title: Novel outcome measures for clinical trials in cystic fibrosis.
abstract: Cystic fibrosis (CF) is a common inherited condition caused by mutations in the gene encoding the CF transmembrane regulator protein. With increased understanding of the molecular mechanisms underlying CF and the development of new therapies there comes the need to develop new outcome measures to assess the disease, its progression and response to treatment. As there are limitations to the current endpoints accepted for regulatory purposes, a workshop to discuss novel endpoints for clinical trials in CF was held in Anaheim, California in November 2011. The pros and cons of novel outcome measures with potential utility for evaluation of novel treatments in CF were critically evaluated. The highlights of the 2011 workshop and subsequent advances in technologies and techniques that could be used to inform the development of clinical trial endpoints are summarized in this review. Pediatr Pulmonol. © 2014 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc.
authors: Department of Pediatric Pulmonology and Allergology, Department of Radiology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Harm A W M
authors: HAWM
authors: Tiddens
authors: Department for Diagnostic and Interventional Radiology, Hufeland Klinikum, Bad Langensalza, Germany.
authors: Michael
authors: M
authors: Puderbach
authors: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors: Jose G
authors: JG
authors: Venegas
authors: Department of Pediatrics, Division of Respiratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Ontario.
authors: Felix
authors: F
authors: Ratjen
authors: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors: Scott H
authors: SH
authors: Donaldson
authors: Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Stephanie D
authors: SD
authors: Davis
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Steven M
authors: SM
authors: Rowe
authors: Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Denver, Colorado.
authors: Scott D
authors: SD
authors: Sagel
authors: Vertex Pharmaceuticals Europe, Abingdon, UK.
authors: Mark
authors: M
authors: Higgins
authors: Vertex Pharmaceuticals, Boston, Massachusetts.
authors: David A
authors: DA
authors: Waltz
keywords: CFTR activity; cystic fibrosis; endpoints; imaging; outcome measures; sputum biomarkers
references: Pediatr Pulmonol. 2012 May;47(5):441-6
references: 22009796
references: PLoS One. 2011;6(8):e23932
references: 21886842
references: J Cyst Fibros. 2014 Jan;13(1):24-8
references: 24022019
references: Eur Respir J. 2011 Dec;38(6):1328-35
references: 21737560
references: Magn Reson Imaging Clin N Am. 2008 May;16(2):275-89, ix
references: 18474332
references: Respir Med. 2009 Jun;103(6):793-9
references: 19246184
references: Proc Am Thorac Soc. 2007 Aug 1;4(4):399-405
references: 17652507
references: Chest. 2009 Dec;136(6):1561-8
references: 19567495
references: Thorax. 2014 Aug;69(8):782-4
references: 24764114
references: J Nucl Med. 2007 Mar;48(3):413-9
references: 17332619
references: Eur J Radiol. 2012 Jun;81(6):1321-9
references: 21429685
references: J Pediatr. 1998 Apr;132(4):589-95
references: 9580754
references: Magn Reson Med. 2009 Sep;62(3):656-64
references: 19585597
references: BMC Pulm Med. 2011 Sep 06;11:45
references: 21896198
references: Am J Respir Crit Care Med. 2014 Apr 15;189(8):956-65
references: 24564281
references: J Int Med Res. 1998 Dec;26(6):304-12
references: 10399112
references: AJR Am J Roentgenol. 2013 Jun;200(6):1294-7
references: 23701067
references: Minerva Anestesiol. 2006 Jun;72 (6):363-7
references: 16682902
references: N Engl J Med. 2007 Nov 29;357(22):2277-84
references: 18046031
references: Lancet Respir Med. 2013 Oct;1(8):630-8
references: 24461666
references: Magn Reson Imaging Clin N Am. 2008 Aug;16(3):385-402, v
references: 18585595
references: Methods Mol Biol. 2011;741:69-86
references: 21594779
references: Pediatr Radiol. 2010 Jun;40(6):844-9
references: 20432002
references: Anesthesiology. 2014 Mar;120(3):683-93
references: 24051392
references: Am J Respir Crit Care Med. 2008 Dec 15;178(12):1238-44
references: 18787217
references: Respir Res. 2010 Jul 09;11:94
references: 20618958
references: J Cyst Fibros. 2014 Mar;13(2):123-38
