Lessons learned from variation in response to therapy in clinical trials  Stanley J. Szefler, MD, Richard J. Martin, MD  Journal of Allergy and Clinical Immunology  Volume 125, Issue 2, Pages 285-292 (February 2010) DOI: 10.1016/j.jaci.2009.10.026 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Variability in FEV1 response (A and B) and methacholine PC20 response (C and D) for BDP-MDI (Fig 1, A and C) and FP-MDI (Fig 1, B and D) for the 3 study doses and the 2-mg/d dose of FP administered through a Diskhaler. Only subjects with complete data sets are included. Reprinted with permission from Szefler et al.3 Journal of Allergy and Clinical Immunology 2010 125, 285-292DOI: (10.1016/j.jaci.2009.10.026) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Asthma control as measured by the Asthma Control Questionnaire (ACQ) over the 16-week ICS or placebo (PBO) continuation trial. The groups are categorized on the basis of the FEV1 results of the previous 6-week ICS trial: nonresponders, 5% or less improvement on ICSs; responders, greater than 5% improvement on ICSs. The only significant within-group difference occurred between the placebo and ICS responder groups (P = .007). Reprinted with permission from Martin et al.4 Note that a clinically significant change in the Asthma Control Questionnaire score is considered to be 0.5 units. Journal of Allergy and Clinical Immunology 2010 125, 285-292DOI: (10.1016/j.jaci.2009.10.026) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 A, Variability of response and differential response to FP and montelukast, as measured by change in FEV1. Four regions show categories of response, defining a favorable response as 7.5% or greater. Mt, Montelukast. The line of identity is designated, with patients favoring montelukast falling above the line, and those favoring fluticasone falling below the line. The concordance correlation with 95% CIs is displayed. B, Difference in FEV1 response between FP and montelukast for individual participants. Each line designates a single participant. Reprinted with permission from Szefler et al.5 Journal of Allergy and Clinical Immunology 2010 125, 285-292DOI: (10.1016/j.jaci.2009.10.026) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Application of clinical trial information to clinical care. Based on the studies presented, the clinician should anticipate that variability to response will occur with each treatment, this variability in response can be associated with patients' characteristics, biomarkers, and genetics, and response to treatment should be monitored for the various outcomes measures, especially symptom control and pulmonary function, to ensure rapid and sustained achievement of asthma control. Journal of Allergy and Clinical Immunology 2010 125, 285-292DOI: (10.1016/j.jaci.2009.10.026) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions