pharmacoepidemiology and drug safety 2017; 26: 71–80

Published online 12 October 2016 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pds.4117

ORIGINAL REPORT

Cross-sectional investigation of drug-related problems among adults

in a medical center outpatient clinic: application of virtual medicine
records in the cloud
Hue-Yu Wang1,2, Ming-Kung Yeh3,4, Chung-Han Ho5,6, Ming-Kuan Hu3 and Yaw-Bin Huang2*
1
Department of Pharmacy, Chi-Mei Medical Center, Tainan, Taiwan
2
College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
3
School of Pharmacy, Graduate Institute of Medical Science, National Defense Medical Center, Taiwan
4
Taipei Hospital, Ministry of Health and Welfare, Taipei, Taiwan
5
Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
6
Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan

ABSTRACT
Purpose To analyze and characterize data regarding the prevalence and types of outpatient drug-related problems (DRPs) found by clinical
pharmacists after implementation of the Virtual Medicine Record in Cloud System (VMRCS).
Methods A cross-sectional study regarding outpatient pharmaceutical care was conducted at a medical center in Taiwan. Patients aged
>20 years old with multiple chronic diseases and polypharmacy were enrolled. In Stage I (1 October–31 December 2014), patients received
pharmaceutical care according to prescription data accessed online in the VMRCS. In Stage II (1 June–31 August 2015), the VMRCS were
pre-download and arranged to the institute’s required format, facilitated DRP detection. Clinical pharmacists then reviewed and evaluated the
prescription data through pre-downloaded VMRCS. Overall, 1539 and 1600 prescriptions were evaluated in these two stages, respectively.
DRPs were recorded using the Pharmaceutical Care Network Europe (PCNE)-DRP.
Results DRPs were found for 50.2% of patients in Stage I and 55.2% in Stage II (p < 0.05) and were most frequently encountered for
“Drugs for the cardiovascular system” and caused by “Inappropriate duplication of therapeutic group or active ingredient.” In terms of
problems, incidence of “Unnecessary drug treatment” was highest. Duplicate medications were most frequently seen for “Drugs for
acid-related disorders.” The efficiency to identify DRPs was at least 2.4 times higher with pre-downloaded prescription data than with
real-time online queries.
Conclusions With VMRCS, DRPs were more easily identified whether patients received medical care in the same hospital or not. DRPs
could be efficiently prevented through the use of pre-downloaded patient prescription data. Copyright © 2016 John Wiley & Sons, Ltd.

key words—drug-related problem; outpatient clinic; Pharmaceutical Care Network Europe (PCNE); polypharmacy; Virtual Medicine
Record in Cloud System (VMRCS)

Received 27 April 2016; Revised 13 September 2016; Accepted 17 September 2016

INTRODUCTION In consequence, concomitant consultations may be

National Health Insurance (NHI) was implemented
in 1995 in Taiwan; it provides universal health
coverage to >99.9% of residents. Patients are now
facing decreased economic obstacles to accessing
medical care and freedom to choose healthcare
providers; patients may therefore change doctors
without a professional referral for the same illness.
*Correspondence to: Y. Huang, 100, Shih-Chuan 1st Road, Kaohsiung 80708,
Taiwan. Email: yabihu@kmu.edu.tw
conducted and medication prescriptions procured
and dispensed illicitly. This means patients can
obtain several prescriptions and thus receive a quan-
tity of drug exceeding their therapeutic needs.1–3
This may lead to increased healthcare utilization
and DRP, including inappropriate duplicate prescrip-
tions, drug–drug interactions, and adverse drug
reactions.3,4 Many studies have found that chronic
diseases such as diabetes, benign prostatic hyperpla-
sia, cardiovascular disease, and even polypharmacy
are susceptible to DRPs.5–8 Among the elderly in
particular, patients with a variety of chronic diseases

Copyright © 2016 John Wiley & Sons, Ltd.

