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P. M. Barrett and E.J. Topol. Pharm-Econogenomics: A New Appraisal. Clin Chem 2013;59:592-594.
Dr. Eric Topol is Director of the Scripps Translational Science Institute and Chief Academic Officer at Scripps Health in La Jolla, California.
This is a podcast from Clinical Chemistry, sponsored by the Department of Laboratory Medicine at Boston Children’s Hospital. I am Bob Barrett.
Genomic research has been widely expected to transform medicine, but progress is not as rapid as some have expected. In the April 2013 issue of Clinical Chemistry, Ramy Arnaout and his colleagues published a paper regarding the cost and the pace of advances in pharmacogenomics. Accompanying that paper was an editorial by Paddy Barrett and Eric Topol. Dr. Topol is Director of the Scripps Translational Science Institute and Chief Academic Officer at Scripps Health in La Jolla, California. He is our guest in today's podcast.
Dr. Topol, pharmacogenomics is thought to offer improvements in drug development and utilization. Is it appropriate to ask the question as to whether this approach will be cost-effective as was done in the recent paper in Clinical Chemistry?
It's not only appropriate to ask the question, it will be inappropriate not to ask it, that is, this is a vital way to make for precision medicine going forward, to avoid major side-effects, the way new drug should be developed, and certainly the way common drugs are out there in medical practice.
Doctor, hasn’t the question of cost-effectiveness been asked previously with respect to other prescription medication such as Warfarin?
Right, the Warfarin model is one that has led to some serious questioning as to whether DNA interactions with drugs are going to make it into the real world. The problem with the Warfarin story were two-fold; one, is that the cost for doing the two gene variants in the Vitamin K receptor and the Cytochrome that's implicated in metabolism of Warfarin, the cost was too high, and the turnaround was too long.
And so, by the time people would get the results back to predict what dose of Warfarin, it would not only take days but they already would have reached steady state for their blood thinning, INR, and it would have been very expensive. So that just doesn’t work. We need to get to point of care inexpensive genotyping, because there is rich data for the use of drugs when we have DNA information for each individual.
We read almost daily about dramatic decreases in the costs of whole genome and exome sequencing. With such rapid changes, how will that affect the whole question of cost- effectiveness estimates?
Well, the whole genome sequencing you can envision someday where most people have this done, and all of their pharmacogenomic interactions are known before they even have a prescription written for them. They would know the dose; they would know the drugs that would induce serious side-effects. That's the dream for the future.
What we need to use whole genome sequencing and exome sequencing today, is for the drugs that are in common use or are being developed to find the specific interactions which have not yet been charted, they haven't been explored even, and that's mainly because the life science industry, Big Pharma, hasn’t been interested in pursuing this whole area.
What about drug development that is not genomically targeted? How could that affect patients and the pharmaceutical companies that pursue that route?
Well, there is a problem today in the US with well over $300 billion of prescription drugs per year, and this is going up rapidly because all the biologics. For example, last year in the US, that was a banner year for drug approvals, there were 12 new drugs for cancer. The cost of treatment for 11 of those 12 drugs is over $100,000, each.
So, we have a problem with very expensive drugs and we need much more judicious, precise use of these medicines. And so genomics offered one way, obviously there are other ways whether it's biomarkers and sensors, but individualized approaches to basically get to a maximum level of efficacy and the avoidance of major side-effects which also not only are potentially life-threatening and serious, but also are extremely costly to manage.
In your editorial, you mentioned the role of the FDA. What's their current stance on this issue, and how would you like to see it evolve? And beyond that, do you think it will evolve?
Well, the FDA has indeed been supportive and has issued pharmacogenomic guidance documents and there are some individuals in FDA who are particularly champions of this whole movement. So, I do think that there is the receptivity there. The bottleneck has not been so much with the FDA, but it's mainly been with biotech and pharma that have not zoomed in to this exciting opportunity.
Well finally, you discussed in your editorial on how drugs will be developed and how they will be used in the future. So, look at ahead, how do you foresee that future and how long will we have to wait before it becomes realized?
Right! Well, my dream is that when a drug is given, it fulfills the guaranteed-to-succeed model, that is, just like any other expensive purchase, if it didn’t work, you wouldn't want to pay for it and you get your money back.
Well, that's where drugs can go, maybe not fully but they can approach that, when we have the appropriate guidance. And that could be, of course, with genomics and not just DNA sequence but other omics like metabolites and proteins and even epigenomics, but it also could be the use of physiologic sensors and basically understanding the science of individuality.
So, I think we will asymptotically approach that goal. It will take a while. But the first step is the belief that we can make a marked difference and improvement from where we are today.
Dr. Eric Topol is Director of the Scripps Translational Science Institute and Chief Academic Officer at Scripps Health in La Jolla, California. He has been our guest in this podcast from Clinical Chemistry.
In 2012, Dr. Topol was voted as the number one most influential physician executive in the United States, in a poll conducted by Modern Healthcare. In February 2013, he was named editor-in-chief of Medscape; an online journal for medical professionals. I am Bob Barrett. Thanks for listening!