`1170-7690/02/0008-0529/$25.00/0
`
`© Adis International Limited. All rights reserved.
`
`Ready-to-Use Injection Preparations
`versus Conventional Reconstituted
`Admixtures
`Economic Evaluation in a Real-Life Setting
`
`Phillipe van der Linden,1 Jacques Douchamps,2 Claude Schmitt 3 and Dominique Forget 4
`
`1 CHU Charleroi, Jumet, Belgium
`2 CHU A. Vésale, Montigny-le-Tilleul, Belgium
`3 MDS Pharma Services, Sèvres, France
`4 Baxter, Maurepas, France
`
`Abstract
`
`Objective: To measure, in a real-life setting, the benefits of using ready-to-use
`(RTU) injection preparations compared with conventional reconstituted admix-
`tures (Admix) in terms of cost savings.
`
`Design and perspective: An economic model was developed, based on a randomised
`study. The perspective of the economic evaluation was that of the hospital adminis-
`tration. A microcosting approach was used to determine costs.
`
`Setting: Department of Cardiac Surgery at the Charleroi University Hospital in
`Belgium.
`
`Study participants: Fifty-eight patients undergoing cardiac surgery under cardio-
`pulmonary bypass were randomised to Admix dobutamine or to the RTU dobu-
`tamine group and were followed up during 24 hours after initiation of dobutamine
`therapy.
`
`Main outcome measures and results: Nursing time was reduced by 32% in the
`RTU group compared with the Admix group. Material cost was also reduced and
`the overall cost savings in the RTU group amounted to a 60% reduction in the
`cost of the conventional Admix process (p<0.001). When drug cost was included
`in the equation, cost savings varied from 1.60 euros (EUR) to EUR21.40 per
`patient depending on dosage. There was no difference between the two groups in
`terms of safety and efficacy. A user satisfaction survey showed that medical staff
`especially welcomed improved ease of preparation and potential for prevention
`of errors and risks of handling.
`
`Conclusion: This study confirmed the potential for RTU forms to reduce nursing
`time associated with preparation and administration of intravenous admixtures
`and to enable overall cost savings.
`
`In the US, the introduction of ready-to-use
`(RTU) medications has contributed to providing
`high quality intravenous (IV) preparations while sim-
`
`plifying the process of delivering small volume par-
`enterals. This system lends itself to more rapid avail-
`ability of the dose and does not require that doses
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 529
`
`

