Table 1.

Study characteristics with classification of medication error contributory factors

Author(s) Year	Country	Study design, Methods used to identify medication errors	Study setting	Study population	Sample size patient	Sample size (errors)	Types of medication error and data collection method	DOACs drug errors listed or investigated	indications		Results	Classification of contributory factors as per Reason’s Accident Causation model
												Active Failure*	Error Provoking Condition**	Latent Condition***
Bruneau et al. [18]	France	Observational prospective study: multicenter	University hospitals	Elderly ≥65 years received and discharged on DOAC and Admitted to acute unit between February and July 2018	157		Prescribing error; retrospective review of medical records	Dabigatran, rivaroxaban, apixaban	AF, VTE, and Others		Prior to admission, (30.6%) had an inappropriate prescription. At discharge, (22.4%) had an inappropriate prescription; The nature of the inappropriateness was under- or overdosing (21.7%)	NR	NR	NR
Dreijer et al. [21]	The Netherlands	A cross-sectional study	Central Medication incidents Registration reporting system(CMR)	Medication error reported to Central Medication incidents Registration reporting system between December 2012 and May 2015	1000 medication error report		Prescribing error Administration error; errors reported to a national reporting system	Dabigatran, rivaroxaban, apixaban	AF		DOACs were the least frequently type of anticoagulant involved in the reports 3% Most anticoagulant medication errors were reported as prescribing errors (37.1%), followed by administering errors (29.8%). The majority of errors made in the prescribing phase arose from incomplete prescriptions. Omission errors were responsible for the highest percentage of errors in the administering phase	NR	NR	NR
Angel et al. [16]	Israel	Retrospective cohort study	University hospital	-	4427	1237	Inadequate treatment; retrospective review of medical records	Apixaban, rivaroxaban, dabigatran	AF		Among the 1237 patients with inadequate treatment, the most common types of errors were DOAC under-dosing (n = 578; 46.7%), VKA when DOAC was indicated (n = 258; 20.9%), DOAC despite contraindication to DOAC (n = 166; 13.4%), and DOAC over-dosing (n = 124; 10.0%).	Mistake: wrong dose	NR	NR
Valentine et al. [44]	USA	Retrospective reviewed database	Pennsylvania Patient Safety Reporting System database	Pennsylvania Patient Safety Reporting System database	1,811	1,546	Duplicate therapy; errors reported to a reporting system	Rivaroxaban, edoxaban, apixaban, dabigatran	AF, DVT, and PE		Of the 1,811 reports, 14.6% (n = 265) were considered ADEs and 85.4% (n = 1,546) were medication errors without harm.	NR	NR	NR
Sennesael et al. [36]	Belgium	Prospective observational study in the emergency departments	Teaching hospitals	Patients admitted with a thrombotic or bleeding event while under DOAC	46	38	Prescribing issues and inadequate monitoring; prospective medication review	Rivaroxaban, apixaban, dabigatran	NVAF, VTE		For the 46 patients taking DOAC, 38 adverse events were evaluated as serious ADRs. Among these, 20 ADRs (53%) were considered to be (potentially) preventable. Prescribing was the main stage of medication process involved in medication error (n = 16), followed by compliance (n = 5).	NR	Inadequate monitoring	NR
Moudallel et al. [31]	Belgium	Retrospective cohort study	University hospital	Hospitalized patients aged ≥60 years with at least one DOAC intake during hospital stay	772	193	Prescribing errors, inappropriate dosing; retrospective review of medical records	Dabigatran, rivaroxaban, apixaban	AF, VTE		Inappropriate dosing occurred in 25.0% of hospitalizations with 23.4, 21.9, and 29.7% for dabigatran, rivaroxaban, and apixaban, respectively (p = 0.084). Under dosing was most prevalent for apixaban (24.5%) compared to dabigatran (14.0%) and rivaroxaban (12.8%), p < 0.001. In 67.1% (apixaban), 26.7% (dabigatran), and 51.2% (rivaroxaban) of underdosed DOAC case	NR	NR	NR
Lafon et al. [30]	France	Prospective observational study:	University hospital	All subjects with DOAC admitted to the Limoges University Hospital ED	198	-	Prescribing errors (incorrect dosage according to age, renal function, co-medications); prospective observation of prescribing records	Rivaroxaban, dabigatran, apixaban	NVAF, VTE		In 16.2% of the cases, the treatment was not in according to the guidelines: 78% for prescribing errors (incorrect dosage according to age, renal function, co-medications) and 22 % for wrong initial indication	Mistake—wrong dose	Lack of experience •Insufficient education/training.	NR
