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Predictors of placebo response in a randomized, controlled trial of phytotherapy in menopause

van Die, Margaret Diana BA, Dip Herb Med1; Teede, Helena J. MBBS, PhD, FRACP2,3; Bone, Kerry M. BSc, Dip Phyt, FNIMH, FNHAA4,5; Reece, John E. PhD1; Burger, Henry G. MD, FRACP6

Menopause:
doi: 10.1097/GME.0b013e318199d5e6
Articles
Abstract

Objective: The aim of this study was to evaluate predictors of the placebo response in a randomized, placebo-controlled, double-blind trial of a phytotherapeutic combination for the treatment of menopausal symptoms.

Methods: A post hoc analysis was conducted on data from 46 placebo participants completing the study. Variables at baseline were investigated for prediction of improvement on any of the endpoints of flushing, depression measured on the Hamilton Depression Inventory, and menopausal symptoms measured on the Greene Climacteric Scale. Hierarchical linear regression analyses were carried out on the individual endpoints, controlling for baseline scores. Multivariate linear regression analysis was also conducted on these three endpoints in combination.

Results: Higher anxiety at study entry predicted placebo response on all three outcome measures individually (flushing: R2 = 0.33, P = 0.03; depression: R2 = 0.34, P < 0.001; and Greene Climacteric score: R2 = 0.24, P = 0.04); and in combination (P = 0.002), as did total Greene Climacteric scores at study entry (R2 = 0.24, P = 0.005). Improvement during nontreatment run-in predicted placebo response for depression (P = 0.005), menopausal symptoms (R2 = 0.28, P = 0.013), and the three combined endpoints (P = 0.015). Severity of scores at baseline predicted subsequent improvement on the Greene Climacteric scores only (r = 0.038, P = 0.009).

Conclusions: These findings may facilitate identification of potential placebo responders in future randomized controlled trials on menopausal symptoms and have relevance to study design in this context. Further research is required.

In Brief

Predictors of the placebo response were investigated in a randomized controlled trial of a phytotherapeutic combination for menopausal symptoms. Higher anxiety at study entry was predictive of the response on the endpoints of flushing, depression, and overall menopausal symptoms.

Author Information

From the 1Royal Melbourne Institute of Technology University, Bundoora, Victoria, Australia; 2Jean Hailes Foundation, Clayton, Victoria, Australia; 3Monash Institute of Health Services Research, Clayton, Victoria, Australia; 4MediHerb, Warwick, Queensland, Australia; 5University of New England, Armidale, New South Wales, Australia; and 6Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.

Received October 29, 2008; revised and accepted December 22, 2008.

Funding/support: MediHerb Australia Pty Ltd provided active and placebo formulations. Financial support was provided by Australian College of Phytotherapy and the Jean Hailes Foundation for Women's Health.

Financial disclosure/conflicts of interest: Assoc. Prof. Kerry Bone is a founder and director of research and development of MediHerb Australia Pty Ltd and is related to Diana van Die (in-law). Diana van Die, as principal investigator, had full access to all of the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analyses.

Address correspondence to: Margaret Diana van Die, School of Health Sciences, Royal Melbourne Institute of Technology University, PO Box 71, Bundoora, Victoria 3083, Australia. E-mail: diana.vandie@rmit.edu.au

©2009The North American Menopause Society