`

`530
`
`van der Linden et al.
`
`be calculated or manipulated further by the medi-
`cal staff. It may also free pharmacists and nurses
`to devote more time to other critical activities as-
`sociated with the safety of intravenous drug deliv-
`ery.
`The RTU system facilitates efficiency, accu-
`racy and safety: efficiency as it streamlines IV
`work flow, creating more time for clinical activities
`and patient interaction, reduces steps in IV prepa-
`ration, eliminates admixing labour, assembly and
`supplies and reduces waste by providing extended
`shelf-life over admixed solutions;[1-4] accuracy as it
`reduces the risk of medication errors, eliminates
`calculations during compounding and guarantees
`accuracy in IV medication labelling;[5,6] and safety
`as it facilitates immediate use in emergency situa-
`tions, ensures sterility and potency with a closed sys-
`tem and eliminates the need for further product ma-
`nipulations.[7] This system may increase acquisition
`costs, but the overall system costs are balanced by
`reduced preparation costs and wastage rates.
`In Europe, such industrial ready-to-infuse drugs
`are almost not existent. Based on previous US ex-
`perience showing the great advantages of this con-
`cept, there was a need to evaluate the potential ben-
`efits of such medications in the context of European
`hospitals. The purpose of this study was to measure
`in the real-life setting the benefits of RTU injection
`preparations as compared with conventional recon-
`stituted admixtures in terms of cost savings. In ad-
`dition, efficacy, safety and user satisfaction were also
`evaluated.
`
`Methods
`
`Patient Population and Treatments
`
`This study was performed in accordance with
`the local Institutional Ethics Committee. All pa-
`tients who participated gave their written informed
`consent. Patients were recruited in the department
`of Cardiac Surgery at the Charleroi University
`Hospital in Charleroi, Belgium. Patients were in-
`cluded if they had undergone cardiac surgery in the
`morning and if during the operation they were eli-
`gible for dobutamine treatment because of a low
`
` Adis International Limited. All rights reserved.
`
`Pharmacoeconomics 2002; 20 (8)
`
`a IVAC P6000 manufactured by Alaris Medical Systems, UK.
`
`cardiac output. Patients were excluded if they pre-
`sented any contraindication found in the Summary
`of Product Characteristics for dobutamine[8] or if
`their expected life duration was below or close to
`1 day.
`Dobutamine intravenous injection was initiated
`in the operating room using either the conventional
`preparation admixed from vials (Admix) by the med-
`ical staff and administered by syringe drivers or using
`the RTU dobutamine administered via an infusion
`pump. The precise dosage is described in table I.
`Patients were randomised to the Admix or the
`RTU group prior to entry in the operation room.
`They were followed up until 24 hours after initia-
`tion of dobutamine therapy.
`
`Economic Evaluation
`
`The perspective of the economic evaluation was
`that of the hospital administration; costs are pre-
`sented as 2001 values. The hypothesis was that ef-
`ficacy and safety of both systems were comparable
`so that the main objective was to measure potential
`cost savings associated with the use of dobutamine
`RTU. For this same reason no long-term differ-
`ences were expected between the two devices and
`the time frame for the economic evaluation was lim-
`ited to the 24 hours following the first infusion of
`dobutamine.
`The evaluation was focused on the direct costs
`
`Table I. Study treatments
`
`Dobutamine admixture Ready-to-use
`dobutamine
`Plastic Viaflex® plus
`containers
`1000mg/250ml
`
`250mg/20ml single
`dose vials as a
`concentrate for infusion
`
`Determined by the
`physician; varies from
`2.5 to 10 µg/kg/min
`depending on patient
`assessments and
`bodyweight
`
`Admixture
`Preparation
`Administration Syringe drivera +
`central venous catheter
`
`Determined by the
`physician; varies from
`2.5 to 10 µg/kg/min
`depending on patient
`assessments and
`bodyweight
`
`Ready to use
`
`Baxter’s Colleague
`infusion pump +
`central venous catheter
`
`Availability
`
`Dosage
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 530
`
`

`

`Economics of Ready-to-Use Administration Devices
`
`531
`
`related to the preparation and the administration of
`dobutamine.
`A microcosting approach was used to determine
`costs. For each patient, medical care used for pre-
`paring and initiating the first cycle of dobutamine
`was precisely documented. When extra cycles were
`needed for a patient, it was assumed that medical care
`consumption for these further cycles would be the
`same as for the first cycle.
`A time-and-motion study, supplemented by a work-
`sampling study (time associated with pump program-
`ming was re-evaluated outside the trial without any
`real patients being involved), was performed to
`evaluate labour time associated with collecting,
`preparing and administering the drug. Preparation
`time started with collection of supplies and fin-
`ished when the admixture was ready to infuse. Ini-
`tiation time ran from the end of preparation to the
`time when the drug was administered to the patient
`and included calculating flow rates, attaching sets,
`and programming pumps. Consumption of all sup-
`plies associated with preparation and initiation was
`also recorded. Drug consumption was measured by
`the amount of dobutamine prepared in both groups.
`Unit costs were abstracted from public data-
`bases. Disposables were costed using market prices
`before negotiation and not including taxes. The costs
`of using syringe drivers and infusion pumps were
`calculated from purchasing prices assuming 5 to
`10 years’ depreciation times depending on the
`medical department. Labour time was valued at the
`wage rate of the site. From the hospital perspec-
`tive, there is no acquisition cost for Dobutrex®1
`since hospitals are reimbursed the full price by the
`Belgian public health insurance.
`In order to facilitate adaptation to other settings
`and countries, an economic model was developed
`that incorporates the broader perspective of the
`health insurance. In the model, the price of dobu-
`tamine RTU was assumed to be the same per unit
`of volume as the price of dobutamine Admix
`which, in Belgium, is 6.69 euros (EUR) for one
`250mg/20ml bottle of Dobutrex® for inpatients
`
`1 The use of the trade name is for product identification
`purposes only and does not imply endorsement.
`
`(2001 values). The model also allowed for varying
`the dosage of dobutamine as doses of dobutamine
`usually administered in the cardiac surgery and in-
`tensive care units where the study was performed
`may differ from the dosage in other settings.
`
`Qualitative Survey
`
`When each patient cycle was completed, the
`medical staff was required to document satisfaction
`with the products. The instruments used were vi-
`sual analogue scales ranging from zero for the worst
`to ten for the best. Medical staff were asked to rate
`ease of preparation, time for preparation, prevention
`of risks of errors and prevention of risks of han-
`dling.
`
`Statistical Methods
`
`Statistical analyses were performed using the SAS
`V8 package. Continuous variables were compared us-
`ing Student’s t-test and categorical variables were
`compared using either Wilcoxon’s non-parametric
`test or the standard chi-square as deemed appropri-
`ate. Cost variables were compared using bootstrap
`t-tests.[9]
`
`Results
`
`Efficacy and Safety
`
`A total of 56 patients were recruited, with 28 in
`each group (table II). Groups were well balanced
`for age, sex ratio, weight and health status. There
`were slightly more females in the RTU group, al-
`though the difference was not statistically signifi-
`cant (p = 0.19). This minor imbalance accounts for
`the difference in mean weight.
`All 56 patients received dobutamine for low
`cardiac output at emergence from cardiopulmo-
`nary bypass. Dobutamine was administered at the
`mean dose of 3.9 µg/kg/min [standard deviation
`(SD) 2.5] in the Admix group and at 5.0 µg/kg/min
`(SD 2.2) in the RTU group (p = 0.10). The duration
`of dobutamine administration was similar in both
`groups, with a mean of 16 hours and 29 minutes
`(SD 5 hours 28 minutes) in the Admix group versus
`
` Adis International Limited. All rights reserved.
`
`Pharmacoeconomics 2002; 20 (8)
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 531
`
`