Ioannidis et al. [27]	Athens, Greece	Prospective study: clinical pharmacists documented all cases where DOACs were prescribed	Private general hospital	Private general hospital	370	42	Prescribing errors (calculated DOACs dosage based on renal function); prospective observation of prescribing records	Rivaroxaban, dabigatran	AF, VTE, PE		A significant amount of patients (11.4%) received DOACs in a way that contradicts the product label guidelines.	•Mistake: wrong dose•Violation: doctor not writing the order not in time	NR	NR
Suknate et al. [41]	Australia	Retrospective review: The relevant data were collected by review of medical records by pharmacists	Teaching hospital	Teaching hospital	200	45	Prescribing error (the most common prescription error was under-dosing and overdosing; retrospective review of medical records	Rivaroxaban, apixaban, dabigatran	AF, VTE, PE		Inappropriate prescription of DOACs appears common, although not associated with complications. The prescription was deemed inappropriate in 45 patients (22.5%). The most common prescription error was under-dosing (for age, weight and renal function, or the indication), which was seen in 23 patients (11.5%). Overdosing was seen in seven (3.5%).	• NR	Lack of knowledge and experience	Lack of medication reconciliation service
Pharithi et al. [32]	Irland	Single centre, retrospective observational cohort study	Teaching hospital	AF patients who had received at least one dose of any of the NOACs	348	-	Prescribing error; retrospective review of medical records	Dabigatran, rivaroxaban, apixaban	AF			NR	NR	NR
Kartas [28]	Greece	Cross sectional study; Data extracted from MISOAC-AF registry	Tertiary care hospital	Adult patients with non-valvular AF or atrial flutter	768	-	Prescribing error; discharge medication review	Dabigatran, Rivaroxaban, Apixaban		AF	Off-label dosing (28.9%) was relevant to more than a quarter of NOAC users, while (23.8%) were underdosed and 21 (5.1%) were overdosed with NOAC	NR	NR	NR
Sheikh-Taha et al. [38]	USA	A retrospective study	Tertiary care center	Adult patients on NOAC between March 1 and June 30, 2017 Huntsville Hospital, Huntsville, Alabama, USA	909	-	Prescribing error; chart review	Dabigatran, rivaroxaban, apixaban, edoxaban		AF, DVT, PE	Almost 23.9% of the patients received doses inconsistent with the package labeling; 13.2% of patients received lower than recommended dosing, while 10.7% received higher than recommended dosing. The prevalence of inappropriate dosing was significantly more frequent among older patients, taking NOACs for AF(30.3%) compared to those using it for DVT/PE treatment (13%) The prevalence of inappropriate dosing was significantly higher in those with lower CrCl, and taking high number of medications	NR	NR	NR
Sharma et al. [37]	USA	Retrospective study: retrospectively reviewed electronic medical records of 41 patients. A clinical pharmacist collected this data.	Teaching hospital	Community-based hospital	41	10	Prescribing error; chart review	Rivaroxaban, apixaban	AF, VTE, and PE		Patients were dosed with 15 mg daily of rivaroxaban for DVT prophylaxis, which were corrected to 20 mg daily dose.	Mistake- wrong dose due to lack of renal dose adjustment and lack of initiation of anticoagulation	NR	NR
Viprey et al. [46]	France	Cross-sectional study: retrospective review; using data from medical records system of the Lyon teaching hospitals	University teaching hospitals	Hospitalized patients	1188	100	Prescribing errors—the appropriateness of the dosage of the drug; retrospective chart review	Dabigatran and Rivaroxaban	AF, DVT, and PE		The highest prevalence of DRPs was found among patients who received rivaroxaban for atrial fibrillation (14·6%; 95% CI, 10·7-18·5). A too low drug dose was the most frequent DRP (n = 56; 4·7%), followed by a too high drug dose (n = 37; 3·1%), contraindication (n = 5; 0·4%), and pharmacokinetic problem requiring dose adjustment (n = 2; 0·2%).	Mistake: wrong dose	NR	NR
Henriksen et al. [25]	Denmark	Descriptive study: retrospective review; three independent specialists in clinical pharmacology evaluated the severity of incident outcomes	University teaching hospitals	Reports to the Patient Safety Database; University Hospital	Not stated	147	Prescribing errors: excess or insufficient dosing; retrospective review	Dabigatran, Rivaroxaban	AF		Dabigatran: Total number within the subgroup (%);30 (21%); potentially Serious (%)—19 (63%)	Mistake: excess or insufficient dosing	System errors	NR
Alghadeer et al. [15]	USA	Retrospective review	University teaching hospitals	Patients that were prescribed dabigatran, rivaroxaban, or apixaban;	113	10	Prescribing error: lack of renal dose-adjustment in patients with reduced renal function was the most common reason for inappropriate use (for specific indication, renal function, age and/or weight); retrospective chart review	Dabigatran, rivaroxaban, and apixaban	STROKE, VTE		The dose of DOACs was unadjusted (for specific indication, renal function, age and/or weight) in 8.8% (n = 10) of patients collectively. All cases were due to unadjusted doses in patients with renal impairment and occurred in 9.2% (n = 6) of patients receiving dabigatran, 8.8% (n = 3) of patients receiving rivaroxaban, and 7.1% (n = 1) of patients receiving apixaban.	Mistake: duplicate therapy and wrong dose	Failure staff to follow policy and procedure. Inadequate laboratory results	NR
