MEDICATION ERRORS ASSOCIATED WITH DIRECT ACTING ORAL ANTICOAGULANTS IN ADULT PATIENT

Abstract

Direct oral anticoagulants (DOACs) are effective therapeutic and/or prophylactic agents for thromboembolic events, such as deep venous thrombosis (DVT), pulmonary embolism (PE), and atrial fibrillation (AF). However, DOACs are also recognised as one of the most commonly concerned drug classes in relation to safety incidents. The purpose of this thesis was to determine the epidemiology of errors and explore the factors contributing to medication errors associated with DOACs from the perspectives of healthcare professionals and patients. The thesis consisted of three main parts: a systematic review and meta-analysis; two retrospective studies, and three in-depth qualitative interview studies. The systematic review and meta-analysis were conducted to determine the prevalence of medication errors associated with DOACs in clinical practice and to identify factors associated with DOACs in adult patients using published literature. Data related to error causation were synthesised using the Reasons Accident Causation Model. The systematic review and meta-analysis were conducted through searching 11 databases, including Medline, Embase and CINHAL, between January 2008 to September 2020. Thirty-two studies were included in the review. The proportion of the study population who experienced either prescription, administration, or dispensing error ranged from 5.3 to 37.3%. The pooled percentage of patients experiencing prescribing error was 20% (95% CI 15-25%; I2 = 96%; 95% PrI 4-43%). Prescribing error constituted the majority of all error types with a pooled estimate of 78% (95%CI 73-82%; I2=0) of all errors. The commonly reported causes were active failures, including wrong drug, and dose for the indication. Mistakes such as non-consideration of renal function, and error-provoking conditions, such as lack of knowledge, were common contributing factors. The second part of this thesis involved two retrospective evaluations undertaken using national and local hospitals’ incident reporting databases in Saudi Arabia and through using a national safety incident reporting database in the United Kingdom (UK). The purpose of this phase was to investigate the types of medication errors and contributory factors associated with DOACs. Using three datasets, including the National Food and Drug Authority (Saudi FDA) database, a total of 199 medication error incidents were analysed. The prescribing error was the most common error type, representing 81.4% of all errors. Apixaban was the most frequent drug associated with error reporting, with 134 (67.3%) incidents, followed by rivaroxaban (18.6%), and dabigatran (14.1%). In the UK, using the National Reporting and Learning System (NRLS) database, a total of 15,730 incident reports received by the NRLS between 01 January 2017 to 31 December 2019 were analysed. A total of 25 deaths were reported, with a further 270 and 55 incidents leading to moderate and severe harm, respectively. A further 8.8% (n=1381) of incidents were associated with a low degree of harm. The third part of this thesis consisted of three theory-driven qualitative studies exploring the views, experiences, and contributory factors related to DOACs medication errors from the perspectives of physicians (n=20), nurses (n=14), pharmacists (n=23), and patients (n=9) in Saudi Arabia. The participants were recruited from three different hospitals setting and regions. The analysis identified several themes: factors related to healthcare professionals (e.g., knowledge, lack of communication with other HCPs, confidence and access to guidelines, patient counselling); factors related to patients (e.g., comorbidity, polypharmacy, lack of knowledge of DOACs, using inappropriate sources of information and communication barriers with HCPs); factors related to the organisation (e.g., guidelines, safety culture and incidents reporting system); factors related to the DOACs medications (e.g., lack of availability of antidotes and dosing issues); and strategies for error prevention/mitigation and promote DOACs safety from staff and patient perspectives (e.g., empowering the role of pharmacists, patient education, opportunities for risk assessments, multidisciplinary working and enforcement of clinical guidelines and needed professional training and routine medication review). The data provided revealed convincing evidence in relation to the prevalence of errors and actual harm caused by such errors when prescribing, dispensing, and administrating DOACs. The key strategies to minimise errors associated with DOACs can be providing interventions to improve education and training of healthcare providers, developing local clinical guidelines, involving pharmacists to lead anticoagulation clinics, improving communication, and adhering to evidence-based strategies