title: New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment.
abstract: Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
authors.affiliation: National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, Sydney Street, London, SW3 6HP, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Cowie
authors.affiliation: National and Kapodistrian University of Athens, School of Medicine, Athens University Hospital Attikon, Athens, Greece.
authors.forename: Gerasimos S
authors.initials: GS
authors.lastname: Filippatos
authors.affiliation: National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, Sydney Street, London, SW3 6HP, UK.|Scientific Advice Working Party European Medicines Agency, Medical Assessor Medicines and Healthcare Products Regulatory Agency (MHRA), London, UK.
authors.forename: Maria de Los Angeles
authors.initials: MLA
authors.lastname: Alonso Garcia
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen (UMG), Göttingen, Germany.|Division of Homeostasis Research, Dept of Cardiology, Charité Campus CVK, Berlin, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Baczynska
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Bloomfield
authors.affiliation: Bristol-Myers Squibb, Rueil-Malmaison, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Borentain
authors.affiliation: Norwegian Medicines Agency, Oslo, Norway.
authors.forename: Karsten
authors.initials: K
authors.lastname: Bruins Slot
authors.affiliation: Vifor Pharma, Zurich, Switzerland.
authors.forename: Maureen
authors.initials: M
authors.lastname: Cronin
authors.affiliation: European Medicines Agency Committee for Advanced Therapy, London, UK.|UMC, Utrecht, the Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Dutch Medicines Evaluation Board (CBG-MEB), Utrecht, the Netherlands.
authors.forename: Amany
authors.initials: A
authors.lastname: El-Gazayerly
authors.affiliation: Novartis Pharmaceuticals, Basel, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gimpelewicz
authors.affiliation: Amgen, Inc., Thousand Oaks, CA, USA.
authors.forename: Narimon
authors.initials: N
authors.lastname: Honarpour
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: Salim
authors.initials: S
authors.lastname: Janmohamed
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Heidi
authors.initials: H
authors.lastname: Janssen
authors.affiliation: Pfizer, Inc., Cambridge, MA, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Kim
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Dominik
authors.initials: D
authors.lastname: Lautsch
authors.affiliation: GlaxoSmithKline, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Laws
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Lefkowitz
authors.affiliation: Cardiology Department, Hospital Universitario La Paz; IdiPaz, CIBER-CV, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Sendon
authors.affiliation: National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, Sydney Street, London, SW3 6HP, UK.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Lyon
authors.affiliation: Cytokinetics, South San Francisco, CA, USA.
authors.forename: Fady I
authors.initials: FI
authors.lastname: Malik
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
authors.affiliation: Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Santiago
authors.initials: S
authors.lastname: Figueroa Perez
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.affiliation: Department of Heart Diseases, Medical University, Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: United Kingdom Medicines and Healthcare Products Regulatory Agency, London, UK.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Bristol-Myers Squibb, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Richard-Lordereau
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Roessig
authors.affiliation: IRCCS San Raffaele Hospital Roma, Rome, Italy.|Cardiovascular Clinical Academic Group, St George's Hospitals NHS Trust, University of London, London, UK.
authors.forename: Giuseppe M C
authors.initials: GMC
authors.lastname: Rosano
authors.affiliation: Celyad, Mont Saint Guibert, Belgium.
authors.forename: Warren
authors.initials: W
authors.lastname: Sherman
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, Cary, NC, USA.
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.affiliation: National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, Sydney Street, London, SW3 6HP, UK.|Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Servier International, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Tyl
authors.affiliation: INSERM, Centre d'Investigation Clinique 1433 and Unité 1116, Université de Lorraine and CHU, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Novartis Pharmaceuticals, Basel, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Boulton
authors.affiliation: Dutch Medicines Evaluation Board (CBG-MEB), Utrecht, the Netherlands.|Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: De Graeff
mesh_terms: D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D032921:Consensus; D017277:Drug Approval; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D017063:Outcome Assessment, Health Care
chemical_list: D002317:Cardiovascular Agents
keywords: Clinical trial; Drug approval; Heart failure