`

`532
`
`van der Linden et al.
`
`Table II. Population characteristics
`
`Characteristic
`
`Age (y) [SD]
`
`Male/female
`
`Dobutamine
`admixture
`(n = 28)
`
`Ready-to-use
`dobutamine
`(n = 28)
`
`67.2 [10.4]
`
`64.0 [11.5]
`
`24/4
`
`20/8
`
`Weight (kg) [SD]
`
`80.7 [16.8]
`
`77.1 [13.7]
`
`Clinical examination
`at inclusion
`
`Normal
`
`Abnormal
`
`15
`
`13
`
`16
`
`12
`
`NS = not significant; SD = standard deviation.
`
`P-value
`
`NS
`
`NS
`
`NS
`
`NS
`
`17 hours and 8 minutes (SD 4 hours 57 minutes) in
`the RTU group (p = 0.65).
`Efficacy was monitored through periodic as-
`sessments of diastolic and systolic blood pressure
`and pulse rate. Blood pressure and pulse rate figures
`were collected from time zero until 24 hours after
`initiation of dobutamine therapy. There was no dif-
`ference between the two groups of patients in terms
`of systolic (p = 0.42) and diastolic (p = 0.58) blood
`pressure nor in terms of pulse rate (p = 0.28). Safety
`was similarly unaffected by the type of device used
`to prepare and administer dobutamine (table III; p
`= 0.33 for the number of patients with at least one
`adverse event). Nineteen patients out of 56 (34%)
`experienced at least one adverse event possibly or
`probably related to study treatment. Only three of
`these patients experienced at least one serious ad-
`verse event. The most frequent adverse events
`were pulmonary infections, haemorrhage, atrial fi-
`brillation and congestive heart failure.
`
`Costs
`
`tion phase using RTU was somewhat offset by a
`longer time spent on initiating the infusion but the
`balance remained favourable for RTU. The time
`saving was 85 seconds per patient (p < 0.01) or
`32% of medical staff time, which translates into
`cost savings of EUR0.45 per patient.
`The administration of Admix requires system-
`atically the use of a 50ml syringe, a needle, a bag
`of physiological serum and a connector whereas the
`preparation of RTU requires only a preparation kit.
`Admix was administered using a syringe driver
`while RTU was administered using an infusion pump.
`Although infusion pumps were more expensive than
`syringe drivers, the overall cost of material needed
`for the preparation and the administration of RTU
`was lower than for Admix, with cost savings of
`EUR2.92 per patient.
`When all costs were summed up, savings showed
`at every step for the RTU form resulting in an over-
`all cost of EUR2.26 per patient versus EUR5.63
`per patient in the Admix group (p < 0.001). Costs
`were reduced by EUR3.37 per patient (95% confi-
`dence interval: –EUR4.42 to –EUR2.48) or 60%
`by using RTU instead of conventional Admix.
`
`Economic Model
`
`Results of the economic model are presented in
`table V which shows the difference in costs per
`patient between Admix and RTU when drug cost
`is incorporated in the calculation and dosage of
`dobutamine is variable. While on average 1.57 vi-
`als of Admix dobutamine were used in this study,
`up to four and even eight vials of Admix dobutam-
`
`Table IV presents the costs associated with col-
`lection of the material, preparation and administra-
`tion of intravenous dobutamine. To estimate 24-
`hour medical care consumption and costs, the data
`collected during the first preparation cycle of
`dobutamine was multiplied by the total number of
`preparation cycles. There were 1.57 preparation
`cycles for Admix dobutamine on average versus
`only 1.00 for RTU dobutamine. In the RTU group,
`labour time was on average lower than in the Ad-
`mix group (85 seconds). Time spared on the prepara-
`
`Table III. Incidence of adverse events
`
`Adverse event
`
`Atrial fibrillation
`
`Acute renal failure
`
`Infection
`
`Haemorrhage
`
`Respiratory distress
`syndrome
`
`Heart failure
`
`Myocardial infarction
`
`Dobutamine
`admixture
`(n = 28)
`
`Ready-to-use
`dobutamine
`(n = 28)
`
`5
`
`1
`
`4
`
`2
`
`1
`
`0
`
`0
`
`5
`
`0
`
`4
`
`2
`
`0
`
`2
`
`1
`
` Adis International Limited. All rights reserved.
`
`Pharmacoeconomics 2002; 20 (8)
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 532
`
`

