"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. "

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.

"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.

I recently read a Times blog post by Mark Henderson because it was referenced by Dan Vorhaus on Twitter. I have to say, I am blown away by the cognitive dissonance here......

entitled " The end of deCODE genetics: are you worried about who holds your DNA?" I was interested in to see whether this was a slash job on deCode or not.....

"Does this worry me? Not really. First of all, as Dr Stefansson pointed out to me yesterday, deCODE was a publicly traded company, listed on the NASDAQ. It was always up for sale, and in a manner of speaking its ownership was changing all the time."

Is he serious? Minor shareholders having access to a company's intellectual property and a hostile board takeover? That is what it would have taken to get the control.....or bankruptcy. Which is yet again another reason why a doctor would be able to protect this data better than a corporation.

Will there be any more doozies in this?

What I found was a hard pill for most to swallow. The end conclusion:

"What's more, though, I've yet to be convinced that there is anything particularly sensitive about an individual's genetic information. For the moment, at least, the sort of genotype data held by deCODEme isn't very useful to anybody other than me -- and even then, its chief value lies in satisfying my curiosity. I'd be much more worried if it was my financial data that was changing hands"

Ok, so here is the problem. Either you believe or you don't believe that your genome will hold useful information that may help predict your risk for disease.

If you do believe, then how could you not be scared about some discovery down the road that may be used against you by the "new owners" of your data?

If you don't believe it is a big deal, then why in the hell did you have the scan in the first place? To write a "news" story? Sorry, I mean PR piece......

In fact that's it. The people who bought these DTC tests were SV tech junkies and piss poor journalists who couldn't get anything else published. Now that they have all used up the story, there is no one left to buy decodeme.......et.al.

I do agree with the writer on one thing: There will be more failures. No amount of PR can fix that.

The Sherpa Says: Either you believe or you don't. For those who do, DeCode's failure should shake you. I am certainly glad I chose the IRB approved Coriell Personalized Medicine Collaborative to do my SNP scan.......

Today's lesson in start up business in the field of DTC Genomics is this.....

I have been railing the last few days so I want to take a step back and examine what exactly is happening in the DTC Genomics space. (By no means an exhaustive list)

Navigenics-Partnering with a concierge medicine group of Internal Medicine physicians, convincing them to use an unvalidated genome scan to practice predictive medicine. Also using clinical language and inferring that this service can be used as such. Also with the new CEO who used to be a muckety muck at Humana Insurance company.........Hmmmmm, add in the PR hype of partnering with Harvard to Educate the pathology residents about microarray testing without the knowledge of Harvard's Clinical genetics teams.....and you have some pretty nefarious stuff going down here.....in the quiet light of day.

Pathway Genomics-Funded by the PayPal Mafia and the Napster Wunderkid split their services into clinical and ancestry. Got grilled at the Institutes of Medicine conference and basically had no good answer for why their service was not the practice of medicine........

23andME-Partnered with anyone they can get their hands on, recently split their service lines into ancestry or clinical OR both......They have had 2 rounds of layoffs, lost one of their founders, moved into the googleplex, have employees leaking info about them online, have cut software engineers and kept the PR/marketing people, pissed off the NYS attorney general and now changed prices AGAIN

TruGenetics-Couldn't find funding and are in holding pattern........who knows what that means. But they did prompt a brief legal review of what would happen if one of the DTC companies goes bankrupt or is sold......Basically, all bets are off and your data will likely be sold off without your consent.

Knome-George Church's vanity plate is still alive and kicking. Partnering with SeqWright and Beijing they are positioned to take care of the rest of the worlds billionaires.......until the price of genome analysis comes plummeting down........

Scientific Match-Still making matches one MHC group at a time.....luckily they don't test for medical conditions.....

DNADirect-Wow! Has Ryan managed to drive under this radar! I am so amazed at what DAN Direct has morphed into. They are in essence a medical practice who also directly competes with generation health on the GBM side. They are also serving as a telegenetics consultation service. In all honesty, DNADirect is the true bellwether here. They have been around since 2004 and have weathered all the shitstorms. Which means, many other companies are likely to follow suit, in a matter of years and at a matter of costs.

DeCode-What was their stock price again???

DNADynasty-Enough Said

There are others, but I think this is a good list to review and think about where they are in the life cycle of direct to consumer genetic testing.

The most interesting of these is DNA Direct. Ryan Phelan started out with a message of:

"You deserve direct access to your genes"

Then became, "We partner with doctors to give you the best care of your genes"

Now is that PLUS, "We help your insurer save money by directing how you pay for your genes"

What has occurred? Well, they saw the law, they also saw that they couldn't survive with just computer science engineers or marketing and PR folk.

Ryan saw that the real growth potential is in caring for people. Why is that important? Because genomic medicine is about medicine and people. Not stock photos and flashy websites.

She is right. I am always amazed by her prescience here. Despite my wailing about here over the years, she has come around to my side....

Will the other companies follow suit? One thing is for sure, Ryan isn't around just because she has raised lots of capital....

The Sherpa Says: I have been here climbing the personalized medicine mountain for a while now. I have seen 'em come and go, but Ryan is a seasoned climber. More of these companies would do better pay attention to her rather than silly price changes....

