Methods
Study design, setting and study
population
This prospective matched case-control study was carried out at Amsterdam
UMC - location VUmc. This is one of two sites of Amsterdam UMC, which is
the largest academic hospital in the Netherlands, with 37,103 hospital
admissions in 2021. Amsterdam UMC - location VUmc has 733 beds and was
accredited for the third consecutive time by the Joint Commission
International in 2022. A computerized physician order entry (CPOE),
including a Computerized Decision Support System (CDSS), was introduced
in 2016. A multidisciplinary Medication Committee, including medical
safety officers with various backgrounds and a multidisciplinary
in-hospital pharmacotherapeutic stewardship team (IPS team), has been
set up to monitor medication safety (19). In the current study, the IPS
team consisted of a junior medical doctor (less than 1 year of work
experience) and a clinical pharmacist (4 years of work experience)
supervised by an internist, some of whom were in training to be clinical
pharmacologists.
All adult (≥ 18 years) patients admitted to three clinical wards
(Internal Medicine, a medical ward; Upper Gastrointestinal Surgery,
Upper GI, a surgical ward; and Otolaryngology and Oncology, a surgical
ward) between 1 January 2019 and 13 March 2020 (start of the first wave
of COVID-19 in the Netherlands) were eligible for inclusion, provided
that they had been hospitalized at least 24 hours before the weekly ward
round. These study wards were selected because of their motivation to
improve on-ward medication safety and had requested pharmacotherapeutic
stewardship by our IPS team.
Intervention
Conform standard practice in Amsterdam UMC - location VUmc, medication
reconciliation was performed by a pharmacy technician at the time of
patient admission. A detailed workflow of this process is described in
supplementary figure 1. At the time of data collection, hospital
pharmacists delivered centralized off-ward services, such as on-call
duty for consultations by other healthcare professionals (doctors,
nurses, and pharmacy technicians) and checking drug dosages and
interactions (20, 21). Clinical pharmacists did not fulfilled posts for
on-ward activities. The Medical Ethics Review Board of the Amsterdam UMC
– location VUmc approved the study procedures (no. 2020.058 ).
All patients admitted to the Internal Medicine and Upper GI wards and
discussed during the weekly ward rounds were eligible for a clinical
medication review (CMR), provided that they were hospital-admitted at
least 24 hours at time of the weekly ward rounds. Evaluation of patients
visited during the weekly ward rounds was the standard of care. A
maximum of 24 hours before the weekly ward rounds a member of the IPS
team inquired which patients were discussed with the ward physicians. In
the clinical ward of Otolaryngology and Oncology, the medication of
admitted patients was not structurally evaluated during ward round prior
to start of this study. To improve on-ward medication safety, this ward
requested pharmacotherapeutic stewardship from the ISP team during a
dedicated moment once a week in which medication of admitted patients
were structurally evaluated. Therefore, doctors on the at the clinical
ward of Otolaryngology and Oncology ward were asked to identify which
patients they thought would benefit from a CMR because they thought that
there were PEs in the patient’s medication list.
Definitions, data collection,
definitions and
outcomes
A potentially inappropriate prescription (PIM) was defined in consensus
with the IPS team as a deviation from local-, national- (e.g., The Royal
Dutch Pharmacists Association database (‘KNMP Kennisbank’), or
international evidence-based guidelines, without pathophysiological
and/or evidence-based arguments recorded in the patient’s medical
record.
A PE was defined in consensus with the team based on the definition of
Dean et al.: an error in the prescribing decision(s) and/or the
(electronic) prescription writing process that could result in
clinically relevant and significant harm to the patient or a diminished
effect of treatment (1) and confirmed by the doctors responsible for the
patient’s in-hospital treatment. Subsequently, PEs were categorized
based on the core outcome set for appropriate medication use of Beuscart
et al. (22) and our previous studies conducted in the same hospital (19,
23).