Hussain et al. [26]	UAE	Retrospective cross-sectional analysis	Tertiary care hospital	Patients who received dabigatran	61	28	Prescribing errors; retrospective review of medical records	dabigatran	NVAF		Inappropriate dose was administered in 7 of the 61 patients prescribed dabigatran.	NR	Inadequate knowledge off label indication	NR
Ghai et al. [22]	UK	Retrospective review: data was collected from two GP practices in BognorRegis.	Primary care hospital	Patients with NVAF who prescribed DOACs	73	-	Documentation error and prescribing and monitoring errors; retrospective review of medical records	Rivaroxaban	NVAF		12 patients despite having impaired renal function (CrCl < 50) were prescribed the higher dose. Patients with impaired renal function (CrCl < 60) did not have their renal function monitored more frequently as is suggested by NICE	Mistake: wrong dose	•Lack knowledge of how to adjust dose CrCls •Poor communication between team members	Lack of training
Basaran et al. [17]	Turkey	Prospective, observational study: patients with NVAF were screened for OAC prescription	University teaching hospitals	Patients with NVAF; outpatient cardiology clinics	148	24	Inappropriate prescribing; prospective review of prescribing records	Dabigatran, rivaroxaban	NVAF		Inappropriate drug use is frequent among patients with DOACs.	Mistake: wrong dose	NR	NR
Roberts et al. [34]	UK	Prospective observational study:	University teaching hospitals	Patients attending AF clinics, acute medical and cardiology wards; teaching hospital	190	41	Prescribing errors (incorrect dosage according to age, renal Function); prospective review of prescribing records	Rivaroxban, apixaban, edoxaban	AF		Apixaban had the highest rate of inappropriate dosage. As most prescribing errors involved inappropriate dose reduction	•Slips and lapse-memory •Mistake- wrong dose	NR	NR
Victoria et al. [45]	UK	Retrospective review: The data was collected for all DATIX system-reported incidents by clinical pharmacists	University teaching hospitals	-	-	25	Prescribing errors(missed dose, wrong dose for indication, incorrect dosage according to age, renal Function); incident reporting system	Rivaroxaban , apixaban, dabigatran, edoxaban	AF		Patients were prescribed the wrong dose for indication, e.g., AF dose of Apixaban for PE. DOACS were often not available on the ward and patients went as long as 48 hours without anticoagulation	Slips—memory lapses •Lapse: wrong correct label	Lack of knowledge and familiarity with DOACs	NR
Keohane et al. [29]	Ireland	Cross-sectional data was collected from inpatients over a 3-week period	University teaching hospitals	Internal medicine and cardiology wards)	30	-	Prescribing errors (inappropriate dose, indication); review of medical records	Rivaroxaban, apixaban and dabigatran	AF		Out of 70% of the patients, almost 10% were on a NOAC for an inappropriate indication and 11% on an inappropriate dose for the CrCl - Potential drug interactions were common, with 63% of patients concomitantly taking a cautioned or contraindicated medication.	Mistake-prescribing for wrong indication and lack of dose adjustment	NR	NR
Glendinning et al. [23]	Australia	Retrospective review: hospital pharmacy provided a list of patients dispensed either apixaban or rivaroxaban; The medication charts and progress notes of these patients were reviewed for prescribing errors and the presence of any subsequent complications	University teaching hospitals	-	250	-	Prescribing error, documentation error; medical charts and progress notes	Rivaroxaban, apixaban	VTE		19.5% of medication charts prescribing DOACs contained errors	NR	NR	NR
Tellor et al. [42]	USA	Retrospective review	Tertiary community hospital	Patients received at least one treatment dose of rivaroxaban	714	445	Prescribing errors: inappropriate dose; retrospective chart review	Rivaroxaban	NVAF, PE, DVT		Of the 445 patients evaluated, 36.9% of patients treated for NVAF and 12.4% treated for VTE were on an inappropriate regimen. The most common errors in the rivaroxaban regimen for VTE treatment were an inappropriate dose (8 patients, 5.7%)	NR	NR	NR
Simon et al. [39]	USA	Retrospective review: a search of the electronic health record (EHR) was conducted	Academic medical centre	Patients seen in outpatient clinics	395	249	Inappropriate prescribing, patient-reported inappropriate use; retrospective chart review	Apixaban, dabigatran, rivaroxaban	NVAF, PE, DVT		Of contacted patients taking rivaroxaban, 24 (23%) reported taking it inappropriately without food, and of contacted patients taking dabigatran, six patients (14%) endorsed inappropriate storage of dabigatran. Ten patients (6%) reported missing at least one TSOAC dose per week.	Mistake- wrong dose and failure to give rivaroxaban without food	NR	NR
