Daniel is a Great Guy!

I wanted to post quickly today on a this whole turf topic again. I thank Daniel over at Genetic-Future (Pound for pound the best new blog in this arena). It took some discourse to figure it out.

What happens normally with genetic testing?
Traditionally a lab scientist, being PhD or MD runs the lab and when results are in writes a report that is to be delivered to......Guess who? A physician. That physician or genetic counselor working with the physician interprets the report clinically at the interface of the patient.......presenting the patient the results and the clinical implications. (This is the part that laboratory scientists often never see)

Eureka! I have finally figured out this whole play!!!!

Why is the state cracking down? When these DTC companies, Genetic, SNP, or not deliver results to the patient/consumer......the traditional method is blown away. There is no trained clinician to "re-interpret" these results in a clinical fashion!

I stumbled across this when Daniel said to me (loosely and not in these exact words)
"If your theory (SNPs + Interpretation = Medicine) then I am practicing medicine." That's when it hit me.....if he delivers these results to a trained professional...as is the existing model of genetics, then he is NOT practicing medicine. Because the clinical professional will then re-interpret the results in a clinical light. This makes tons of sense. Why? Most lab physicians and scientists have never spent a day taking care of a patient clinically.... Some have, but not most.

So, I finally get why all the lab guys (and gals) are freaking out at my comments and attacking with the "Physicians are trying to get more turf!"

The simple answer is, "That is Bull$h!z" The lab guys are actually trying a power play here. They are the ones trying to increase their turf without playing by the clinical rules. Why? Because they never had to play by them before! It all makes sense to me. How can we expect non-clinicians to adhere to clinicians' rules? They never had to before....other than this one huge rule......"The results always go to the physician/clinician."

The Sherpa Says:
This regulation is because scientists crossed the line into clinical, NOT because the clinicians want more work...Trust me, they have more than enough. The buffer is already there, no one is making any new rules....these are the same 'ol rules.....that are not being followed. That's all.

60 is the trigger for Alzheimers

Finally, a weekday post! I know, I have gotten in this vicious cycle of posting on the weekends and keeping them up for the first few days of the week, just so those readers who don't check the rss or even switch on a CPU on the weekends don't miss a beat. Listen, I read Tim Ferriss' book too...but I now have to step it up.....

Today I want to bring an interesting topic to light. Why are people scared of genetic testing? Is it the discrimination (which doesn't exist) or is it something more deeply rooted like "Genetic Determinism"? In counseling for things like breast cancer risk, some often say..."You may have outlived your risk for early onset breast cancer" This is a sticking point for me.....Who ever outlives genetic risk? Completely, I mean. There are so many variables out there that can give you cancer...who is to say that just because you are 65 your BRCA mutation won't give you that cancer? I couldn't be hard pressed to say that so vociferously. I say this because even with the strongest genetic influences there is always an exception. This is exactly the case with Alzheimers and ApoE4.

Well now a study recently released called the Arizona ApoE4 Cohort Longitudinal Study of Cognitively Normal Individuals (Say that 3 times fast) indicates that 60 may be the age of kickoff for cognitive decline in ApoE4 carriers.

According to the article in Internal Medicine News......
There is a particular pattern of decline in ApoE4 homozygotes (2 copies) that tend to precede any diagnosis of mild cognitive impairment (a stage prior to full blown alzheimers or other dementia). Or prior to anything that can be seen on radiologic brain imaging....

So what does this mean for the clinician? It is huge....Instead of outliving your risk...we now may identify those with ApoE4 who will likely get Alzheimers......CAUTION, these results are currently being replicated and I wouldn't want to promise anyone that we have a perfect ApoE4 phenotype detector quite yet. But it is important to have this....Why? Because up to 10-40% of homozygotes will NEVER develop Alzheimers. So when can we say you have "Outlived your risk"? The answer is never...but we can say "You will be less likely to have ApoE4 related Alzheimers than someone who is your same age with this cognitive deficit." That is what should be said.

