MANAGERIAL

Economic Value of Pharmacist-Led Medication

Reconciliation for Reducing Medication Errors
After Hospital Discharge
Mehdi Najafzadeh, PhD; Jeffrey L. Schnipper, MD, MPH; William H. Shrank, MD, MSHS; Steven Kymes, PhD;
Troyen A. Brennan, MD, JD, MPH; and Niteesh K. Choudhry, MD, PhD

D
isruptions to, and changes in, a patient’s outpatient medica-
tion regimen occur frequently during hospitalization. This
ABSTRACT
often results in discrepancies between drugs prescribed at dis-
charge and the medications outpatient providers believe that patients OBJECTIVES: Medication discrepancies at the time of
hospital discharge are common and can harm patients.
should be on. Although the majority of such discrepancies do not have
1
Medication reconciliation by pharmacists has been shown
clinically important effects, their consequences can be profound. These to prevent such discrepancies and the adverse drug events
events are defined as preventable adverse drug events (ADEs) because (ADEs) that can result from them. Our objective was to
estimate the economic value of nontargeted and targeted
they are caused by medication discrepancies that could have been medication reconciliation conducted by pharmacists and
avoided. It is estimated that 2.4% to 4.1% of all hospital admissions are pharmacy technicians at hospital discharge versus usual care.
directly related to ADEs, and up to 69% of those ADEs are preventable.2-5 STUDY DESIGN: Discrete-event simulation model.
There are other circumstances in which the presence of a medication
METHODS: We developed a discrete-event simulation
discrepancy has not yet resulted in an ADE, but may still be costly and/
model to prospectively model the incidence of drug-related
or may expose patients to the risks of additional testing or monitoring.6 events from a hospital payer’s perspective. The model
Medication reconciliation by pharmacists at hospital discharge assumptions were based on data published in the peer-
reviewed literature. Incidences of medication discrepancies,
is a possible strategy to reduce medication discrepancies and sub- preventable ADEs, emergency department visits,
sequent ADEs. Several systematic reviews have found that medi- rehospitalizations, costs, and net benefit were estimated.
cation reconciliation significantly reduces the risk of medication
RESULTS: The expected total cost of preventable ADEs was
discrepancies.7-9 Despite this, not all studies evaluating the impact estimated to be $472 (95% credible interval [CI], $247-$778)
of medication reconciliation on health resource utilization (HRU) per patient with usual care. Under the base-case assumption
that medication reconciliation could reduce medication
have found beneficial effects.10-19 These findings naturally raise ques- discrepancies by 52%, the cost of preventable ADEs could
tions about the economic value of this intervention and how the be reduced to $266 (95% CI, $150-$423), resulting in a
balance between the costs and benefits of the intervention could be net benefit of $206 (95% CI, $73-$373) per patient, after
accounting for intervention costs. A medication reconciliation
optimized by, for example, selectively targeting high-risk patients. intervention that reduces medication discrepancies by
Accordingly, we conducted a simulation-based cost-benefit at least 10% could cover the initial cost of intervention.
Targeting medication reconciliation to high-risk individuals
analysis to estimate and compare the economic value of 3 strategies
would achieve a higher net benefit than a nontargeted
at hospital discharge: a) usual care (no intervention), b) nontar- intervention only if the sensitivity and specificity of a
geted medication reconciliation for all patients, and c) targeted screening tool were at least 90% and 70%, respectively.
medication reconciliation that uses a screening tool to identify CONCLUSIONS: Our study suggests that implementing a
patients at high risk of postdischarge ADEs. pharmacist-led medication reconciliation intervention at hospital
discharge could be cost saving compared with usual care.

METHODS Am J Manag Care. 2016;22(10):654-661

Overall Approach
We developed a 2-part discrete-event simulation to prospectively
model the sequence of events that occur within the 30 days after

