WHITE PAPER

The Role of Infusion Pump Technology in Optimizing Efficiency
in Cancer Care Delivery
Results of a simulated chemotherapeutic regimen with the Plum 360® infusion system
vs. a competitive system
JW Beard, MD, MBA; Zehra Madhany, RN, MS, BBA; Heather Witek, RN, BSN

Overview
In this white paper, we examine the impact of technology in cancer care delivery. A hypothesis of improved chemotherapy
delivery metrics with the Plum 360 infusion pump is presented, along with results of a bench study (n=5) supporting
greater efficiency (p<0.001) and a reduced number of air-in-line alarms (p<0.001). A review of infusion safety that aligns theobservations of the study to known patient and healthcare provider safety considerations is also presented.

Introduction
The cancer care delivery model has undergone significant change in the past twenty years. In particular, the shift to valuebased healthcare is driving the development of cancer care that is both clinically effective and cost-efficient. Since theearly 1990s, we have seen the delivery of chemotherapy move from the hospital setting to the outpatient environment.1
In 2003, the Medicare Prescription Drug, Improvement, and Modernization Act substantially reduced payment rates forchemotherapy drugs given in an outpatient setting.
Despite the decrease in outpatient reimbursement and an increase in hospital employment of physicians, the overall
impact on cancer care delivery setting is not yet clear. Additional considerations include the coming adoption of U.S.
Pharmacopeial Convention <800> (USP<800>) and its impact on workflow
requirements during the administrationof hazardous drugs.

With the use of chemotherapy increasingand cost pressure continuing to decrease
reimbursement, improvements in the efficiency
of chemotherapy delivery is essential.

With the use of chemotherapy increasing
and cost pressure continuing to decrease
reimbursement, improvements in theefficiency of chemotherapy delivery isessential. The Plum 360 infusion pump may provide a unique opportunity for time and cost savings in cancer carethrough the concurrent delivery of two compatible infusion agents.

In addition, the Plum 360 infusion system utilizes unique technology that allows air to be removed through a secondary
administration port and a pumping mechanism that may decrease air bubble formation. This creates opportunities tosave time, reduce exposure to hazardous drugs, and minimize wasted medication.

This document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

Objectives
We examined the capability of the Plum 360 infusion pump technology to concurrently deliver two compatible medications
through a single line, combined with its ability to maintain a closed system by removing air via backpriming technology.
We hypothesized that this translates into quantifiable benefits when used in cancer therapy.

Methods
Performance of the Plum 360 infusion system was compared to a competing large volume infusion
pump, which is currently in service in the United States. Both pumps were evaluated using a simulated
chemotherapy session based on a treatment protocol for ovarian cancer.2 Time required for pump deliveryof prehydration, premedication, and chemotherapy was the primary data gathered from the study. The
number of air-in-line alarms recorded was a secondary data point.
The testing setup included clinically relevant configurations of both the Plum 360 and the competitor's system. The Plum360 configuration included a Plum 360 pump SW15.02, a single primary PlumSet® IV tubing set, and two secondary tubingsets. The competitor's configuration included a single channel large volume infusion pump, a single primary tubing set,
and two secondary tubing sets. The simulated infusion solutions included a compatible prehydration and premedication
regimen and the chemotherapeutic agent. Concurrent administration of the prehydration and premedication was simulated
but this protocol is not meant to replace or supersede clinical judgment.
In the study setting, participants prepared solutions and executed a simulated chemotherapy protocol. The protocol wascompleted five times per device. The times and events are presented in Table 1.