A clinical medication review (CMR) was defined in consensus with the
team based on the definition of Griese-Mammen et al.: is an evaluation
of a patient’s medication use with the aim of optimizing medicine use
and improving health outcomes and avoiding medication wastage (4). In
this study, all CMRs were performed by the multidisciplinary IPS team.
An adverse drug event (ADE) was defined as injury resulting from medical
intervention related to a drug (24, 25).
Deprescribing refers to the process of careful withdrawal of an
inappropriate medication, supervised by a healthcare profession with the
goal of managing polypharmacy and improving outcomes (26, 27).
The IPS team applied a three-step procedure (figure 1): Step 1: A
CMR was performed by the IPS team’s clinical pharmacist and junior
doctor maximally 24 hours before the weekly ward round, using a standard
procedure. All PIMs detected were collected and documented in a
standardized template. Step 2: Integrated in the weekly ward
round, all identified PIMs were discussed face-to-face with the ward
doctor(s), supervisor(s), nurses, and other relevant medical specialists
involved with a patient (clinical ward members). In practice, this meant
that the medication list was checked by all clinical ward members. When
finished, the clinical ward members asked if the IPS team had anything
to add. This face-to-face communication helped ensure that consensus was
reached on medication optimization. The clinical ward members could
accept or reject the PIM(s) identified by the IPS team. If accepted, the
IPS team labelled the PIM as a PE with clinical relevance. Step
3: The rationale behind medication adjustment (e.g., starting,
stopping, or switching) and recommendations for medication monitoring or
follow-up were documented in the patient’s electronic patient record by
the IPS team, using a standardized template to ensure uniformity. The
ward members could use this information in the discharge letter to
subsequent healthcare professionals, e.g., the patient’s GP. On the
Otolaryngology and Oncology ward, doctors contacted the patient’s GP by
telephone to inform them about the CMRs findings and adjustments made to
the patient’s medication regimen, adjustments that were documented in
the post-discharge plan.
To account for potential differences in patient characteristics of the
selected and non-selected patients, a matched case-control design was
applied to compare PEs between patients admitted to the Otolaryngology
and Oncology ward (cases) and patients admitted to the Internal Medicine
and Upper GI wards (controls). All data were recorded in a
password-protected electronic case report form (CRF) by Castor EDC
(www.castoredc.com).
The primary outcome was the number of PEs detected during
hospitalization by the IPS team. Secondary outcomes were the type of
PEs; where the identified PEs originated; and the number of (potential)
adverse drug events (ADEs) detected by the IPS team and reported to the
Junior Adverse Drug Event Manager team (28).
Data analysis and statistical
methods
Descriptive statistics were generated per study ward, and variables are
given as frequencies and percentages for categorical variables and
median values (interquartile range (IQR) and range) for non-normally
distributed continuous variables. Patient characteristics were compared
between all patients on the three wards using the Pearson Chi-square
test for categorical characteristics and the Kruskal-Wallis test for
non-normally distributed continuous variables, to investigate potential
confounding variables in the association between ward and PEs. Outcome
measures were compared between the wards with a Poisson regression
(number of PEs) or a logistic regression (at least one PE). Since
patients differed in important variables, patients on the Otolaryngology
and Oncology ward (cases) were 1:1 matched with patients on Internal
Medicine and Upper GI Tract wards (controls) based on age (± 10 years)
and on the number of prescriptions at the time of the CMR (± 1). Patient
characteristics were compared between cases and controls using the
Pearson Chi-square test for categorical characteristics and the
Mann-Whitney U-test for non-normally distributed continuous variables.
The number of PEs was compared between cases and controls using a
Poisson regression, with the number of prescriptions as offset. The rate
ratio (RR) with a corresponding 95% confidence interval (CI) was used
as the effect size. Whether or not PEs were detected was compared
between cases and controls using a Pearson chi-square test. The odds
ratio (OR) with a corresponding 95% confidence interval (CI) was used
as the effect size. For all tests, the two-sided significance level was
set at 0.05.