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AB STR A CT
Introduction: Intensive care units (ICUs) are the most frequent setting dopamine dose delivered were $46,995 for premix, $47,625 for com-
for serious medical errors, which not only have serious health conse- pounding center, $101,934 for MINIBAG Plus, and $108,870 for drug
quences but also an economic impact. In this article, using a theoretical prepared in the ICU. The variability of these results is higher for
model, we evaluate four medication administration systems: conven- compounding center than for premix, and even higher for MINIBAG Plus
tional preparation by nursing staff, MINIBAG Plus delivery system, and nurse delivery. Conclusions: The use of premix drugs can be a cost-
compounding center preparation, and premix drugs. Methods: We saving strategy, which decreases medical errors in drug administration in
designed a decision tree model from a third-party payer perspective, the ICU, particularly if it is part of an integral error reduction program.
and the time horizon of the acute event. Local costs, in Colombian pesos
Keywords: drug administration schedule, drug delivery systems,
(US $1 ¼ 1784 COP$), were obtained from tariff manuals, medication costs
economics, intensive care units, medication errors.
from Sismed information system, and clinical variables from the pub-
lished literature, and uncertainty was dealt with by an expert panel. The Copyright & 2014, International Society for Pharmacoeconomics and
drug used for the model was dopamine. Results: Average costs for each Outcomes Research (ISPOR). Published by Elsevier Inc.
Conflict of interest: This study was supported by an unrestricted grant from Baxter Colombia.
* Address correspondence to: Diego Rosselli, Faculty of Medicine, Clinical Epidemiology and Biostatistics Department, Pontificia
Universidad Javeriana, Carrera 7 No. 40-62, Piso 2 Hospital San Ignacio, Bogotá, Colombia.
E-mail: diego.rosselli@gmail.com.
2212-1099$36.00 – see front matter Copyright & 2014, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.vhri.2014.05.001
VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 20–24 21
Table 1 – Classification of medical errors by Calabrese et al. [9], as per error type clustering used by the authors
and the corresponding incidence probability (once an error has occurred).
Category Definition Error type Probability (%) Reference
A Quasi error
B Wrong drug, not administered No harm 92 [10]
C Medication administered without consequences
D Monitoring required but no symptoms Mild harm 6.33 [10]
E Symptoms development, management required
Moderate harm 1.44 [6]
F Hospital stay is required or increased
G Permanent consequences develop
Severe harm 0.42 [6]
H Risk of death (anaphylaxis, cardiac arrest)
I Death Death 0.21 [6]
results in the patient’s death (Table 1). The time horizon of medi- 1 year. Costs are in Colombian pesos (COP $) as for 2012 (as
cation error is, therefore, quite variable. Most errors lead to either reference, the exchange rate for July 2012 was US $1 ¼ COP $1784).
minor harm or no harm at all, while it has been estimated that about
2% of the errors cause significant injuries to patients [9]. Model Assumptions
Calabrese et al. [9] proposed another error classification consid-
The main assumption of the model is that error incidence rates at
ering both drug administration route (e.g., subcutaneous adminis-
Colombian ICUs are similar to those published elsewhere. Calcu-
tration, IV bolus, and IV infusion) and drug class (e.g., antibiotics,
lations are based on a “typical” ICU adult patient.
sedatives, vasopressors, and insulin). Despite the fact that no other
potential medication errors (microbiological contamination, com-
pounding errors such as wrong dilutant or drug concentration Error risks
miscalculation) were considered in this trial, error rate exceeded To estimate error risks, a literature review was carried out using
the one reported in the previously described study as it reached 74.5 MeSH “Medication Errors,” “Drug Administration Schedule,”
errors per 100 patient-days. Overall, an error occurs in about 7% of “Drug Delivery Systems,” and “Intensive Care Units” as search
all parenteral drug administrations [10]. Medication dosing errors criteria. A total of 272 abstracts were reviewed; 27 articles were
(118 of 861 recorded errors) had the most serious consequences as selected for full-text review, of which 20 [4,5,9–11,13–27] reported
they resulted in permanent harm in three patients and in the death error rates. Among 113 ICUs from 27 countries, the only data from
of other three patients. Other studies [3,11] report even higher error the region came from Brazil [17] and from 6 ICUs (3 Argentinean
rates regarding medication administration at the ICUs, reaching up and 3 Brazilian) included in the study by Valentin et al. [5]. Error
to 1 daily error per patient, on average [12]. probabilities used in the model (based on Nuckols et al. [14]), for
Apart from having severe consequences on the patients’ each individual drug administration, were as follows: 0.01 for
health, errors have serious financial consequences [13]. In a compounding center preparation (by pharmacists), 0.08 for bed-
sample of ICU patients in Switzerland (n ¼ 333), Nuckols et al. side preparation by nursing staff, 0.03 for MINIBAG Plus, and
[14] showed preventable IV drug administration–related adverse 0.0027 for premix drugs. For our base-case scenario, we selected
events in 94 patients (28%). Such adverse events were associated the error rates of Taxis and Barber [6] and Klopotowska et al. [10]
with an extended hospital stay (mean 4.8 days) as well as with because they were on the conservative side (we preferred to
increased costs (mean US $4500) versus the control group. underestimate the risk) and because they include a wide range of
The objective of this study was to develop an economic error consequences. Only one reference [15] included error rates
evaluation model to estimate the costs and outcome impact of for compounding centers versus premix medication. For the
four different IV drug administration systems (assuming the sensitivity analysis, we arbitrarily assumed a wide range after
same drug) at the ICU setting in Colombia. discussions with our expert panel. In error probabilities, we
considered it unpractical to convert rates to probabilities. We
used rates as probabilities because of the short time frame.
