Eric Topol Makes The Case for Personalized Medicine

Eric Topol's commentaries in Science and the San Diego Union Tribune underscore the important role commercialization plays in the development, adoption and spread of medical innovations, in this case personalized medicine.  Topol observes the resistance of cliniicians -- and the comparative effectiveness claque -- to genomics as a tool for selecting and enhancing treatment:

"While physicians and the life science industry have done little to advance the use of testing for drug-gene interactions, now the pharmacy benefit managers (PBMs) Medco and CVS/Caremark, which collectively administer the employer prescription plans for nearly 100 million Americans, are stepping up. They are introducing wide-scale genotyping for certain drugs, like Plavix or Tamoxifen, and many anti-cancer medications.

Understatement of the year. 

In his Science article Topol describes as clinical inertia and academic squabbling over methodology continues,   PBMs are setting up the infrastructure for the routine use of genetic testing:

There is a simple way to confirm and quantify the extent of platelet response to clopidogrel, using a variety of point-of-care platelet function tests, each of which has been clinically validated to predict long-term prognosis. Furthermore, the information is highly practical, because patients who do not respond to the antiplatelet drug can have their platelet suppression achieved by using higher doses of clopidogrel or prasugrel (Effient) or by using alternative antiplatelet agents that are expected to be approved in the months ahead. Still, the medical community takes no initiative in routinely genotyping patients who are taking clopidogrel. In March 2010, the U.S. Food and Drug Administration (FDA) put a “black box” warning on clopidogrel that addresses the issue of risk in “poor metabolizers,” as defined by genotyping (8). However, months after this action was taken, it remains exceptionally rare for a patient receiving clopidogrel to undergo genotyping. The lesson here is clear: The medical community is unwilling to change clinical practice and wants more evidence, even in the wake of a significant regulatory body warning.

This reluctance on the part of clinicians has left the door wide open for PBMs. These companies can pitch to their clients—large employers—that they are benefiting their employees by avoiding the use of a drug that won’t work or isn’t being administered at an effective dose. For the exceptionally common clopidogrel medication, which costs $4 to $5 per day, the rationale for more precise use and the avoidance of major adverse outcomes seems attractive. In the next year or two, this medication will become generic, so that routine determination of genotype and, if necessary, platelet responsiveness could provide marked cost savings by avoiding the use of a proprietary drug when unnecessary.

As Eric notes, commercialization carries pluses and minuses, the balance of which could have been enhanced in favor of patients if doctors and researchers had not been engaged in nit-picking and grant seeking.

"Promoting the right drug, the right dose, and the right cost for patients may well improve the competitiveness of PBMs.

But the potential benefits for PBMs go far beyond this pitch. Under the pretext of personalized medicine, these companies potentially may charge patients or insurance companies for genotyping services—for which the market has doubled over the past 5 years —while at the same time also profiting from the drugs prescribed and sold. This may represent a conflict of interest or at least the potential perception of double- or triple-dipping. It will be important for PBMs that pursue such initiatives to be transparent about their genotyping strategies and drug recommendations."

Still, as Topol notes, it is the PBMs and large health plans -- and the DTC firms in their own haphazard way -- making personalized medicine mainstream.  And the long term benefit or externality may be what Ralph Snyderman has envisioned:  the regular use of pharmacogenomic data from the sequencing of our own genome to promote prospective and personalized medicine for specific illnesses.   Unfortunately it seems that clinicians, regulators (now most particularly the comparative effectiveness crowd) and academia (that see their grant receiving status threatened in some strange way by clinical adoption of gene testing) are way behind the curve and out of sync with patients, payors and entrepreneurs.  As Topol notes:

"The lack of alignment will probably be further exacerbated in the next phase of genomic medicine, in which whole-genome sequencing becomes commonplace. The first clinically annotated sequence, albeit requiring a team of 30 investigators and 600 person-hours, demonstrated 63 pharmacogenomic variants of clinical relevance . As more information becomes available from genome-wide association studies that provide actionable data, such as recently reported regarding interferon therapy for hepatitis C , the era for routine pharmacogenomics may finally shift into high gear. In the end, we may ultimately view the surprise movement by PBMs and drugstores as having helped catapult genomic medicine forward. "

Read the full article here.