`

`Economics of Ready-to-Use Administration Devices
`
`533
`
`Table IV. Medical care consumption and costs
`
`Dobutamine
`admixture
`
`Ready-to-use
`dobutamine
`
`Labour time
`First preparation cycle
`
`material collection
`
`24 sec
`
`1 min 31 sec
`
`5 sec
`
`54 sec
`
`preparation
`
`initiation
`
`54 sec
`
`1 min 57 sec
`
`Number of preparations
`
`1.57
`
`1.00
`
`Total labour time
`
`4 min 22 sec
`
`2 min 57 sec
`
`Labour cost
`Hourly wage rate
`
`Total labour cost
`
`EUR17.85
`
`EUR1.32
`
`EUR17.85
`
`EUR0.87
`
`Materials (quantity; unit cost)
`50ml syringe
`1.57/patient;
`EUR0.35
`
`Drawing needle
`
`Bag of NaCl 0.9%
`(100ml)
`
`Connector
`
`Syringe driver
`
`Preparation kit
`
`1.57/patient;
`EUR0.02
`
`1.57/patient;
`EUR1.36
`
`1.57/patient;
`EUR0.59
`
`1 day; EUR0.67
`
`Infusion pump
`Number of vials/Viaflex®
`Total material cost
`
`Labour cost + material
`cost
`EUR = euros.
`
`1.57
`
`EUR4.31
`
`EUR5.63
`
`1/Viaflex®;
`EUR0.36
`
`1 day; EUR1.03
`
`1.00
`
`EUR1.39
`
`EUR2.26
`
`ine may be used for a single patient in other hospi-
`tals. The model shows that in all cases, with the
`lowest RTU dosage, there would be overall cost
`savings no matter the number of bottles of Admix
`dobutamine usually administered of at
`least
`EUR1.20 per patient and up to EUR12.50 per pa-
`tient. It also shows that cost savings may be further
`improved by selecting the appropriate dosage of
`RTU. For example, if the usual dose of Admix
`dobutamine is four bottles per patient, the optimal
`choice for the type of RTU would be the 1000mg/
`250ml dosage. Cost savings would be higher than for
`lower dosage RTU forms because the 1000mg/
`250ml RTU would not need to be replaced thus
`saving precious nursing time. By selecting the appro-
`priate RTU dosage, potential cost savings would range
`
`between EUR1.60 and EUR 21.40 per patient. Ta-
`ble V may be a used as a tool for pharmacists to
`select the optimal dosage of RTU they will order
`from the pharmaceutical company.
`The calculations behind the economic model that
`was developed based on the results of the trial are
`detailed in table VI. As an example, the costs of
`administering the total dose of 250mg, 500mg,
`750mg or 1000mg of dobutamine to one patient
`using either Admix or RTU 500mg were compared.
`The cost of administration included the cost of
`nursing staff, material cost and drug cost. The cal-
`culation further reinforces the fact that the RTU form
`is cost saving as compared to the Admix form when
`the amount of drug used is comparable. Cost sav-
`ings result because of a lower material cost and be-
`cause the RTU form allows for a longer adminis-
`tration time and thus fewer preparation cycles.
`
`User Satisfaction
`
`User satisfaction was very good on average for
`both groups (figure 1). Medical staff welcomed the
`introduction of the RTU form, citing ease of prep-
`aration, potential benefits in terms of prevention of
`errors and of risks of handling, and time savings.
`The only drawback they noted was the administra-
`tion process which required long and unusual pro-
`gramming of the infusion pump.
`
`Table V. Cost savings (euros) per patient per day associated with
`the use of ready-to-use (RTU) dobutamine compared with
`dobutamine admixture
`
`No. of dobutamine
`vials needed
`per patient
`
`RTU dosage
`
`250 mg/
`250ml
`
`500 mg/
`250ml
`
`1000 mg/
`250ml
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`–1.60
`
`–3.10
`
`–4.70
`
`–6.30
`
`–7.80
`
`–9.40
`
`–11.00
`
`–12.50
`
`–4.70
`+1.10a
`–8.80
`
`–3.00
`
`–12.80
`
`–7.00
`
`–16.90
`
`–1.20
`
`–11.00
`+8.10a
`–1.70
`
`–11.60
`
`–21.40
`
`a Cases when the cost of RTU would be higher than the cost of
`dobutamine admixture.
`
` Adis International Limited. All rights reserved.
`
`Pharmacoeconomics 2002; 20 (8)
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 533
`
`