72 h.-y. wang et al.
who attend various clinics are at risk for
polypharmacy, and subsequent DRPs, 9–15 the main
causes being persistence of symptoms, multiple
chronic diseases, inability to understand doctors’
explanations, and distrust of diagnosis and
treatment.1,16–18Clinical pharmacists involved in
multidisciplinary teams can effectively solve and
prevent DRPs in elderly patients with multiple
chronic diseases. However, the outcome of such ser-
vices also depends on identification of DRPs,
appropriate recommendations by pharmacists, and
the rate of physician acceptance of pharmacists’
proposals.5
NHI identification cards (NHI-IC card) carry
patient information, allowing ease of access to
various clinical institutions. In July 2013, the Virtual
Medicine Record in Cloud System (VMRCS) was
created by the NHI agency, to offer medical
professionals with a Virtual Private Network (VPN)
access to patient medication data, within the three
months.
This study aimed to analyze and characterize data
regarding the prevalence and types of outpatient DRPs
found by clinical pharmacists after two stages of
implementation of VMRCS, and to evaluate the
efficiency of identifying DRPs between stages.
METHODS
Study design
This was a cross-sectional study that analyzed outpa-
tient DRPs via VMRCS at a medical center in
Taiwan. Patient records/information were anonymized
and de-identified prior to analyses.
Subject characteristics
Patients with multiple chronic diseases, aged above
20, with polypharmacy and visiting different medical
departments for medical services within three months
were enrolled. A three-month period was chosen
because refilled prescriptions are valid for three
months in Taiwan. In addition, VMRCS was con-
ducted through the Health Insurance Agency website,
and inquiries about patients’ medical records were
restricted to the past three months. Medical depart-
ments included cardiology, endocrinology, neurology,
and internal medicine (e.g., gastroenterology, geriat-
rics, psychiatry, and chest medicine). Hematology,
oncology, gynecology, obstetrics, and surgery were
excluded because of pharmacist qualifications and
ethical considerations.
Copyright © 2016 John Wiley & Sons, Ltd.
Pharmaceutical Care Network Europe working group
on drug-related problems (PCNE-DRP) v6.2 classifi-
cation system. The PCNE-DRP v6.2 includes four
primary domains for problems (nine grouped
subdomains), eight primary domains for causes (37
grouped sub-domains), and five1 primary domains
for interventions (17 grouped sub-domains).19 This
system has been considered complete compared with
other classification systems.20
NHI Virtual Medicine Record in Cloud System
(VMRCS). VMRCS includes patient information for
the past three months such as the outpatient depart-
ment (OPD) visit date, hospitalization date, diagnoses,
prescriptions, dispensing source, first five letters of the
ATC code21 for every drug prescribed, generic and
brand names of drugs, dosage, regimen duration
(days), and days of drug remaining.
Stage I (October 1 to December 31, 2014): In outpa-
tient clinics, physicians and pharmacists can access
real-time prescription data via VMRCS among differ-
ent hospitals for patients together with their own
medical personnel-IC cards and patient NHI-IC cards,
because hospitals have permission to enter the health
care information network service system (VPN)
platform.
For this stage, patients visited clinical pharmacists in
the pharmacy care unit for online inquiries regarding
patient prescription data in the VMRCS before
attending the OPD. DRPs were probed and recorded
according to guidelines from PCNE DRP v6.2.19
Recommendations for optimizing medication were
then offered by pharmacists to physicians caring for
patients in the OPD via the internal computer system.
Stage II (June 1 to August 31, 2015): In addition to
the viewing function mentioned above, a download
function was activated in 2015. Through the medical
data transmission interface (provided by the NHI
agency), hospitals make requests to download
patients’ information from the VMRCS for patients
who have next-day OPD appointments to hospital
computers at midnight on the request day, and accord-
ing to the institute’s requirement, the online VMRCA
(appendix 3) is arranged to the institute’s required
format (Appendix 4) in order to highlight any medica-
tion duplication information.
In this stage, clinical pharmacists reviewed and eval-
uated patient prescription data in advance and
recorded all DRPs found. Medication recommenda-
tions were then offered in the same way to physicians
Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
DOI: 10.1002/pds
 application of the virtual medicine record in cloud
caring for patients in the OPD. Instead of waiting for
the VPN connection to conduct online queries and
read medication information during visits (as in Stage
1), medication profiles in the second stage were
