Methods
Study design
We conducted a cluster randomised controlled trial designed to assess the effectiveness and safety of an EHR-based intervention to encourage use of NSAIDs for adult inpatients, with the ultimate goal of improving NSAID use without adding ineffective EHR burden for clinicians. Clinicians were the unit of randomisation, and outcomes were compared for patient encounters exposed to a clinician randomised to the intervention or control arm. Clinicians were only randomised if they used the pain panel in the core admission order set. Patients and the public were not involved in the design or conduct of the research.
Site and subjects
Our study was conducted at three hospital sites associated within a single academic hospital system (University of California, San Francisco (UCSF)).
We studied adult patients (≥18 years) during the time period between 3 March 2022 and 3 March 2023. We excluded encounters if the clinician was not exposed to the pain panel of the core admission order set. This included encounters for patients admitted by a small number of services with pre-existing pain treatment pathways with separate pain medication panels, as well as encounters where the patient was expected to have only ‘mild pain’ assessed by clinicians in the admission order set. In both these cases, the clinician bypassed the admission pain order set and so were not exposed to the intervention. Finally, any clinician associated with the neurosurgery service was not randomised and was not presented with prechecked orders for NSAIDS due to concern for epidural haematoma with NSAID use.
This article followed Consolidated Standards of Reporting Trials reporting guidelines extension for cluster randomised trials (online supplemental eAppendix 1).11
Randomisation of clinicians
Clinicians were randomised to the intervention or control group at the moment they first interacted with the pain medication panel of the core admission order set and remained in their randomised group for the remaining period of the trial. Randomisation was blocked and stratified by non-surgical versus surgical services, to ensure balance within each of these groups (figure 1). We included a power calculation to ensure adequate enrolment (online supplemental eAppendix 2).
Figure 1CONSORT diagram (attached separately). CONSORT, Consolidated Standards of Reporting Trials.
Description of the intervention
As in our previous study, our institution uses a standard admission order set for most adult hospital admissions. The order set includes essential admission orders including vital sign frequency, lab frequency, intravenous fluid options, tube and drain management, diet choices and venous thromboembolism prophylaxis. Our intervention was embedded in the pain management section.
Clinicians randomised to the intervention arm had NSAIDs prechecked every time they admitted a patient (online supplemental eAppendix 3). They were able to UNcheck NSAIDs if desired. Clinicians randomised to the control arm saw the same NSAID choice and had to either choose an NSAID or click an option to specify that the patient had a contraindication to NSAIDs to admit a patient.
In both intervention and control versions of the pain panel, text immediately below the order panel provided decision support as follows: ‘Celecoxib: Do not use in patients with a history of ischaemic heart disease, stroke, recent CABG or heart failure. Ketorolac or ibuprofen: Avoid in patients on therapeutic anticoagulant therapy, acute or chronic kidney disease (estimated glomerular filtration rate (eGFR)<60), gastrointestinal (GI) bleeding in last 6 months, most transplant patients, heart failure’ in order to alert clinicians to specific contraindications to NSAID use.
Data sources
We used data from the EHR data warehouse (Clarity), which included billing data in the form of International Classification of Diseases, Tenth Revision (ICD-10) codes, to detect evidence of GI bleeding or acute kidney injury as well as clinician ordering activity, medication administration records and pain score data from nursing flow sheets. We also included hospital discharge prescribing data. We calculated the Charlson Comorbidity Score using previously generated code for administrative databases.12
Pain scores at our institution are determined using the Numeric Rating Scale, which is a self-reported scale with 0 being no pain and 10 being the worst possible pain.13 14 Scores are recorded by nurses in nursing flow sheets.
Outcomes
Because patient encounters may begin before an admission order (ie, the patient being seen in emergency department or in operating room) and can happen anytime during a calendar day, the available time for a medication to be ordered or administered within a 24-hour time period can vary. For this reason, we elected to focus most of our outcome measures on whether the event had occurred by the end of the first full hospital day, defined as the second midnight of admission. We did this to ensure the capture of a full hospital day, as patients admitted at 11pm would only have 1 hour of time in hospital day 1.
Our primary outcome was the placement of an NSAID order by the end of the first full hospital day. Secondary outcomes included administration of NSAIDs by the end of the first full hospital day, patient pain scores by the end of the first full hospital day including highest and average pain score and total oral morphine equivalents (OMEs) the day before discharge using a common equivalence calculator.15 OME is a commonly used approximations to compute equianalgesic doses between different types of opioids.15 We also calculated the opioid equivalence of the discharge prescription using the morphine equivalent daily dose.15
We analysed three adverse events as potential clinical harms from NSAID use: in-hospital death, new GI bleed and new acute kidney injury. Clinical harms were defined as a new diagnosis not present on admission. We classified clinical harms by extracting data from Clarity (death) as well as both the patient’s inpatient problem list and coded diagnoses that are attached to the hospital account and entered by a medical coder within 2 weeks after the patient is discharged. We used ICD10 codes to define these diagnoses including eGFR16 (online supplemental eAppendix 4). Finally, we identified patients with preadmission-documented contraindications to an NSAID (chronic kidney disease, organ transplant, allergy, history of GI bleed) using historical coding, billing and patient’s problem lists as well as the patient’s eGFR on admission. We performed stratified analysis on the group of patients with contraindications to NSAIDs to better understand clinical harms in that specific subset.
Statistical analysis
Baseline characteristics were expressed as numbers and percentages for categorical variables and mean with SD for continuous variables. Differences between control and intervention baseline characteristics were compared by χ2 or t-test for categorical and continuous variables, respectively. We reran each variable to ensure normality, and for non-normal data reported outcomes as median and IQR.
Because our unit of randomisation was the ordering clinician, but effects were measured at the encounter level, we first tested whether there were differences between clinician groups in terms of observable baseline characteristics, which there were not (online supplemental eAppendix 4). Additionally, we performed a stratified analysis on baseline patient-level data, including only the first patient encounter to see if there were any differences at the patient level.
We then used mixed-effects logistic regression models for each dichotomous outcome, clustering by admitting clinician, to analyse primary and secondary outcomes for each hospital admission exposed to the intervention via their admitting clinician. Data analyses were performed during the month of March 2023. Statistical significance was declared based on p≤0.05. No multiple testing adjustments were performed. All analyses were performed by using R V.4.0.5.