Thursday, December 31, 2009

Another Year, Another Bankruptcy


Tally Time. It is time again to see whether my predictions for 2009 were right. Or if I was way off the mark.

The Highly Likelies first
1. Francis Collins will become the Director of the NIH........You Betcha I pegged that one.
2. We will see a pharmacogenetics lawsuit......Well, still haven't seen that yet, despite the FDA label changes

Batting 500, next up

Long Shots

1. X Prize winner: PacBio, ok, maybe I was a year early on this one
2. Oprah's gene scan bougus. Guess what? It Was!

Still at 500, who's next


Ok, these are what they say they are. Ridiculous. I don't think I can be held to the same standards for these swing for the fences.....

1. Mark Cuban Buys the rights to the 23andME database. Ok, I was off. DeCode tried to steal it and Google keeps dumping money into it......Both just as crazy as if Cuban would buy it......
Maybe we call that a fly out?

2. Next-Next-Next gen Sequencing will have heard of nanopore right? Is this Next-Next Gen? Or Next-Next-Next Gen? Hmmm. Foul Ball!

3. The last one is so silly I don't think it was meant to be called...........The US fracturing into territories and fighting against the world.......Not quite yet.

So on to this year's doozies!

Highly Likely

1. Another DTC failure......yes. I won't say which one.
2. One of the DTC Genomics companies will get into clinical care. They will set up shops. It may be a newcomer or an old dog. But it will happen.
3. We will have data on PGx testing with Plavix. And it will support the use.


1. Francis and Kari will start the Population Genome Study in the US
2. The XPrize will be won by Complete Genomics.


1. Again, Mark Cuban will Buy Sergey's share of 23andMe's database
2. Myriad will lose the first round of hearings re: their gene patents......

The Sherpa Says: If Kansas went bye bye last year, this year we will have to "Pay no attention to the man behind the curtain!"

Thursday, December 24, 2009

Lp(a) Maybe there's something there that wasn't there before?

I unwrapped the NEJM this week and to my surprise it has a Lp(a) stuff in it. One of the things we do to prevent heart disease is take family histories. We also check cholesterol levels and include something called a Cardio-CRP. One thing we haven't been including is a Lp(a). Why? The only data I see that is good on this is on women.

We use validated risk tools like Reynolds and Framingham Risk. It was with great interest that I read about this recent "candidate gene" model of assessment for Lp(a) genetic link to levels and risk. Clarke et. al.

They also looked at the other GWAS linked regions and what they found was most surprising in my mind.

LPA, which encodes apolipoprotein(a), was the only true "candidate" gene on this custom array that was significantly associated with coronary disease.

Now why would the other regions not be as strongly linked? Or better yet, why was Lp(a) more likely to be linked and associated?

Well, LPA the gene produces a protein called Lp(a) which is hypothesized to carry oxidized proinflammatory phospholipids, thus promoting inflammation in coronary arteries in turn creating niduses for clot and heart attack.

What do the other regions do? Dunno. I think that is the teaching point here.

GWAS great for illuminating possible pathology, which then in turn must be dissected and validated.

Candidate screens are good for risk markers IFF there is some hint of WTF the proteins are doing for the disease.

This is why I am just flummoxed by the fact that people are still pushing tests which have little to no clinical use or even prognostic capabilities.

Listen, you want to discover yourself? Go get a cholesterol, Glycohemoglobin, and complete blood count. Check your blood pressure, check your BMI. If any of these are abnormal, go seek professional help.

But please, please, please don't use SNPs that have no science behind them as true science or clinical markers. research them, sure. But using them like MDVIP has........Risky guys.

Which reminds me. I am taking care of a patient who recently left MDVIP.......the patient had the Navigenics SNP scan done.........what do I find on family history?

The patient met Bethesda Criteria for HNPCC.........

Guess someone was too busy scanning Unproven SNPs.

That being said, this current study by Clarke suggests a few things

1. Two LPA SNPs explain approximately 36% of the overall variance in plasma Lp(a) lipoprotein levels. That could be like the CRP story. Yeah CRP levels but no association with risk. Big Whoop, but....

2. Both SNPs (one coding for the amino acid substitution I4399M and the other non coding) are associated with coronary disease. Ahem, like to see some replication here......But it could be true.

