Ceschi 2021 Oi 210724 1631040648.26526

Original Investigation | Pharmacy and Clinical Pharmacology
Effect of Medication Reconciliation at Hospital Admission

on 30-Day Returns to Hospital
A Randomized Clinical Trial
Alessandro Ceschi, MD, MSc; Roberta Noseda, PhD; Michela Pironi, MSc; Nicole Lazzeri, MSc; Ottavia Eberhardt-Gianella, MSc; Saida Imelli, MSc; Sara Ghidossi, MSc;
Stefano Bruni, MSc; Alberto Pagnamenta, MD; Paolo Ferrari, MD
Abstract Key Points

Question Is medication reconciliation
IMPORTANCE According to international recommendations, hospitals should use medication
effective in improving health care
reconciliation to prevent medication errors and improve patient safety.
outcomes when targeted to patients at
increased risk of medication
OBJECTIVE To assess the impact of medication reconciliation at hospital admission on patient-
discrepancies and medication-related
centered health care outcomes.
harms because of older age,
polypharmacy, or both conditions?
DESIGN, SETTING, AND PARTICIPANTS This parallel group, open-label randomized controlled trial
used centralized randomization to the intervention group (ie, individuals with medication Findings In this randomized clinical trial
reconciliation) or control group (ie, individuals with only standard, physician-acquired medication of 1702 Swiss patients aged 85 years or
history). Outcome assessors and data analysts were blinded to group allocation. Participants older, with more than 10 medications at
included 1702 patients aged 85 years or older, with more than 10 medications at hospital admission, hospital admission, or meeting both
or meeting both conditions at 2 regional secondary teaching hospitals in southern Switzerland. Study conditions, the proportion of patients
duration was 14.5 months, from November 1, 2018, to January 15, 2020. Data were analyzed from with unplanned all-cause hospital
December 2018 through March 2020. returns within 30 days after initial
discharge did not differ among those
INTERVENTIONS Medication reconciliation was performed at hospital admission in 3 steps: (1) the who received medication reconciliation
pharmacy assistant obtained the list of the patient’s current medications (ie, the best possible at hospital admission vs those who
medication history [BPMH]); (2) the clinical pharmacist led reconciliation of the BPMH with the list of did not.
home medications recorded at hospital admission by the attending physician (according to the
Meaning Despite the clinical validity of
hospital standard procedure); and (3) medication discrepancies were communicated to the
medication reconciliation, this study did
attending physician, and, when necessary, medications prescribed at admission were adapted.
not find an impact of this intervention
on patient-centered health care
MAIN OUTCOMES AND MEASURES The primary outcome was a composite postdischarge health
outcomes among a selected patient
care use variable quantified as the proportion of patients with unplanned all-cause hospital visits
population at increased risk of
(including visits to the emergency department and hospital readmissions) within 30 days after
medication discrepancies.
discharge from the hospital when medication reconciliation took place. A time-to-event analysis was
performed.
+ Visual Abstract
RESULTS Among 1702 patients (median [interquartile range] age, 86.0 [79.0-89.0] years; 720
[42.3%] men), 866 patients (50.9%) were allocated to the intervention group and 836 patients
+ Invited Commentary
(49.1%) to the control group. The primary outcome occurred among 340 participants (39.3%) in the + Supplemental content
intervention group and 330 participants (39.5%) in the control group (P = .93). In time-to-event Author affiliations and article information are
analyses at study closeout, unplanned all-cause hospital visits to the emergency department (log- listed at the end of this article.
rank P = .08) and unplanned all-cause hospital readmissions (log-rank P = .10) occurred similarly in
the intervention and control groups.
(continued)
Open Access. This is an open access article distributed under the terms of the CC-BY License.
JAMA Network Open. 2021;4(9):e2124672. doi:10.1001/jamanetworkopen.2021.24672 (Reprinted) September 16, 2021 1/13
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JAMA Network Open | Pharmacy and Clinical Pharmacology Effect of Medication Reconciliation at Hospital Admission on 30-Day Returns
Abstract (continued)
CONCLUSIONS AND RELEVANCE These findings suggest that medication reconciliation at hospital
admission has no impact on postdischarge health care outcomes among patients aged 85 years or
older, with more than 10 medications at hospital admission, or meeting both conditions.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03654963
JAMA Network Open. 2021;4(9):e2124672. doi:10.1001/jamanetworkopen.2021.24672
Introduction
Medication reconciliation is the systematic process of obtaining the most accurate list of all
medications a patient is currently taking (ie, the best possible medication history [BPMH]), including
medication name, dosage, frequency, and route. This list is to be compared with the list of
medications ordered by a physician at admission, transfer, or discharge in order to provide correct
medications to the patient at all interfaces of care within the hospital.1
According to international recommendations, hospitals should use medication reconciliation to
prevent medication errors and improve patient safety.2-4 In Switzerland, the Swiss Patient Safety
Foundation, following the national pilot program “Progress! Safe Pharmacotherapy at the Interface
Points” (2014-2016), published recommendations for safe pharmacotherapy at interfaces of care,
emphasizing the importance of carrying out systematic medication reconciliation.5 In addition, the
Swiss Federal Office of Public Health promotes the introduction of medication reconciliation in Swiss
health care institutions.6
Errors in medication use process are among the most common causes of in-hospital morbidity
and mortality.7 Unintended medication discrepancies (eg, omissions, duplications, and dosing errors)
can occur across transitions of care and, if not identified and resolved, may place the patient at risk
of medication-related harm, thus negatively impacting the quality and safety of patient care.8
Studies from 20129and 201910 suggest that medication reconciliation reduces the number of
medication discrepancies. However, because of heterogeneity among studies; variation in type,
intensity, and duration of interventions; and differences in timing of follow-up measurements in the
most recent systematic reviews, meta-analyses, and overviews of systematic reviews, evidence for
the effectiveness of medication reconciliation in patient-centered outcomes and health care use is
inconclusive.11,12
To date, 1 randomized clinical trial (RCT), not yet included in recent systematic reviews or meta-
analyses, found that an extended intervention composed of medication review at admission and
medication reconciliation at discharge significantly reduced the number of emergency department
(ED) visits and readmissions within 6 months from discharge compared with usual care at 4 acute
admission wards in Denmark.13 Although the study was adequately powered, with a large sample
size, the assessment of the primary composite outcome at 6 months could have been biased by
factors unrelated to the targeted intervention on medication use. Indeed, medication-related
readmissions within 6 months of inclusion were not significantly reduced in the extended
intervention group compared with the usual care group. Moreover, the study population included
patients aged 18 years or older with 5 or more medications at hospital admission. Therefore, older
patients with fewer than 5 medications were not included in the study. However, these patients
represent a subpopulation with increased frailty and increased risk of adverse health outcomes. For
these patients, medication use (regardless of the overall number of medications taken) can be
complex and potentially associated with medication-related problems and increased morbidity and
mortality, likely imposing a large economic burden on health care resources.14-16
Considering polypharmacy (ie, having >10 medications at hospital admission), older patient age
(ie, ⱖ85 years), or both conditions as inclusion criteria, this parallel group RCT aimed to assess the
impact of medication reconciliation at hospital admission on a composite postdischarge health care

