Interpreting clinical trial results of patient-perceived onset of effect in asthma: methods and results of a Delphi panel

ABSTRACT

Objective: The purpose of this study was to determine if empirically observed differences in patient perception of, and satisfaction with, onset of effect between an active maintenance treatment and placebo are clinically meaningful to practicing clinicians. A secondary objective was to determine the lowest threshold for a clinically meaningful difference in terms of both between-group differences and maximum acceptable placebo effect.

Methods: Twelve community-based healthcare professionals participated in a Delphi consensus panel. Panelists were provided with blinded results of two clinical trials showing statistically significant treatment effects for treatment A (budesonide/formoterol [Symbicort^*]) over placebo in the proportion of patients who could perceive the medication working right away and the proportion of patients satisfied with this perception. Panelists were then asked to respond to a series of questions to identify a threshold for clinically important differences in patient-perceived onset of effect and satisfaction with speed of onset of effect. All expert panelists participated in two rounds of the Delphi process.

* Symbicort Inhalation Aerosol, AstraZeneca LP, Wilmington, DE, USA

Results: Panelists were unanimous in their conclusion that the statistically significant results from the two trials were clinically meaningful. According to these practitioners, the empirical results presented to them, showing that patients could feel a maintenance inhaler therapy work right away, were meaningful to clinical decision-making, and the attribute could potentially improve patient adherence with therapy. A group consensus was reached that a minimum active treatment response for these outcomes should range from 50% to 75% and be 2–3 times larger than the placebo response, with a maximum placebo effect of 26–40%.

Conclusion: A Delphi panel study of practitioners was used to establish a meaningful range of response and a minimal important difference for interpreting results of clinical trials in which patient perception of onset of effect and satisfaction with this perception are tested. While the views of this panel may not be generalized to the entire population of practitioners in the United States, results provide insight into how a typical practitioner is likely to view clinical trial results and how the information might be used in clinical practice.

Key words: :

• Asthma
• Delphi
• Perceived onset of effect
• Satisfaction

Transparency

Declaration of funding

Funding for this study and for publication of this article was provided by AstraZeneca.

Declaration of financial/other relationships

N.K.L. has disclosed that she is employed by United Biosource. D.M. and C.D.O. have disclosed that they are employees and stockholders of AstraZeneca. L.K. has disclosed that she is a consultant to United Biosource Corp. S.W. has disclosed that he was employed by AstraZeneca at the time of the study.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she is on the speakers' bureau of AstraZeneca. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgments

The authors thank the following clinicians for participating in their Delphi panel (all USA): Jeffrey Alken, Wenonah, NJ; Nabil John Azar, Gates Mills, OH; Larry F. Berman, Charlotte, NC; Brian Burlew, Allentown, PA; Kathleen Eloise Ellstrom, Loma Linda, CA; Michelle Harkins, Albuquerque, NM; Kyle Hogarth, Chicago, IL; Alan Kaufman, Bronx, NY; Suzanne C. Lareau, Albuquerque, NM; Noreen Linn, White Plains, NY; Dianne Locke, Chesterfield, VA; Sheldon Spector, Los Angeles, CA. No editorial assistance was provided for the preparation of the manuscript.

Notes

* Symbicort Inhalation Aerosol, AstraZeneca LP, Wilmington, DE, USA

* Symbicort Turbuhaler, AstraZeneca, Lund, Sweden

† Symbicort Inhalation Aerosol, AstraZeneca LP, Wilmington, DE, USA