Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative.

Hemophilia A and B are rare, X-linked bleeding disorders. My Life, Our Future (MLOF) is a collaborative project established to genotype and study hemophilia. Patients were enrolled at US hemophilia treatment centers (HTCs). Genotyping was performed centrally using next-generation sequencing (NGS) with an approach that detected common F8 gene inversions simultaneously with F8 and F9 gene sequencing followed by confirmation using standard genotyping methods. Sixty-nine HTCs enrolled the first 3000 patients in under 3 years. Clinically reportable DNA variants were detected in 98.1% (2357/2401) of hemophilia A and 99.3% (595/599) of hemophilia B patients. Of the 924 unique variants found, 285 were novel. Predicted gene-disrupting variants were common in severe disease; missense variants predominated in mild-moderate disease. Novel DNA variants accounted for ∼30% of variants found and were detected continuously throughout the project, indicating that additional variation likely remains undiscovered. The NGS approach detected >1 reportable variants in 36 patients (10 females), a finding with potential clinical implications. NGS also detected incidental variants unlikely to cause disease, including 11 variants previously reported in hemophilia. Although these genes are thought to be conserved, our findings support caution in interpretation of new variants. In summary, MLOF has contributed significantly toward variant annotation in the F8 and F9 genes. In the near future, investigators will be able to access MLOF data and repository samples for research to advance our understanding of hemophilia.

Knowledge and therapeutic gaps: a public health problem in the rare coagulation disorders population.

Rare coagulation disorders (RCDs) present a considerable and multifaceted public health risk. Although inherited RCDs affect a minor segment of any local healthcare delivery system, their global impact is major and highlight the challenges of delivering healthcare services to any rare disease population. These include but are not limited to: (1) a general lack of knowledge about and familiarity with the genetic and clinical implications of the disorder among affected patients, and both urgent and specialty care providers; (2) the potential for preventable morbidity and mortality related to delayed diagnosis and treatment; (3) the lack of safe and effective therapies; and (4) minimal research activity to establish and improve standards of care. A multiagency national partnership has established an approach to address these problems through development of a clinical, genetic, and treatment-related web-based data-collection tool that will: (1) generate a reliable, sufficient knowledge base for these disorders; (2) facilitate new product licensure through subject identification and access to comparative historical treatment data; and (3) serve as an effective tool for outcomes research and post-licensure product surveillance. To maximize impact, this database is being harmonized with a European data-collection effort. Database development and harmonization is in progress. A resource library was completed and disseminated to major national and international bleeding disorder websites to provide state-of-the-art patient and provider education on each RCD. We believe that this model is effective and adaptable to other rare conditions.

A community-based partnership to promote information infrastructure for bleeding disorders.

Specialists in rare disorders often face challenges in collecting surveillance and research data. As movement toward more fully realizing the potential of electronic health information gains momentum, practitioners who treat individuals with rare disorders are in need of public-private support to tap into the advantages offered by the developing electronic information technologies and the interoperability standards promulgated by the USDHHS. The not-for-profit American Thrombosis and Hemostasis Network (ATHN) was created in 2006 to provide stewardship of a secure, national, web-based database to support federally funded hemophilia treatment centers (HTCs) across the country. In pursuit of its mission to support clinical outcomes analysis, research, advocacy, and public health reporting in the hemostasis and thrombosis community, ATHN has established a spectrum of community-based partnerships. This paper describes the process and public health benefits of creating formal relationships with 127 of the 134 HTCs from 12 regional networks across the U.S., government agencies such as the CDC, Health Resources and Services Administration, and NIH; consumer-based organizations; and industry leaders. This community-based partnership model can be applied to other rare disorders communities with high economic and public health impact.

Snomed® CT: The Fit with Classification in Health.

Classification systems are the primary means for automated retrieval and analysis of healthcare data from individual patient medical records. This article will provide a brief history and overview of the two most comprehensive and advanced controlled clinical terminologies in the world: the Systematized Nomenclature of Medicine Reference Terminology (SNOMED® RT), and Clinical Terms Version 3 (CTV3). A discussion will follow of the merger of these two terminologies into a single new work, SNOMED® Clinical Terms (SNOMED® CT), as released in early 2002, how it is used to retrieve data, how it differs from a classification, and the opportunities open to health information management professionals to expand their roles as information managers through their knowledge of SNOMED CT.