ATHN 8: PUPs Matter Study
ATHN 8: PUPs Matter Study
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.
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.
Inclusion Criteria:

 -  Congenital hemophilia A; FVIII </=5% or congenital hemophilia B; FIX </=5%;

 -  Birth date on or after January 1, 2010;

 -  Care established at one of the participating HTCs;

 -  Co-enrollment in the ATHNdataset; and

 -  Parent or authorized guardian can provide informed consent

 Exclusion Criteria:

 -  Patients who are referred to the HTC with no record of bleed and factor utilization
 data