use variable. This was quantified as the proportion of patients with unplanned all-cause hospital visits
(including visits to the ED and hospital readmissions) within 30 days after initial discharge, a time
when patients may still be using the medications they were using at discharge and a reasonable
latency period between intervention and assessed outcomes.
Methods
This RCT was approved by the local ethics committee of Swissethics, the Swiss Association of
Research Ethics Committees, with exemption from obtaining informed consent for participants
allocated to the control group following the Zelen design.17 A copy of the study protocol is available
in Supplement 1. All patient data obtained from the control group were routinely recorded in
electronic health records (EHRs), without need of obtaining additional data for the study. All
participants randomized to the intervention group received a participant information sheet and a
consent form describing the study and providing sufficient information to make an informed decision
about their participation in the study. When recruited patients were cognitively unable to
meaningfully participate in the study, the participant information sheet and consent form were
provided to the individuals’ caregivers or legal representatives, who were afterward actively involved
(on behalf of cognitively impaired patients) during pharmacist assistant–led interviews used obtain
information for the BPMH. This study followed Consolidated Standards of Reporting Trials
(CONSORT) reporting guideline.
Study Design and Participants

This was a parallel group RCT conducted at 2 secondary teaching hospitals in southern Switzerland
from November 1, 2018, to January 15, 2020. These hospitals are part of the Ente Ospedaliero
Cantonale (EOC) network of public hospitals, which comprises 4 sites across southern Switzerland.
Eligible participants were patients aged 85 years or older, with more than 10 medications at
hospital admission (ie, home medications recorded by the attending physician in an unstructured and
nonsystematic manner), or meeting both conditions. Patients were excluded if they were admitted
to an intensive care unit without reaching inpatient wards, had planned hospital stays shorter than
48 hours, or were admitted to an EOC hospital ward within the previous 3 months with discharge
at home.
All consecutive eligible patients admitted to the hospitals were identified through the hospital
EHRs and recruited if aged 85 years or older, if they had more than 10 medications at hospital
admission, or if they met both conditions. Each participant was enrolled 1 time only over the
study period.
The parallel group design included the intervention group, with medication reconciliation, and
the control group, with standard, physician-acquired medication history. In the control group,
recording of patient home medications occurred in an unstructured manner, with neither the option
to consult pharmacists nor the possibility for the attending physician to directly access EHR data
from other regional or national hospitals, clinics, or pharmacies to review medication lists and refill
histories.
Randomization and Blinding Procedures

