A Forum for Improving Drug Safety

It’s time to express your opinion on whether warfarin (Coumadin) DNA testing should be paid for by insurance. The Center for Medicare and Medicaid Services (CMS) has initiated a study of this topic and is accepting public comment until September 3, 2008 at http://www.cms.hhs.gov/mcd/viewtrackingsheet.asp?from2=viewtrackingsheet.asp&id=224&.

In the interests of the approximately 500,000 patients who begin warfarin therapy every year, I’m in agreement with Larry Lesko of the FDA that warfarin DNA testing should be widely adopted. This linked article by him clearly summarizes evidence in favor of warfarin testing that has built up over the years. The contrary position outlined at http://www.ctaf.org/content/general/detail/814 focuses on the lack of evidence from prospective clinical trials without citing contrary evidence. This standard of proof is unreasonable in this application and I believe that adherence to unreasonably difficult standards of proof for pharmacogenetic tests has resulted in harm to many, many patients.

It’s important that you comment on this study because the decision made by CMS will have a wide impact on patient access to these tests that represent one of the greatest opportunities for Personalized Medicine to improve healthcare. A recent story in the Pharmacogenomics Reporter has many of the details http://www.pgxreporter.com/issues/6_33/features/148791-1.html.
I have since posted a public comment myself, here is the text:

The American College of Medical Genetics review of a decade or more of warfarin dose variability research, estimates that 23% of the variance is due to polymorphism in the VKORC1 gene and 17% in the CYP2C9 gene, compared to 9% for weight and 7% for age. These estimates are not in dispute and there is virtually no evidence contradicting them.

Physicians would not prescribe without age, weight and other clinical information, yet continue do so without genetic test results. Waiting for more trials to further prove that the use of genetic testing will improve health outcomes is dangerous to patient safety.

Would you drive with 16% visibility when you could have 56%? Let’s draw a comparison; say that 23% of traffic fatalities involve alcohol, 17% involve drugs, 9% involve poor driving conditions and 7% involve drivers with less than two years of driving experience. We cannot eliminate young drivers or poor driving conditions, but it is safe to assume that reducing the number of drivers drinking or on drugs would reduce the number of traffic fatalities. If this were held to the same difficult standards some propose for warfarin DNA testing, we would need a blinded study proving that reducing the number of drivers on alcohol and drugs would decrease the chance of automobile fatalities before action could be taken. How many lives would be lost in the interim?

“First do no harm” is not being followed if we ignore 40% of the causes of dose variability in a drug with a narrow therapeutic index in which misdosing causes a high incidence of adverse thromboses and dangerous bleeding events. As John Concato, MD, Director, VA Clinical Epidemiology Research Center at Yale University says “Putting what we know into practice would prevent more disease than worshiping at the altar of randomized trials.”

Please take the time to let your voice be heard on this important matter.