Stephen C Mathai1, Milo A Puhan, Diana Lam, Robert A Wise. 1. Johns Hopkins University School of Medicine, Division of Pulmonary and Critical Care Medicine, 1830 E. Monument Street, Room 516, Baltimore, MD 21205, USA. smathai4@jhmi.edu
Abstract
RATIONALE: Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension (PAH), the minimal important difference (MID) of the 6-minute walk test (6MWT) has not been well defined for this population of patients. OBJECTIVES: To estimate the MID in the 6MWT in patients with PAH. METHODS: Study subjects from the clinical trial of tadalafil in PAH, a 16-week, parallel-group, randomized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist, were eligible. 6MWT was performed using a standardized protocol. Distributional and anchor-based methods were used to estimate the MID; the latter method used the Physical Component Summary Score (PCS) of the Medical Outcomes Study 36-item short form (SF-36). MEASUREMENTS AND MAIN RESULTS:Four hundred five subjects were analyzed. Domains of the SF-36 were weakly to modestly associated with 6MWT. Change in the PCS of the SF-36 was most strongly associated with change in 6MWT (r = 0.40, P < 0.001) and thus was selected as the anchor for subsequent anchor-based analyses. Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m, whereas anchor-based analyses yielded an estimate of 38.6 m. CONCLUSIONS: Using both distributional and anchor-based methods, the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implications for (1) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy, and (2) sample size calculations for future study design.
RCT Entities:
RATIONALE: Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension (PAH), the minimal important difference (MID) of the 6-minute walk test (6MWT) has not been well defined for this population of patients. OBJECTIVES: To estimate the MID in the 6MWT in patients with PAH. METHODS: Study subjects from the clinical trial of tadalafil in PAH, a 16-week, parallel-group, randomized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist, were eligible. 6MWT was performed using a standardized protocol. Distributional and anchor-based methods were used to estimate the MID; the latter method used the Physical Component Summary Score (PCS) of the Medical Outcomes Study 36-item short form (SF-36). MEASUREMENTS AND MAIN RESULTS: Four hundred five subjects were analyzed. Domains of the SF-36 were weakly to modestly associated with 6MWT. Change in the PCS of the SF-36 was most strongly associated with change in 6MWT (r = 0.40, P < 0.001) and thus was selected as the anchor for subsequent anchor-based analyses. Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m, whereas anchor-based analyses yielded an estimate of 38.6 m. CONCLUSIONS: Using both distributional and anchor-based methods, the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implications for (1) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy, and (2) sample size calculations for future study design.
Authors: Roland M du Bois; Derek Weycker; Carlo Albera; Williamson Z Bradford; Ulrich Costabel; Alex Kartashov; Lisa Lancaster; Paul W Noble; Steven A Sahn; Javier Szwarcberg; Michiel Thomeer; Dominique Valeyre; Talmadge E King Journal: Am J Respir Crit Care Med Date: 2010-12-03 Impact factor: 21.405
Authors: Vallerie V McLaughlin; David B Badesch; Marion Delcroix; Thomas R Fleming; Sean P Gaine; Nazzareno Galiè; J Simon R Gibbs; Nick H Kim; Ronald J Oudiz; Andrew Peacock; Steeve Provencher; Olivier Sitbon; Victor F Tapson; Werner Seeger Journal: J Am Coll Cardiol Date: 2009-06-30 Impact factor: 24.094
Authors: Dan Turner; Holger J Schünemann; Lauren E Griffith; Dorcas E Beaton; Anne M Griffiths; Jeffrey N Critch; Gordon H Guyatt Journal: J Clin Epidemiol Date: 2009-10-01 Impact factor: 6.437
Authors: Serge A van Wolferen; Marielle C van de Veerdonk; Gert-Jan Mauritz; Wouter Jacobs; J Tim Marcus; Koen M J Marques; Jean G F Bronzwaer; Martijn W Heymans; Anco Boonstra; Pieter E Postmus; Nico Westerhof; Anton Vonk Noordegraaf Journal: Chest Date: 2010-09-23 Impact factor: 9.410
Authors: Robyn J Barst; Ronald J Oudiz; Anthony Beardsworth; Bruce H Brundage; Gerald Simonneau; Hossein A Ghofrani; David P Sundin; Nazzareno Galiè Journal: J Heart Lung Transplant Date: 2011-01-21 Impact factor: 10.247
Authors: Anne E Holland; Catherine J Hill; Tshepo Rasekaba; Annemarie Lee; Matthew T Naughton; Christine F McDonald Journal: Arch Phys Med Rehabil Date: 2010-02 Impact factor: 3.966
Authors: M A Puhan; D Chandra; Z Mosenifar; A Ries; B Make; N N Hansel; R A Wise; F Sciurba Journal: Eur Respir J Date: 2010-08-06 Impact factor: 16.671
Authors: Gaëtane C Michaud; Colleen L Channick; Chad R Marion; Robert M Tighe; James A Town; Andrew M Luks; Jeremy B Richards; Sucharita Kher; Prerna Mota; Gina Hong; Natalie E West; Craig Rackley; Luke Neilans; Josanna Rodriguez-Lopez; Hilary DuBrock; Cassie C Kennedy; Diana J Kelm; Carey C Thomson Journal: Ann Am Thorac Soc Date: 2015-09
Authors: Manuel J Richter; Ralph Schermuly; Werner Seeger; Youlan Rao; Hossein A Ghofrani; Henning Gall Journal: Pulm Circ Date: 2016-12 Impact factor: 3.017
Authors: Raymond L Benza; Mardi Gomberg-Maitland; Teresa Demarco; Adaani E Frost; Adam Torbicki; David Langleben; Tomas Pulido; Priscilla Correa-Jaque; Michael J Passineau; Howard W Wiener; Mayumi Tamari; Tomomitsu Hirota; Michiaki Kubo; Hemant K Tiwari Journal: Am J Respir Crit Care Med Date: 2015-12-01 Impact factor: 21.405