654   OCTOBER 2016  www.ajmc.com

 Economic Value of Medication Reconciliation

hospital discharge for a hypothetical cohort of

TAKE-AWAY POINTS
patients who did, and did not, receive medica-
tion reconciliation. Consistent with the ex- ›› Medication discrepancies at the time of hospital discharge are common and can harm patients.
isting literature,6 we categorized medication ›› Little is known about the economic value of implementing medication reconciliation by
discrepancies that were associated with harm pharmacists and whether this intervention is more cost-effective when targeted to those
most at risk of medication discrepancies.
as preventable ADEs and those not associated
›› A medication reconciliation intervention that reduces medication discrepancies by at least
with harm as “potential” ADEs. We categorized 10% could cover the initial cost of intervention.
both preventable ADEs and potential ADEs ›› Our results suggest that, despite the use of relatively costly pharmacists and pharmacy
technicians, the cost savings from avoided rehospitalizations would more than offset the
into those that were (or were potentially) cost of the intervention.
life-threatening, serious, or significant. Non-
significant events were considered, by defini-
tion, to not be a medication discrepancy. of cognitive impairment. We also assumed that approximately 60% of
Our model first estimated the incidence of medication discrep- patients were hospitalized with acute coronary syndrome, 30% with
ancies, preventable ADEs, their associated major HRUs (ie, emer- acute heart failure, and 10% with both diagnoses.
gency department [ED] visits and rehospitalizations), and costs
among patients who did not undergo reconciliation (Figure 1 [A]). Estimates of Medication Discrepancies and
We then used the distribution of outcomes from the initial phase Subsequent Events
of the simulation to compare the impact of 3 interventions (Figure The incidences of medication discrepancies, preventable ADEs, and
1 [B]): a) a nontargeted pharmacist-led medication reconciliation potential ADEs for patients not undergoing medication reconcilia-
intervention for all patients, b) a targeted pharmacist-led medica- tion were estimated using the distribution of observed events in the
tion reconciliation intervention in which only patients at high risk control arm of the PILL-CVD study.6 The distribution of events in the
of ADEs were intervened upon, and c) usual care (no intervention). usual-care arm of PILL-CVD is summarized in eAppendix Figure A.
Our modeling approach and structure have been explained in the In this study, 25 of the 125 (20%) patients with preventable ADEs were
eAppendix (eAppendices available at www.ajmc.com). rehospitalized or visited an ED. Based on a case-by-case analysis of
We used a cost-benefit analysis framework and conducted our these patients by 1 study author (JLS), we determined that 24 of these
analysis from the perspective of a hospital that was at risk for the ADEs were potentially amenable to medication reconciliation activi-
added cost of any intervention and the savings from avoiding HRUs ties at the time of hospital discharge (as opposed to postdischarge
due to preventable ADEs. All costs were estimated in 2014 US dol- activities, such as monitoring for ADEs).
lars and, when necessary, unit costs were converted to 2014 prices The proportion of patients who had rehospitalizations, ED visits,
using reported changes in the consumer price index.20 Consider- or both events, was based on the observed rates in this trial6 and
ing the short period of analysis, no discount rate was applied. All another large clinical trial.17 In the base-case analysis, we assumed
simulations were developed using Arena version 12.00 (Rockwell that the intervention could reduce the risk of rehospitalization due
Automation Technologies, Inc, Milwaukee, Wisconsin). to preventable ADEs, amenable to medication reconciliation, by 52%
(ie, a relative risk of 0.48). This was based on an average effectiveness
Patient Characteristics rate of medication reconciliation observed in 4 published studies
The characteristics of the simulated cohort were assumed to be similar of at least moderate methodological quality.11,14,15,21 The estimated
to populations in the studies that were the basis of our assumptions effectiveness of the intervention may vary as a function of care set-
about event probabilities (Table 1).6 The model assumptions and ting, patient characteristics, composition of the healthcare team
event probabilities are based on data from the Pharmacist Interven- responsible for delivery of the intervention, and services that were
tion for Low Literacy in Cardiovascular Disease (PILL-CVD) study.6 In bundled with medication reconciliation.7,8 As a result, we varied our
this randomized clinical trial, 851 patients hospitalized with acute assumptions of effectiveness extensively in the sensitivity analysis.
coronary syndromes or acute decompensated heart failure were
randomized to receive either a pharmacist-assisted intervention (ie, Patient Targeting
medication reconciliation, inpatient pharmacist counseling, low- In order to estimate the impact of limiting medication reconcili-
literacy adherence aids, and individualized telephone follow-up) or ation to high-risk patients (ie, those patients most likely to have a
usual care after hospital discharge. Similar to the trial population, postdischarge ADE due to a medication discrepancy), we assumed
the simulated cohort was assumed to have an average age of 60 years, that patients underwent screening with a tool that could predict,
have a median 14 years of education, and to be 60% male. We assumed with some accuracy, the risk of ADEs based on the patient’s charac-
that approximately 10% of the hypothetical cohort had inadequate teristics at the time of hospital discharge. A perfect screening tool
health literacy and 8.7% had marginal, and that 11.5% had some level could exactly discriminate patients with and without preventable