reviewed through the VMRCS before patients’ visits,
facilitating identification of duplicated medication,
thereby saving significant time and ensuring thorough
review.
Clinical pharmacists
Clinical pharmacists were attending pharmacists
qualified through the Taiwan Society of Health-
System Pharmacists and had been trained in recogniz-
ing ATC codes and classifications, DRP identifications
(main sources of pharmacology information22–24), and
classifications using PCNE-DRP as a pharmacist
specialization.
They had to (i) interview patients with appointments
and review their prescription data and chemical test
results before OPD visits; (ii) identify DRPs; (iii)
deliver recommendations for optimizing medication
to physicians; and (iv) follow up to see whether
physicians accepted recommendations for improving
drug safety, if DRPs were resolved, and if treatment
outcomes were improved.
DRP identification processes
DRP identifications and ratings were conducted
according to pharmacology information22–24 and
through consensus among the three pharmacists. DRP
identification processes were as follows. First, the clin-
ical pharmacist integrated a patient’s medical records
Figure 1. The process of drug-related problem (DRP) identification
Copyright © 2016 John Wiley & Sons, Ltd.
73
through the institute and VMRCS, listed the DRPs,
and made classifications according to the PCNE-
DRP. The listed DRPs were then re-classified accord-
ing to the PCNE-DRP by a second pharmacist to
ensure consistency; if findings were inconsistent,
re-classification was completed by a third pharmacist.
Classification proceeded only if at least two pharma-
cists’ DRP classifications were identical. If DRP classi-
fication remained inconsistent, consensus was reached
through discussion (Figure 1, Appendices 4–6).
Data collection and statistical analysis
All data were collected from the pharmacy
department. Further medical data related to patient
information were collected from hospital records.
Data are presented medians with a range for contin-
uous variables and numbers with a percentage for
categorical variables. Age was treated as a continuous
variable but did not pass the normality test; therefore,
the Wilcoxon rank-sum test was used to compare
differences between Stage 1 and Stage 2. Regarding
categorical variables, Pearson’s chi-square test or
Fisher’s exact test for categorical variables was used
to compare differences between groups. A logistic
regression was used to estimate the association
between each DRP and stage. Odds ratios (ORs) and
95% confidence intervals (CIs) were calculated in the
multivariable logistic regression after adjusting for
potential confounding factors such as age, sex, and
medical department. Significance was set at p < 0.05.
All analyses were conducted using SAS v 9.4 (SAS
Institute, Inc, Cary, NC).
Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
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74
RESULTS
Subject characteristics and DRPs
A total of 389 146 outpatients were screened and are
summarized in Figure 1. Among them, 59 012
polypharmacy patients (15.2%; 29 585 in Study Stage
I (group SI), 29 427 in Study Stage II (group SII)) were
eligible for analyses. There was no significant differ-
ence in the number of patients in each group with
multiple visits to different departments of the hospital
or different hospitals (5.2%, 1539/29 585 in SI; and
5.4%, 1600/29 427 in SII) (p = 0.23). Among outpa-
tients at risk for DRPs, 237 patients in SI and 841 in
SII were found to need pharmaceutical care and/or
recommendations for optimizing medication. Further
analyses revealed DRPs for 119 patients in SI and
449 in SII (50.2% vs. 55.2%; p < 0.05) (Figure 2).
Table 1 presents DRP characteristics. Regarding
age, the number of elderly patients (aged >65 years)
appeared to be greater than that of non-elderly patients
in both groups (accounting for 54% and 96% of partic-
ipants in SI and SII, respectively). Patients’ minimum
and maximum ages were 39 and 97 years, respectively,
whereas the DRP population’s median age was 65 and
Figure 2. Study flow chart, VMRCS: Virtual Medicine Record in Cloud System, PCNE-DRP: Pharmaceutical Care Network Europe-Drug-Related Problem
Copyright © 2016 John Wiley & Sons, Ltd.
h.-y. wang et al.
74 years in these two groups, respectively. Most
patients came from the cardiology department in both
groups (61 and 175 patients; 51.3% and 39.0%,
respectively).
According to the ATC classification system, the
drugs for which DRPs developed at the first level were
classified into seven groups in SI and 14 in SII; Group
A (alimentary tract and metabolism) and Group C
(cardiovascular system) were the most frequent for
patients in both stages (Table 1).
Prevalence of drug-related problems
Preliminary results of analyses of DRPs are shown in
Table 2: 119 DRPs were found in SI, including 145
causes and 107 recommendations for optimizing med-