Now the real quandary..."How can we stop it from getting worse doc?" That is for another post.

The Sherpa Says:
Too many in the genetics field are quick to give medical advice. I warn that perhaps we should check our training and liability insurance before we start doing this. I recommend that all of us in this field work together to provide the best care possible. I never say never and never say always....in genetics as in life, there are NEVER any definitive answers...except "sometimes" and "it depends" That being said..........We should always be performing routine screening exams on carriers of any genetic changes. Confused yet? Don't be. Just follow my lead.

New England Journal, Prostate Cancer and Babel

Remember when I said that all of these association studies had weak Odds Ratios? I also said in the Sherpa's golden rules of genome wide association study that any OR less than 2 is probably not better than a family history. Here we have a study in the NEJM listing a powerful combination of SNP data AND Family History. This was e-published back in January, but I draw your attention to it again as it deserves notice.

In a significant meta analysis it is shown that the OR if you have a first degree relative with prostate cancer is 2.5 I hope Genome-Boy and his trusty side kick Prosty are reading!

Well, this study and its shortcomings...There are some. This study Blows mere family history out of the water. This study, dubbed CAPS, evaluated Prostate Cancer in Sweden.

The analysis of SNPs revealed 5 SNPs which had significant risk implicated...Here's the kicker, if a person has 4 SNPs and Family History, then your Odds Ratio for Having Prostate Cancer is.....get this 9.46 compared to the men who had none of these factors.

Take That PSA and Digital Rectal Exam!

Now where does this study have shortcomings?

1. It is retrospective and this is subject to bias, therefore needing prospective analysis before we will use it.

2. This population is a relatively homogeneous population that breeds nationally

3. Only one of the SNPs has an identifiable gene. Without a gene, we can only guess what role the SNP may play let alone devise a medication or treatment to offset these effects

The Sherpa Says:
This is what I am talking about! When replicated prospectively...and this will be, this will be a powerful tool to use for risk stratification. To my journalistic friends, please don't report the Odds Ratio as if it were a relative risk! To my prostate prone friends....cheer up. Prostate Cancer is rarely a killer.

One Fifth of GDP!

What are we doing? Why isn't it working? In a recent report by the Centers for Medicare and Medicaid it turns out the US will be spending one-fifth of it's GDP on healthcare. Here is the big question.....Will we be more healthy as a result?

I started this blog to demystify and inform about the field of personalized medicine (A dying term as far as I am concerned....especially because clinicians and the public do not understand it)

Let's call it like it is Genomic Medicine or more affectionately Molecular Medicine. Why are we spending so much and getting so little for it? It is called the One Size Fits all model. Last night I ast at a talk given by a physician friend of mine. We were at a very nice restaurant named Valbella! and I was amazed.......the big pharma mantra keeps on being the same...."This is the right Drug for All Patients"

From: Health Spending Projections Through 2017: The Baby-Boom Generation Is Coming To Medicare

Growth in public spending, on the other hand, is expected to accelerate toward the end of the projection period as the leading edge of the baby-boom generation becomes eligible for Medicare. From the sectoral perspective, prescription drug spending growth is projected to decelerate in 2007, driven by slower price growth, but is expected to accelerate through 2017 as utilization increases.

Why are we using more drugs? Several reasons. One being lower target thresholds for numbers like cholesterol. i.e. more and more people will have cholesterol numbers "High Enough" to be placed on a medication. Huh? Well we have target numbers to treat for LDL (lowsy cholesterol), blood pressure, blood sugar...etc all based on your pre-event risk of event.

As it stands we like to risk stratify for heart attacks based on everything but family history of heart disease. Therefore, in order to reduce the incidence of heart attacks we need to treat a higher number of patients...... This NNT for cholesterol lowering medications is around 40:1

Why so high? Well from the public health perspective it is not that high a number. You put 40 people on a medication to prevent ONE 10-15k USD cardiac cath. The cost of the other 39 people on the pills? Less than the cath and long term sequelae.