Simple randomization across study sites was carried out by the EOC clinical trial unit by creating a
unique list of randomized patients using computerized random number generation. Allocation of
randomized participants was initially set as 1:1. However, at 3 months from the start of the study, the
number of participants allocated to the intervention and control groups was unbalanced because
496 of 1362 participants (36.4%) allocated to the intervention group had not received the
intervention for several reasons (Figure 1). Therefore, randomization was recalibrated to a 2:1
allocation (intervention group vs control group).

The trial was open label. Therefore, owing to the nature of the intervention, clinical pharmacists
(M.P., N.L., O.E.G., S.I., and S.G.) and pharmacy assistants, along with participants allocated to the
intervention group, were aware of the study, while outcome assessors (R.N. and A.P.) and data
analysts (R.N., S.B., and A.P.) remained blinded.
Procedures
Eligible patients randomized to the intervention group received medication reconciliation according
to 3 steps: At first, the pharmacy assistant compiled an ex novo comprehensive list of the patient’s
current medications at hospital admission (including medications used in chronic therapy and those
taken on an as-needed basis) and obtained the BPMH. To confirm the accuracy of the BPMH, the
pharmacy assistant used 2 or more sources of information, including, when possible, an interview
with the patient or the patient’s caregiver or legal representative, in addition to referral letters and
prescription and medication lists from primary care physicians, community pharmacists, nursing
homes, and home care. Pharmacy assistants received training and instructions from clinical
pharmacists (M.P., N.L., O.E.G., S.I., and S.G.) face to face and through guiding documents to learn
about medication reconciliation procedures and to familiarize themselves with the use of EHRs. This
was done to enhance data quality and decrease the amount of missing or incomplete data,
inaccuracies, and excessive variability in measurements. Clinical pharmacists had a consolidated
experience in the medication reconciliation process from a previous in-house pilot study18 and
previous working experience abroad, where the clinical pharmacist is responsible for the entire
medication reconciliation process. In the subsequent step, the clinical pharmacist reconciled the
BPMH with the list of home medications recorded at hospital admission by the attending physician
(according to the hospital standard procedure). To resolve medication discrepancies that were
Figure 1. Study Flowchart
2533 Patients assessed for eligibility
335 Patients excluded

109 Lack of study personal resources
85 Randomization >48 h from admission
33 Less than 48 h to complete intervention
32 Discharge or ward transition at randomization
23 Time to complete intervention expired
19 Hospital stay <48 h
13 Informatics error
11 Clinical conditions
5 Impossible to request consent
2198 Patients randomized
1362 Patients allocated to intervention group 836 Patients allocated to control group
496 Patients who did not receive allocated intervention

163 Consent not signed by legal representative within 48 h
148 Consent not signed by patient
54 Clinical conditions
48 Discharge or ward transition at randomization
26 Hospital stay <48 h
18 Time to complete intervention expired
12 No medications at home
8 Impossible to request consent from the patient
6 Lack of study personal resources
4 <48 h To complete the intervention
2 Language problems
2 Randomization >48 h from admission
2 Insufficient number of information sources
3 Informatics error
866 Patients allocated to intervention group and analyzed 836 Patients allocated to control group and analyzed

unclear or difficult to evaluate and to propose adaptation of the pharmacotherapy prescribed at