Results
TABLE 1: RESULTS3
Primary Endpoint

Plum 360

Competitor

Premedication 50 mL

37 minutes, 56 seconds(fluid and compatiblepremedication ranconcurrently)

60 minutes, 9 seconds(fluid for 30 minutes,
7 seconds, followed bypremedication for 30
minutes, 2 seconds)

Chemotherapeutic placebo* 300 mL

179 minutes, 24 seconds

182 minutes, 26 seconds

Average total time to complete the infusion protocol

217 minutes, 21 seconds

242 minutes, 35 seconds

Time difference-25 minutes, 15 seconds

N/A% Time difference

-12%

N/A

Prehydration 250 mL
Average infusion time in minutes(average of 5 cycles, including
air clearance tasks)

Statistical analysis – difference in minutes, one-sided t-test

p < 0.001

Primary Endpoint
Air-in-line alarms

Plum 360

Competitor

Total number

021

Average number per cycle

04.2

Statistical analysis - difference in observed counts, chi-squared testp < 0.001*The chemotherapeutic placebo may represent paclitaxel or other agentsThis document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

Discussion

Primary endpoint analysis of the time required to complete thesimulated chemotherapy infusion protocol demonstrated atime savings with the Plum 360 infusion system that averaged
25 minutes, 15 seconds (p<0.001).
This difference in time can be attributed to the unique
technology of the Plum 360 infusion system that enables
concurrent delivery of two compatible medications througha single channel. In this case, the Plum 360 infusion systemprovided prehydration and premedication simultaneously
over an average time of 37 minutes, 56 seconds.

FIGURE 1: AIR-IN-LINE ALARMS
2521

20 Number of Alarms

This pump evaluation, utilizing a simulated
chemotherapy regimen, revealed significant
differences between the two infusion
systems, in both primary and secondary endpoints.

151050-4.200

Plum 360
Average

Plum 360
Total

Competitor
Average

Competitor
Total

Over the course of three administration cycles, thecompetitive pump registered a total of 21 air-in-line
alarms while the Plum 360 registered zero alarms.

In contrast, the competitor's pump was limited to delivering asingle infusion through the single pump channel. (Note: Competing pumps can be configured to have multiple channels atincremental cost and footprint.)
The competitor single infusion requirement led to delivery of prehydration averaging 30 minutes, 7 seconds, followed bydelivery of the premedication averaging 30 minutes, 2 seconds for an average combined time of 60 minutes, 9 seconds.
The difference in infusion times between the pumps for prehydration and premedication was 22 minutes, 13 seconds(p<0.001). The infusion time required for the delivery of the simulated chemotherapeutic agent was similar for both pumps
as concurrent delivery with this agent is not indicated (p=0.10).
Thus, where opportunity for concurrent medication delivery is possible, the Plum 360 infusion system creates the potential
for significant time savings. Over the total study period simulating infusion delivery for five patients, the Plum 360 pumpedfor 18 hours, 7 minutes, while the competitorpumped for 20 hours, 13 minutes, for an overall timedifference of 2 hours, 6 minutes.
For an ovarian cancer patient receiving therapy
matching this protocol, this represents over an hourand fifteen minutes less in the infusion chair overthree cycles.

Concurrent medication delivery, alongwith a reduction in air-in-line alarms madepossible with the Plum 360, can potentiallysave a patient an hour and fifteen minutesof chair time over three cycles.

The impact of the time savings gains moresignificance with shorter duration infusion protocols.
For example, if the chemotherapeutic agent in this protocol was infused over one hour instead of three, the percentage oftime savings would increase from 12% to 23%. A 23% reduction in infusion time would enable an infusion center to treat
approximately five patients in the same amount of time it currently takes to treat four. Further significant opportunities fortime savings with concurrent administration exist as patients frequently require additional infusions such as electrolytes,
medications, and blood products.
This document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

The high incidence of alarms withthe competitor's pump may lead to a
scenario where multiple pumps arealarming simultaneously, stretching
staff and delaying alarm resolution.