3. After adjustment for the plasma Lp(a) lipoprotein level, the association between LPA genotypes and coronary disease was abolished. Well.....that means to me, phenotypic testing with Lp(a) levels may be more useful than I had thought.....And definitely more useful than genotype testing.

The Sherpa Says: Hmmmm, maybe we will see much more of this trend. Non-genetic molecular testing being more valuable than genetic testing for risk prediction.....Wait a sec'

Wednesday, December 23, 2009

Merry Christmas

Ho Ho Ho!

As I begin to enter year 3 of this blog I have refined my thinking and working to effect change. Personalized medicine delivery will change soon, so will personal genomics. I hope to create some of this next year. Until then, Merry Christmas everybody!

The Sherpa Says: And to All a Good Night!

Thursday, December 17, 2009

Navigenics for 23andMe prices?

Yes, That is correct. As if this stuff couldn't get any cheaper. It does.

Happy, healthy holidays! Holiday offer: Our #genetic service for $499 (half off). Use code naviholiday2009 at checkout."

That straight from the mouths of the Navigenics Babes, Seriously. Do you know Katie Kihourany?

Everyone including Daniel MacArthur is yelping about the DeCodeMe free analysis offer, but I have yet to hear anyone screming about the 500 USD drop in price of Navigenics service. Ladies and Gentlemen, this is a 50% price cut.

In what world do you cut your service cost in half? This didn't even happen with the iPhone. Seriously?

This is a bad, bad sign coming from the team at Navigenics. Nearly a year ago they launched Annual Insight for 499.....Now the whole ship is up for 499........

I have yet to see how this market is the market for Whole Genome Testing. In fact, my assessment is that whole genome sequencing will not be used widely until it costs less than 300 USD.

Why? Can your genome data play crazy videos of Will Smith? What about making a phone call and downloading songs? No?

Well, what can a whole genome do for you? Good question. The iPhone wins because in it's ads it shows you what it can do......

These tests and the whole genome have not shown that utility. That's why they are cutting their costs.....because the can't show that they have use........

And that is precisely why deCode is offering its analysis service for free. They want to show you what they do........

The Sherpa Says: Like I said before, climbing Everest with one Crampon a windbreaker and a map is not what most rational people want to do......

Thursday, December 10, 2009

AJHG is in and my Favorite Muin is in it! But He Is NOT the Father!

"With breast cancer as an example, we examined the combined effect of uncertainties in population incidence rates, genotype frequency, effect sizes, and models of joint effects among genetic variants on lifetime risk estimates. We performed simulations to estimate lifetime breast cancer risk for carriers and noncarriers of genetic variants. We derived population-based cancer incidence rates from Surveillance, Epidemiology, and End Results (SEER) Program and comparative international data. We used data for non-Hispanic white women from 2003 to 2005. We derived genotype frequencies and effect sizes from published GWAS and meta-analyses. For a single genetic variant in FGFR2 gene (rs2981582), combination of uncertainty in these parameters produced risk estimates where upper and lower 95% simulation intervals differed by more than 3-fold. "

Did you get that?

They took a look at what it really means to give point estimates for lifetime risk of disease comparing with population risk data. In this case they chose breast cancer.......and FGFR2

Their conclusion?

Epidemiologic parameters involved in computation of disease risk have substantial uncertainty, and cumulative uncertainty should be properly recognized. Reliance on point estimates alone could be seriously misleading.

Do you get what they are saying? Let me break it down this way. When I see a patient for BRCA testing they always ask

"How high is my risk?"

I say: " is a range."

Most people don't like ranges. In our little rat brains we think a range means uncertainty and probably a little guessing. Most patients don't like to go to doctors who give ranges or guesses.

Nor do people like buying things that don't give them "exacts" People very often, when left to their own devices would choose black and white over gray. They just don't like feeling uncertain.

That's precisely the big problem with how genetic testing has been marketed.

Think about it.

On 23andMe: Find your Norovirus resistance!!


Sounds pretty certain to me.....

Do you get it?

Well, the answer is simple. Nothing in life is certain. Nothing, except death and taxes.

This study shows that if your model relies on too many uncertainties, your risk model fails. This is the biggest problem with the DTC Genomics companies' models. They are based on too much uncertainty and as such fall in the realm of fortune teller rather than risk prognosticator.

This is precisely why I have said "Data is Data, but Data can be Garbage."

And Garbage In = Garbage Out.