hospital admission, the clinical pharmacist referred to the attending physician. Lastly, physicians
determined changes to patient pharmacotherapy. Throughout the intervention, the pharmacy
assistant actively involved patients (or their caregivers or legal representatives) only during the
interview. Medication reconciliation was performed within 48 hours from participant recruitment in
the study. Patients allocated to the control group received only the standard physician-acquired
medication history at hospital admission.
Baseline data collected from each participant consisted of age at admission, sex, number of
medications at hospital admission, primary diagnosis, and disposition status. The following variables
were additionally collected solely in the intervention group: number of medication discrepancies,
number of unjustified medications added, number of omitted medications, number of incorrect
medications by frequency, number of incorrect medications by name, number of incorrect dose
strengths, number of incorrect galenic forms (ie, the pharmaceutical formulation of a medication),
interview duration, time required to obtain BPMH, and overall duration of medication reconciliation
procedure. These variables, along with numerical identification codes (defined by the EOC
Information and Communications Technology Department [ICT]), first collected within a database
created ad hoc for study purpose were subsequently transferred to the electronic case report form
(CRF), for which the ICT (which was responsible for data management) and the biostatistician (A.P.
and S.B.) had authorization for data entry.
Outcomes
The primary outcome was a composite postdischarge health care use variable quantified as the
proportion of patients with unplanned all-cause hospital visits (including visits to the ED and hospital
readmissions, including to the intensive care unit, at any of 4 regional hospitals encompassed by the
EOC) within 30 days after initial discharge. Planned visits, which do not involve going through the ED,
were not counted in the assessment of the primary outcome. These data were retrieved by the ICT
from existing administrative data sources and integrated within the CRF.
Secondary outcomes were assessed during the first inpatient stay (ie, when study recruitment
occurred) and consisted of the period prevalence of adverse drug events (ADEs) occurring during the
hospital stay, length of hospital stay (LOS), number of in-hospital deaths, and number of resources
used during the hospital stay (ie, laboratory tests, radiologic exams, and electrocardiograms). The
active pharmacovigilance system at the Regional Pharmacovigilance Centre of southern Switzerland
was used to measure the prevalence of ADEs during the hospital stay. This is an electronic system
that actively and continuously screens EHRs for predefined words and word combinations related to
ADEs (eMethods in Supplement 2). Therefore, EHRs identified through this system and referring to
patients aged 85 years or older, with more than 10 medications at admission, or meeting both
conditions were manually assessed for a drug-event causal relationship (using the World Health
Organization [WHO]–Uppsala Monitoring Centre causality assessment system19) and validated to
discard false-positive cases. Subsequently, ADEs were categorized as nonserious or serious (using
WHO seriousness criteria for resulting in death, being life threatening, prolonging hospitalization,
resulting in persistent disability or incapacity, or determining other clinical conditions). The outcome
assessor (R. N.) was masked to group allocation (without access to the database of baseline data or
CRF) and had practical experience in causality assessment from daily pharmacovigilance activity. The
number of in-hospital deaths, laboratory tests, radiographic exams, and electrocardiograms and the
LOS were retrieved from administrative data sources that were already in use at the EOC for other
purposes. The ICT integrated all secondary outcome measures within the CRF.
Sample Size Estimation

Based on previous data extracted from the EOC administrative databases, a positive composite
outcome variable was expected in approximately 30% of participants from the control group. To
detect a minimal clinically relevant difference (set at 6%) in that composite outcome variable

between the intervention and the control groups with a 0.80 statistical power and a .05 significance
level, a sample size of 1718 patients was estimated by Pearson χ2 test. Sample size calculation was
performed using PASS statistical software version 15.0.3 (NCSS).
Statistical Analysis
An independent biostatistician (A.P.) blind to trial group allocation analyzed the data following a
prespecified statistical analysis plan. Quantitative data were summarized as median with
interquartile range (IQR). Qualitative data were presented as absolute numbers with percentages.
For the primary outcome, the proportion of patients with unplanned all-cause hospital visits
(including visits to the ED and hospital readmissions) within 30 days after initial discharge was
compared in the intervention vs the control group using the χ2 or Fisher exact test, as appropriate.
A time-to-event analysis was performed at study closeout (ie, 30 days after inclusion of the last
patient). This was done to assess differences in the occurrence of unplanned all-cause hospital visits
to the ED and unplanned all-cause readmissions to ward in the intervention vs the control groups.
Outcome variables were unplanned all-cause hospital visits to the ED and unplanned all-cause
hospital readmissions, separately assessed by Kaplan-Meier curves. Time-to-event curves in the
intervention and control groups were compared using the log-rank test. All tests were performed
2-sided, and P < .05 was considered statistically significant. All statistical analyses were performed
using Stata statistical software version 15 (StataCorp). Data were analyzed from December 2018
through March 2020.
Results
Among 2533 patients eligible for the study, 1702 individuals were included. Median (IQR) patient age
was 86.0 (79.0-89.0) years, and 720 (42.3%) were men. There were 866 participants (50.9%)
assigned to the intervention group and 836 participants (49.1%) assigned to the control group
(Figure 1). The median (IQR) age was 86.0 (79.0-89.0) years for the intervention group and 86.0
(79.8-90.0) years for the control group; there were 500 (57.7%) women in the intervention group
and 482 (57.7%) women in the control group. Table 1 shows the baseline characteristics of study
participants.
Among 866 patients from the intervention group, 830 individuals (96.0%) had 1 or more
medication discrepancies, with a median (IQR) 6 (4-9) discrepancies per patient. Among these
participants, 797 individuals (96.0%) had medication discrepancies in chronic therapy (median [IQR]
4 [3-7] discrepancies per patient receiving chronic therapy). The most frequently occurring
discrepancies among patients in the intervention group were medication omission (567 participants
[68.3%] from the intervention group had medication omissions in chronic therapy, and 517
participants [62.3%] had medication omissions in as-needed therapy), followed by incorrect
medication name, incorrect dosage regime, incorrect dose amount, unjustified medications not
prescribed to the patient at home, and incorrect galenic forms (Table 2).
The median (IQR) time for a complete intervention of medication reconciliation was 55 (40-70)
minutes. This included a median (IQR) 15 (10-25) minutes for the interview and 40 (30-50) minutes
for the search, analysis, and validation of the sources of information used to obtain the BPMH;
evaluation of medication discrepancies; and communication of discrepancies to the attending
physician.
Primary Outcome
The primary outcome occurred among 340 participants (39.3%) in the intervention group and 330
participants (39.5%) in the control group (P = .93). In time-to-event analyses at study closeout,
unplanned all-cause hospital visits to the ED occurred similarly in the intervention and control groups
(P = .08) (Figure 2A). No statistically significant difference was found for unplanned all-cause
hospital readmissions in the intervention group vs control group (P = .10) (Figure 2B).