Methods
We designed a decision tree–type economic model using TreeAge
Pro Healthcare 2009 (Fig. 1). Four alternatives for IV drug delivery
were considered: use of premix drugs, compounding center
preparation, bedside preparation at the ICU by a nurse (but using
a buretrol set), and MINIBAG Plus use (flexible closed system bag
with a vial adaptor—a point-of-care activated device). Baseline
data included in the model were extracted from international
medical journal publications (see Table 1) and subsequently
discussed and validated by an expert panel independently
selected by the investigators (with no sponsor participation).
The panel was composed of an internal medicine specialist, a
surgeon, two physicians specialized in pharmacology, and a
pharmacist. Dopamine was selected as the drug for the model
because it shows a larger cost difference between premix and
competitors. We used a third-party payer perspective (Colombian
health system), and the time horizon was the length of ICU stay Fig. 1 – Decision tree outline. Errors include preparation-
(which is similar to that reported in the literature); no discount related, contamination, and biological risk errors. ICU,
rate was applied because the period of analysis was shorter than intensive care unit.
22 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 20–24
Costs Dopamine cost was obtained from annual sales (March 2011-
March 2012) according to Sismed (an official source of medication
Cost calculation for compounding center preparation price and sales volume information). In total, 17,555 units were
Initially, costs were obtained from a large compounding center
sold during this 12-month period. Because the unit value and
that prepares medications and parenteral nutrition solutions for
market share of dopamine were both known, we estimated a
four high-complexity hospitals in Bogota. The microcosting
weighted mean cost of COP $2910. For premixed dopamine, we
technique was used, in which administrative costs were distrib-
used the unit cost supplied by the manufacturer (COP $17,930), as
uted between oncology drugs, parenteral nutrition, antibiotics,
well as for MINIBAG Plus delivery system (COP $4,800).
and other medications. Staff at this center includes 99 people, 78
of whom are pharmacists on different working schedules. Payroll
is almost COP $ 350 million, of which 30% corresponds to the
preparation of antibiotics and 52% to the preparation of other Error costs
drugs. On a monthly basis, 150,000 units are prepared (antibiotics In 2011, Carey and Stefos [12] published in Health Economics an
50,000, other drugs 95,000, remaining ones corresponding to article in which they calculated the frequency of a series of errors
oncology drugs and parenteral nutrition). These data result in and quantified their costs. On the basis of a population from the
an estimated unit value of COP $17,552 for chemotherapy, COP US veterans database (n ¼ 71.349 patients at risk), the researchers
$14,306 for total parenteral nutrition, COP $2,050 for antibiotics, estimated the median costs of a medical care–associated infec-
and COP $1,888 for other drugs, before applying a profit margin; tion (US $42,309–US $60,199), sepsis (US$25,891–US $30,515), and a
because of economies of scale, this last cost was the one used for work accident (pinching or laceration) (US$ 5,059–US $9,448). The
the lower limit of our model. For estimation of costs, three cost for the latter was higher than the one reported by Rivard
additional hospital mixing centers were studied, in which unit et al. [28] in 2008 (US $3359).
preparation costs ranged between COP $3,938 and COP $14,306 Because costs in Colombia are significantly lower [29], follow-
through microcosting techniques (we used COP $4,923 and COP ing discussion with the experts we assumed that harmless errors
$17,883 as margins for the sensitivity analysis, applying a 25% (which account for 91.6% of the errors) do not incur costs, minor
profit margin). This wide range of costs could be accounted for by errors (6.3%) incur an additional cost of COP $50,000 each,
the proportion of resources allocated to the preparation of intermediate errors (those leading to extended hospital stay by
oncology drugs and parenteral nutrition products (whose costs 2.4 days, and accounting for 1.4% of the errors) incur costs of COP
and profit margin are both higher) and the volume of prepared $3.1 million, and serious errors (0.6%) incur costs of COP $3.56
medications. In the model, for the base case, we used an average million. Despite the literature review, error costs were finally
cost of COP $13,468 per drug prepared at the compounding center. estimated by the expert panel, who believe that these costs are
much lower than those reported in the literature.
