Revisions: 174

Rare plasma protein coagulation disorders may result in a hemorrhagic or a thrombotic tendency based upon the specific coagulation factor affected and the associated level of deficiency. The treatment advances achieved for hemophilia A and B over the last two decades have not been mirrored in advances for these other disorders. Table 1 provides a listing of these very rare plasma protein deficiencies.

Due to the rarity of these disorders, the costs of research and development and of conducting clinical trials are often prohibitive when balanced against the potential market. For these reasons, individuals with rare coagulation factor disorders have limited or no options for treatment and suffer increased morbidity from their disease. Investigator-initiated Investigational New Drug protocols for use of a medication in these disorders places significant burden on the investigator and the manufacturer and therefore may preclude treatment of patients with rare deficiencies with potentially useful agents. In the US, these problems have created a dangerous lack of access to appropriate therapy for a small but important subset of the coagulation disorders community.

Regulatory pathways for product licensure have been geared towards collection of data in more prevalent conditions. Increased availability of specific safe and effective replacement products has hinged upon development of regulatory guidelines to allow submission of limited data sets for initial licensure of therapeutic products targeted towards these rare disorders with commitments to track adverse events post licensure. In addition, for each of these disorders, a national data system is required to develop the knowledge base necessary to advance care and treatment for these disorders and to allow data comparison or grouping to achieve international harmonization. Table 2 lists gaps in areas that play a pivotal role in advancing the knowledge base and care of individuals affected with these disorders.

Therefore, MASAC supports a multifaceted approach to address these identified gaps. These broad based approaches include:


1. Improved diagnostic capability underpinned by accurate laboratory testing.



2. Disease-specific education easily and widely accessible for all caregivers.



3. Collaboration with national and international agencies that interface with affected populations on all levels (CDC, ATHN, FDA, EN-RBD, NIH, NHF, WFH).



4. Development of improved data sources to increase knowledge of disease-associated sequelae, treatments utilized, and associated adverse events.




5. Increased range of therapeutic interventions available for treatment.



6. Increased research in rare disorders, both basic science and clinically orientated.



7. Advocacy to improve diagnosis, knowledge, treatment, care and outcomes.



8. Identification and promotion of disease-specific centers of excellence for care including the Hemophilia Treatment Center network and other identified care sources.

MASAC recommends continued targeted activities to achieve improved diagnostic capabilities, education of care providers regarding these disorders, knowledge of sequelae experienced throughout the lifespan, increased therapeutic products for treatment, and research, advocacy, and international data harmonization to ultimately improve the care of all individuals affected with very rare plasma protein deficiencies. Collaboration across all agencies involved in the care and treatment of these individuals is required on an ongoing basis to achieve desired outcomes and long-term goals.

Please see the current version of the MASAC document titled, "MASAC Recommendations Concerning Products Licensed for the Treatment of Hemophilia and Other Bleeding Disorders," for specifics regarding available products for treatment of these disorders.