The secondary endpoint of the number of air-in-line
alarms was chosen due to the implications of this alarm
condition on workflows and the potential risk of harm topatients and caregivers.
We studied air-in-line alarms by simulating the infusionof paclitaxel since the drug presents challenges forinfusion pumps, given its viscous nature and its observed
tendency to “outgas,” leading to air bubbles or “froth” inthe infusion tubing. 4,5

The presence of air-in-line may lead to a number of potential problems for patients and clinicians such as air-in-line
alarms, infusion delays, disconnects of the IV set, risk of exposure to hazardous drugs, and the financial cost of wastedmedication. Episodes of air-in-line require time to resolve, which may result in extended infusion times. During the infusionof the simulated protocol, the competitor's pump experienced a total of 21 air-in-line alarms, 18 of which occurred during
the infusion of the paclitaxel placebo, for an average of 4.2 air-in-line alarms per protocol run. The Plum 360 system
experienced zero air-in-line alarms throughout the entire study period. The difference in the rate of air-in-line alarms wasstatistically significant (p<0.001).
The high incidence of alarms with the competitor's pump may lead to an infusion center scenario where multiple pumps
are alarming simultaneously, stretching staff resources and delaying alarm resolution. Alarm management is a significant
patient safety issue and has been highlighted by The Joint Commission through the 2014 National Patient Safety Goal on
Alarm Management. The safety goal indicates that a high incidence of alarms has been associated with staff ignoring or
disabling them, putting patient safety at risk.6
The lower number of air-in-line alarms with the Plum 360 system may be attributed to the physics of the volumetric pumping
mechanism and the capability to capture air in the PlumSet cassette's air trap chamber. The competitor’s system doesn’t
have an air trapping system and utilizes a peristaltic pumping mechanism.
The process of clearing air from the IV set differs between the pumps and has
implications for efficiency and safety. The PlumSet used in the Plum 360 infusion
system can capture 1 mL of air in its air trap before the alarm is activated. The system
also has the capability to clear air through the secondary cassette port by utilizing thebackprime feature of the pump, allowing the clinician to maintain a closed system.
Removing air from the competitor's pump line requires the clinician to choose
from several manual options—“flicking” the air up the tubing into an infusion bag,
aspirating the air from a Y-port, or disconnecting the tubing from the patient to prime
the air through the tubing. The 21 air-in-line alarms from the competitor’s pump all
required manual clearing.

The PlumSet cassette allows for theclearing of air using a backpriming
feature to maintain a totally closed
system throughout chemotherapy
administration.

Disconnecting and priming air through the infusion line can have safety and financial
implications. First, a disconnected line may expose the patient and clinician to ahazardous drug. Second, when clearing takes place by disconnecting and priming
the line, medication intended for the patient is lost, potentially resulting in inaccurate
dosing and cost to the facility. The unique capability of the Plum 360 to remove
air from an infusion without disconnecting the line may minimize hazardous drug
exposure and medication waste.

This document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

FIGURE 2: PLUMSET CASSETTE

Competitor

Plum 360

With the Plum 360, there is no need to use different head heights for secondary drug administration, increasing patient
safety by eliminating the opportunity for the secondary infusion to "back up" into the primary infusion.

An additional significant risk arising from disconnections of an IV set is contamination of the patient’s infusion line.
Despite best efforts to use aseptic technique, repeated access of peripheral IVs, PICC lines, or subcutaneous infusion
ports increases the possibility of contamination and infection. In this study, the clinician was able to remedy the air inline by using the "flicking" method. Failure of this method could have required disconnecting and reconnecting the tubing
every time air needed to be cleared from the line.
The requirement to adjust the head height of IV bags to ensure accurate infusion also has implications for the safetyof secondary infusion administration. The Health Quality Ontario research team identifies administration of secondary
infusions as a high-risk task due to requirements for programming and physical IV tubing setup, which may be nonintuitiveand prone to error.7
Important secondary infusion considerations include the presence of a head height differential, use of a back check valve,and connection of the secondary infusion above the pump.7 In this study, the competitor's pump requires a specific headheight adjustment when a secondary medication is attached to the primary line. If head height is not adjusted accurately,
the pump may siphon or draw fluid fromthe incorrect source, leading to medication
error and potential patient harm.8 Industry
examples of head height differential
requirements include a range from 8 to 20
inches for large volume infusion pumps.

Alarm management is a significant patient
safety issue and has been highlighted by The
Joint Commission through the 2014 National
Patient Safety Goal on Alarm Management.