references: 24315208
references: Am J Respir Crit Care Med. 2014 Jun 1;189(11):1328-36
references: 24697683
references: Pediatr Pulmonol. 2009 Dec;44(12):1180-5
references: 19911370
references: Am J Respir Crit Care Med. 1996 Feb;153(2):752-60
references: 8564129
references: Proc Am Thorac Soc. 2007 Aug 1;4(4):387-98
references: 17652506
references: Thorax. 2012 Jun;67(6):509-16
references: 22201161
references: Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L834-40
references: 14660487
references: Chest. 2013 Nov;144(5):1659-70
references: 23868694
references: Paediatr Respir Rev. 2011 Dec;12(4):264-70
references: 22018042
references: Am J Respir Crit Care Med. 2013 Sep 1;188(5):626-7
references: 23992595
references: J Magn Reson Imaging. 2011 Nov;34(5):1206-11
references: 21932361
references: Eur Respir J. 2011 Apr;37(4):806-12
references: 20693248
references: Am J Respir Crit Care Med. 2005 Dec 1;172(11):1463-71
references: 16301301
references: Chest. 2012 Nov;142(5):1259-66
references: 22595153
references: Chest. 2009 Nov;136(5):1220-8
references: 19696124
references: N Engl J Med. 2010 Nov 18;363(21):1991-2003
references: 21083385
references: Eur Respir J. 2003 Sep;22(3):497-502
references: 14516141
references: Pediatr Pulmonol. 2012 Jun;47(6):567-73
references: 22170734
references: PLoS One. 2013 Sep 10;8(9):e73905
references: 24040112
references: N Engl J Med. 2006 Jan 19;354(3):241-50
references: 16421365
references: N Engl J Med. 2013 May 23;368(21):1963-70
references: 23692169
references: J Pediatr. 2010 Dec;157(6):1006-1011.e1
references: 20630539
references: Thorax. 2011 Jun;66(6):481-8
references: 21422040
references: Invest Radiol. 2007 Oct;42(10 ):715-25
references: 17984769
references: Am J Respir Crit Care Med. 2000 May;161(5):1760-2
references: 10806185
references: Thorax. 2008 Feb;63(2):129-34
references: 17675316
references: J Cyst Fibros. 2011 Jun;10 Suppl 2:S53-66
references: 21658643
references: J Aerosol Med Pulm Drug Deliv. 2013 Jun;26(3):157-64
references: 23517172
references: Am J Respir Crit Care Med. 2012 May 15;185(10 ):1096-103
references: 22403801
references: Am J Respir Crit Care Med. 2005 Nov 1;172(9):1128-32
references: 16100015
references: J Magn Reson Imaging. 2007 May;25(5):910-23
references: 17410561
references: Chest. 2010 Oct;138(4):919-28
references: 20472865
references: Am J Respir Crit Care Med. 2005 Feb 1;171(3):249-56
references: 15516530
references: BMC Pulm Med. 2014 Feb 27;14 :28
references: 24576297
references: Eur Respir J. 2013 Aug;42(2):371-9
references: 23314900
references: Radiology. 2012 Sep;264(3):868-75
references: 22829680
references: Respir Med. 2010 Dec;104(12):1834-42
references: 20637585
references: J Pediatr. 2004 Nov;145(5):689-92
references: 15520781
references: Thorax. 2006 Jan;61(1):80-5
references: 16244089
references: PLoS One. 2013 Oct 24;8(10):e77114
references: 24204751
references: Eur Radiol. 2006 Oct;16(10):2147-52
references: 16673092
references: Pediatr Pulmonol. 2013 Nov;48(11):1081-8
references: 23401260
references: AJR Am J Roentgenol. 2013 Aug;201(2):W235-44
references: 23883238
references: PLoS One. 2014 Feb 20;9(2):e89341
references: 24586701
references: AJR Am J Roentgenol. 2008 Feb;190(2):335-43
references: 18212218
references: Expert Rev Mol Diagn. 2011 Mar;11(2):197-206
references: 21405970
references: Chest. 2013 Aug;144(2):498-506
references: 23538783
references: Am J Respir Crit Care Med. 2012 Nov 1;186(9):857-65
references: 22904182
references: Clin Biochem. 2004 Nov;37(11):1031-6
references: 15498533
references: Thorax. 2009 Oct;64(10 ):876-82
references: 19541686
references: Am J Respir Crit Care Med. 2014 Jul 15;190(2):175-84
references: 24927234
references: Int J Immunopathol Pharmacol. 2011 Apr-Jun;24(2):423-32
references: 21658316
references: Proc Am Thorac Soc. 2007 Aug 1;4(4):406-17
references: 17652508
references: Am J Respir Cell Mol Biol. 2007 Jul;37(1):57-66
references: 17347447
references: Nat Rev Drug Discov. 2012 Apr 30;11(5):349-50
references: 22543461
references: Chest. 2013 Jan;143(1):14-8
references: 23276841
references: J Magn Reson Imaging. 2010 Dec;32(6):1409-20
references: 21105145
references: Am J Respir Crit Care Med. 2003 Dec 15;168(12):1471-5
references: 12969869
