Clinical Research: Phase 1 - Phase 4

Considerations for Clinical Studies in Heavy Menstrual Bleeding

Heavy menstrual bleeding (HMB) is one of the most common gynecologic disorders among women of reproductive age, accounting for up to one-third of all gynecologic office visits.1 HMB refers to bleeding associated with regular ovulatory cycles and involves blood loss greater than 80 ml per month. It is a subcategory of abnormal uterine bleeding (AUB), a broad term describing menstrual cycle irregularities involving frequency, regularity, duration, or volume of flow.2,3 The condition can adversely impact quality of life and can result in anemia.

In this blog post, we explore key operational and methodological considerations for HMB clinical studies.

Operational and methodological considerations in HMB trials

Clinical trials of therapeutics for HMB involve unique operational and methodological considerations that should be addressed in the study design. Such considerations include:

  • Defining eligibility requirements to specify included and excluded causes of HMB, for example, fibroids or bleeding disorders, often defined in part by The International Federation of Gynecology and Obstetrics (FIGO) PALM-COEIN classification system which separates the causes of AUB into structural and nonstructural etiologies.
  • Providing training for performance of pelvic ultrasounds to ensure consistency.
  • Using a central reader for pelvic ultrasounds to ensure consistent interpretation.
  • Measuring blood loss and associated issues, including specifying the method of measurement.
  • Addressing potentially high screen-failure rates due to patients’ subjective assessment of their menstrual bleeding as heavy when the measured quantity is less than the quantity required by inclusion criteria.
  • Mitigating declining participation due to requirements related to the use and collection of sanitary products.
  • Minimizing patient discontinuations based on the perceived burden of study participation.

Key risks and mitigations in HMB studies

Risk 1: High screen-failure rate

HMB studies may suffer from high screen-failure rates because the menstrual blood loss that patients experience as heavy may not meet the definition of 80 ml per month.

Potential strategies for mitigating high screen-failure rate include:

  • Developing a robust prescreening questionnaire.
  • Creating paper and electronic prescreening tools that help patients track relevant information before bringing patients in for screening.
  • Leveraging data from patients already enrolled in the study to refine the prescreening activities for future patients.
  • Using a centralized recruitment vendor.

Risk 2: Inconsistency in use and collection of sanitary products

In clinical studies, accurate measures of menstrual blood loss are essential for evaluating the efficacy of drugs and medical devices for HMB. To assess monthly blood loss, studies of therapies for HMB typically use the alkaline hematin method – a chemical measurement of blood in used sanitary products. Patients are provided with specific sanitary products that must be packaged and returned after use, in accordance with the study protocol. These products are then shipped to a lab to assess blood loss.

Ensuring the collection of valid endpoint data entails adherence to requirements that are out of the norm for both sites and patients. Potential strategies for mitigating inconsistency in the use and collection of the sanitary products necessary for endpoint data include:

  • Ensuring the patient stipend is commensurate with the perceived burden associated with collecting, storing, and transporting used sanitary products.
  • Providing patients with bags that allow easy, discreet transport of study supplies.
  • Providing brand-name sanitary products that are approved for use with the alkaline hematin method.
  • Having site staff complete standard fields on collection bag labels before distribution.
  • Ensuring sites educate patients on the requirement to use only those sanitary products provided for the study.
  • Demonstrating proper storage of sanitary products to patients at the first site visit.
  • Providing an IRB-approved reference guide with clear instructions on the collection and storage of sanitary products.
  • Having site staff confirm that all outer bags are adequately sealed when received from patients.

Assistance with your HMB program

As a CRO committed to improving healthcare outcomes for women, Premier Research is dedicated to advancing and accelerating the clinical development of more effective treatments for HMB. Our team understands how to address key operational issues and mitigate risks in HMB trials, helping sponsors optimize their likelihood of study success. To learn more about our women’s health clinical trial expertise, click here.

[1] Marsh EE, et al. Prevalence and knowledge of heavy menstrual bleeding among African American women. Int J Gynaecol Obstet. 2014;125(1):56-69.

[2] Davis E, Sparzak PB. Abnormal Uterine Bleeding. StatPearls Publishing, 2021.

[3] Whitaker L, Critchley HO. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016;34:54-65.