Table 2 – Selected variables used in the model, with wide intervals used for the sensitivity analysis.
Variable Base case ($) Low ($) High ($) Source
Sensitivity Analysis measured at a single ICU; however, they were not very different
from what has been reported in the literature, except for the
The tornado simulation (Fig. 2) showed which variables could
article by Rivard et al. [28] who reported shorter times; this might
change the decision (using the ranges preestablished by the
be because their study was undertaken at a cardiology ICU in
authors). The variable with the greatest effect on total cost is
which fewer antibiotics are used; preparation times of these
the nurse salary, affecting all the four alternatives, but not
drugs are lengthier.
modifying the final decision. Critical variables were the costs of
Our per-error costs were lower than those reported in the
medication (in this case dopamine), and of compounding center
literature; according to Nuckols et al. [14], adverse events asso-
preparation, as well as the probabilities of errors that could cause
ciated with drug errors increased hospitalization costs by 53% (on
harm, and the rate of error with premix medication.
average, US $6,647 were added to the baseline costs of US $12,529)
We found in the one-way sensitivity analysis that if each
and were related to a longer stay (4.8 days more). Mortality rate
preparation in the compounding center costs more than $13,468,
attributable to errors is also probably underestimated in our
premix would be cost saving. This cost is one of the variables
model. Rothschild et al. [13] in 1490 patient-days found 54 cases
with higher uncertainty in our model, so each institution should
of errors, which either led to death (n ¼ 2), imminent danger (n ¼ 5),
be careful when estimating this particular cost. The difference
or “some” consequence (n ¼ 28) or prolonged the length of stay
between the premix cost and plain medication is also important.
(n ¼ 19). In the study by Thomas et al. [30], among 3691 incidents
The two-way sensitivity analysis of the cost of premix and plain
resulting in harm, 13 (0.35%) led to the patient’s death, 40 (1.1%)
dopamine shows that up to a difference of $15,000 in prices, the
to serious harm, 327 (8.9%) to moderate harm, and 857 (23.2%) to
premix would still be cost saving. If we assume ranges from
minor harm, while 2454 (66.5%) led to no harm at all. With these
$1,000 to $10,000 for plain dopamine and $18,000 to $20,000 for
data in mind, it is likely that our model underestimated the
premix dopamine, the premix will be cost saving 42% of the times
financial impact of medical errors. Further national studies on
for the possible combinations. Another two-way sensitivity
the subject are required [29].
analysis for the error probability of compounding center and
Sales of dopamine in Colombia, according to official data,
premix shows that costs favor one or the other in a very similar
accounted for 17,555 vials in a 12-month period (2011–2012). If our
rate. In an in-hospital compounding center, the probability of
assumptions are correct, the Colombian health system could save
error is higher, which would favor the premix alternative.
up to COP $1.1 billion (around half a million US dollars) if
premixed dopamine were used.
Of the four drug delivery systems, the one showing higher
cost variability is the compounding center drug preparation, for
Discussion
two reasons: the first one is economies of scale. A large mixing
This report has certain limitations: First, it is mainly based on center can expect lower marginal costs, thereby having signifi-
foreign studies, error probabilities are not adjusted to medication cant differences compared with the final costs of a small com-
type, and local costs are approximate. Drug delivery times were pounding center. The other one is opportunity cost; oncological
Table 3 – Probabilities are per error occurring in IV drug administration in the ICU, with wide intervals used for
the sensitivity analysis.
Error Base case Low High Source
Error probabilities for bedside preparation by nursing staff 0.08 0.04 0.12 [14]
Error probabilities for MINIBAG Plus 0.03 0.005 0.05 [14]
Rate of error compounding center 0.01 0.005 0.05 [15]
Rate of error premix 0.0027 0.001 0.05 [15]
Probability of “mild” consequences error 0.063 0.010 0.300 [10]
Probability of “moderate” consequences error 0.014 0.001 0.050 [6]
Probability of “severe” consequences error 0.004 0.001 0.020 [6]
ICU, intensive care unit; IV, intravenous.
24 VALUE IN HEALTH REGIONAL ISSUES 5C (2014) 20–24
Fig. 2 – Tornado diagram showing variables with the greatest effect on the results. Dark bar shows critical variables, those that
can change the least costly alternative between compounding center and premix. The x-axis represents the change in mean
cost. ICU, intensive care unit.
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