Klein and colleagues write,
In the early 20th century discovery of blood groups led to the first example of “precision medicine.” By matching blood donors with their recipients, personalized therapy improved transfusion safety.1 In the 1960s, the National Institutes of Health (NIH) established a partitioned data set on a mainframe computer with 2700 blood donors phenotyped by serology for 20 red blood cell antigens. Combining mid-20th century genetic typing technology with the emerging field of informatics served to enhance donor-recipient compatibility and red blood cell inventory management. “Extended typing” simplified transfusion for patients with red blood cell antibodies, reduced the risk of future red blood cell alloimmunization, and became standard management for patients with sickle cell disease. However most hospitals faced with transfusion compatibility problems still tried to identify antigen-negative red blood cell units by screening local inventories with inefficient, labor-intensive serologic assays.
Now in the 21st century and with the emergence of initiatives on precision medicine, inexpensive molecular typing paired with powerful bioinformatics has enabled mass-scale red blood cell genotyping. The genes encoding the significant blood group antigens have been cloned. DNA sequence differences have been correlated with red blood cell antigen expression. Rapid screening for nucleotide polymorphisms in blood group coding sequences has been accomplished. A new generation of automated DNA analyzers will supplement, and could replace, serology methods for selecting the most suitable red blood cell units for patients with multiple alloantibodies. Web-based data storage and analytics are revolutionizing the provision of antigen-negative blood with an efficiency scarcely conceived of just a decade ago. Although currently not practical, providing extended antigen matching by molecular techniques to all patients should improve typing accuracy and reduce alloimmunization.2 A broader genetic database is important for locating uncommon red blood cell units, those negative for common antigens or combinations of antigens, and is particularly valuable for countries such as the United States with genetically diverse, multiethnic populations.
After the approval of the first human erythrocyte antigen genotyping kit in May of 2014, the Palmetto MolDX program pretty rapidly put out a fully favorable LCD coverage policy, and finalized it quickly. The LCD is L35827 (Molecular RBC Phenotyping, here).
This is just about as fast as LCD production occurs in the wake of an FDA approval. I attended the FDA advisory board on this topic in spring 2014, and it was amazingly smooth. Basically, the FDA staff (who normally take a somewhat adversarial tone to any product under review), said "this is great"...of course, in a detailed and fact-based way. The company gave its presentation, as did several additional speakers, and the panelists deliberated briefly and voted "thumbs up" to the product.
What outcomes or RCTs did MolDX look at?
It's not a field that lends itself to RCTs...you wouldn't deliberately treat one arm of subjects with poorly matched blood and another arm with correctly matched blood. While MolDX reviewed a series of papers in its LCD, they do not discuss exactly-how-much patients would be better off, or exactly-how-much patient harm would be avoided. It was clear that genomically matched blood would be "better" by some degree for problematic patients than serologically matched blood. Once there was no significant doubt that the genomic approach was "better," the LCD was complete and favorable. The discussion is worth reading (for what was NOT required as much as what WAS available; I've put a cloud version of the key technology assessment text here.)
Coding? Pricing?
The coding for RBC genotyping is currently a Tier II CPT code, Level 4, 81403. Codes of that type don't enter the CMS gapfill/crosswalk process. MolDX publishes a Tier 2 pricing guide for several dozen genes, but HEA genotyping doesn't appear to be on it, yet (their document M00005, V7, update 2/2015, here).
Footnote.
Q&A on the publicly summitted draft LCD comments, Medicare article A54230, is here.
