CFTR biomarkers: time for promotion to surrogate end-point?

被引：87

作者：

De Boeck, K. ^{[1
]}

Kent, L. ^{[2
,3
]}

Davies, J. ^{[4
]}

Derichs, N. ^{[5
,6
]}

Amaral, M. ^{[7
,8
]}

Rowe, S. M. ^{[9
]}

Middleton, P. ^{[10
]}

de Jonge, H. ^{[11
,12
]}

Bronsveld, I. ^{[13
]}

Wilschanski, M. ^{[14
]}

Melotti, P. ^{[15
]}

Danner-Boucher, I. ^{[16
,17
]}

Boerner, S. ^{[18
]}

Fajac, I. ^{[19
]}

Southern, K. ^{[20
]}

de Nooijer, R. A. ^{[13
]}

Bot, A. ^{[21
]}

de Rijke, Y. ^{[22
]}

de Wachter, E. ^{[23
,24
]}

Leal, T. ^{[25
]}

Vermeulen, F. ^{[1
]}

Hug, M. J. ^{[26
]}

Rault, G. ^{[27
]}

Nguyen-Khoa, T. ^{[28
,29
]}

Barreto, C. ^{[30
]}

Proesmans, M. ^{[1
]}

Sermet-Gaudelus, I. ^{[31
]}

机构：

[1] Univ Hosp Leuven, Louvain, Belgium

[2] Univ Ulster, Belfast, Antrim, North Ireland

[3] Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland

[4] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Gene Therapy, London, England

[5] Charite, CFTR Biomarker Ctr, Berlin, Germany

[6] Charite, Cyst Fibrosis Ctr, Dept Paediat Pulmonol & Immunol, Berlin, Germany

[7] Univ Lisbon, Ctr Human Genet, Natl Inst Hlth Dr Ricardo Jorge, P-1699 Lisbon, Portugal

[8] Univ Lisbon, Dept Chem & Biochem, Fac Sci, P-1699 Lisbon, Portugal

[9] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[10] Westmead Millennium Inst, Ludwig Engel Ctr Resp Res, Westmead, NSW, Australia

[11] Erasmus Univ, Med Ctr, Dept Paediat Gastroenterol, Rotterdam, Netherlands

[12] Erasmus Univ, Med Ctr, Dept Biochem, Rotterdam, Netherlands

[13] Univ Med Ctr, Utrecht, Netherlands

[14] Hebrew Univ Jerusalem, Sch Med, Hadassah Univ Hosp, Pediat Gastroenterol Unit, IL-91010 Jerusalem, Israel

[15] Azienda Osped Univ Integrata Verona, Ctr Fibrosi Cist, Verona, Italy

[16] Hop G&R Laennec, Lab Explorat Fonct, Nantes, France

[17] Hop G&R Laennec, Serv Pneumol, Nantes, France

[18] Univ Cologne, CF Ctr Cologne, D-50931 Cologne, Germany

[19] Univ Paris 05, Hop Cochin, Serv Explorat Fonct, Paris, France

[20] Univ Liverpool, Dept Womens & Childrens Hlth, Liverpool L69 3BX, Merseyside, England

[21] Erasmus MC, Sophia Childrens Hosp, Dept Biochem, Rotterdam, Netherlands

[22] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[23] Univ Ziekenhuis Brussel, Dept Pediat Pulmonol, Brussels, Belgium

[24] Univ Ziekenhuis Brussel, CF Clin, Brussels, Belgium

[25] Catholic Univ Louvain, B-1200 Brussels, Belgium

[26] Univ Med Ctr, Freiburg, Germany

[27] Ctr Perharidy, Ctr Reference & Competence Mucoviscidose, Roscoff, France

[28] Hop Necker Enfants Malad, AP PH, CRCM, Dept Biochem A, Paris, France

[29] Hop Necker Enfants Malad, AP PH, CRCM, Dept Paediat Pulmonol, Paris, France

[30] Hosp Santa Maria, Dept Paediat, Lisbon, Portugal

[31] Univ Paris 05, Hop Necker Enfants Malad, INSERM, U845, Paris, France

来源：

EUROPEAN RESPIRATORY JOURNAL | 2013年 / 41卷 / 01期

关键词：

Clinical trials; cystic fibrosis transmembrane conductance regulator; intestinal current measurement; nasal potential difference; surrogate end-point; sweat test; NASAL POTENTIAL-DIFFERENCE; CYSTIC-FIBROSIS PATIENTS; TRANSMEMBRANE CONDUCTANCE REGULATOR; INCREASED NA+ CONDUCTANCE; HUMAN AIRWAY EPITHELIUM; BORDERLINE SWEAT TEST; CL-CHANNEL FUNCTION; GENE-TRANSFER; STOP MUTATIONS; IN-VIVO;

D O I：

10.1183/09031936.00057512

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.

引用

页码：203 / 216

页数：14

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