Secondary Outcomes
The overall period prevalence of ADEs (including serious and not serious ADEs) occurring during the
hospital stay was 11 ADEs (1.3%) in the intervention group and 14 ADEs (1.7%) in the control group
(P = .49). When only serious ADEs that prolonged hospitalization were evaluated, no statistically
significant difference was found between the intervention group (5 ADEs [0.6%]) and control group
(6 ADEs [0.7%]; P = .77). Median (IQR) LOS was 8 (5-13) days in the intervention group and 8 (4-13)
days in the control group (P = .23). There were 19 in-hospital deaths (2.2%) in the intervention group
and 23 such deaths (2.8%) in the control group (P = .55). The median (IQR) number of laboratory
tests was 9.5 (4.0-23.0) in the intervention group and 9.0 (4.0-20.0) in the control group (P = .31).
The 2 groups each had a median (IQR) 1 (0-2) radiologic exams and 1 (0-1) electrocardiograms.
Table 1. Baseline Characteristics of Study Participants
No. (%)
Intervention group Control group
Characteristic (n = 866) (n = 836)
Age ≥85, y 314 (36.3) 397 (47.5)
>10 medications at hospital admission 301 (34.8) 295 (35.3)
Age ≥85 y and >10 medications at hospital admission 251 (29.0) 144 (17.2)
Age, median (IQR), y 86.0 (79.0-89.0) 86.0 (79.8-90.0)
Men 366 (42.3) 354 (42.3)
Women 500 (57.7) 482 (57.7)
No. of medications at hospital admission, median (IQR) 12 (9-16) 11 (6-13)
Primary diagnosisa
Certain infectious and parasitic diseases 26 (3.0) 27 (3.2)
Diseases of the blood and blood-forming organs and certain 7 (0.8) 10 (1.2)
disorders involving the immune mechanism
Diseases of the circulatory system 138 (15.9) 148 (17.7)
Diseases of the digestive system 88 (10.2) 93 (11.1)
Diseases of the ear and mastoid process 8 (0.9) 5 (0.6)
Diseases of the eye and adnexa 1 (0.1) 0
Diseases of the genitourinary system 74 (8.5) 49 (5.9)
Diseases of the musculoskeletal system and connective tissue 73 (8.4) 59 (7.1)
Diseases of the nervous system 31 (3.6) 25 (3.0)
Diseases of the respiratory system 105 (12.1) 102 (12.2)
Diseases of the skin and subcutaneous tissue 9 (1.0) 16 (1.9)
Endocrine, nutritional, and metabolic diseases 19 (2.2) 24 (2.9)
Factors influencing health status and contact with health services 0 2 (0.2)
Injury, poisoning, and certain other consequences of external 142 (16.4) 132 (15.8)
causes
Mental and behavioral disorders 48 (5.5) 40 (4.8)
Neoplasms 45 (5.2) 43 (5.1)
Symptoms, signs, and abnormal clinical and laboratory findings 52 (6.0) 61 (7.3)
not elsewhere classified
Disposition status
Home 545 (62.9) 478 (57.2)
Nonmedical institution or nursing home 221 (25.5) 229 (27.4)
Non-medical institution 3 (0.3) 6 (0.7)
Rehabilitation institution 46 (5.3) 52 (6.2)
Abbreviation: IQR, interquartile range.
Hospital or clinic 19 (2.2) 29 (3.5)
a
Psychiatric institution or clinic 13 (1.5) 19 (2.3) Diagnosis categories are from the International
Statistical Classification of Diseases and Related
Death 19 (2.2) 23 (2.8)
Health Problems, Tenth Revision (ICD-10).

