Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network

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.

Trial registration: ClinicalTrials.gov NCT00894543 NCT01178892 NCT01418209.

Conflict of interest statement

Conflicts of interest/financial disclosures: [Table: see text]

Figures

FIG. 1. Menopausal Strategies: Finding Lasting Answers to Symptoms and Health leadership structure

NIA, National Institute on Aging; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NCCAM, National Center for Complementary and Alternative Medicine; OWH, Office of Research on Women's Health.

FIG. 2. Menopausal Strategies: Finding Lasting Answers to Symptoms and Health recruitment and follow-up

VMS, vasomotor symptoms; SSRI, selective serotonin reuptake inhibitor.