Measurement properties of an asthma symptom and rescue medication use diary

Abstract

Introduction: Assessment of symptoms and rescue medication use are well-established endpoints for clinical trials evaluating asthma treatment. Objective: To evaluate the measurement properties of an asthma symptom and rescue medication use (ASRMU) diary for clinical trials involving asthma patients aged ≥12 years. Methods: Interviews with 35 patients were conducted to confirm the importance of key concepts in the ASRMU diary. Scores of symptom and rescue medication use were converted to symptom-free days (SFD) and rescue-free days (RFD). Test–retest reliability and equivalence (based on intra-class correlation coefficients [ICCs]) between paper-and-pencil and electronic (eDiary) versions were evaluated in a prospective study in 47 patients. Responsiveness of the ASRMU diary was evaluated through differences in percentage of SFD and of RFD by treatment group in eight asthma clinical trials that assessed inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA), alone or in combination. A ninth placebo-controlled study calculated effect sizes. Minimal important differences (MID) were determined using anchor-based methods from two trials and by interviewing 11 patients. Results: Patient interviews supported content validity for the ASRMU diary. Test–retest reliability was acceptable for SFD (ICC:0.70–0.75), but varied for RFD (ICC:0.58–0.78). Paper-and-pencil and eDiary modes of administration were equivalent (SFD, ICC = 0.84; RFD, ICC = 0.70). ICS/LABA had the largest percentage of SFD and RFD, followed by monotherapy and then placebo. MIDs were 7.7–14.7% for SFD and 8.4–15.6% for RFD. Conclusions: The ASRMU diary captures the disease-specific concepts of greatest importance to asthma patients and provides important information for asthma diagnosis and treatment evaluation.

• Development
• fluticasone furoate/vilanterol
• fluticasone propionate/salmeterol
• patient-reported outcomes
• psychometrics

Acknowledgements

The authors wish to acknowledge Rob Arbuckle and Laura Maguire from Adelphi Values for their contributions to the conduct of the qualitative research with adult and adolescent asthma patients described in this article; Dr Eugene R. Bleecker for his review and input on the first two drafts of this manuscript and Lori McLeod from RTI Health Solutions for her psychometric input on the analysis of minimum important differences and review of this aspect in the final manuscript.

Declaration of interest

Funding for this study was provided by GlaxoSmithKline (GHO-11-5062). At the time of this study, M.C. and S.M. were employed by RTI Health Solutions, which provides research and consulting services to help biopharmaceutical companies successfully develop and gain market approval for their products. As salaried employees, M.C. and S.M. work with various companies but do not receive direct payment or honoraria from them for services rendered. Current GlaxoSmithKline co-authors H.S. and L.J., as well as former GlaxoSmithKline colleague and co-author, P.D., were involved in writing the manuscript and in the decision to submit the manuscript for publication. H.S. and L.J. are employees of and hold stock in GlaxoSmithKline.

Supplementary material available online.

Supplementary E-Tables 1–7.