title: Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome: Executive summary.
abstract: Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares, Spain.|Cardiology Department, Hospital Universitario 12 de Octubre, Spain.|Universidad Complutense de Madrid, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Bueno
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, The Netherlands.|Dutch Medicines Evaluation Board, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: de Graeff
authors.affiliation: Bristol-Myers Squibb, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Richard-Lordereau
authors.affiliation: Université Paris-Descartes Cochin-Hôtel Dieu Hospital, French National Agency for Medicines and Health Products Safety, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.affiliation: Centre for Cardiovascular Science, University and Royal Infirmary of Edinburgh, UK.
authors.forename: Keith Aa
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Novartis Pharmaceuticals, USA.
authors.forename: Carola P
authors.initials: CP
authors.lastname: Friedman
authors.affiliation: Sanofi, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Gaudin
authors.affiliation: Dutch Medicines Evaluation Board, The Netherlands.
authors.forename: Amany
authors.initials: A
authors.lastname: El-Gazayerly
authors.affiliation: Daiichi Sankyo Development Ltd, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Goldman
authors.affiliation: Bayer Pharma AG, Inc., Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hemmrich
authors.affiliation: Trent Cardiac Centre, Nottingham University Hospitals, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Henderson
authors.affiliation: Astra Zeneca R&D, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Himmelmann
authors.affiliation: Department of Cardiology, University of Tartu, Estonia.|Estonian State Agency of Medicines, Estonia.
authors.forename: Alar
authors.initials: A
authors.lastname: Irs
authors.affiliation: Pfizer, Inc., USA.
authors.forename: Neville
authors.initials: N
authors.lastname: Jackson
authors.affiliation: Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.affiliation: Medizinische Klinik, Universitätsklinikum Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Austrian Agency for Health and Food Safety, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Laslop
authors.affiliation: GlaxoSmithKline, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Laws
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, USA.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Pfizer, Inc., UK.
authors.forename: Seleen
authors.initials: S
authors.lastname: Ong
authors.affiliation: Medicines and Healthcare Products Regulatory Agency, UK.|St Thomas Hospital, University of London, UK.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Department of Cardiology, University Hospital, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Roffi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Hospital Roma, Italy.|Cardiovascular and Cell Sciences Institute, University of London, UK.
authors.forename: Giuseppe Mc
authors.initials: GM
authors.lastname: Rosano
authors.affiliation: Food and Drug Administration, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Rose
authors.affiliation: Department of Cardiovascular Sciencies, University of Leuven, Belgium.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Sinnaeve
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, USA.
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Thygesen
authors.affiliation: Department of Cardiovascular Sciencies, University of Leuven, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.affiliation: Institut de Recherches Internationales Servier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Varin
authors.affiliation: Onze Lieve Vrouwe Gasthuis (OLVG), The Netherlands.
authors.forename: Freek Wa
authors.initials: FW
authors.lastname: Verheugt
authors.affiliation: Scientific Advice Working Party, European Medicines Agency, UK.|Cardiology, Imperial College Healthcare, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: de Los Angeles Alonso García
mesh_terms: D054058:Acute Coronary Syndrome / Q000503:physiopathology / Q000628:therapy*; D000789:Angina, Unstable / Q000628:therapy; D002309:Cardiology / Q000458:organization & administration*; D003643:Death; D004493:Education / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D000072658:Non-ST Elevated Myocardial Infarction / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D015424:Reperfusion / Q000379:methods; D018570:Risk Assessment; D000072657:ST Elevation Myocardial Infarction / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods
keywords: Acute coronary syndrome; clinical trials; endpoint determination; myocardial infarction; unstable angina