ication; and 449 DRPs were found in SII, including
524 causes and 398 recommendations. “Unnecessary
drug treatment” was found for 204 problems, which
accounted for 35.9% of all DRPs. “Adverse drug
events, non-allergic” and “Effect of drug treatment
not optimal” were the second and third most
frequently seen DRPs, at 14.3% and 12.3% in this
study, respectively.
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DOI: 10.1002/pds
 application of the virtual medicine record in cloud 75
Table 1. Characteristics of patients with drug-related problems (DRP) in Stage I, and the difference was statistically significant.
two stages
To avoid the effect of confounding factors, we used
Stage 1 Stage 2 multivariable logistic regression adjusted by ATC
n = 119 n = 449
(%) (%) p-value codes A, B, C, M, N, R, age, gender, and department
to remove potential interference. Post-analysis, the
Age group measurements of OR for DRP codes P3.2, C1.3,
Median (range) 65 (47–90) 74 (39–97) <0.0001*
20–64 55 (46.2) 18 (4.0) <0.0001* C1.4, and C1.6 in SII still indicated a significant differ-
65–79 48 (40.3) 294 (65.5) ence, and the drugs most prescribed were for the
≥80 16 (13.5) 137 (30.5) alimentary tract and metabolism, cardiovascular sys-
Gender
Male 73 (61.3) 231 (51.2) 0.0491† tem, and nervous system in this study period (data
Female 46 (38.7) 220 (48.8) not shown). In particular, for C1.6 (too many drugs
Department prescribed for indication) the OR was 17.8 (95%CI
Internal Medicine 2 (1.7) 117 (26.1) <.0001‡
Cardiology 61 (51.3) 175 (39.0) 4.7–68.2, p < .0001), indicating that the batch
Neurology 11 (9.2) 107 (23.8) downloading strategy was more effective in identify-
Endocrinology 45 (37.8) 42 (9.4) ing excessive drug prescriptions than the online
Other 0 8 (1.8)
ATC group ad-hoc query system (Table 3).
A: Alimentary tract and 25 (21.0) 122 (27.2)
metabolism
B: Blood and blood 4 (3.4) 29 (6.5) Incidence of duplicates
forming organs
C: Cardiovascular system 60 (50.4) 167 (37.2)
Table 4 shows the top 10 classes of drugs related to
D: Dermatologicals 2 (1.7) 3 (0.7) DRPs and their quantity of duplicates and duplicate
G: Genitourinary system 0 8 (1.8) rates. The total of 402 is 70.8% of all DRPs. Among
and sex hormones
H: Hormone therapy 0 6 (1.3)
the top 10 classes of drugs, the incidence of duplicates
J: Anti-infective for 0 2 (0.5) was found to be as high as 40.5%. The top three
systemic use classes of DRPs were A10, C09, and C10. Regarding
L: Antineoplastic and 0 2 (0.5)
immunomodulating agents
classes of duplicate rates, A02, C07, and N05 were
M: Musculo-skeletal 10 (8.4) 41 (9.1) the top three classes of duplicated drugs.
system
N: Nervous system 16 (13.5) 38 (8.5)
P: Anti-parasitic products, 0 1 (0.2) DISCUSSION
insecticides,and repellents
R: Respiratory system 2 (1.7) 28 (6.2)
S: Sensory organs 0 1 (0.2) The model of VMRCS for pharmaceutical care for
V: Various 0 1 (0.2) outpatient visits overcomes inter-institutional restric-
tions in obtaining prescription history of patients,
ATC: Anatomical Therapeutic Chemical classification system.
*Wilcoxon rank-sum test. thereby enabling physicians and pharmacists to review
†
‡
Chi-square test. all diagnostic and medication information for the prior
Fisher exact test. three months at different medical institutions. Many
studies have reported that computerization or the
engagement of a sufficient number of clinical pharma-
Regarding causes of DRPs, “Drug selection (C1)” cists resulted in improved DRP detection and corre-
was most frequently related to the following distribu- sponding improvements in medication safety.25 In
tions: “Inappropriate duplication of therapeutic group SII, we implemented batch-download prescription data
or active ingredient” (18.0% of total, and accounting from VMRCS using computer technology. Clinical
for 8.4% and 20.5% in each stage, respectively), “Too pharmacists quickly identified DRPs in advance and
many drugs prescribed for the condition” (17.3%), reviewed complete medication records via computer;
and “Inappropriate combination of drugs” (12.1%). this may have resulted in superior DRP identification
At the intervention prescriber level (I1), the accep- in SII compared with SI. Hu et al. also reported on a
tance rate of clinical pharmacists’ recommendations national computerized physician order entry system
was 80.8% (408/505). At the intervention drug level using NHI-IC cards, which enables sharing of
(I3), the recommendation “Drug stopped” (48.3%) complete patient health information and medication
was most frequent; followed by “Drug changed to” history among hospitals, would enhance patient
(19.7%) and “New drug started” (16.6%). safety.4 However, outpatient visits may be prolonged
As shown in Table 2, the OR values of P3.2, C1.3, if physicians read and evaluate prescription informa-
C1.4, C1.6, and I1.3 were higher in Stage II than in tion during these visits.