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MANAGERIAL

FIGURE 1. Model Structure

A. Modeling the sequence of events in usual care strategya

Life-threatening/ More
serious ADE ADEs
Medication Harm
discrepancies (ADE)
No more
Significant ADE
ADEs

Patient Usual Record End

discharged care events follow-up

LEGEND

No medication Life-threatening/ More Create

discrepancies serious pADE pADEs
No harm Exit
(pADE)
Assign
No more
Significant pADE Chance node
pADEs

B. Modeling the impact of intervention on outcomes among patients simulated in part Ab

No ED/
hospitalization
TP Effect
MedRec
size
FN ED/
hospitalization
Screening
FP Record Exit
outcomes study

TN No No ED/
Simulated MedRec hospitalization LEGEND
patient
Create
MedRec ED/ Exit
all hospitalization
No Assign
screening
Usual Chance node
care Decision node

ADE indicates an adverse drug event as a result of medication discrepancies; ED, emergency department visit; FN, false negative; FP, false positive; MedRec, medica-
tion reconciliation; pADE, a potential ADE as a result of medication discrepancies; PILL-CVD, Pharmacist Intervention for Low Literacy in Cardiovascular Disease
study; TN, true negative; TP, true positive.
a
Modeling the sequence of events within the 30 days after hospital discharge for a hypothetical cohort of patients in usual care strategy (ie, no medication reconcili-
ation). Incidences of medication discrepancies for individual patients were modeled based on observed probabilities in the PILL-CVD clinical trial. Patients who
experienced medication discrepancies either were harmed (ie, developed a preventable ADE) or were exposed to harms due to these discrepancies (ie, potential
ADEs). The possibility of having more than 1 preventable ADE or potential ADE has been modeled. All event histories were recorded for individual patients to emulate
the likelihood and distribution of events under the usual care arm of the PILL-CVD clinical trial.
b
Modeling the impact of targeted and nontargeted intervention on outcomes among patients simulated in part A. Patient-specific incidences of events in part A
were used as counterfactuals under usual care and for determining the true status of patients under targeted intervention (ie, whether they would have developed
preventable ADEs under usual care). The model simulates the impact of medication reconciliation on the likelihood of reducing discrepancies and subsequent
rehospitalizations and ED visits. Although all patients are assumed to receive medication reconciliation under a nontargeted intervention strategy, only those with TP
and FP screening results underwent medication reconciliation. The model then calculated and recorded costs associated with intervention, rehospitalizations, and ED
visits resulting only from preventable ADEs. The overall costs of usual care, nontargeted intervention for all patients, and targeted intervention were estimated and
compared by aggregating individual patients’ costs.

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 Economic Value of Medication Reconciliation

ADEs, based on the information available at TABLE 1. Model Parameters

discharge, and would only assign the former Base
Range Citation
to receive the intervention. Case
Given the sensitivity and specificity of this Proportion of patients with preventable ADEs 29.2% Beta (125-303) 6
tool, we assigned patients into 4 categories: a) Proportion of patients with potential ADEs 30.8% Beta (132-296) 6
true positive, who would have had a prevent- Proportion of patients with preventable
30.4% Beta (38-87) 6
able ADE and were assigned to receive the inter- ADEs who also had potential ADEs
vention; b) false positive, who would not have Probability that a preventable ADE is: 6
had a preventable ADE but were assigned to the Life-threatening 2.9% Beta (5-165) 6
intervention; c) false negative, who would have Serious 14.1% Beta (24-146) 6
had a preventable ADE but were not assigned to 1 – beta (5-165)
Significant 82.9% 6
receive the intervention; and d) true negative, to beta (24-146)
who would not have had a preventable ADE and Number of preventable ADEs per patient
6
were not assigned to receive the intervention. who had at least 1 preventable ADE
We assumed that the effectiveness of targeted 1 76%
interventions was similar to that of the nontar- 2 17%
geted strategy, in which medication reconcilia- 3 4%
tion was offered to all patients. 4 2%
≥5 1%
Costs
Probability of major resource utilization
Average cost per rehospitalization was based 19.2% Beta (25-100) 6
among patients with preventable ADEs
on recent estimates by the Agency for Health Percentage that require ED visit only 25.0% Beta (6-18) 6
Research and Quality.22 The cost per ED visit Percentage that require hospitalization only 29.2% Beta (7-18) 6
was based on estimated charges in the same
Percentage that require hospitalization
report, which were calculated by applying an 45.8% Beta (11-14) 6
and ED visit
estimated cost-to-charge ratio of 0.55.23,24 A 3% Relative risks of events in medication
penalty rate was applied to all rehospitaliza- reconciliation versus usual care (no 0.48 (0-1) Assumption
tion costs to reflect the current policies for medication reconciliation)
readmission payment adjusted amount.25 Sensitivity of screening tool for predicting
70% (10%-100%) Assumption
preventable ADEs
Intervention costs were calculated using es-
timated average pharmacist time per reconcili- Specificity of screening tool for predicting
70% (10%-100%) Assumption
preventable ADEs
ation and average salary and benefit payments
26