The Sherpa Says: with any risk model there is uncertainty, no surprise there. But the real surprise is the marketing of it as CERTAINTY to an unsuspecting and primed for certainty public.

Tuesday, December 8, 2009

What about the SACGHS registry? Another missed opportunity?

Remember this? From GenomeWeb

“After extensive fact-finding, consultation, and analysis, the committee found significant gaps in the US system of oversight of genetic testing that can lead to harms,” SACGHS states in the report. “The committee also identified novel opportunities that would enhance oversight.”

What are these novel opportunities to enhance oversight?

"As reported by Pharmacogenomics Reporter in February, the establishment of a mandatory, web-based registry for all laboratory-developed tests is one of the main vehicles the committee is proposing in order to improve how the federal government regulates genetic tests [see PGx Reporter 02-20-2008]. "

The 21st Meeting of SACGHS will occur in February of 2010. I wonder if this recommendation has gone on deaf ears. With all the turmoil surrounding health reform, will HHS take genetic test regulation up? One of 3 or 4 things may happen.

1. Health reform happens, billions flow into HHS and they form a committee to set the SACGHS recommended registry up.

2. Health reform happens, they are so busy that this gets queued.

3. Health reform doesn't happen. Nor does the Registry.

4. Health reform doesn't happen, thus the HHS has the time and attention to set up this registry.

But what I really want to know is: "Will the HHS including DTC genomic testing give these companies a perceived seal of approval?"

Better yet, will these companies be listed?

PWC has said Personalized Medicine will grow at 11% (How the hell they come up with that figure g-d only knows) Do I think DTC genomics will be included in the growth? Probably not. This type of testing will not grow until it is less than 100 USD.

The Sherpa Says: Like I said before, unless PM can cure cancer or prevent HIV it is likely to be difficult to sell. No matter how many meetings Harvard/Scripps/Etc has. What needs to happen is promotion of physicians (like my group) who are actually implementing PM.

Tuesday, December 1, 2009

15 Days Away Gives Time for Perspective.

"Although there appears to be a clear relationship between UGT1A1 genotype and severe neutropenia (and some evidence of a relationship with severe diarrhea) there is no evidence to support or refute the hypothesis that a modified initial and/or subsequent dose of irinotecan will change the rate of these severe adverse drug reations." -EGAPP working group analysis of UGT1A1 testing

That is where most of personalized medicine (PM) is at today.

Why is this important? Because this precise clinical set of questions will be worked out over the next 10 years.

While I have been taking a break from posting some things have become crystallized.

The first thing: In an economic downturn, your genomic/PM product better have intrinsic value.
Chances are, if you have to have big celebrities and open bars to launch, you need to rethink the product.

The second thing: If you think you can take science to market in less than 5 years, then you need to do one of 3 things.

1. Immediately Cure Cancer

2. Prevent HIV infection

3. No, there are just 2 PM things that will work here.

Do I think there are products that don't involve direct basic science that will help personalize medicine which CAN go to market quicker than the 10 year revolution we are about to undergo?

Yes. But none involve PhD geneticists. They involve computer scientists, automation, email, etc.

This latest bubble of DTC Genomics existed just so the SV could cut their teeth on genetics for the big bite 5 years from now.

Why is the Sherpa such a naysayer?
I am not. I am a realist planning the ascent of the next tier.

That Tier is clinical utility.
Yes we still have the missing heredity here. But let's say that will come in the next 5 years.....maybe We still have 5 to go.

Those 5 will be used for clinical studies, for outcome and guidance of therapies.
But that is only the next tier.

Pragmatic physicians and scientists will demand replication, some will fail, ultimately casting doubt on the field as a whole.

This will further driving pragmatism and encourage naysayers.

Don't believe me. You have heard the new mammographic guidelines from USPSTF, right? Pragmatists have always said we don't need so many mammos....

Now so does Consumer Reports !!!

Many people place their trust in Consumer Reports. It is clear, they too see a case for overspending.

In an economic environment a savvy entrepreneur will look for targets like Asia.

As a doctor, I know most PM tools are on the horizon, so I pragmatically pick up my pen and pedigree.....

I am at my ICOB meeting today and am posting this from there. We will be going over several genes and variants. I am excited because OSUMC has now partnered with CPMC......there is no doubt this project will continue to grow in strength and importance as we have quite a cohort.

The Sherpa Says: Poor PM, attacks on every front. But don't worry, in the end, we win.