Copyright © 2016 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
DOI: 10.1002/pds
76 h.-y. wang et al.
Table 2. Differences in classifications of drug-related problems in the two study stages (According to PCNE classification for DRP version 6.2)
Stage 1 n Stage 2 n
Problems (%) (%) P* OR 95% CI
P1 Treatment effectiveness: There is a (potential) problem with the (lack of) effect of the pharmacotherapy
P1.1 No effect of drug treatment/therapy failure 1 (0.8) 3 (0.7) 1.00 0.8 0.1–7.7
P1.2 Effect of drug treatment not optimal 21 (17.7) 49 (11.0) 0.04 0.6 0.3–1.0
P1.3 Wrong effect of drug treatment 4 (3.4) 27 (6.0) 0.27 1.9 0.7–5.5
P1.4 Untreated indication 23 (19.3) 29 (6.5) <0.0001 0.3 0.2–0.5
P2 Adverse reactions: Patient suffers, or will possibly suffer, from an adverse drug event
P2.1 Adverse drug event (non-allergic) 22 (18.5) 59 (13.2) 0.13 0.7 0.4–1.1
P2.2 Adverse drug event (allergic) 0 3 (0.7) 1.00 1.8 0.1–36.4
P2.3 Toxic adverse drug event 5 (4.2) 7 (1.6) 0.07 0.4 0.1–1.2
P3 Treatment costs: Drug treatment is more expensive than necessary
P3.1 Drug treatment costlier than necessary 6 (5.0) 37 (8.2) 0.3 1.7 0.7–4.1
P3.2 Unnecessary drug treatment 24 (20.2) 180 (40.1) <0.0001 2.7 1.6–4.3
P4 Other
P4.1 Patient dissatisfied with therapy despite optimal clinical and economic treatment
outcomes
P4.2 Unclear problem/complaint. Further clarification necessary 3 (2.3) 7 (1.6) 0.4 0.6 0.2–2.4
P4.3 Need for laboratory test (added for this study’ requirements) 10 (8.4) 48 (10.7) 0.5 1.3 0.6–2.7
Causes
C1 Drug selection: DRP cause related to the selection of the drug
C1.1 Inappropriate drug (incl. contra-indicated) 17 (14.3) 26 (5.8) 0.02 0.4 0.2–0.7
C1.2 No indication for drug 12 (10.1) 44 (9.8) 0.91 1.0 0.5–1.9
C1.3 Inappropriate combination of drugs, or drugs and food 4 (3.4) 65 (14.5) 0.0004 4.9 1.8–13.8
C1.4 Inappropriate duplication of therapeutic group or active ingredient 10 (8.4) 92 (20.5) 0.0021 2.8 1.4–5.6
C1.5 Indication for drug treatment not noticed 2 (1.7) 3 (0.7) 0.33 0.4 0.1–2.4
C1.6 Too many drugs prescribed for indication 3 (2.5) 95 (21.2) <0.0001 10.5 3.3–33.6
C1.7 More cost-effective drugs available 7 (5.9) 20 (4.945) 0.51 0.7 0.3–1.8
C1.8 Synergistic/preventive drug required and not given 3 (2.5) 4 (0.9) 0.16 0.4 0.1–1.6
C1.9 New indication for drug treatment presented 27 (22.7) 25 (5.6) <0.0001 0.2 0.1–0.4
C2 Drug form: DRP cause related to the selection of the drug form
C2.1 Inappropriate drug form 1 (0.8) 5 (1.1) 1.0 1.3 0.2–11.4
C3 Dose selection: DRP cause related to the selection of the dosage schedule
C3.1 Drug dose too low 5 (4.2) 12 (2.7) 0.4 0.6 0.2–1.8
C3.2 Drug dose too high 12 (10.1) 12 (2.7) 0.00 0.2 0.1–0.6
C3.3 Dosage regimen not frequent enough 0 2 (0.5) 1.00 1.3 0.1–27.9
C3.4 Dosage regimen too frequent 2 (1.7) 9 (2.0) 1.00 1.2 0.3–5.6
C3.5 No therapeutic drug monitoring 7 (5.9) 49 (10.9) 0.10 2.0 0.9–4.4
C3.6 Pharmacokinetic problem requiring dose adjustment 5 (4.2) 3 (0.7) 0.01 0.2 0.0–0.7
C3.7 Deterioration/improvement of disease state requiring dose adjustment 3 (2.5) 19 (4.2) 0.66 1.7 0.5–5.9
C4 Treatment duration: DRP cause related to the duration of therapy
C4.1 Duration of treatment too short 0 3 (0.7) 1.0 1.9 0.1–36.4
C4.2 Duration of treatment too long 2 (1.7) 13 (2.9) 0.75 1.7 0.4–7.8
C5 Drug use/administration process: DRP cause related to the way the patient uses the drug or has the drug administered, in spite of proper instructions
(on the label, package, or leaflet)
C5.1 Inappropriate timing of administration and/or dosing intervals 4 (3.4) 1 (0.2) 0.01 0.1 0.0–0.9
C5.2 Drug underused/under-administered (deliberately) 4 (3.4) 1 (0.2) 0.01 0.1 0.0–0.9
C5.5 Wrong drug taken/administered 2 (1.7) 2 (0.5) 0.19 0.3 0.0–1.9
C6 Logistics: DRP cause related to the logistics of the prescribing and dispensing process
C6.1 Prescribed drug not available 2 (1.7) 1 (0.2) 0.11 0.1 0.0–1.5
C7 Patient: DRP cause related to the personality or behavior of the patient
C7.1 Patient forgets to use/take drug 1 (0.8) 0 0.21 0.1 0.0–2.2
C7.2 Patient uses unnecessary drug 2 (1.7) 0 0.04 0.1 0.0–1.1
C7.3 Patient takes food that interacts 0 2 (0.5) 1.00 1.3 0.1–27.9
C7.4 Patient stores drug inappropriately 2 (1.7) 0 0.04 0.1 0.0–1.1
C8 Other
C8.1 Other cause; specify 1 (0.8) 4 (0.9) 1.00 1.1 0.1–9.5
C8.2 No obvious cause 5 (4.2) 12 (2.7) 0.38 0.6 0.2–1.8
Intervention
I0.0 No intervention 3 (2.5) 49 (10.9) 0.00 4.8 1.5–15.7
I1 At prescriber level
I1.1 Prescriber informed only 0 1 (0.2) 1.00 1.3 0.1–27.9
I1.3 Intervention proposed, approved by prescriber 66 (55.5) 342 (76.2) <0.001 2.5 1.7–3.8
I1.4 Intervention proposed, not approved by prescriber 41 (34.5) 56 (12.5) <0.001 0.3 0.2–0.4
I2 At patient/carer level
I2.1 Patient (medication) counseling 10 (8.4) 5 (1.1) <0.001 0.1 0.0–0.4