Mean cost per hospitalization $10,000 ± 20% 22

to pharmacists and pharmacy technicians.27 We
Median charge per ED visit $713 ± 20% 24
assumed that pharmacy technicians, rather
than pharmacists, conducted 50% of medica- Cost-to-charge ratio for ED visits 0.55 209/383 23

tion reconciliation-related tasks (eg, taking Penalty for rehospitalization 3% 25

medication histories) in order to reduce the Mean pharmacist time per reconciliation
46.2 ± 50% 26
intervention cost. Pharmacists were assumed (minutes)

to supervise technicians and do some of the Mean annual salary of pharmacist $120,850 ± 20% 27
tasks, like patient counseling or order review, Mean annual salary of pharmacy technician $30,370 ± 20% 27
themselves. This assumption was varied in Overhead costs, including fringe and benefit 25% Assumption
the sensitivity analysis. We also assumed that ADE indicates an adverse drug event occurring as a result of medication discrepancies; ED, emergency
department.
a medication history conducted by a pharmacy
technician under a pharmacist’s supervision
was as effective as that of one conducted by a pharmacist alone.28-30 properties, and patients’ characteristics. A probabilistic sensitivity
analysis also was performed to examine distribution of our point
Sensitivity Analysis estimates, given uncertainty of the model parameters, by varying
We performed extensive 1-way and 2-way sensitivity analyses to in- all of our model parameters simultaneously.31-33 We also reported
vestigate the net benefit of medication reconciliation interventions credible intervals based on probabilistic sensitivity analyses that
under different assumptions for our model parameters, screening reflect uncertainty of simulated point estimates.

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TABLE 2. Outcomes of Usual Care and Nontargeted Medication Reconciliation During the First 30 Days After Hospital Discharge,
Assuming Different Effectiveness of Interventiona
RRb = 0.48
Intervention Usual Care (base case) RR = 1 RR = 0.8 RR = 0.5 RR = 0
Number of ED visits caused by preventable ADEs
4.8 2.1 4.5 3.6 2.2 0.0
(per 100 patients)
Number of hospitalizations caused by preventable
4.3 2.0 4.2 3.4 2.1 0.0
ADEs (per 100 patients)
Number of interventions (per 100 patients) 0 100 100 100 100 100
472 266 511 416 275 39
Total cost per patient, $ (95% CI)
(247-778) (150-423) (285-814) (234-651) (153-436) (7-73)
206 –39 56 197 432
Net benefit, $ (95% CI) ref
(73-373) (–101 to 27) (–23 to 151) (70-361) (204-733)
ADE indicates an adverse drug event occurring as a result of medication discrepancies; CI, credible interval; ED, emergency department; ref, reference; RR, rela-
tive risk.
a
Parentheses indicate 95% credible intervals from probabilistic sensitivity analyses estimated using Monte Carlo simulation.
b
RR is relative risk of preventable ADEs in intervention versus usual care.

