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An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women

Gerlinger, Christoph PhD; Gude, Kerstin MD, PhD; Hiemeyer, Florian MSc; Schmelter, Thomas PhD; Schäfers, Matthias MD, PhD

doi: 10.1097/gme.0b013e31823de8ba
Original Articles

Objective: The aim of this study was to derive an empirically validated definition of treatment responders for the reduction of moderate to severe hot flushes in postmenopausal women.

Methods: This study used prospective blinded data analysis from a placebo-controlled study to investigate the efficacy of a treatment of moderate to severe hot flushes in postmenopausal women. Seven hundred ten postmenopausal women with at least 50 moderate to severe hot flushes per week participated in the study. The participants recorded the number of moderate to severe hot flushes each day in a diary. They also assessed their satisfaction with treatment on a Clinical Global Impression–improvement rating scale. Changes in the weekly number of moderate to severe hot flushes were compared with participants’ self-assessments to derive an empirically validated minimal clinically important difference. This anchor-based value was compared with the conventional half-SD rule for minimal clinically important difference in participant-reported outcomes.

Results: Anchor- and distribution-based minimal clinically important differences between “no change/worse” and “minimally improved” were an absolute reduction of 19.1 and 18.6 in the weekly number of moderate to severe hot flushes, respectively. In addition, the threshold between “minimally improved” compared with “much improved or better” was determined, based on the anchor method, as an absolute reduction of 40.3 in the weekly number of moderate to severe hot flushes.

Conclusions: A responder was defined as having at least an improvement of 19.1 hot flushes per week at week 4 and an improvement of 40.3 hot flushes per week at week 12.

Changes in the weekly number of moderate to severe hot flushes were compared with participants’ self-assessments of treatment satisfaction. A responder was defined as having at least an improvement of 19.1 hot flushes per week at week 4 and an improvement of 40.3 hot flushes per week at week 12.

From 1Global Clinical Statistics and 2Global Clinical Development Therapeutic Area Primary Care and Women’s Healthcare, Bayer Pharma AG, Berlin, Germany.

Received September 12, 2011; revised and accepted October 19, 2011.

Funding/support: This study was funded by Bayer Pharma AG, Berlin, Germany.

Financial disclosure/conflicts of interest: All authors are full-time employees of Bayer Pharma AG.

Study registry: clinicaltrials.gov (NCT00446199).

Address correspondence to: Christoph Gerlinger, PhD, Global Clinical Statistics, Bayer Pharma AG, 13342 Berlin, Germany. E-mail: Christoph.Gerlinger@bayer.com

© 2012 by The North American Menopause Society.