(Continues)

Copyright © 2016 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
DOI: 10.1002/pds
 application of the virtual medicine record in cloud 77
Table 2. (Continued)
Stage 1 n Stage 2 n
Problems (%) (%) P* OR 95% CI
I3 At drug level
I3.1 Drug changed to …. 18 (15.1) 52 (11.6) 0.29 0.7 0.4–1.3
I3.2 Dosage changed to …. 7 (5.9) 28 (6.2) 0.90 1.1 0.5–2.5
I3.3 Formulation changed to …. 0 5 (1.1) 0.59 2.9 0.2–53.6
I3.4 Instructions for use changed to …. 2 (1.8) 13 (2.9) 0.75 1.7 0.4–7.8
I3.5 Drug stopped 27 (22.7) 145 (32.3) 0.05 1.6 1.0–2.6
I3.6 New drug started 23 (19.3) 36 (8.0) 0.0003 0.4 0.2–0.6
I4 Other intervention or activity
I4.1 Other intervention (specify) 3 (2.5) 23 (5.1) 0.32 2.1 0.6–7.0

Numerous studies have noted that elderly patients
are at increased risk of DRPs during the medication
use process, which can lead to adverse clinical
outcomes.6,11–13,26,27 This may be related to
polypharmacy, pharmacokinetics/pharmacodynamics,
and cognitive and functional alterations among elderly
people.28 Nonetheless, one study found that DRPs
among a non-elderly group of patients with diabetes
(56.7%) were slightly more common than among an
elderly group with diabetes.29 In our study, DRPs were
most common among elderly patients (87.5%); how-
ever, this might be because of the inclusion criteria
of multiple chronic diseases, particularly for the
VMRCS batch downloads in SII (Table 1). In any
case, identification of different DRP subtypes among
the elderly will result in better outcomes regarding
DRP prevention, detection, and control.30
The prevalence of DRP classification in these results
(Table 3) is similar to that of previous studies,11,12,14,31
indicating that unnecessary drug prescriptions often
lead to DRPs in the elderly in Taiwan, similar to other
countries. This is likely because the elderly often suf-
fer from multiple simultaneous chronic diseases, and
require visits to multiple departments, leading to
multi-drug therapies, potentially inappropriate dupli-
cation or combinations of drugs, and drug–drug
interactions.
The most common DRPs in both stages were
“Unnecessary drug treatment,” (20.2 and 40.1%),
“Adverse drug event, non-allergic” (18.5 and 13.2%),

