Defining appropriate outcome measures in pulmonary arterial hypertension related to systemic sclerosis: a Delphi consensus study with cluster analysis.

OBJECTIVE Outcome measures for pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) are only partially validated. The aim of the present study was to establish an expert consensus regarding which outcome measures are most appropriate for clinical trials in PAH-SSc. METHODS Sixty-nine PAH-SSc experts (rheumatologists, cardiologists, pulmonologists) rated a list of disease domains and measurement tools in an Internet-based 3-stage Delphi consensus study. In stages 2 and 3, the medians of domains and measurement tools and frequency distributions of ratings, along with requests for re-ratings, were distributed to respondents to provide feedback. A final score of items was identified by means of cluster analysis. RESULTS The experts judged the following domains and tools as most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure and cardiac function both measured by right heart catheterization and echocardiography, exercise testing measured by 6-minute walking test and oxygen saturation at exercise, severity of dyspnea measured on a visual analog scale, discontinuation of treatment measured by (serious) adverse events, quality of life/activities of daily living measured by the Short Form 36 and Health Assessment Questionnaire disability index, and global state assessed by physician measured by survival. CONCLUSION Among experts in PAH-SSc, a core set of outcome measures has been defined for clinical trials by Delphi consensus methods. Although these outcome measures are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present measures, as well as potential research measures, in further studies.

[1]  M Abu-Shakra,et al.  Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. , 1996, British journal of rheumatology.

[2]  Horst Olschewski,et al.  Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. , 2004, European heart journal.

[3]  J. Crisp,et al.  The Delphi method? , 1997, Nursing research.

[4]  R. Barst,et al.  Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease , 2007, Annals of the rheumatic diseases.

[5]  R. Naeije,et al.  End points in pulmonary arterial hypertension: the way forward , 2004, European Respiratory Journal.

[6]  M. Humbert,et al.  Need for improved outcome measures in pulmonary arterial hypertension related to systemic sclerosis. , 2006, Rheumatology.

[7]  T. Fleming,et al.  Sildenafil citrate therapy for pulmonary arterial hypertension. , 2005, The New England journal of medicine.

[8]  Shirley A. Olsen,et al.  Group planning and problem-solving methods in engineering management , 1982 .

[9]  Robert C. Kohberger,et al.  Cluster Analysis (3rd ed.) , 1994 .

[10]  M. Humbert,et al.  Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. , 2005, Arthritis and rheumatism.

[11]  Richard N. Shiffman,et al.  Metadata-driven Delphi rating on the Internet , 2005, Comput. Methods Programs Biomed..

[12]  Roberta M. Roth,et al.  A Delphi approach to acquiring knowledge from single and multiple experts , 1990, SIGBDP '90.

[13]  D. Mccrory,et al.  Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. , 2004, Chest.

[14]  Orris,et al.  INHALED ILOPROST FOR SEVERE PULMONARY HYPERTENSION , 2002 .

[15]  Stuart Rich,et al.  Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of Disease , 2000, Annals of Internal Medicine.

[16]  G. W. Milligan,et al.  An examination of the effect of six types of error perturbation on fifteen clustering algorithms , 1980 .

[17]  W. Seeger,et al.  Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension. , 2004, Journal of the American College of Cardiology.

[18]  M. Humbert,et al.  Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. , 2002, Journal of the American College of Cardiology.

[19]  M. Wood,et al.  Analysis and interpretation of data. , 1978, The Journal of family practice.

[20]  S. Kimmel,et al.  Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. , 2003, Chest.

[21]  Avid,et al.  BOSENTAN THERAPY FOR PULMONARY ARTERIAL HYPERTENSION , 2002 .

[22]  P. Tugwell,et al.  The OMERACT filter for Outcome Measures in Rheumatology. , 1998, The Journal of rheumatology.

[23]  N. Bellamy.  Clinimetric concepts in outcome assessment: the OMERACT filter. , 1999, The Journal of rheumatology.

[24]  W. Taylor.  Preliminary identification of core domains for outcome studies in psoriatic arthritis using Delphi methods , 2005, Annals of the rheumatic diseases.

[25]  H. C. van Paassen,et al.  Treatment of pulmonary arterial hypertension. , 2005, The New England journal of medicine.

[26]  Roberta M. Roth,et al.  A workshop approach to acquiring knowledge from single and multiple experts , 1990, SIGBDP '90.

[27]  D. Hunter,et al.  Qualitative Research: Consensus methods for medical and health services research , 1995 .

[28]  S. Rich,et al.  Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. , 2002, American journal of respiratory and critical care medicine.

[29]  R. Barst,et al.  Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. , 2007, Annals of the rheumatic diseases.

[30]  M. Suarez‐Almazor,et al.  Current status of outcome measure development for clinical trials in systemic sclerosis. Report from OMERACT 6. , 2003, The Journal of rheumatology.

[31]  H. A. Lingstone,et al.  The Delphi Method: Techniques and Applications , 1976 .

[32]  D. Badesch,et al.  Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebocontrolled study , 2001, The Lancet.

[33]  D. Badesch,et al.  Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary hypertension: a placebo-controlled study. , 2001, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[34]  K. Wasserman,et al.  Erratum: Beraprost therapy for pulmonary arterial hypertension (Journal of the American College of Cardiology (2003) 41 (2119-2125)) , 2003 .

[35]  A. Torbicki,et al.  Guidelines on diagnosis and treatment of pulmonary arterial hypertension , 2004 .

[36]  A. Torbicki,et al.  End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives. , 2004, Journal of the American College of Cardiology.

[37]  R. Dixon,et al.  Sitaxsentan therapy for pulmonary arterial hypertension. , 2004, American journal of respiratory and critical care medicine.

[38]  M. Mayes,et al.  Development of a provisional core set of response measures for clinical trials of systemic sclerosis , 2007, Annals of the rheumatic diseases.

[39]  K. Wasserman,et al.  Beraprost therapy for pulmonary arterial hypertension. , 2003, Journal of the American College of Cardiology.

[40]  M. Dougados,et al.  ASAS/EULAR recommendations for the management of ankylosing spondylitis , 2005, Annals of the rheumatic diseases.