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.