Estimating a meaningful reduction in menstrual blood loss for women with heavy menstrual bleeding

Abstract

Objective:

A dichotomy exists within the treatment of heavy menstrual bleeding (HMB); guidelines and expert opinion recommend that clinical management be guided by subjective, patient-centered measures, yet clinical trials often describe treatment efficacy in terms of objective reductions in menstrual blood loss (MBL). The purpose of this investigation was to correlate subjective and objective aspects of HMB treatment by identifying the minimum change in MBL that would be considered meaningful to women.

Research design and methods:

Receiver operating characteristic (ROC) curve analyses were performed using data from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of a novel, oral formulation of tranexamic acid (Lysteda). The study enrolled women ages 18–49 years with a history of cyclic HMB. Menstrual blood loss was measured objectively using the alkaline hematin method and subjectively using the Menorrhagia Impact Questionnaire (MIQ), a patient-reported outcome instrument previously validated in an HMB population. Additional subgroup analyses were performed after stratification by low (80–160 mL/cycle) or high (>160 mL/cycle) baseline MBL.

Clinical trial registration:

NCT00401193 (NIH Clinical Trials Registry)

Results:

A total of 278 women were included in the ROC analyses. The best balance of sensitivity and specificity was achieved for predicting a patient-perceived meaningful improvement in MBL, at a cut point of 36 mL/cycle. Absolute reductions in MBL that were considered meaningful were more modest in women with lower baseline MBL (22 mL/cycle) and greater in women with higher baseline MBL (47 mL/cycle). However, an approximately 22% MBL reduction was meaningful to the majority of women in either the low or high baseline MBL subgroups.

Conclusions:

Reducing measurable MBL by 36 mL/cycle, or approximately 22%, was considered to be a meaningful improvement for the majority of women with HMB in this study population.

Key words:

• Menorrhagia
• Minimally important change
• Pharmacologic therapy
• Quantitative
• Responder analysis
• Tranexamic acid

Transparency

Declaration of funding

Financial support for this study was provided by Xanodyne Pharmaceuticals, Inc. and Ferring Pharmaceuticals Inc.

Declaration of financial/other relationships

Dr Lukes receives or has received research support from Xanodyne, Ethicon, Merck, Bayer, Luitpold, Hologic, National Improvement for Women's Healthcare, Duramed, NIH, CDC/ATPR, Smith & Nephew, Trent Foundation, and AMS. She consults with and/or has served on speakers’ bureaus for Ferring, Xanodyne, Hologic, AMS, Bayer, Interlace Medical, Microsulis, AMAG, Daichii, and Myriad. Dr Muse receives or has received research support from Amgen, Wyeth Research, Xanodyne, Merck, and CONRAD and has served as a consultant or on speakers’ bureaus for Ferring, Lilly, Merck, and Wyeth. Dr Richter receives or has received research support or has acted as a consultant for Pfizer, Astellas Pharmaceuticals, Xanodyne, Uromedica, IDEO as well as receiving Pfizer and Warner Chilcott Education grants. Dr Moore is an employee of Xanodyne. Dr Patrick has acted as a consultant for Amgen, Meritage, Amylin, Pfizer, and Merck.

Acknowledgments

The authors would like to thank Arkady Rubin, PhD, for statistical consultation and Crystal Murcia, PhD, and The JB Ashtin Group for editorial assistance with this manuscript. This assistance was funded by Xanodyne Pharmaceuticals, Inc. and Ferring Pharmaceuticals Inc.

Excerpts from this manuscript were presented at the American Congress of Obstetricians and Gynecologists (ACOG); San Francisco, CA; May 15–19, 2010.

Notes

*Lysteda is a registered trade name of Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.

*Lysteda is a registered trade name of Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.