`

`van der Linden et a1.
`
`lele VL Sample cost calculations
`No. of dobumatine
`Cost component
`Vials needed Per Patient
`2
`
`Dobutamine adnixture
`quantity
`
`mil 00st (euros)
`
`Ready-to—use dobutam'ne (500mg)
`quantity
`mil cost (euros)
`
`3
`
`4
`
`Labour
`Material
`
`5 min 38 sec
`2 sets
`
`Syrilge or pump
`Dmg
`Total cost
`
`1
`2 vials
`20.37
`
`Labour
`Material
`
`8 min 27 sec
`3 sets
`
`Syr’nge or pump
`Drug
`Total cost
`
`1
`3 vials
`30.22
`
`Labour
`Mater‘al
`
`11 min 16 sec
`4 sets
`
`Symge or pump
`Drug
`Total cost
`
`1
`4 vials
`40.07
`
`17.85Mr
`2.32
`
`0.67
`6.69
`
`17.85Ihr
`2.32
`
`0.67
`6.69
`
`17.8511"
`2.32
`
`0.67
`6.69
`
`2 min 56 sec
`1 set
`
`1
`1 ViafleX“
`15.65
`
`5 min 52 sec
`2 sets
`
`1
`2 Vallex"
`31.30
`
`5 min 52 sec
`2 sets
`
`1
`2 \rlallex“3
`31.30
`
`17.85Ihr
`0.36
`
`1.03
`13.39
`
`17.85Ihr
`0.36
`
`1.03
`13.39
`
`17.85Ihr
`0.36
`
`1.03
`13.39
`
`Dlscusslon
`
`This prospective randomised study provided
`evidence that in the real-life setting RTU injection
`preparations offer significant benefits over con-
`ventional reconstituted admixtures in terms of time
`
`and cost savings and in terms of user satisfaction.
`In addition, efficacy and safety were also monitored
`and proved to be comparable.
`While this study was conducted in the context
`of a hospital in Belgium, it may be anticipated that
`the savings identified will likely be of the same
`type in other contexts and other countries. Other
`studies have evaluated the potential benefits asso-
`ciated with the use of RTU preparations. Detoumay
`et all '0] have observed cost savings of EURO.23 per
`injection in the context of five European hospitals
`in five different countries. The design of their study
`was more simple than the current study in that med-
`ical care consumption figures were drawn from a
`process model. Barber et all1 '1 studied prefilled
`injections of heparin in two London hospitals and
`found that nursing time for preparation and admin-
`istration using prefilled syringes was reduced from
`129 seconds to 68 seconds when compared with
`conventional systems. Adenl '21 in Germany estimated
`
`that the use of prefilled forms could save up to 50%
`of the cost associated with intravenous injections.
`Other studies in Spainm] found results consistent with
`the present one; in particular, savings due to reduced
`wastage when using prefilled syringes were iden-
`tified. The present study differs from previous ones
`in many respects. It was performed in a real-life set-
`ting, with patients undergoing a major surgical pro—
`cedure receiving a continuous infusion that could
`last up to more than 20 hours.
`
`El Ready-louse domtamhe
`I Am dobutamlne
`
`Easyto
`
`Prevention of
`I'lSIlS related
`tonath
`Preverltlonot
`rlsksolerrors
`
`11me requled
`tor preparation
`
`Fly. 1. Users'
`
`6 Act lntemallond Lhited. Al rlgrts reserved.
`
`Plum 2002; Z) (8)
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLc — Exhibit 1034 — Page 534
`
`