RESULTS eAppendix Figure B. We found that the initial cost of the intervention
would be more than offset by the savings from averted events as long
In a cohort of 10,000 patients not undergoing medication recon- as it reduced medication errors by at least 10%. The results of 1-way
ciliation, we estimated that 5090 would have at least 1 medication sensitivity analysis suggest that the net benefit is most sensitive to
discrepancy within the first 30 days after hospital discharge. These the effectiveness of intervention, the proportion of preventable ADEs
medication errors would result in 3807 preventable ADEs and 5230 that result in a rehospitalization or ED visit, and the average length of
potential ADEs. Preventable ADEs would result in 421 rehospitaliza- stay for patients who had an ADE-related rehospitalization (Figure 2).
tions and 496 ED visits. Overall, the average cost of preventable ADEs The results of our probabilistic sensitivity analysis are presented
was estimated to be $472 (95% credible interval [CI], $247-$778) per in eAppendix Figure C. We found that the uncertainty around net
patient in the usual care strategy. benefit ranges between –$2 and $577 per patient, with 99% of the
simulated trials resulting in a positive net benefit.
Medication Reconciliation for All
Patients
FIGURE 2. One-Way Sensitivity Analyses Evaluating the Effect of Model Assumptions
Assuming that pharmacist-led medication on Net Benefit of a Nontargeted Medication Reconciliation Interventiona
reconciliation for all patients at hospital
discharge could reduce medication errors by Time (minutes) required for
performing intervention 69 23
52%, and therefore would reduce HRU due to (base case = 46 minutes, low = 23, high = 69)
preventable ADEs amenable to medication Proportion of patients with ADEs
reconciliation by the same proportion, the who require an ED visit or rehospitalization 8.9% 26.7%
(base case = 17.8%, low = 8.9%, high = 26.7%)
number of rehospitalizations and ED visits
Average length of
related to preventable ADEs would be reduced ADE-related rehospitalization 0.5 1.5
(base case = 1 day, low = 0.5, high = 1.5)
to 199 and 215, respectively, with this strategy.
Share of pharmacist versus
This reduction in hospitalizations and ED vis- pharmacy technicians in intervention 100% 0%
(base case = 50%, low = 0%, high = 100%)
its would reduce the overall cost per patient
to $266 (95% CI, $150-$423). This estimate RR of ADE in intervention arm
(base case = 0.48, low = 1, high = 0) 1 0
includes the cost of medication reconciliation
-50 0 50 100 150 200 250 300 350 400 450 500
of approximately $39 per patient. Therefore,
performing medication reconciliation for Net Benefit of Intervention ($)
High Low
all patients at the time of hospital discharge
would result in a significant net benefit of
$206 (95% CI, $73-$373) per patient. ADE indicates an adverse drug event as a result of medication discrepancies; RR, relative risk (of ADEs in
the intervention arm versus usual care).
The impact of altering our assumptions a
Each bar shows changes in the magnitude of net benefit if a particular parameter in the model was
about the effectiveness of medication rec- varied in the specified range, holding every other parameter at its base case value. Only parameters with
the largest influence on net benefit have been presented in this figure. The vertical line indicates the net
onciliation are presented in Table 2 and benefit if all model parameters were set at their base-case values.

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 Economic Value of Medication Reconciliation

TABLE 3. Net Benefit ($) of Targeted Intervention Compared With No Interventiona,b that resulted from medication discrepancies
Sensitivity within 30 days after hospital discharge from
1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 $472 per patient to $266. This resulted in a net
0.1 208 172 163 132 114 85 66 42 23 4 savings of $206 per patient, after accounting
for the cost of the intervention. The magni-
0.2 200 178 163 134 112 83 75 50 26 –11
tude of this savings could be increased if a
0.3 204 177 162 144 117 95 82 51 13 –5
screening tool, with very high sensitivity and
0.4 208 181 162 135 112 102 64 54 22 –1
modest specificity, was used to identify and
Specificity

