Study design and setting
This prospective cross-sectional study was conducted in Thailand between June 11 and September 30, 2020. The Research Ethical Committee of the Faculty of Medicine, Chiang Mai University (No. 197/2020 on June 8, 2020) approved this research protocol. We obtained informed consent from all participants in the study. We followed the strengthening the reporting of observational studies in epidemiology (STROBE) statement recommendations.[16] The study was carried out in accordance with ethical guidelines of the Faculty of Medicine, Chiang Mai University. We prospectively registered this study on the Thai Clinical Trials Registry (TCTR20200610005) on June 10, 2020. We have complied with the latest version of the Declaration of Helsinki (2013).
Study population
EPs, EMRs, or ECNs who worked in a hospital in Thailand were invited to participate in this study voluntarily. ECNs were registered nurses (RN), emergency nurses (EN), and emergency nurse practitioners (ENP). RNs, ENs, and ENPs were nurses who cared for the patients in the ED. Moreover, RNs passed a basic emergency medicine short course. ENs passed an intermediate emergency medicine course. ENPs were a specialist emergency nurses who passed a full emergency medicine course for the nurse.
Nurses have generally studied clinical pharmacology emphasizing drug preparation and administration to a patient. Meanwhile, physicians have studied emphasizing the indication and contraindication of each drug for specific diseases. Because ECNs are inevitably involved in drug preparation and administration, ECNs were enrolled in this study to determine the ability of DDI knowledge. In some emergencies, physicians may focus on indications of drugs given to their patients leading to less awareness of the risk of DDI. Although nurses cannot authorize which drugs should be prescribed to their patients, the ECN could be a key person to alert physicians of potential DDIs in prescribing drugs, especially in time-sensitive emergency circumstances.
Study conduct and data collection
An invitation message was sent through social media, such as a specific social media group of emergency personnel. Recruitment via social media and an online survey platform was used because this method could effectively enroll personnel anywhere in Thailand. Moreover, the participant’s convenience in responding to this survey could encourage them to complete it more than the paper-based method. The study was introduced as follows: “Importance: This research participant is only for an emergency physician, an emergency medicine resident, or an emergency care nurse. If you are out of the scope of this profession, please send this survey to those you know.“ in an invitation message to ensure the participant was the target profession. Participants gave informed consent and answered the questionnaire through a secure internet-based examination survey using the Research Electronic Data Capture (REDCap) platform.[17].
The survey consisted of baseline characteristics (including potential factors) and multiple-choice questions (MCQs; 40 points) of DDI. If the survey was performed multiple times by one individual, only the score from the first time would be used for analysis. The score was sent to each participant via email after the data collection period.
Baseline characteristics included age, sex, academic degree, academic position, academic year of EMR, ECN level, emergency medicine experience, clinically pharmacological or toxicological training (including the time since the last completion or recertification of the clinically pharmacological or toxicological training), the advanced cardiovascular life support (ACLS) training (including the time since the last ACLS training), prior experience of DDI checker book and application use.
Prespecified factors in primary and secondary outcomes were profession (EP, EMR, or ECN), emergency medicine experience, clinically pharmacological or toxicological training, last completed or recertified ACLS training, prior experience of DDI checker book, and application use. These factors were planned to use in adjusting in multivariable analysis.
In ACLS course, some emergency drugs and their DDIs were taught in this course. For example, adenosine is prescribed to terminate supraventricular tachycardia, which was taught in the ACLS course. Patients concurrently using theophylline may diminish adenosine’s therapeutic effect as DDI, and a higher adenosine dose may be required to achieve its therapeutic effect. Therefore, medical personnel who recently passed the ACLS course might remember this DDI.
A DDI checker book may be available in a medical textbook, such as internal medicine, clinically pharmacological or toxicological textbook. Nowadays, a DDI application or web-based checker is widely available. However, the emergency personnel had a variety of generations of education. Some of them had utilized the early version of the DDI checker available in the platform as a book before it became an application or web-based tool. This study’s objective was to include various generations of emergency personnel; therefore, DDI checker book use experience was included as a factor even though currently DDI is used as an application or web-based checker.
The DDI questions were designed based on the classification of DDIs from the Lexicomp® Drug Interactions database from Lexi-Interact®.[18] DDI risk rating was classified into five levels: risk rating X (avoid combination), risk rating D (consider therapy modification), risk rating C (monitor therapy), risk rating B (no action needed), and risk rating A (no known interaction). Forty pairs of drugs were selected based on the chance to be used concomitantly (eight pairs with risk rating X, seven pairs with risk rating D, five pairs with risk rating C, and twenty pairs with risk ratings B or A). The correct answer is worth 1 point each, making the total score 40 points. The proportion of questions regarding risk ratings B or A to risk ratings X, D, or C was designed to be 1:1 (20: [8 + 7 + 5] = 20:20). The reason for grouping all risk ratings into three choices in MCQ was easy to answer and persuasion to complete all 40 MCQs. Internet-based examination survey in this study was available in the supplementary material.
Outcome measures
The primary outcome was the examination score of all-risk ratings of common DDI from MCQs of the DDI questions. Secondary outcomes focused on examination scores of risk ratings X, D, and C. Moreover, we planned to identify an academic year of EMR (the first, second, and third residency years) associated with knowledge of all-risk rating DDI as a subgroup analysis.
Sample size estimation
In biostatistics literature, a sample size of approximately 30 participants per variable has better power to detect a small effect size in regression analysis.[19] In our study, the sample size was also estimated by the formula as 30 participants per factor. With six prespecified factors, a sample size of 180 participants was estimated. To achieve 20% missing or incomplete data, a sample size of 225 participants was planned for enrollment.
Data analysis
Descriptive data were presented as a number, percentage, mean, median, standard deviation, and interquartile range as appropriate. Categorical data were compared by the chi-squared test or Fisher’s exact test, as appropriate. Continuous data were compared by one-way analysis of variance (ANOVA) or the Kruskal-Wallis test, as appropriate. The Shapiro-Wilk test and data visualization was used to determine normal distribution. Missing data were planned to handle by the multiple imputation method. Univariable (unadjusted) and multivariable (adjusted) regression analyses of the means were used to determine the association between characteristics, prespecified factors and the knowledge score. The Stata version 16 (Stata Corp LLC, College Station, Texas, USA) was used for statistical analysis. Statistical significance was determined at p < 0.05.