"As I had postulated before, in order to move towards a profitable direction the DTC companies would have to choose "Medically Relevant" or "Novelty Testing" From this recent email sent to me by a reader it is clear, 23andME is Choosing to become a clinical service, without accepting the clinical responsibility."

This from my post February 14 2009

That was the day the announced that they were doing BRCA testing. Since then we have created a little video that may now be running through the silicon valley.........

Why?

Because, at the Spittoon (brrrrrrr-ding) they have announced that they will be splitting their service into 2 different types of tests

The first "A Novelty Test" which will be solely for ancestry.
23andMe Ancestry Edition – $399

The second "A health test" which will be solely for medicine while still disclaiming it is not. 23andMe Health Edition – $429

"With the launch of the 23andMe Health Edition we are releasing 13 new carrier status reports. These reports will help you know more about what may be in store for the next generation. We are expanding our cystic fibrosis panel report to cover the full panel of mutations recommended by the American College of Medical Genetics, as well as several additional mutations. We will also be providing data for most of the mutations routinely screened for in the Ashkenazi Jewish population, including those associated with Tay-Sachs disease, Canavan disease and Bloom’s syndrome.

We are also continuing to expand our drug response offerings. The next report to come out, Pseudocholinesterase Deficiency, contains information for anyone who will be undergoing surgery."

Ok, a couple of things.

First-This health test IS a MEDICAL test. I have sent off CF carrier screening medically, I have also sent off for Malignant Hyperthermia testing as well.........

Each has their own limitations which I have had to counsel patients about........For an hour a piece.

Second and more importantly, this appears to be another price change for the 23andME service.

If it turns out this company gets eaten up by Google, I am certain google will then own your genome scan data.....So I have one thing to say to the consumer

"If you want google to own your genome data, then by all means buy a 23andMe test"

Buyer beware here, please. I only ask and beg the proper authorities to uphold the current laws and regulate appropriately to protect the public health and welfare.

Why do I say this? Because a BRCA test or a CF carrier screen which was inappropriate that has been performed already on the public, without medical regulation, or without proper medical guidance could cause harm.

Lastly, this is likely a salvage play to keep the ancestry service before the feds come sweeping in......shut the medical service down.

I am certain.

Well, at least they (Feds and 23andSerge) have heard us........we only grow stronger because we are correct and hold to the theory that "What's Important IS What Is Important"

The Sherpa Says: Democratization is important, but so is not dying.......Why mix hair color with BRCA testing? I am glad Serge sees that too.......But now that leaves the health test as "Not for Fun" Looks like quite a change in defense of Mountain View's medical practice without doctors.....

Is it any surprise that insurance companies have no clue what the hell is going on with genetic testing?

You see, there are a set of ICD9 codes that can mean 2C19 testing or hepatitis pcr........

The coding system doesn't allow the companies to run their algorithms accurately......

Insurers have no clue which is which and they are getting banged out for these tests.

Don't believe me, just take a look at what United has done with their BRCA testing (which BTW has their own codes)

"By instituting a prior notification policy and placing Myriad in charge of determining which patients get tested, United Healthcare can monitor more closely which of its policy holders are receiving testing on BRACAnalysis."

Add in the SGO guidelines which suggest a 5% BRCA carrier risk may be worthwhile and you can see why the companies are looking to stop the carnage or testing overuse.

Myriad on the other hand would beg to differ. They see years of under utilization as something to combat. And they are very successful at it, just check out MYGN.

The answer is somewhere in the middle. What is a responsible insurance company to do?

Answer: Generation Health.

What happens when genetic testing costs less than 100 bucks? Well, then maybe Generation Health will need to speak with me regarding a diversification company we are working on.....

With other PBM companies actively looking at new automated strategies for GBM (not glioblastoma multiforme) Generation Health is an interesting play.

I remember speaking with a certain player who also was involved with the DTC companies, who agreed with me. DTC is a bull$h!t play, benefits management of real testing, hyperlipids, HCM, etc are where the puck will be......From the Genome Web article (HT Turna Ray)

"The partnership will also “allow the companies to explore future programs in the medical diagnostics arena to encourage appropriate and cost-effective testing for certain hereditary diseases, and eliminate unnecessary testing where evidence for clinical validity and utility is lacking,” the collaboration partners said in a statement. "

We talked about this for some time (unnamed MD and myself) and then.....radio silence.......Only to show up with funding and some small hits.

They chose genetic counselors instead of my band of geneticists......

These guys are moving in the right direction. The industry is shaping up and guess what the killer app for genetic testing is?????

That's right, actual, honest, regulated medical testing........ Go figure.

Now, who gets what, how is it paid for, how is it used?

These are the questions that will need to be solved.

Until of course the accuracy and cost of a genome is less than 500 USD Which could be quite a while.

Meaning, Generation Health has about 10 years of life as the company it is right now. Not bad.

Imagine saving insurers millions per year, then taking 10-20% of those savings......... per year CVS/Caremark is a great partner and now owner/investor.........A very strategic investment.

My guess is that the DTC companies will fall in line or perish. Then labs will have to start marketing better, offer faster turnaround times and there will be "preferred" lab status.....per insurer.

Basically creating a super confusing land mine for physicians and patients. Just like radiology, just like surgery, just like chemo, just like......medicines

The Sherpa Says: Finally, corporations and investors are figuring out what IS important. Staying alive and having your medications work!!