If you really want to lower costs, start identifying those who will maximally benefit from the medication. Then the NNT could turn into 20:1 or maybe even 5:1

This is the power of what genomic medicine can do. That is why everyone at the governmental level is excited. Imagine the cost cutting that could be done for the rock bottom price of a one time 1000 USD FULL GENOME SEQUENCE! When will this happen? Soon....but not immediately. We need some good outcomes data and that may be ready by 2017. We will gradually see genomic medicine evolve over the next 10 years...but we are practicing it in its simplest form already.

The Sherpa Says:

You want Genomic Medicine? Then call congress to pass GINA. You want the power of whole genome sequencing? Then fund sequencing technologies. You want better testing and more evidence behind them? Then get tested through your physician. But if you want status quo, be scared of genetic discrimination, buy online tests to perpetuate the fear, hide those results from your provider, AND believe that your genes are your full fate. This is the uninformed path we have laid out in front of us. Please join me in switiching paths.

Shaking Chills, Houston Texas and 1000 USD

I couldn't figure out whether I was hallucinating from the fevers or if the email I received from a reader was correct. He said "Could you explain this to me, from 350k now to 1k? How could this be"

He was of course speaking about the PacBio (Like Pacific Sunwear/PacSun) technology and press release that Reuters put out there. Man why can't I get on Reuters at the drop of a hat?

From the release
" A California company predicts it will soon be able to sequence an entire human gene map in four minutes, for just $1,000."

"It will change health care forever if it works," Hugh Martin, the chief executive officer of the company, said in a telephone interview on Monday

Martin thinks Pacific Biosciences' new technology will be able to get a human genome done in about 4 minutes.

Yes, my wonderful readers. These are the key words in this news release. From that tone, it sure doesn't sound like a finished deal yet! There are several things to consider with this new technology including the cost to implement and its fidelity of genome analysis. But don't be surprised if someone builds a better mousetrap soon. But the short answer is....Genome for a Grand? Don't hold your breath.

That being said....I want to re-emphasize the benefit of directed testing. This is a good market and now DNADirect it appears has a direct competitor. DNA Traits dot com is a place where you can get free genetic counseling. At rock bottom prices of 75/hr at DNA Direct I am flummoxed on how they actually pay their counselors. Now you go and say that their service is so insignificant that it is FREE? Come on....where is the business plan here? Some way they have to be making a profit...Dr Bettinger covers this company very nicely on his blog.

Their list of advisors includes a Critical Care Medicine/Population Geneticist. Great for geneaology....."Doron Behar has multi-year background experience in the development of genetic testing for the public using a direct internet based customer approach." It appears he IS a mitochondrialist! Unfortunately on the site I couldn't find the names of the genetic counselors willing to work for free :(

The website even has the DNA Direct feel to it. Interestingly, now I may have figured out where my Houston readers are coming from. Houston, Redwood City, Mountain View, Cambridge, San Fran, NY, DC these are all my hotspots for daily readers. I wonder why.

Lastly I saw a quote from Dr. Bruce Korf. I will email Dr Korf today and as how he feels about his name on the DNA Traits site.

DNATraits agrees with the recommendations set forth by the American College of Medical Genetics in their Statement on Direct-To-Consumer Genetic Testing. In this statement, Bruce Korf, MD, PhD, says, "It is critical that individuals ask for a referral to a genetic expert who can help in determining what tests might be advisable and in interpreting results."

More importantly, if testing is even advisable at all. I have some difficulty with FREE counseling without stating what those counselors are actually working for. I hope it is not commission......

The Sherpa Says:
No I am not hallucinating. The genetic and genomic market just got a little more crowded. Once again.....I ask that we make informed decisions regarding our testing and get some professional advice. FREE advice is just that. Even a free initial eval should be followed up with care that is paid for. As for an MD only reviewing POSITIVE results...what about the Maybes? Is a Negative really a negative? I would want an MD to review all results. Why? Because it is just good care and should be the standard of care. We can't cut corners in genetics, no matter how stretched we are. This goes true for a sodium level or an extremely complex genetic test.