references: Chest. 2012 Sep;142(3):718-24
references: 22383668
references: Ann Am Thorac Soc. 2013 Apr;10(2):S1-S11
references: 23607855
references: J Cyst Fibros. 2014 Sep;13(5):528-33
references: 24485874
references: J Nucl Med. 2011 Nov;52(11):1713-20
references: 21990575
references: Am J Respir Crit Care Med. 2010 Dec 1;182(11):1387-97
references: 20622043
references: Pediatr Pulmonol. 2000 Jul;30(1):16-24
references: 10862158
references: PLoS One. 2013 Jul 26;8(7):e66955
references: 23922647
references: N Engl J Med. 2011 Nov 3;365(18):1663-72
references: 22047557
references: Am J Respir Crit Care Med. 2006 Oct 1;174(7):787-94
references: 16840743
references: Am J Respir Crit Care Med. 2007 Apr 15;175(8):822-8
references: 17234902
references: N Engl J Med. 2003 Oct 9;349(15):1433-41
references: 14534336
references: Thorax. 2012 Jan;67(1):12-8
references: 21825083
references: J Cyst Fibros. 2009 Jan;8(1):71-8
references: 18957277
references: PLoS One. 2014 Feb 12;9(2):e88567
references: 24533110
references: PLoS One. 2011;6(9):e24399
references: 21949714
references: J Magn Reson Imaging. 2010 Dec;32(6):1370-8
references: 21105141
references: Thorax. 2010 Jul;65(7):594-9
references: 20627915
references: Radiology. 2004 May;231(2):434-9
references: 15064392
references: Eur Respir J. 2011 May;37(5):991-3
references: 21532015
references: JAMA. 2012 Jun 6;307(21):2269-77
references: 22610452
references: Am J Respir Crit Care Med. 2005 May 1;171(9):1015-9
references: 15640364
references: Eur Radiol. 2007 Mar;17 (3):716-24
references: 16941092
references: J Cyst Fibros. 2004 Aug;3 Suppl 2:157-8
references: 15463950
references: N Engl J Med. 2005 May 12;352(19):1992-2001
references: 15888700
references: Int J Biomed Imaging. 2007;2007:23624
references: 17710253
references: J Aerosol Med. 2000 Summer;13(2):73-86
references: 11010597
references: Am J Respir Crit Care Med. 2013 Jun 1;187(11):1219-25
references: 23590265
references: Am J Respir Crit Care Med. 2011 Mar 15;183(6):752-8
references: 20935113
references: Pediatr Pulmonol. 2006 Dec;41(12):1218-25
references: 17068822
references: J Pediatr. 2008 Aug;153(2):S4-S14
references: 18639722
references: Am J Respir Crit Care Med. 2012 Oct 15;186(8):732-9
references: 22859523
references: Thorax. 2012 Oct;67(10):874-81
references: 22752198
references: Eur Respir J. 2003 May;21(5):848-54
references: 12765432
references: Pneumologia. 2011 Jul-Sep;60(3):150-4
references: 22097438
references: Pediatr Pulmonol. 2013 Mar;48(3):229-35
references: 22553157
references: Am J Respir Crit Care Med. 2011 Oct 1;184(7):751-2
references: 21965011
references: Proc Am Thorac Soc. 2007 Aug 1;4(4):328-33
references: 17652495
references: J Cyst Fibros. 2004 Aug;3 Suppl 2:165-9
references: 15463952
references: J Pediatr. 2009 Nov;155(5):623-8.e1
references: 19616787
references: IEEE Trans Med Imaging. 2002 Dec;21(12):1445-9
references: 12588028
references: J Breath Res. 2008 Sep;2(3):037004
references: 21386165
references: Eur Respir J. 2005 Feb;25(2):317-23
references: 15684297
references: Eur Respir J. 2003 Dec;22(6):972-9
references: 14680088
references: Gastroenterology. 2004 Oct;127(4):1085-95
references: 15480987
references: JAMA. 2003 Oct 1;290(13):1749-56
references: 14519709
references: Lancet. 2001 Dec 8;358(9297):1964-5
references: 11747924
references: J Thorac Imaging. 2011 Nov;26(4):301-16
references: 22009083
references: Thorax. 2010 May;65(5):379-83
references: 20435858
references: Lancet. 2008 Aug 30;372(9640):719-27
references: 18722008
references: Thorax. 2014 Jan;69(1):39-45
references: 24021874
references: PLoS One. 2013;8(2):e56868
references: 23457632
references: Proc Am Thorac Soc. 2007 Aug 1;4(4):359-63
references: 17652502
references: Chest. 2011 Jul;140(1):178-85
references: 21148242
references: Gastroenterology. 2004 Jan;126(1):32-41
references: 14699484
references: Magn Reson Med. 2009 Feb;61(2):299-306
references: 19165879
references: Thorax. 2007 Apr;62(4):341-7
references: 17121870
references: PLoS One. 2012;7(8):e42748
references: 22916155
references: Am J Respir Crit Care Med. 2013 Aug 15;188(4):456-60
references: 23742699
references: J Cyst Fibros. 2012 Mar;11(2):100-7
references: 22035905
references: Pediatr Pulmonol. 2014 Dec;49(12):1256-7
references: 24500911