Discussion
In this RCT, medication reconciliation performed at hospital admission in a selected patient
population aged 85 years or older, with more than 10 medications at hospital admission, or meeting
both conditions had no impact on the proportion of patients with unplanned all-cause hospital visits
(ie, ED visits and hospital readmissions) within 30 days after initial discharge. Moreover, unplanned
all-cause hospital visits to the ED and unplanned all-cause hospital readmissions during the study
period occurred similarly in the intervention and control groups. No effect was found on secondary
health care outcomes, defined as the prevalence of ADEs during the hospital stay, LOS, in-hospital
deaths, and resources used during the hospital stay quantified as number of laboratory tests,
radiologic exams, and electrocardiographic exams.
Table 2. Medication Discrepancies in the Intervention Group

Discrepancies per patient, Patients with discrepancies,
Discrepancy type median (IQR) No. (%) (N = 830)
Medication discrepancies
Chronic treatment 4 (3-7) 797 (96.0)
As needed 2 (1-4) 581 (70.0)
Omission
As needed 2 (1-3) 517 (62.3)
Incorrect medication name
As needed 1 (1-1) 13 (1.6)
Incorrect dosage regime
As needed 1 (1-1.5) 75 (9.0)
Incorrect dose amount
As needed 1 (1-1) 43 (5.2)
Unjustified medications (not prescribed
to the patient at home)
As needed 1 (1-2) 55 (6.6)
Incorrect galenic forms
As needed 1 (1-1) 11 (1.3)
Abbreviation: IQR, interquartile range.
Figure 2. Kaplan-Meier Survival Estimates for Outcomes Since Study-Related Discharge
A Unplanned all-cause hospital visits to ED B Unplanned all-cause hospital readmissions

1.0 1.0
Log-rank P = .08 Log-rank P = .10
0.8 0.8
Probability of outcome
Probability of outcome
0.6 0.6
Control group
0.4 0.4
Intervention group
Control group
0.2 0.2
Intervention group
0 0
0 50 100 150 200 250 300 350 400 450 500 550 0 50 100 150 200 250 300 350 400 450 500 550
Analysis time, d Analysis time, d
No. at risk No. at risk
Control group 836 424 301 225 176 133 85 55 25 6 Control group 836 662 528 415 332 251 175 111 51 15
Intervention group 866 413 298 204 146 96 71 47 26 2 Intervention group 866 677 524 401 312 215 153 104 48 2

The results of the present study are in line with the current uncertain and low-quality evidence
regarding the measurable effect of medication reconciliation on patient-centered clinical
outcomes.10-12 Although there is ample evidence of the effect of medication reconciliation in
reducing the number of medication discrepancies,20 the evidence on the clinical impact of such a
reduction is equivocal because of heterogeneity in settings, patient populations, and typologies of
interventions across studies.10-12
To date, 1 RCT13 has found that an extended intervention composed of medication review at
admission and medication reconciliation at discharge significantly reduced the number of ED visits
and readmissions within 6 months from discharge compared with usual care at 4 acute admission
wards in Denmark. Nevertheless, the assessment of the primary composite outcome at 6 months in
that RCT could have been biased by factors unrelated to the targeted intervention on medication
use, as confirmed when medication-related readmissions within 6 months of inclusion were assessed
and no significant reduction was found in the extended intervention group compared with the usual
care group. Aiming at selecting a patient population that could have reasonably benefited from
medication reconciliation at hospital admission, restricted inclusion criteria based on older age (ie,
aged ⱖ85 years), polypharmacy (arbitrarily defined as >10 medications at admission), or both
conditions were applied in our trial. While polypharmacy is often defined as routinely taking a
minimum of 5 medications,21 there is no standard, universally accepted definition.14 Indeed,
assigning a numeric threshold is not always useful, especially when considering older patients with
age-related physiological changes, a greater degree of frailty, and multiple coexisting conditions.22
Regardless of the number of medications used, older patients represent a population at increased
risk of drug-drug interactions, ADEs, falls, cognitive impairment, and nonadherence.15,23,24 On the
other hand, although the prevalence of polypharmacy increases as the population ages and
experiences multiple chronic conditions,14 polypharmacy also concerns other age groups, including
children and younger adults with specific diagnoses.25 Moreover, regardless of age, as the number of
medications increases, the rate of medication discrepancies increases.18 Consistently, the patient
population in the present study also included younger adults with more than 10 medications at
hospital admission.
Most patients who received medication reconciliation had 1 or more medication discrepancies,
while, for ethical reasons, it was not possible to assess medication discrepancies in the control group.
Assuming a similar risk of medication discrepancies at baseline in the intervention and control
groups, patient harm from medication discrepancies, quantified as the proportion of unplanned
all-cause hospital visits (ie, ED visits and hospital readmissions) occurring at the latest within 30 days
from discharge was similar in the 2 groups.
Concerning secondary health care outcomes evaluated in this study, medication reconciliation
did not show any effect. In the intervention and control groups, the number of ADEs that occurred
during hospital stays was relatively low, similar to the prevalence reported in inpatient settings in
other countries.26 Moreover, previous studies11 assessing the impact of medication reconciliation on
ADEs did not find differences as compared to usual care. The system used in our study to detect
ADEs was based on a reliable methodology of active pharmacovigilance previously set up at the
Regional Pharmacovigilance Centre of southern Switzerland at the EOC and calibrated to minimize
the false positive rate.27 Notably, such a system assumed that key terms referring to possible ADEs
were recorded in patients’ EHRs by health care personnel, a requisite that could have potentially
been met by a minority of personnel only, thus potentially resulting in a low ADE rate at baseline.
A 2021 prepost study28 involving patients with colorectal cancer and other chronic diseases
undergoing elective colorectal surgery did not find a statistically significant change in mean LOS
following a multifaceted program of medication reconciliation at all transitions of care. Mortality as
clinical outcome for all causes or related to medication has been assessed by few studies at various
time points, and they did not find a significant reduction in mortality after medication
reconciliation.11,12,29 Additionally, resource use quantified as numbers of laboratory tests, radiologic

