ATHN 8: Previously Untreated Patients (PUPs) Matter Study
Condition: Hemophilia; Hemophilia A; Hemophilia B; Hemophilia A With Inhibitor; Hemophilia B With Inhibitor; Haemophilia B Without Inhibitor; Haemophilia A Without Inhibitor; Haemophilia
MeSH terms: Hemophilia A; Hemophilia B
Study type: Observational

Summary: 
      This is a multi-center cohort study of approximately 250 previously untreated patients (PUPs)
      with congenital moderate to severe hemophilia A or B in a network of up to 50 US Hemophilia
      Treatment Centers (HTCs). Participants will be followed as they receive their first 50
      exposure days (ED) to clotting factor replacement product, both prospectively and
      retrospectively. The data collected on evolving treatment practices will define the incidence
      and risk factors for inhibitor development during the high risk period of first 50 ED and
      improve the outcomes of this vulnerable population.
    

Detailed description: 
      This multi-center, longitudinal, observational, prospective and retrospective study of
      previously untreated patients (PUPs) with moderate to severe hemophilia A or B during the
      initial 50 exposure days (ED) to clotting factor replacement product or until the development
      of a confirmed inhibitor. The Primary Investigators have designed the study to utilize the
      American Thrombosis and Hemostasis Network (ATHN) electronic infrastructure to leverage
      existing data and enable the collection of more in-depth clinical and laboratory data on
      PUPs. The study aligns with the National Hemophilia Foundation Medical and Scientific
      Advisory Council (MASAC) recently issued Recommendation #243 which includes: "Regardless of
      which option is chosen, all PUPs should be enrolled in the ATHN data collection system or a
      clinical trial to assess outcomes." Co-enrollment in the ATHNdataset by participants is
      required. The total study duration is planned for 6 years.

      The primary objective is to determine the percentage of patients with confirmed inhibitors
      within the first 50 ED. Confirmed inhibitors are defined as two consecutive positive
      inhibitor titers (per CDC laboratory criteria; >0.5 Nijmegen Bethesda Units for hemophilia A
      and >0.3 Nijmegen Bethesda Units for hemophilia B) on different blood samples which result in
      change in treatment recommendations.

      Please note - the treatment regimen will be at the discretion of the participants' hemophilia
      caregivers. No treatment products are being provided by the study nor will the participants
      be paid. However, inhibitor titer testing will be provided at no cost to participants by the
      Centers for Disease Control and Prevention (CDC).

      All study procedures and follow-up will be timed to coincide with scheduled hemophilia care
      whenever possible. Ad hoc, quarterly follow-up, annual and final visits are for participants
      who have not met study endpoints (50 ED or inhibitor development) prior to enrollment.

      Data collected will include eligibility, demographics, medical history (co-morbidities,
      surgery/procedures, immunizations and allergies), hemophilia history (severity, genotype and
      family history), birth history, inhibitor testing results, detailed treatment product(s)
      usage, bleeding events, bleeding disorder related medical visits during the study, and EUHASS
      adverse events.

      Sub-studies

      A number of sub-studies are planned with pharmaceutical sponsors to collect information from
      patients about their specific product use. Participation in these product specific
      sub-studies is optional and sub-study visits will be planned to coincide with HTC visits. The
      sub-study will collect information from patients about their perception and use of treatment
      products, physical activity levels and other general health questions. This data will be
      collected via questionnaire.

      Data Collection System

      All data collected will be entered into electronic case report forms (eCRFs) within the
      secure ATHN System by HTC site personnel. All participating study sites will have in place a
      current, executed Data Use and Business Associate Agreement (DUBAA) with ATHN.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        The study will enroll a cohort of 250 participants born with hemophilia on or after January
        1, 2010 who meet the eligibility criteria and are receiving care from one of the
        participating HTCs.
      
Keywords: Hemophilia; Previously Untreated Patients (PUPs); Clotting Factor Replacement Products; Haemophilia