title: Impact of FDA guidance for developing diabetes drugs on trial design: from policy to practice.
abstract: In 2008, the US Food and Drug Administration (FDA) issued guidance requiring robust assessment of cardiovascular safety for all antidiabetic drugs to be licensed in the future. Here, we review the circumstances giving rise to the FDA guidance and describe the characteristics of clinical trials registered on ClinicalTrials.gov in the 36 months before and after the guidance was issued. We noted a doubling in the number of cardiovascular outcome trials registered and a sixfold increase in the median number of patients included in cardiovascular outcome trials in the latter 36 months. As the size and duration of follow-up for these trials increases, the clinical trials industry will need to adapt. The present review summarizes current attempts to streamline trial design and management to meet the requirements efficiently while adhering to the highest scientific standards.
authors.affiliation: Diabetes Trials Unit, University of Oxford, Churchill Hospital, Old Road, Headington OX3 7LJ, UK. angelyn.bethel@dtu.ox.ac.uk
authors.forename: M Angelyn
authors.initials: MA
authors.lastname: Bethel
authors.forename: Harald
authors.initials: H
authors.lastname: Sourij
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology; D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D019983:Guideline Adherence; D006291:Health Policy; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D017410:Practice Guidelines as Topic; D012107:Research Design; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D007004:Hypoglycemic Agents
references.citation: J Am Coll Cardiol. 2003 Nov 19;42(10):1757-63
references.pmid: 14642684
references.citation: N Engl J Med. 2007 Aug 30;357(9):844-6
references.pmid: 17687124
references.citation: Lancet. 2005 Oct 8;366(9493):1279-89
references.pmid: 16214598
references.citation: JAMA. 2005 Nov 23;294(20):2581-6
references.pmid: 16239637
references.citation: N Engl J Med. 2007 Jun 14;356(24):2457-71
references.pmid: 17517853
references.citation: Am Heart J. 2008 Oct;156(4):633-40
references.pmid: 18926145
references.citation: Lancet. 2004 Sep 11-17;364(9438):911-2
references.pmid: 15364170
references.citation: N Engl J Med. 2010 Aug 26;363(9):803-6
references.pmid: 20660395
references.citation: Diabetes. 2005 Aug;54(8):2460-70
references.pmid: 16046315
references.citation: JAMA. 2007 Sep 12;298(10):1180-8
references.pmid: 17848652
references.citation: N Engl J Med. 2011 Mar 3;364(9):789-91
references.pmid: 21366470
references.citation: Diabetes Care. 2006 May;29(5):1039-45
references.pmid: 16644634
references.citation: N Engl J Med. 2011 Mar 03;364(9):829-841
references.pmid: 21366474
references.citation: Fed Regist. 2010 Sep 29;75(188):59935-63
references.pmid: 20879180
references.citation: Diabetologia. 1996 Jun;39(6):701-9
references.pmid: 8781766
references.citation: N Engl J Med. 2011 Jul 7;365(1):3-5
references.pmid: 21651388
references.citation: N Engl J Med. 2011 Mar 3;364(9):852-60
references.pmid: 21366476
references.citation: Diabetes. 2002 Mar;51(3):797-802
references.pmid: 11872682
references.citation: Arterioscler Thromb Vasc Biol. 2003 Dec;23(12):2203-8
references.pmid: 12958047
references.citation: Diabetes Care. 2004 Feb;27(2):484-90
references.pmid: 14747233
references.citation: Diabetes Care. 2001 Apr;24(4):710-9
references.pmid: 11315836
references.citation: Am J Gastroenterol. 2003 Jan;98(1):175-9
references.pmid: 12526954
references.citation: Lancet. 2009 Jun 20;373(9681):2125-35
references.pmid: 19501900
references.citation: JAMA. 2008 Sep 3;300(9):1069-71
references.pmid: 18768418
references.citation: J Manag Care Pharm. 2008 Jul-Aug;14(6):523-31
references.pmid: 18693776
references.citation: Biostatistics. 2010 Jul;11(3):383-4
references.pmid: 20538872