Ten-Year Canadian National Prospective Data On Utilization of Anti-Hemophilic Concentrates: Indications and Trends

In response to the transfusion-transmitted AIDS epidemic the Commission of Inquiry on the Blood System in Canada recommended the development of a monitoring and tracking system of product usage. The Association of Hemophilia Clinic Directors of Canada (AHCDC) implemented the Canadian Hemophilia Assessment and Resource Management System (CHARMS) to track factor concentrates (FC) from the sole suppliers, Canadian Blood Services (CBS) and Hema-Quebec (HQ), to hospitals and to patients' homes.

To identify the indications and locations for infusions of factor VIII (FVIII), factor IX (FIX), recombinant factor VIIa (rFVIIa) and FVIII inhibitor bypass activity (FEIBA) and review utilization during 2000–2009.

All Canadian patients with hemophilia attend the 26 Canadian Hemophilia Treatment Centres (HTCs) and are registered with the Canadian Hemophilia Registry (CHR; ahcdc.ca) from which they receive a unique number suitable for anonymizing data. HTCs receive product and infusion data from the blood suppliers (CBS, HQ), regional hospitals and patients. HTCs enter these data into their clinic-based CHARMS software program and then export the data to the national database (CentrePoint) where data are validated.

From 2000 to 2009, 2,904 patients received, predominantly, FVIII (902 million Units) and FIX (240 million Units). A total of 2,386(82%) had congenital bleeding disorders listed in the Canadian Hemophilia Registry. The remaining 518 were not registered because they either did not have inherited factor deficiency or had registrations pending. Most of FVIII and FIX was infused by patients at home: 90% to 95% for FVIII and 85% to 94% for FIX. The yearly amount of FVIII infused increased over time; this was accounted for by an increase in the number of patients who were treated shown by positive and significant correlation(r=0.89; p=0.04), not so by amount infused per patient which remained constant (p=0.57). Furthermore, there was a linear relationship between an increase in patients and increased utilization, each additional patient predicting for an increased utilization of 96,217 units (P=.04). The highest proportional utilization of both FVIII and FIX was for prophylaxis, and this proportion increased over time, while the proportion used for bleeding remained steady. In 2009, the proportions used for prophylaxis were 73% and 60% for factor VIII and factor IX respectively; for bleeding the proportions were 16% and 30%, for surgery 1% and 4%, for immune tolerance induction 3% and 1%, and unclassified use was 6% and 5% respectively. Among inhibitor by-passing products, rFVIIa was the product most used by patients without bleeding disorders, 20% of VIIa being used by these patients but only 6% of FIEBA. FIEBA was predominant over rFVIIa for prophylaxis in children. Improvements in data collection included a notable decrease in the proportion of Unclassified usage; for FVIII from 12–36% each year from 2000–2004 to 6–16% from 2005–2009; for FIX from 14–41% each year before 2005 to 4–14% after 2004. Specifically, the decrease in Unclassified infusions of FVIII from 16% in 2005 to 6% in 2009 showed a statistically significant trend (p=.02).

1) Data collection became reliable after 2004 when the proportion of Unclassified indications and the annual increase in patient numbers fell to low levels; hence subsequent trends should be compared with the period 2005–2009. 2) The increase in total annual FVIII concentrate use is accounted for by the annual increase in patient numbers, not by the annual use per patient, 3) FC are increasingly being infused for prophylaxis. 4) The major site of infusion is at home, which is outside the scope of the existing tracking system and which comprises only blood suppliers and hospitals; hence, HTCs and a comprehensive data collection system, CHARMS in this case, are both required components of an effective national tracking system and 5) a tracking system involving the entire supply and treatment chain is essential for predicting utilization and planning for future needs.

Walker:Baxter Corporation: Research Funding. Iorio:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; BioGen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Heddle:Baxter: Research Funding; Association of Hemophilia Clinic Directors of Canada: Research Funding. Chan:Bayer: Consultancy; Boehringer ingelheim: Member of DMSB for Clinical Trial, Member of DMSB for Clinical Trial Other; Aventis: Chair of Steering Committee, Chair of Steering Committee Other; BMS: Chair of Adjudication Committee Other.