exams, and electrocardiographic exams resulted in low numbers in our study that did not allow any
reasonable conclusion.
Strengths and Limitations

This trial has several strengths that challenge the quality of the literature that claims evidence of
medication reconciliation effectiveness on patient-centered clinical outcomes.10-12 Inclusion criteria
were defined in order to select a patient population reasonably associated with an increased risk of
medication errors and potentially related harms. Because of complex health conditions associated
with older age irrespective of the number of medications at admission or the high number
medications at admission taken by younger patients, the study population represented a suitable
target population among which medication reconciliation may have produced measurable
effects on clinical outcomes. Pharmacy assistants and clinical pharmacists led the intervention
according to a well-established, structured stepwise procedure, which was easily implemented.
In addition, the study has several methodological strengths, including independent observers for
outcome verification and the largest, to our knowledge, randomly selected patient sample size
to date.
This study also has several limitations that may explain why we did not find an effect of
medication reconciliation at hospital admission on direct patient outcomes. First, the primary
composite outcome was assessed regardless of the causes that led to a hospital revisit within 30 days
from discharge. This choice could have masked the real proportion of hospital revisits that occurred
because of medication-related harms. Although hospital revisits that occurred because of
medication-related harms were likely rare, they could have reasonably happened within 30 days
from discharge, when patients were likely still using the medications they were using at discharge.
Owing to the limited human resources available, medication discrepancies identified in the
intervention group were not assessed for their clinical relevance in potentially causing an adverse
drug event. Such an assessment could have provided useful information about the potential risk of
hospital returns because of medication-related harms at 30 days from discharge or later. In this
context, in addition to the assessment of hospital returns, it could have been worth exploring out-of-
hospital visits in the ambulatory care setting. Second, the choice of performing a single-component
intervention of medication reconciliation at admission was a double edge-sword. On the one hand, it
may have involved the most delicate phase among the interfaces of care. However, on the other
hand, not having a continuum at the subsequent interfaces of care, especially not performing
medication reconciliation at discharge, made finding a difference in the hard patient-centered
outcomes very unlikely. Third, the design of the study, with the intervention performed at 2 hospitals
within a regional subarea of Switzerland, reduced the generalizability of the findings. Indeed, at 30
days from discharge, a relatively high proportion of unplanned all-cause hospital visits (including ED
visits and hospital readmissions) was observed in the control group. Although that high proportion
could have been related to the multiple coexisting conditions that typically affect older patients (who
represented most of the study population), lower proportions were reported in other centers in
different countries.13 Moreover, the older age of study participants may have not adequately
represented all patients for whom medication reconciliation may be indicated. A fourth potential
problem was that of spillover or contamination, which could have occurred if physicians exposed to
the intervention changed their practice by applying elements learned from the intervention to
patients allocated to the control group. Fifth, another possible explanation for the lack of an effect
found for medication reconciliation at hospital admission on direct patient outcomes may be that
discrepancies identified during the intervention, albeit communicated by the clinical pharmacist to
physicians, may not have been considered.