Table 3. Multivariable logistic regression of the two study stages with drug-related problems (P), causes (C), and intervention (I)
PCNE-DRP code Characteristic OR 95%CI

P3.2 Unnecessary drug treatment 2.7 1.5–4.9*

C1.3 Inappropriate combination of drugs, or drugs and food 3.6 1.1–11.3*
C1.4 Inappropriate duplication of therapeutic group or active ingredient 2.4 1.1–5.4*
C1.6 Too many drugs prescribed for indication 17.8 4.7–68.2*
I1.3 Intervention proposed, approved by prescriber 2.8 1.6–4.9*

Multivariable logistic regression adjusted by ATC codes A, B, C, M, N, R, age, gender, and department.
PCNE-DRP: Pharmaceutical Care Network Europe drug-related problem; OR: odds ratio; 95%CI: 95% confidence interval, with stage I as reference category.
*p < 0.05.

Table 4. The top 10 drug-related problems and their distributions

Third-level ATC code Description Total n Duplicate n Duplicate (%) of the class Duplicate (%) of the total

C10 Lipid-modifying agents 92 22 23.9 5.5

A10 Drugs used in diabetes 70 12 17.1 3.0
C09 Agents acting on the renin–angiotensin system 52 24 46.2 6.0
A02 Drugs for acid-related disorders 41 29 70.7 7.2
M04 Antigout preparations 31 7 22.6 1.7
B01 Antithrombotic agents 30 12 40.0 3.0
C08 Calcium channel blockers 25 10 40.0 2.5
N05 Psycholeptics 23 23 100.0 5.7
C07 Beta-blocking agents 20 18 90.0 4.5
R05 Cough and cold preparation 18 6 33.3 1.5
Total 402 163 40.5

ATC code: ATC/DDD Index 2015.

