title: Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs.
abstract: BACKGROUND
  There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction.
  
  
  OBJECTIVE
  To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities.
  
  
  METHODS
  (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies.
  
  
  RESULTS
  Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice.
  
  
  CONCLUSIONS
  Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.
authors: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge Stockholm, Sweden ; Medicines Use and Health, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde Glasgow, UK.
authors: Brian
authors: B
authors: Godman
authors: Clinical Pharmacology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna Stockholm, Sweden.
authors: Rickard E
authors: RE
authors: Malmström
authors: Clinical Pharmacology Service, Vall d'Hebron University Hospital, Fundació Institut Català de Farmacologia, Autonomous University of Barcelona Barcelona, Spain.
authors: Eduardo
authors: E
authors: Diogene
authors: Department of Medicine, Hutt Valley DHB Lower Hutt, Wellington, New Zealand.
authors: Sisira
authors: S
authors: Jayathissa
authors: Public Health and Intelligence Business Unit, NHS National Services Scotland Edinburgh, UK.
authors: Stuart
authors: S
authors: McTaggart
authors: Department of Healthcare Development, Public Healthcare Services Committee, Stockholm County Council Stockholm, Sweden ; Department of Medical Sciences, Uppsala University Uppsala, Sweden.
authors: Thomas
authors: T
authors: Cars
authors: Medicines Use and Health, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde Glasgow, UK.
authors: Samantha
authors: S
authors: Alvarez-Madrazo
authors: Austrian Medicines and Medical Devices Agency Wien, Austria.
authors: Christoph
authors: C
authors: Baumgärtel
authors: Agency for Health Technology Assessment Warsaw, Poland.
authors: Anna
authors: A
authors: Brzezinska
authors: Department of Finance, Faculty of Business, Economics and Statistics, University of Vienna Vienna, Austria ; Hauptverband der Österreichischen Sozialversicherungsträger Vienna, Austria.
authors: Anna
authors: A
authors: Bucsics
authors: Centre for Primary Care, Institute of Population Health, University of Manchester Manchester, UK.
authors: Stephen
authors: S
authors: Campbell
authors: Department of Healthcare Development, Public Healthcare Services Committee, Stockholm County Council Stockholm, Sweden.
authors: Irene
authors: I
authors: Eriksson
authors: Green Templeton College, University of Oxford Oxford, UK.
authors: Alexander
authors: A
authors: Finlayson
authors: Health Insurance Institute Ljubljana, Slovenia.
authors: Jurij
authors: J
authors: Fürst
authors: Medicines Reimbursement Department, National Health Insurance Fund Vilnius, Lithuania.
authors: Kristina
authors: K
authors: Garuoliene
authors: Basque Office for HTA, Ministry of Health and Consumer Affairs, Basque Government Basque Country, Spain.
authors: Iñaki
authors: I
authors: Gutiérrez-Ibarluzea
authors: Norwegian Medicines Agency Oslo, Norway.
authors: Krystyna
authors: K
authors: Hviding
authors: Kassenärztliche Vereinigung Hessen Frankfurt am Main, Germany.
authors: Harald
authors: H
authors: Herholz
authors: Pharmaceutical Drug Department, Azienda Sanitaria Locale of Verona Verona, Italy.
authors: Roberta
authors: R
authors: Joppi
authors: Department of Medicines and Pharmacoeconomics, Republic Institute for Health Insurance Belgrade, Serbia.
authors: Marija
authors: M
authors: Kalaba
authors: State Agency of Medicines Tartu, Estonia.
authors: Ott
authors: O
authors: Laius
authors: Department of Epidemiology and Health Promotion, Public Health School Warsaw, Poland ; Drug Management Department, National Health Fund Warsaw, Poland.
authors: Kamila
authors: K
authors: Malinowska
authors: Division of Health Systems and Public Health, Health Technologies and Pharmaceuticals, WHO Regional Office for Europe Copenhagen, Denmark.
authors: Hanne B
authors: HB
authors: Pedersen
authors: Faculty of Medicine, University of Banja Luka Banja Luka, Bosnia and Herzegovina ; Ministry of Health and Social Welfare Banja Luka, Bosnia and Herzegovina.
authors: Vanda
authors: V
authors: Markovic-Pekovic
authors: Hauptverband der Österreichischen Sozialversicherungsträger Vienna, Austria.
authors: Jutta
authors: J
authors: Piessnegger
authors: Wissenschaftliches Institut der AOK (WidO) Berlin, Germany.
authors: Gisbert
authors: G
authors: Selke
authors: IRDES Paris, France.
authors: Catherine
authors: C
authors: Sermet
authors: Department of Pharmacology and Therapeutics, Trinity College Dublin Dublin, Ireland.
authors: Susan
authors: S
authors: Spillane
authors: Faculty of Pharmacy, Comenius University and Faculty of Medicine, Slovak Medical University Bratislava, Slovakia.
authors: Dominik
authors: D
authors: Tomek
authors: Ministry of Health Zagreb, Croatia.
authors: Luka
authors: L
authors: Vončina
authors: Unit for Clinical Pharmacology, University Hospital Rijeka Rijeka, Croatia.
authors: Vera
authors: V
authors: Vlahović-Palčevski
authors: Independent Consumer Advocate, VIC Melbourne, Australia.
authors: Janet
authors: J
authors: Wale
authors: HTA Consulting Cracow, Poland.
authors: Magdalena
authors: M
authors: Wladysiuk
authors: Dutch Institute for Rational Use of Medicine Utrecht, Netherlands.
authors: Menno
authors: M
authors: van Woerkom
authors: Barcelona Health Region, Catalan Health Service Barcelona, Spain.
authors: Corinne
authors: C
authors: Zara
authors: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge Stockholm, Sweden.
authors: Lars L
authors: LL
authors: Gustafsson
keywords: critical drug evaluation; dabigatran; demand-side measures; managed introduction new medicines; registries