The Plum 360 technology automates
secondary delivery, eliminating the needfor head height adjustments (Figure 2). This, in turn, reduces the risk of IV solution and medication administration error.
The Health Quality Ontario research team’s summary of the benefits of the Plum infusion system includes the following: norequirement for bag height differential is required; there is secondary infusion line occlusion detection; and the secondaryinfusion cannot “back up” into the primary infusion.7
This document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

Conclusion
The need to provide the highest quality of care in the most efficient and cost-effective manner has driven the continued
shift from inpatient to outpatient cancer treatment. To this end, optimizing the workflow associated with cancer caredelivery by leveraging technology in the administration of infusion therapy can deliver quantifiable savings in treatment
times and improved patient experience.

The Plum 360 infusion system may havesignificant benefits in efficiency andair management when compared to acompeting large volume infusion pump.

The use of the Plum 360 infusion system allows forthe concurrent delivery of compatible medicationsat independent rates directly to the patient. In ourbench study comparison with a standard large
volume infusion pump, the Plum 360 demonstrated
a statistically significant 25 minute, 15 second
infusion time savings when delivering a simulated
chemotherapeutic protocol.

In the outpatient oncology setting, time savings can translate into improved quality of life for patients (i.e., less time at theinfusion center) and improved efficiencies for the facility. In addition, the Plum 360 infusion system showed a statisticallysignificant difference (lower) in the number of air-in-line alarms that have multiple clinical consequences.
With the coming adoption of USP <800>, the task of clearing air from infusion lines will have additional significant
implications.9 USP <800> requires the use of closed system transfer devices when administering hazardous drugs. The
backprime feature of the Plum 360 system provides a closed system mechanism to remove air. Facilities using competitive
devices may need to revisit procedures and protocols to determine safe air removal practices using closed system transfer
devices.
Infusion pumps are an excellent example of a medical technology that can add value in the delivery of cancer care. This
investigation provides an initial evaluation of the Plum 360 pump in oncology and highlights the need for a more robust
evaluation of the technology in clinical practice. The results of this bench study suggest that the Plum 360 infusion
system may have significant benefits in efficiency and air management when compared to a competing large volumeinfusion pump. Future studies in the oncology setting will provide valuable insights into the Plum 360 pump’s ability todeliver quantifiable efficiencies within healthcare.

This document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

References
1.
2.
3.
4.
5.
6.
7.
8.
9.

Dollinger M. Guidelines for hospitalization for chemotherapy. Oncologist. 1996;1:107-111.
Paclitaxel Injection, USP [package insert]. Paramus (NJ): WG Critical Care; 2013. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020262s051lbl.pdf. Accessed March 16, 2017.
ICU Medical. Data on file. 2016.
Gelderblom H, Verweij J, Nooter K, et al. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation.
Eur J Cancer. 2001;37(13):1590-1598.
Matsaridou I, Barmpalexis P, Salis A, et al. The influence of surfactant HLB and oil/surfactant ratio on the formation andproperties of self-emulsifying pellets and microemulsion reconstitution. AAPS PharmSciTech. 2012;13(4):1319-1330.
The Joint Commission. The Joint Commission announces 2014 National Patient Safety Goal. Joint Commission Perspectives.
2013;33(7)Cassano-Piché A, Fan M, Sabovitch S, et al. Multiple intravenous infusions phase 1b: practice and training scan. Ont HealthTechnol Assess Ser. 2012;12(16):1-132.
Koczmara C, Jelincic V. Secondary lines require “primary” attention. Dynamics. 2006;17(4):23-24.
U.S. Pharmacopeial Convention. USP <800> Hazardous Drugs–Handling in Healthcare settings. Available at https://www.usp.
org/sites/default/files/usp_pdf/EN/m7808.pdf. Accessed March 16, 2017.

This document contains a drug product containing a boxed warning. Please refer to manufacturers' package inserts for full prescribing information.

About the Authors
JW Beard, MD, MBA; Zehra Madhany, RN, MS, BBA; and Heather Witek, RN, BSN are all employees of ICU Medical Inc.

©2017 ICU Medical Inc.

800.824.7890 | www.icumed.com | P17-1088