Copyright © 2016 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
DOI: 10.1002/pds
78 h.-y. wang et al.
and “Effect of drug treatment not optimal” (17.8 and
11.0%; Table 2). This result resembles that of Silva
et al.11 and Delgado Silveira et al.,14 although
“Unnecessary drug treatment” was less frequently
reported by these authors.
Regarding the causes of DRPs, C1.3 (“Inappropriate
combination of drugs, or drugs and food”), C1.4
(“Inappropriate duplication of therapeutic group or
active ingredient”), and C1.6 (“Too many drugs
prescribed for indication”) were the most frequently
reported in our study (Table 2). In other studies, inad-
equate dose, inadequate interval, inappropriate
duplication, potential interactions, and drug not taken
or not administered were more common.15,27,29,32 Col-
lectively, these findings suggest that the inappropriate
duplication and combination of drugs were common
factors leading to DRPs.
The differences in frequency of DRPs in the above-
mentioned studies and this study may be attributed to
three causes. First, the study populations are different.
Previous studies mostly involved inpatients or patients
visiting only a medical institute, thus minimizing
patient visits to other institutes for medical help within
three months. Second, in this study, patients’ prescrip-
tion data were obtained through the VMRCS, which
lifts restrictions across institutions and allows queries
of patients’ medication information. These advantages
were not present in the above-mentioned studies. In
the study by Chan et al., the study population was also
outpatients in clinics of a medical center, but only intra-
institutional information was available and assessments
of drug duplication were limited to patients who had
visited multiple departments. 15 Thus, medications pre-
scribed at other institutions remained unknown, possi-
bly resulting in an underestimation of inappropriate
duplicate medication events. Third, different DRP clas-
sification tools were used. Some developed their own
standards for studies, while others used classifications
of PCNE-DRP V5.0 or V6.2. Classification and coding
between V5.0 and V6.2 are not compatible; therefore,
V6.2 was used in both stages of this study.
The classes of drugs related to high incidence of
DRPs according to the ATC 3rd-level code were
“Alimentary tract and metabolism,” “Cardiovascular
system,” “Musculo-skeletal system,” and “Nervous
system,” which accounted for approximately 80% of
all DRPs in both stages. The major causes were inap-
propriate medication duplication, combinations
because of patients visiting different institutes, or ad-
verse drug reactions. Similar results were found previ-
ously in an elderly outpatient setting.14,31 The
duplicate rate in total DRP was mostly accounted for
by the drug classes “Drugs for acid-related disorders,”
Copyright © 2016 John Wiley & Sons, Ltd.
“Agents acting on the renin–angiotensin system,” and
“Psycholeptics” (Table 4). Antiacid agents are rou-
tinely prescribed because most patients believe that all
drugs do harm to the stomach and ask for these pre-
scriptions, and may even receive these agents from dif-
ferent departments of the hospital and/or from different
hospitals. Clinical pharmacists therefore play an impor-
tant role in patient education about medications.
The second most frequent duplicate medication in
the study was “Agents acting on the renin–angiotensin
system” for lowering blood pressure, protecting the
cardiovascular system, and treating diabetic nephropa-
thy. .33,34 If patients with simultaneous cardiovascular
disease, diabetes, and stroke go to different depart-
ments for medical care, duplicate medication may eas-
ily occur. In addition, excessive doses of these classes
of drugs may increase the risk of side effects, such as
decreased blood pressure, hyperkalemia, and deterio-
ration of renal function. 35
Duplicate medication was frequently seen for
“Psycholeptics” as well. Among these drugs, benzodi-
azepine and zolpidem were the most duplicated. Users
were mainly elderly with multiple chronic diseases
and difficulty falling asleep. Duplications in this class
of drugs may lead to drug dependency and lethargy,
increasing the risk of falls.36 Focusing on the “unnec-
essary drug treatment” problem among outpatients,
our study verified that pre-downloaded batch data
was 2.4–3.6 times more successful in identifying un-
necessary prescriptions than online access.
LIMITATIONS
This was a single-center study with a short implementa-
tion period (two stages of three months each). The
VMRCS was not complete for all outpatient clinics in
the hospital. Therefore, this might limit its generaliz-
ability. In addition, given that information downloaded
from the VMRCS must be checked patient-by-patient
by dedicated clinical pharmacists, and pharmacists take
care of over three thousand outpatients a day, potential
for error or negligence exists. Moreover, if this model
could be used as a blueprint for future expansion and
implementation, a computer system might be devel-
oped to automatically detect DRPs between institutes
and VMRCS, allowing the VMRCS to more strongly
affect drug safety and medication cost savings.
CONCLUSION
Using the VMRCS, DRPs were more easily identified
whether patients received medical care in one or more
hospitals. DRPs could be efficiently prevented and
Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
DOI: 10.1002/pds
 application of the virtual medicine record in cloud
patient safety widely improved using pre-downloaded
patient prescription data. Our findings may also inform
the future expansion and development of an automatic
system for detecting DRPs between institutes and
VMRCS, thereby minimizing inappropriate duplica-
tion prescriptions.
CONFLICT OF INTEREST
The authors declare no conflict of interest
KEY POINTS
• With VMRCS, potential DRPs were more easily
identified whether patients received medical care
in the same hospital or not.
• Potential DRPs could be efficiently prevented
and patient safety improved through the use of
pre-downloaded patient prescription data.
• The DRP “Unnecessary drug treatment,” and the
causes “Inappropriate combination of drugs” and
“Inappropriate duplication of therapeutic group”
were the most common.
ETHICS STATEMENT
The study was approved by the Institutional Review
Board (Chi Mei Medical Center, IRB No. 10307-005).
ACKNOWLEDGEMENTS
We would like to express our gratitude to the person-
nel at the Integrated Care Clinic Team for their input
on this study and Mr. Min-Jung Wang for his assis-
tance in obtaining patient data from OPDs. We also
wish to thank Dr. Richard H. Davis as a second
language teacher.
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SUPPORTING INFORMATION
Additional supporting information may be found in
the online version of this article at the publisher’s
web site.
Pharmacoepidemiology and Drug Safety, 2017; 26: 71–80
DOI: 10.1002/pds