0.5 209 187 155 143 112 91 67 44 21 2

target patients at higher risk of preventable
0.6 222 194 185 156 127 102 75 57 30 6 postdischarge ADEs.
0.7 220 200 184 146 125 103 83 60 37 2 More than half of hospitalized patients are
0.8 218 206 174 153 127 104 86 60 37 22 estimated to have 1 or more medication discrep-
0.9 224 199 179 149 135 114 86 63 38 20 ancy after hospital discharge.6,8 ADEs resulting
1 232 200 179 157 137 115 82 61 44 11 from these discrepancies result in the rehospi-
a
The net benefit ($) of the targeted intervention compared with no intervention for different assump- talization of approximately 4% of discharged
tions for sensitivity and specificity of screening tool, assuming base-case effectiveness of intervention patients.6 This highlights the opportunity for
(relative risk = 0.48).
b
The highlighted cells indicate combinations of sensitivity and specificity where the net benefit of the interventions that can prevent medication dis-
targeted intervention exceeds the net benefit of not targeting ($206).
crepancies to both improve quality and lower
costs. Medication reconciliation at the time of
Medication Reconciliation for Targeted Patients hospital discharge involves a bundle of activities including patient
The net benefit from targeting medication reconciliation under counseling and communication with outpatient providers.
our base-case assumptions of 70% sensitivity and 70% specificity Although careful medication reconciliation at hospital dis-
was $146 savings per patient, which was not superior to the savings charge can potentially eliminate many discrepancies in discharge
from a nontargeted approach ($206 per patient). The impact of medication orders,7,8 it, not surprisingly, has a more limited ef-
alternating our assumptions about sensitivity and specificity of the fect on other types of medication errors that occur during the
screening tool are presented in Table 3 and eAppendix Figure D. postdischarge period. For example, patient misunderstanding of
We found that the net benefit could be as high as $232 per patient, their medication regimen could lead to additional discrepancies
if the specificity and sensitivity of a screening tool were 100%. The after discharge.10 Likely for this reason, reconciliation programs
net benefit could exceed that which we obtained in the base-case that include a telephone follow-up after discharge—along with
analysis as long as the sensitivity and specificity of the screening other, more conventional features such as coordination with
tool were at least 90% and 70%, respectively. However, in general, physicians, patient education, and transition coaching—have,
improving the sensitivity of the screening tool has larger impact on in general, been more effective.17,34
net benefits than improving specificity. For example, a screening tool Our results suggest that despite the use of relatively costly phar-
with 100% sensitivity resulted in a net benefit of $222 per patient macists and pharmacy technicians, the cost savings from avoided
even if the specificity was only 60%. rehospitalizations would more than offset the cost of the interven-
The added value of a targeted intervention increased as the effec- tion. This is consistent with the limited existing cost-effectiveness
tiveness of the intervention decreased and the cost of intervention evidence.35,36 The value of medication reconciliation could be in-
increased. For example, if medication reconciliation reduced the creased if it were preferentially used for individuals at the highest
risk of medication discrepancy by 20% (rather than 52%) and is more risk of ADEs. This is consistent with the fact that many of the most
expensive (eg, because it is performed by pharmacists rather than effective medication reconciliation interventions reported in the
a combination of pharmacist technicians and pharmacists), then a literature are those that were targeted interventions, rather than
targeted intervention is the preferred approach. administered to all patients.18,19 Several studies have attempted to
develop risk prediction models for hospital readmissions with
acceptable accuracy.37,38 However, these models tend to predict
DISCUSSION risk of all rehospitalizations in the first 30 days after discharge
Although pharmacist-led medication reconciliation reduces and, therefore, are not necessarily calibrated to predict the risk of
medication errors that commonly occur after hospital discharge, readmission specifically resulting from medication errors.1
its economic value has not been completely evaluated. We found The estimates of costs and benefits of medication reconciliation
that this intervention, when performed at the time of hospital in our study assume that those paying for medication reconcilia-
discharge, reduced the cost of rehospitalizations and ED visits tion interventions are the same ones that share the savings from