`

`Economics of Ready-to-Use Administration Devices
`
`535
`
`In the conditions of the present study, the an-
`nual savings can be estimated by multiplying the
`number of intravenous injection cycles performed
`on average through the year by the EUR3.37 per
`patient savings identified. With approximately 2000
`vials of Admix dobutamine administered annually
`and assuming that an average 1.57 vials are needed
`for each patient, the annual savings for the hospital
`would be around EUR4300.
`Valuation of cost savings due to reduced nurs-
`ing time may be controversial. It may be argued that
`savings in nursing time may not translate into ac-
`tual cost savings because it is unlikely that hospi-
`tals will actually make adjustments to nursing staff
`and thereby actually save money. However, the sav-
`ings in labour time could be invested in other tasks
`especially at patients’ bedside. Furthermore, even
`without valuing nursing time, cost savings were iden-
`tified with the use of RTU forms. Savings in the pres-
`ent study would amount to EUR2.92 per patient, cor-
`responding to approximately EUR3700 on an annual
`basis.
`Labour time can be further reduced with the in-
`troduction of improved infusion pumps. The pro-
`gramming of the pumps used in this study proved
`especially awkward. A more user-friendly programme
`was further developed by the manufacturer. A work-
`sampling study was conducted with the staff that
`participated in the trial. Three operators were observed
`while they were running the initiation phase and time
`was measured for both the Admix with the syringe
`driver and the RTU with the new infusion pump. A
`total of ten measures for each operator and both sys-
`tems were performed. Mean initiation time and
`standard deviation were 29 seconds (SD: 3.5) for the
`Admix versus 43 seconds (SD: 4.1) for the RTU.
`No significant difference between operators was
`observed. These times were significantly shorter
`than those measured during the trial. This observa-
`tion can be explained by the fact that this work-sam-
`pling study was not performed in real-life condi-
`tions. These results provide further evidence that
`labour time associated with the use of RTU will be
`reduced as compared with Admix. Nursing time
`
`saved would amount to 2 minutes 30 seconds per
`patient using the new infusion pump.
`
`Conclusion
`
`A RTU form of dobutamine was evaluated in a
`study performed in patients undergoing cardiac
`surgery in a major hospital in Belgium. The study
`was conducted in real-life conditions and the RTU
`form was compared with the usual Admix prepa-
`ration and administration process. Safety and effi-
`cacy of the two systems do not differ significantly.
`The economic analysis conducted using these real-
`life observations showed that both the nursing time
`and the material costs for preparation and admin-
`istration of dobutamine were significantly lower
`with the RTU form than with the Admix one. From
`the perspective of the hospital, overall cost savings
`per patient amounted to EUR3.37 which corresponds
`to a 60% reduction of the total cost. When the per-
`spective of the healthcare system as a whole was
`taken, and drug cost incorporated in the equation, the
`results suggested a potential cost savings of at least
`EUR1.60 per patient and up to EUR21.40 per pa-
`tient depending on the dose of dobutamine prescribed
`and on the dosage of RTU selected. A user satis-
`faction survey showed that medical staff especially
`welcomed improved ease of preparation and po-
`tential for prevention of errors and risks of handling.
`
`Acknowledgements
`
`This study was supported by an educational grant from
`Baxter, Inc.
`
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` Adis International Limited. All rights reserved.
`
`Pharmacoeconomics 2002; 20 (8)
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 535
`
`

`

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`Correspondence and offprints: Claude Schmitt, MDS
`Pharma Services Health Economics, 6 avenue de la
`Cristallerie, 92316 Sevres Cedex, France.
`E-mail: claude.schmitt@mdsps.com
`
` Adis International Limited. All rights reserved.
`
`Pharmacoeconomics 2002; 20 (8)
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1034 – Page 536
`
`