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Considerations For Clinical Studies In Heavy Menstrual Bleeding

clinicaltrial-female

Heavy menstrual bleeding (HMB) is a common form of Abnormal Uterine Bleeding (AUB). which is denoted by bleeding of abnormal quantity, duration or schedule. HMB refers to bleeding that is regular, associated with ovulatory cycles and involves monthly blood loss greater than 80 ml, double the normal quantity. HMB compromises quality of life for many women and can result in anemia. Approximately 15% of women with HMB have von Willebrand Disease, a genetic bleeding disorder.

Causes of AUB can be structural or nonstructural as summarized in the International Federation of Gynecology and Obstetrics (FIGO) PALM-COEIN classification system, where “PALM” represents the structural causes Polyp, Adenomyosis, Leiomyoma and Malignancy and hyperplasia, and COEIN represents the nonstructural causes Coagulopathy, Ovulatory dysfunction, Endometrical, Iatrogenic and Not yet classified.  The disorders summarized in the PALM-COEIN classification are often addressed by inclusion/exclusion criteria in clinical trials of treatments for HMB.

"Accurate measures of menstrual blood loss are essential for evaluating the efficacy of drugs and medical devices for HMB"

Accurate measures of menstrual blood loss are essential for evaluating the efficacy of drugs and medical devices for HMB. The gold standard measure is the alkaline hematin method, a chemical measurement of blood in used sanitary products. This method is required in studies of drugs for HMB. Patients are given specific sanitary products and must package and return in accordance with the study protocol. The sanitary products are then shipped to a lab that uses the alkaline hematin method to assess the blood loss for each patient. The Pictorial Blood Loss Assessment Chart (PBAC) is a validated tool that is used in clinical trials of medical devices such as endometrial ablation systems.

Operational and Methodological Considerations in HMB Trials

Clinical trials of therapeutics for HMB involve unique operational and methodological considerations. Such considerations include:

  • Defining eligibility requirements to ignore or specify included and excluded causes of HMB (e.g., fibroids or bleeding disorders)
  • Providing training to ensure consistency in performance of pelvic ultrasounds
  • Use of a central reader for pelvic ultrasounds to ensure consistent interpretation
  • Measurement of blood loss and associated issues, including:
    • Specification of the method of measurement (likely the gold-standard alkaline hematin method)
    • Ensuring that subjects use the distributed sanitary products and do not inadvertently dispose of used sanitary products based on habit
    • Ensuring correct subject labeling and sealing of bags provided for collection of sanitary products.
    • Ensuring that sites understand and can address storage requirements for study supplies.
  • Potentially high screen-failure rates due to patients’ subjective assessment of their menstrual bleeding as heavy when the measured quantity is less than required by inclusion criteria
  • Subjects declining participation because of requirements related to use and collection of sanitary products
  • Patient discontinuations based on the perceived burden of study participation

Key Risks and Mitigations in HMB Studies

Risk 1: A high screen-failure rate

There can be a high screen-failure rate in HMB studies because the menstrual blood loss that patients experience as heavy may not meet the definition of 80 ml per month.

Mitigations 

  • Develop a robust prescreening questionnaire.
  • Create paper and electronic prescreening tools to assist patients in tracking relevant information prior to bringing patients in for screening
  • Use data from subjects previously enrolled in the study to increase the robustness of prescreening activities for future subjects
  • Use a centralized recruitment vendor

Risk 2: Inconsistency in use and collection of sanitary products as required for endpoint data with the alkaline hematin method

Mitigations

  • Ensure the patient stipend is commensurate with the perceived burden associated with collecting, storing, and transporting used sanitary products
  • Provide subjects with a bag that allows easy, discreet transport of study supplies between the site and home and discreet bags for use away from home
  • Ensure sites educate subjects on the requirement to use only sanitary products provided for the study
  • Consider providing name-brand sanitary products approved for use with the alkaline hematin method
  • Have site staff complete standard fields on collection bag labels prior to distribution
  • At Visit 1, provide a demonstration of proper storage of sanitary products during the study
  • Provide an IRB-approved reference guide on collection and storage of sanitary products
  • Have site staff confirm that all outer bags are sealed properly when received from subjects
If you are developing women’s health products Make Your First Decision the Right Decision - Health Decisions

For Assistance With Your HMB Program

As a CRO committed to improving healthcare outcomes for women, Health Decisions is determined to advance and accelerate clinical development of improved treatments for HMB. In addition, the Health Decisions clinical team understands how to address key operational issues and mitigate risks in HMB trials. Please contact us to explore how Health Decisions can assist with efficient, timely development of your investigative product for treatment of HMB.

The Leading Full-Service Women’s Health CRO from Pre-IND or -IDE to Regulatory Approval and Beyond
Health Decisions is a full-service CRO specializing in clinical development of drugs, diagnostics, medical devices and combination drug/devices in all areas of women’s health as well development of diagnostics for all therapeutic areas. Our experience, expertise, site network and KOL and investigator relationships enable us to address the challenges of developing women’s health products in areas including general gynecology indications, contraception, sexual health, infertility, obstetrics, menopause and osteoporosis and other indications that affect women disproportionately and profoundly, including autoimmune disorders and malefactor infertility. Health Decisions is headquartered in Durham, NC.