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MANAGERIAL

reduced postdischarge HRUs. The extent to which this is true varies ADEs. Future studies should more directly make the link between
tremendously at present; however, it most certainly will increase interventions and reductions in postdischarge healthcare utiliza-
dramatically in the near future. For example, in 2015, approximately tion in order to increase the precision of cost-benefit estimates.
20% of Medicare payments are based on non–fee-for-service pay-
ment models. This share is expected to increase to 30% by 2016 Acknowledgments
The authors would like to thank Sunil Kripalani, MD, MSc, and Kathryn Gog-
and to 50% in 2018.39 These models included bundled payments, gins, MPH, both of Vanderbilt University, for providing unpublished data
in which providers are at risk for the cost of any readmissions from the PILL-CVD study that were crucial for developing the current analysis.
occurring in the 30-to-90-day period after discharge.
Author Affiliations: Division of Pharmacoepidemiology and Pharmaco-
Similarly, accountable care organizations put providers at risk economics, Department of Medicine, Brigham and Women’s Hospital and
for the total cost of care of the populations they serve; these in- Harvard Medical School (MN, NKC). Division of General Internal Medicine
(JLS), Department of Medicine, Brigham and Women’s Hospital and Harvard
centives have encouraged providers to target readmissions as an
Medical School. Hospitalist Service (JLS, NKC), Department of Medicine,
opportunity to improve care and reduce costs. Moreover, Medicare Brigham and Women’s Hospital and Harvard Medical School, Boston, MA;
has introduced readmission penalties broadly, and these penalties CVS Health (WHS, SK, TAB), Woonsocket, RI.
Source of Funding: This work was supported by an unrestricted grant
have led to much greater focus on readmission rates. As a whole, from CVS Health to Brigham and Women’s Hospital.
these payment models are critical to creating the business case for Author Disclosures: Drs Shrank, Kymes, and Brennan are employees and
hospitals to invest in interventions such as mediation reconciliation. stockholders of CVS Health. Dr Choudhry has received a grant from CVS
Health. The authors report no other relationship or financial interest with
Factors other than the intervention cost might limit the imple- any entity that would pose a conflict of interest with the subject matter of
mentation of medication reconciliation. Pharmacists or other this article.
healthcare professionals conducting this intervention must have Authorship Information: Concept and design (TAB, SK, MN, JLS, WHS);
acquisition of data (TAB, NKC, SK, MN, WHS); analysis and interpretation
access to accurate and timely information about inpatient and of data (TAB, NKC, SK, MN, JLS, WHS); drafting of the manuscript (NKC,
outpatient mediations. As such, the availability of electronic health MN); critical revision of the manuscript for important intellectual content
(TAB, NKC, SK, MN, JLS, WHS); statistical analysis (MN); obtaining funding
records40 that can facilitate obtaining medication records from (NKC); and supervision (NKC).
different points of care will directly affect the feasibility and suc- Address Correspondence to: Mehdi Najafzadeh, PhD, Division of Pharma-
cess of medication reconciliation.41 Patient-specific barriers, such coepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital,
Harvard Medical School, 1620 Tremont St, Ste 3030, Boston, MA 02120. E-
as lower education level and language and other communication mail: [email protected].
barriers, could limit the successful implementation of medication
reconciliation in some healthcare settings.
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THE AMERICAN JOURNAL OF MANAGED CARE®  VOL. 22, NO. 10    661

eAppendix

Design and structure of the simulation model

We developed a discrete-event simulation (DES) model to simulate the distribution of events
observed in the Pharmacist Intervention for Low Literacy in Cardiovascular Disease study
(PILL-CVD) (a randomized control trial) and to estimate the health resource utilization (HRU)
and spending associated with those events. We simulated the effect of targeted and nontargeted
medication reconciliation interventions on overall costs, after accounting for the cost of the
intervention itself. For this purpose, we first developed a model to prospectively simulate the
chain of events that occurred within the 30 days after discharge from hospital in a cohort of
hypothetical patients who did not receive medication reconciliation (ie, usual care) (Figure 1A).
To do this, we created a hypothetical cohort of 10,000 patients and tracked them through their
first 30 days after hospital discharge. All probabilities were based on event rates in the control
arm of the PILL-CVD trial. The incidence of medication errors; potential adverse drug events
(ADEs); preventable ADEs (significant, serious, and life-threatening); major HRUs (emergency
department [ED] visits and rehospitalizations); and costs associated with those HRUs were
derived from the peer-reviewed literature and were simulated and recorded for each patient.
In the second part of the simulation (Figure 1B), we used the distribution of events among the
simulated cohort in the initial phase to compare 3 interventions: a) usual care (no intervention);
b) a pharmacist-led medication reconciliation intervention for all patients; and c) a targeted
pharmacist-led medication reconciliation intervention. To do this, we created identical clones of
the cohort in the usual-care arm and their history of events (simulated in the initial phase) and
assigned them to 1 of the 3 interventions. Conditional on our assumptions about the effectiveness
of interventions that were derived from the peer-reviewed literature, the impact of interventions
on number of medication errors, preventable ADEs, potential ADEs, rehospitalizations, ED
visits, and overall costs were estimated and compared with the usual-care arm. We used cost-
benefit analysis from a hospital payer’s perspective in that the cost of intervention and savings
resulting from avoiding HRUs due to preventable and potential ADEs were accounted for in the
analysis. All the simulations were developed using Arena Version 12.00 (2007 Rockwell
Automation Technologies, Inc, Milwaukee, Wisconsin).
Figure A. Number of Events During the First 30 Days After Hospital Discharge Among 428
Patients in the Usual Care Arm of the PILL-CVD Randomized Clinical Triala
Lif e-threatening ADE (N = 2)

