Table 1.

Summary of key activities across Europe to improve the quality and efficiency of prescribing of dabigatran (Godman et al., 2008, 2009a,c, 2011a, 2012d; Holmström et al., 2009; Janusinfo, 2009, 2012a,b; KVH - Aktuell, 2010; Martikainen et al., 2010; Wettermark et al., 2010a,c; Boehringer Ingelheim, 2011b; Gustafsson et al., 2011; Neue Arzneimittel, 2011; Stockholms läns landsting, 2011; Vončina et al., 2011; Keele University School of Pharmacy, 2012; Medicin & Läkemedel, 2012; Midlands Therapeutic Review and Advisory Committee [MTRAC], 2012; Östergötland, 2012; Persson et al., 2012; Davidson et al., 2013).

Timing	Examples of activities among European countries and regions
Pre-launch (principally education)	Swedish counties:
	(A) Östergötland County Council
	•Update of the previous report on the prevalence of atrial fibrillation in Östergötland •Establishing a working party with broad representation from the departments of cardiology and internal medicine, primary health care, representatives from the warfarin polyclinics, epidemiologist and health economists associated with the Drug and Therapeutics Committee (DTC) •Scientific publication of the cost-effectiveness model for dabigatran for the prevention of stroke based on Östergötland by the Centre for Medical Technology Assessment, Linköping University, in collaboration with Östergötland County Council •Consensus action plan agreed 12 months before dabigatran was registered for the prevention of stroke in patients with AF •Recommendation from the DTC to classify dabigatran as a “focus-drug”, i.e., the prescribing unit will be responsible for the cost of the drug. If however patients are entered into the County Council’s quality assessment program, the cost will be borne by the County Council. Decision by the County Council to follow the recommendation of the DTC •Resources for treating patients allocated in the 2011–2012 County Council drug budgets •Communication plan implemented
	(B) Stockholm County Council
	•Systematic and long-term involvement of medical and scientific expertise in the development of guidelines and advise to patients and prescribers through the Regional Drugs and Therapeutic Committee (DTC) and clinical pharmacologists •Extensive pre-launch activities with key messages broadcasted both to the public and to prescribers through websites of the DTC as well as the Swedish Medical Journal •Appreciable number of pre-launch meetings and training sessions with all major physician groups around the key issues and concerns with dabigatran as well as its likely place in care •Production of educational folders regarding dabigatran, slide kits, published articles, and data on the Janus website as well as published information for patients •Forecasting the potential budget impact in 2011 and 2012 ahead of launch and monitoring this in practice •Development of a laboratory method to monitor dabigatran in plasma with LC-MS/MS technology, and recommending sampling in the introductory phase to build a knowledge database. This to be followed by more situation-based sampling to improve patient safety in the future
Peri-launch (principally education)	(A) West Midlands (Region – England)
	•Development of guidance stating that warfarin remains the first-line option for anticoagulation in patients with AF at high risk of a stroke, and primary care trusts (have been replaced by Clinical Commissioning Groups from April 1, 2013) should ensure optimal existing warfarin therapy services – including access to INR clinics, use of computerized decision-support software, and access to drugs for patients who are allergic to warfarin (the latter rare in practice) •In addition in view of the considerable financial implications, dabigatran treatment should only be prescribed for patients: °with co-morbidities who are adherent to warfarin monitoring and lifestyle requirements but need frequent co-prescribed medications that interact with warfarin and affect the patients’ time in the therapeutic range (TTR) °who are adherent to monitoring and lifestyle requirements but whose TTR remains unacceptable despite attempts to optimize treatment with warfarin (TTR rates should be set locally)
	(B) Germany
	•Physician Associations stressing when launched that the current knowledge regarding safety with dabigatran was insufficient to answer all questions, and physicians should be careful with prescribing particularly in the elderly •The reporting of deaths from excessive bleeding further endorsed these concerns. As a result, limited prescribing in practice in ambulatory care
	(C) Slovenia
	•Reimbursed in conjunction with a complex price:volume agreement
Post-launch (principally education and enforcement)	(A) Austria (enforcement)
	•Ex ex-ante approval by the head physician of the patient’s social health insurance fund before reimbursement of dabigatran; otherwise 100% co-payment (mirroring other situations) •Renal function has to be assessed and recorded prior to initiation of therapy with dabigatran through determining Creatinine-Clearance (CrCl) levels to exclude patients with severe renal dysfunction (=CrCl < 30 ml/min). In addition during treatment, renal function has to be monitored where a decline is envisaged, e.g., patients with hypovolemia, dehydration, and the use of specific additional medication, and renal function has to be assessed at least once a year in patients aged 75 or older, and/or in patients with compromised renal function
	(B) Finland (enforcement)
	•Reimbursement restricted to patients with risk factors where satisfactory control has not been reached with warfarin; alternatively, warfarin cannot be prescribed due to side-effects or contra-indications •Enforcement at the pharmacy with on average 16 days needed for requests to be centrally reviewed and authorized. Hundred percent co-pay without authorization
	(c) Slovenia
	•Education of all involved specialists and primary care physicians on key safety aspects/adverse events with dabigatran •Prescribing restrictions (Enforcement): •Only reimbursed if initiated by an internist or neurologist and prescribed according to agreed indications, e.g., only reimbursed in patients already on warfarin if they are unstable with TTR < 65 •Patients have to be followed in a tertiary or secondary care anticoagulation center. Patients can be followed in primary care but only if authorized by the tertiary or secondary care center. •Every patient has to be registered in a database and followed by the IT anticoagulation program •Anticoagulation centers have to report once yearly to the tertiary center regarding the number of patients experiencing minor and major bleeding, thromboembolic events, as well as any deaths from bleeding or thromboembolism with dabigatran