Conclusions
The findings of this study suggesting that medication reconciliation at hospital admission had no
impact on postdischarge health care outcomes among patients aged 85 years or older, with more
than 10 medications at hospital admission, or meeting both conditions fit neatly into the ongoing
debate about whether it is reasonable to expect an impact of medication reconciliation on health
care outcomes.30,31 Although it is unlikely that medication reconciliation is ineffective, the overall
quality of the literature remains mixed and low.10-12 By contrast, the face validity (ie, the clinical
importance) of medication reconciliation is unquestionable, given that WHO and many other
international organizations consider it a milestone in the control of safe medication use and a
necessary part of good clinical care.2-4 Future studies are warranted to assess the overall impact of
medication reconciliation at admission and discharge in the hospital, as well as in the ambulatory care
setting, particularly among populations of any age with complex medication regimens.
ARTICLE INFORMATION
Accepted for Publication: July 8, 2021.
Published: September 16, 2021. doi:10.1001/jamanetworkopen.2021.24672
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Ceschi A
et al. JAMA Network Open.
Corresponding Author: Alessandro Ceschi, MD, MSc, Division of Clinical Pharmacology and Toxicology, Institute
of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Via Tesserete 46, 6900
Lugano, Switzerland ([email protected]).
Author Affiliations: Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of
Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland (Ceschi, Noseda, Pironi, Lazzeri,
Eberhardt-Gianella, Imelli, Ghidossi); Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland (Ceschi,
Pagnamenta); Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland (Ceschi,
Ferrari); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland
(Ceschi); Hospital Pharmacy Service, Institute of Pharmacological Sciences of Southern Switzerland, Ente
Ospedaliero Cantonale, Lugano, Switzerland (Pironi, Lazzeri, Eberhardt-Gianella, Imelli, Ghidossi); Department of
Information and Communications Technology, Ente Ospedaliero Cantonale, Bellinzona, Switzerland (Bruni);
Department of Intensive Care, Ente Ospedaliero Cantonale, Bellinzona, Switzerland (Pagnamenta); Division of
Pneumology, University of Geneva, Geneva, Switzerland (Pagnamenta); Department of Nephrology, Ente
Ospedaliero Cantonale, Lugano, Switzerland (Ferrari); Prince of Wales Hospital Clinical School, University of New
South Wales, Sydney, New South Wales, Australia (Ferrari).
Author Contributions: Drs Ceschi and Ferrari had full access to all of the data in the study and take responsibility
for the integrity of the data and the accuracy of the data analysis. Dr Ceschi and Ms Noseda contributed equally as
first coauthors; Drs Pagnamenta and Ferrari contributed equally as last coauthors.
Concept and design: Ceschi, Noseda, Pironi, Lazzeri, Eberhardt-Gianella, Imelli, Pagnamenta, Ferrari.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Ceschi, Noseda, Bruni, Pagnamenta, Ferrari.
Critical revision of the manuscript for important intellectual content: Ceschi, Pironi, Lazzeri, Eberhardt-Gianella,
Imelli, Ghidossi, Pagnamenta, Ferrari.
Statistical analysis: Noseda, Bruni, Pagnamenta, Ferrari.
Administrative, technical, or material support: Ceschi, Pironi, Lazzeri, Eberhardt-Gianella, Imelli, Ghidossi,
Bruni, Ferrari.
Supervision: Ceschi, Pagnamenta, Ferrari.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by internal funding from the Ente Ospedaliero Cantonale.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.

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SUPPLEMENT 1.
Trial Protocol
SUPPLEMENT 2.
eMethods
SUPPLEMENT 3.
Data Sharing Statement

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Original Investigation | Pharmacy and Clinical Pharmacology

Effect of Medication Reconciliation at Hospital Admission

Abstract Key Points

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TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03654963

JAMA Network Open. 2021;4(9):e2124672. doi:10.1001/jamanetworkopen.2021.24672

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Study Design and Participants

Randomization and Blinding Procedures

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Figure 1. Study Flowchart

2533 Patients assessed for eligibility

335 Patients excluded

2198 Patients randomized

496 Patients who did not receive allocated intervention

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unclear or difficult to evaluate and to propose adaptation of the pharmacotherapy prescribed at

Sample Size Estimation

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Table 1. Baseline Characteristics of Study Participants

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Table 2. Medication Discrepancies in the Intervention Group

Figure 2. Kaplan-Meier Survival Estimates for Outcomes Since Study-Related Discharge

A Unplanned all-cause hospital visits to ED B Unplanned all-cause hospital readmissions

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Strengths and Limitations

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