Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Apr 3;3(1):22.
doi: 10.1186/s41687-019-0109-2.

Evaluating minimal important differences and responder definitions for the asthma symptom diary in patients with moderate to severe asthma

Gary Globe  1 , Ingela Wiklund  2 , Maria Mattera  3 , Hao Zhang  1 , Dennis A Revicki  4
Affiliations

Evaluating minimal important differences and responder definitions for the asthma symptom diary in patients with moderate to severe asthma

Gary Globe et al. J Patient Rep Outcomes. .

Abstract

Background: The Asthma Symptom Diary was developed to assess severity of symptoms in patients with moderate to severe asthma, and has evidence supporting reliability and validity. Only limited information is available on sensitivity to change and responder definitions for the Asthma Symptom Diary.

Objectives: Main study objectives were to evaluate sensitivity to change and provide responder definitions for clinically meaningful effects for the Asthma Symptom Diary.

Methods: This is a secondary analysis of Phase II clinical trial data in patients with moderate to severe asthma, Asthma Symptom Diary (ASD) was collected daily during the 24-week study. The Asthma Control Questionnaire and the Patient Global Assessment were collected at baseline, and week 12 and 24. Analysis of covariance (ANCOVA) models were used to evaluate sensitivity to change in Asthma Symptom Diary scores after 12 and 24 weeks of treatment. Anchor-based methods, using Asthma Control Questionnaire and Patient Global Assessment defined anchors, were used to identify minimal important differences and various responder criteria for changes in mean 7-day ASD score, symptomatic days, and minimal symptom days.

Results: Sample was 59% female, 81% White, with a mean age of 47.3 (SD = 13.6) years. ANCOVAs demonstrated significant differences in baseline to week 12 and week 24 changes in mean 7-day Asthma Symptom Diary scores and symptomatic days by Asthma Control Questionnaire (all p < 0.001) and Patient Global Assessment anchors (all p < 0.001). Meaningful responders, from the patient's perspective, were defined as improvements of 0.5-0.6 points (SD = 0.6; scale range 0 to 4) in mean 7-day Asthma Symptom Diary scores, and as a reduction of 2 to 3 Asthma Symptom Diary-based symptomatic days.

Conclusion: The Asthma Symptom Diary was responsive to changes in clinical status in patients with moderate to severe asthma. Responder definitions were identified, including symptomatic days, for evaluating individual level treatment effects in clinical trials.

Keywords: Asthma; Asthma symptom diary; Interpretation guidelines; Minimal important difference; Responder definitions; Responsiveness to change.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The clinical trial protocol was approved by an Institutional Review Board (Chesapeake Research Review; Pro00007797), and each patient provided written informed consent before participating in the study.

Consent for publication

Not applicable.

Competing interests

DAR and IW are employees of Evidera. Evidera received funding from Amgen Inc. for the conduct of this study and for the preparation of the manuscript.

DAR has research grants with and receives consulting fees from Amgen Inc., Allergan, GlaxoSmithKline, Abbvie, and Takeda.

GG and HZ are employees and shareholders of Amgen Inc.

MM is currently an employee of the PRO Consortium (formerly was employed by Evidera).

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Cumulative Distribution Curves for 7-Day Average ASD Scores by ACQ Based Responder Criteria. a Baseline to Week 12 by ACQ-5 Response. b Baseline to Week 24 by ACQ-5 Response. PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline and at 12 weeks or 24 weeks
Fig. 2
Fig. 2
Cumulative Distribution Curves for 7-Day Average ASD Scores by PGA Based Responder Criteria. a Baseline to Week 12 by PGA Response. b Baseline to Week 24 by PGA Response. PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline and at 12 weeks or 24 weeks
Fig. 3
Fig. 3
Cumulative Distribution Curves for ASD Symptomatic Days by ACQ Based Responder Criteria and PGA Based Responder Criteria. a Baseline to Week 12 by ACQ-5 Response. b Baseline to Week 24 by ACQ-5 Response. c Baseline to Week 12 by PGA Response. d Baseline to Week 24 by PGA Response. PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline and at 12 weeks or 24 weeks
Fig. 4
Fig. 4
a Cumulative Distribution Curves for ASD Minimal Symptom Days-1 by ACQ Based Responder Criteria PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline b Cumulative Distribution Curves for ASD Minimal Symptom Days-1 by PGA Based Responder Criteria. PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline and at 12 weeks or 24 weeks
Fig. 5
Fig. 5
a Cumulative Distribution Curves for ASD Minimal Symptom Days-2 by ACQ Based Responder Criteria PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline and at 12 weeks or 24 weeks. b Cumulative Distribution Curves for ASD Minimal Symptom Days-2 by PGA Based Responder Criteria. PRO analysis set includes all subjects who are enrolled and have Asthma Symptom Diary measurement at baseline and at 12 weeks or 24 weeks
See this image and copyright information in PMC

References

    1. Akinbami, L. J., Moorman, J. E., & Liu, X. (2011). Asthma prevalence, health care use, and mortality: United States, 2005-2009. National Health Stat Report, 1–14. - PubMed
    1. Braido F, Brusselle G, Guastalla D, Ingrassia E, Nicolini G, Price D, et al. Determinants and impact of suboptimal asthma control in Europe: The international cross-sectional and longitudinal assessment on asthma control (LIAISON) study. Respir Res. 2016;17:51. doi: 10.1186/s12931-016-0374-z. - DOI - PMC - PubMed
    1. Busse WW, Morgan WJ, Taggart V, Togias A. Asthma outcomes workshop: Overview. J Allergy Clin Immunol. 2012;129:S1–S8. doi: 10.1016/j.jaci.2011.12.985. - DOI - PMC - PubMed
    1. Cappelleri JC, Zou KH, Bushmakin AG, Alvir JMJ, Alemayehu D, Symonds T. Patient-reported outcomes: Measurement, implementation and interpretation. Boca Raton: Chapman & Hall/CRC Biostatistics Series; 2014.
    1. Centers for Disease Control, Asthmas Surveillance Data, March 2016 (2016). www.cdc.gov/asthma/asthma data. Accessed June 29, 2016.

LinkOut - more resources