Greenberg-Schwartz et al. [24]	USA	Retrospective review	Community hospital	-	-	-	Errors included inaccurate renal and hepatic dosing adjustments, incorrect dosage based on indication and duplication of anticoagulation agents; retrospective review of medical records	Rivaroxaban	NVAF, PE, DVT		Errors included inaccurate renal and hepatic dosing adjustments, incorrect dosage based on Indication and duplication of anticoagulation agents. Educational program “LEARN” reduced the error from 31.7 to 22%	Slips- acronym errors •Lapse—duplicate therapy	NR	Insufficient education/training opportunities
Stevenson et al. [40]	USA	A retrospective review and prospective observational case series; Data for cases were collected by different poison system staff members	Poison control center	Dabigatran, rivaroxaban exposures into the California Poison Control System	Not stated	49	Therapeutic error: patient mistakenly ingested or was given another individual’s medication; retrospective and prospective review of medical records	Dabigatran and rivaroxaban	DVT		There were 7 cases of dabigatran accidental extra dosing. The excess doses ranged from 75 to 750 mg	NR	NR	NR
Troncoso et al. [43]	Spain	Observational study: Retrospective review; electronic clinical records	Primary healthcare centres	Patients with AF who have been prescribed dabigatran and rivaroxaban	2324	197	inappropriate prescribing; retrospective chart review	Dabigatran, rivaroxaban	AF		Some patients had not been prescribed dabigatran or rivaroxaban even though they were potentially suitable candidates for these drugs.	Slip-wrong dose and wrong choice dose	NR	NR
Donaldson et al. [20]	USA	began as a retrospective review of patients on dabigatran therapy and continues as a prospective, intention-to-treat analysis, completed by a pharmacist-managed anticoagulation clinic	Anticoagulant clinics	Patients on dabigatran therapy; Pharmacist managed anticoagulation clinic	221	54	Prescribing errors; retrospective chart review	Dabigatran	VTE, PE, stroke		Of the 54 patients experiencing an ADE, five patients (9.3%) should have been on a lower dose based on renal function and/or concurrent drug interactions.	NR	NR	NR
Schwartz et al. [35]	USA	Retrospective review	Community hospital	-	-	-	Prescribing errors (incorrect dosage according to age, renal function) Inappropriate indication-inappropriate time of administration (dietary interactions); retrospective review of medical records	Dabigatran	AF		Educational activities “CARE” reduce prescribing error from 40% to 28%.	NR	NR	NR
Desai et al. [19]	USA	Cross-sectional: retrospective review; The medication error reports in MEQI are collected by healthcare professionals	Nursing Home	Individual medication error incidents reported by North Carolina nursing homes to the MEQI	Not stated	1623	Prescribing, documenting or Monitoring errors; retrospective chart review	Dabigatran	AF		Anticoagulant errors were more likely to be associated with patient harm (2% vs 1%, p = 0.001) compared to all other errors.	Slip and lapse-pharmacy dispensing issue and drug name confusion, incorrect transcription.	•Inadequate knowledge •Lack communication •Distraction, •Work overload •failure staff to follow policy and procedure and inadequate information •Shift change	NR
Piazza et al. [33]	USA	Retrospective review: physicians, pharmacists, and a hospital patient safety officer reviewed all reported anticoagulant-related events	Tertiary care Hospital	Inpatient anticoagulant-associated medication errors;	Not stated	226	Transcription errors: missed medication doses; retrospective chart review	Not stated	AF, DVT		Of 463 anticoagulant-associated ADEs, 226 were medication errors (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR	Slips and lapse: transcription errors Mistakes: wrong medication prescribed for the indication	NR	NR

ADEs adverse effect events, ADR adverse drug reaction, AF atrial fibrillation, CrCl creatinine clearance, DOACs non-vitamin K antagonist oral anticoagulants, DRP drug-related problem, DVT deep vein thrombosis, MEQI Medication Error Quality Initiative, NR not reported, NVAF non-valvular atrial fibrillation, OAC oral anticoagulants, TSOAC target specific oral anticoagulants, VKA vitamin K antagonist; VTE venous thromboembolism

^*Active failures are unsafe acts committed by people who are in direct contact with the patient or system. They take a variety of forms including slips and lapses (errors in task execution), mistakes (errors in planning), and procedural violations (rule breaking)

^**Error-producing conditions within the workplace (e.g., time, pressure, under staffing, inadequate equipment, fatigue and inexperience)

^***Latent failures which arise from decisions made by policy makers, leaders, and top-level management