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Methods for the design of vasomotor symptom trials: the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network

Newton, Katherine M. PhD1; Carpenter, Janet S. PhD, RN, FAAN2; Guthrie, Katherine A. PhD3; Anderson, Garnet L. PhD3; Caan, Bette DrPH4; Cohen, Lee S. MD5; Ensrud, Kristine E. MD, MPH6; Freeman, Ellen W. PhD7; Joffe, Hadine MD5; Sternfeld, Barbara PhD4; Reed, Susan D. MD, MPH8; Sherman, Sheryl PhD9; Sammel, Mary D. ScD10; Kroenke, Kurt PhD11; Larson, Joseph C. MS3; LaCroix, Andrea Z. PhD3

Menopause:
doi: 10.1097/GME.0b013e31829337a4
Original Articles
Abstract

Objective: This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials.

Methods: Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ω-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network’s structure and governance are also discussed.

Conclusions: The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.

Author Information

From the 1Group Health Research Institute, Seattle, WA; 2School of Nursing, Indiana University, Indianapolis, IN; 3Data Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, WA; 4Division of Research, Kaiser Permanente of Northern California, Oakland, CA; 5Massachusetts General Hospital/Harvard Medical School, Boston, MA; 6VA Medical Center/University of Minnesota, Minneapolis, MN; 7Departments of Obstetrics/Gynecology and Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA; 8Department of Obstetrics/Gynecology and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA; 9National Institute on Aging, US National Institutes of Health, Bethesda, MD; 10Center for Clinical Epidemiology and Statistics, University of Pennsylvania School of Medicine, Philadelphia, PA; and 11VA Center of Excellence for Implementing Evidence-Based Practice and Indiana University School of Medicine, Indianapolis, IN.

Received December 3, 2012; revised and accepted March 4, 2013.

Clinical Trial Registration: NCT00894543, NCT 01178892, and NCT 01418209 (http://www.clinicaltrials.gov).

Funding/support: This study was funded by the National Institutes of Health as a cooperative agreement issued by the National Institute on Aging, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Center for Complementary and Alternative Medicine, and the Office of Research on Women’s Health (U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700).

Financial disclosure/conflicts of interest: K.M.N. has received research support from Integrated Diagnostics. L.S.C. has received research support from Astra-Zeneca Pharmaceuticals, Bristol-Myers Squibb, Cephalon Inc., GlaxoSmithKline, National Institute on Aging, National Institute of Mental Health, Ortho-McNeil Janssen, and Sunovion Pharmaceuticals Inc., and has served in the advisory board of or as consultant to PamLab LLC and Noven Pharmaceutical. K.E.E. has served in the Data Monitoring Committee of Merck Sharpe and Dohme. E.W.F. has received research support from Forest Laboratories Inc., Xanodyne Pharmaceuticals, Bionovo, and Wyeth. H.J. has received research support from Astra-Zeneca Pharmaceuticals, Bayer HealthCare, Cephalon/Teva, Eli Lilly, Forest Laboratories Inc., GlaxoSmithKline, Sanofi-Events (product support only), Sepracor Inc., and Wyeth-Ayerst Pharmaceuticals; has received speaking honoraria from Eli Lilly and GlaxoSmithKline; and has served in the advisory board of or as consultant to Abbott Laboratories, Eli Lilly, Forest Laboratories Inc., JDS-Noven Pharmaceuticals, Sanofi-Events, Sepracor Inc., Sunovion, and Wyeth-Ayerst Pharmaceuticals. M.D.S. has served as consultant to Swiss Precision Diagnostics GmbH and as statistical reviewer for the American Journal of Obstetrics and Gynecology. A.Z.L. has served in the Scientific Advisory Board of the Global Longitudinal study of Osteoporosis in Women (GLOW); has received an unrestricted research grant from the University of Massachusetts Center for Outcomes Research, Proctor and Gamble, and Sanofi; and was an attendee at a one-time consultants’ meeting for Pfizer to evaluate evidence on hormone therapy and breast density. Other authors report no conflict of interest.

Address correspondence to: Katherine M. Newton, PhD, Group Health Research Institute, Seattle, WA. E-mail: newton.k@ghc.org

© 2014 by The North American Menopause Society.