No error
n = 209 Potential f or Serious ADE (N = 78)
Usual-care arm harm (pADE)
n = 132
n = 428 N = 237
N = 407 Signif icant ADE (157)
No actual harm
n = 132
N = 237 No potential f or harm (N = 0)

Error
n = 219
N = 407
Lif e-threatening ADE (N = 5)

13% resulted in ED visits or rehospitalization

Harm (ADE) Serious ADE (N = 24)
n = 125
N = 170
Signif icant ADE (141)

ADE indicates preventable adverse drug event; ED, emergency department; error, medication
discrepancy; pADE, potential adverse drug event.
a
In the Pharmacist Intervention for Low Literacy in Cardiovascular Disease study (PILL-CVD),
a total of 25 major health resource utilizations (HRUs) (6 emergency department [ED] visits, 7
rehospitalizations, and 11 both ED visits and rehospitalizations) occurred among 125 patients
who had at least 1 preventable adverse drug event (ADE) in the usual-care arm amenable to
medication reconciliation. Overall, 170 preventable ADEs occurred among these 125 patients
within the first 30 days of hospital discharge in the usual-care arm. Therefore, the ratio of HRU
events to number of preventable ADEs was 14.7% (25/170 =14.7%), while the ratio of HRU
events to number of patients with preventable ADEs was 17.8% (25/125 = 20%).
Figure B. Net Benefit of Medication Reconciliation for All Patients Versus Usual Care for
Different Assumptions About Effectiveness

Net  benefit  of  interven+on  for  different  RR  of  

preventable  ADE  
500  
Net  benefit  per  pa+ent  receving  

400  
interven+on  ($)  

300  

200  

100   Base case

0  
1   0.9   0.8   0.7   0.6   0.5   0.4   0.3   0.2   0.1   0  
-­‐100  
RR  of  preventable  ADE  for  interven+on  versus  no  interven+on  
Figure C. Distribution of Net Benefit Under the Base-Case Scenario, Estimated Using
Probabilistic Sensitivity Analysisa
Distribu+on  of  Net  Benefit  of  Interven+on  for  All  
Pa+ents,  Probabilis+c  Sensi+vity  Analysis  
300  
250  
200  
Frequency  

150  
100  
50  
0  
0   50   100  150  200  250  300  350  400  450  500  550  
Net  benefit  ($)  

a
This distribution represents the likelihood of true net benefit and how uncertain we are about the
estimated net benefit ($206 per patient) given the uncertainty of our model parameters. For this
probabilistic sensitivity analysis, a complete set of model parameters were drawn from their
probability distribution and, conditional on that particular set of parameter values, expected net
benefit was estimated by simulating outcomes in 10,000 patients. The process was repeated for
1000 distinct realizations of model parameters, and the distribution of net benefit for these 1000
runs has been shown in this Figure.
Figure D. Net Benefit of Targeted Intervention ($) Versus Usual Care for Different Assumptions
for Sensitivity and Specificity of Screening Tool

(A)

0.9

0.8

0.7
$200-$250

Specificity
0.6 $150-$200
$100-$150
0.5
$50-$100

0.4 $0-$50
-$50-$0
0.3

0.2

0.1
1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

Sensitivity
(B)

Net benefit of targeted intervention compared to no intervention,

as a function of screening tool charactristics, RR=0.8,
Pharmacist share=100%
1

0.9

0.8

0.7

Specificity
0.6
$40-$60
0.5 $20-$40
$0-$20
0.4
-$20-$0
0.3 -$40--$20

0.2

0.1
1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

Sensitivity

(A) Under the base-case scenario that we assume, intervention can reduce discrepancies by 52%
and pharmacist involvement was 50%.
(B) We assume that intervention can reduce discrepancies by 20% and that pharmacist
involvement was 100%. Net benefit of nontargeted intervention compared with usual care was
$30 per patient under this scenario.
These Figures show the expected net benefit of targeted intervention for a given sensitivity and
specificity of the screening tool. For example, assuming that sensitivity and specificity of the
screening tool both were 70%, the net benefit would be expected to be in the $100-$150 range
under the base-case scenario.