A few months late to the party....

This month's Internal Medicine News has Dr. Patricia Ganz on the cover.

I couldn't help but say, "Why does she look familiar???" But then I read and remembered

"Few physicians feel prepared to interpret findings from direct-to-consumer genetic tests and incorporate the results into clinical practice, according to speakers at a National Academy of Sciences workshop on DTC genetic testing."

Ahh, yes, she was at the National Academy meeting which served as the official hammer to DTC genomics....

These first intro words from the one of many articles in the Internal Medicine News about Genomics hits home

"Few physicians feel prepared to interpret findings from direct-to-consumer genetic tests" I have a serious question.

If these "tests" are for "fun" and not to be used for medicine, then why should it matter if doctors feel prepared to interpret these tests......

Should they not be interpreting these tests at all?

Since, after all, they are "not to be used for medicine".......

Well, unfortunately, the marketing firms and PR firms have pitched these little babies right next to other OTC medical treatments.......

Which means, the public will "Think" of these tests as medical.

And hell, why not?

Freaking 23andSergey is testing for the Ashkenazi Jewish BRCA founder mutations and placing the results right next to IBD, prostate cancer and heart disease, which BTW is right next to ear wax type.......

The biggest problem here is the confusion of "Medically important" with non medically important.......

When a consumer reviews important sounding stuff with non important sounding stuff, the non important looks more interesting, because it comes with stuff that "Can keep me from dying!!!!" This is the problem here.

And despite what Howard Levy of JHUMC says, I am not down with this problem continuing to exist.......we have allowed it to happen way too many times.....

My prediction is that clinicians will tune out this noise of DTC and use it as another excuse to tune out TRUE CLINICAL GENETICS......How do I know this? Because I know community physicians. They are WAYYYY different from the academic clinicians out there......

Dr Levy is incorrect in assuming that DTC will push the clinician to "Learn Genetics or Consult a geneticist"

Hell, most geneticists couldn't tell you what a heart attack and it's treatment entails these days. Unless of course they have had one. You should have seen the talk about Brugada up in New Haven, what a mess! I leave aside the IM genetics brethren here.....which are less in number than astronauts.......

And now that the team in Mountain View put out a press release about pure swill, it is all too clear to me what the hell is going on.

These guys are desperate. They need to live, or else the empowered genetics patient will die.

Or so they think.

This couldn't be further from the truth.

Genetics and Genomics is doing just fine without these boondoggles...... Do we need NYT spreads to survive and thrive? The answer: No.

Why?
1. Francis Collins is head of NIH
2. Obama proposed bills supporting Personalized Medicine
3. Major corporations are investing in useful genetic technology
4. Clinical research is progressing nicely in the PGx space
5. Clinicians like myself are organizing and practicing personalized medicine

So, I ask you "Why should we support something that distracts from the reality of genomic medicine?"

So we can have them figure out the interpretation algorithms? Well, they have shown what a complete hash of that they made...... For seven diseases, 50% or less of the predictions of two companies agreed across five individuals

So we can get the public supporting Genetics in Medicine? I think we know that the public supports us, with or without them.......In fact they support us more WITHOUT them!!! Because what the public fears can actually legally happen especially if a company goes belly up......

So they can carry out the next level of collaborative research? Have you seen the latest joke research? No thanks, I'll stick with Coriell for now...Maybe Scripps too.......

Suffice to say, from my view point on the mountain, these guys (DTC Genomics) are actually parasites, sucking the energy from the movement. They contribute nothing but hype, which now will turn to backlash......

In conclusion, this backlash will detract more from the movement than the hype added to it.

The Sherpa Says: Why continue to support something that in the long run will damage credibility with community physicians and the public? Why?

Ok, Fine, Back to Plavix

Did anyone else see this?

Scripps and Eric Topol are going to be doing testing for 2C19 polymorphisms in their interventional dept.

"Scripps physicians will initially offer the genetic tests to elective stent patients before they undergo their procedures at Scripps Green Hospital. Eventually, Scripps may extend the offering to its other facilities across San Diego County."

I have been prodding Greenwich Hospital to do this.....I hope they do......They could be the El Camino of the East.

What are these guys, Topol et.al going to be doing? "Scripps patients carrying the gene risk variants will be considered for three treatment choices following their stent procedures, each on an individualized basis. Patients will either:

• Be given a routine 75 milligram dose of Plavix with careful surveillance;
• Be given a 150 milligram dose of Plavix, which has recently been shown to be safe and effective in patients showing lack of response to Plavix; or
• Be given the newly approved medicine Effient (prasugrel), which is not affected by the gene variant Cytochrome (CYP) 2C19."

So there you have it. A cutting edge medical facility doing this. I am only all too certain we will see about 20 hospitals follow in their footsteps in 2010.....

The Sherpa Says: Wha? These guys are like a year behind me......I have been doing this since January........

This Just In. 23andMe to go to GPs. I love my readers!!

That's correct. 23andSergey are going to offer GPs deep discounted SNP scans to General Practitioners in England.

As she is interviewed by The Times!!!

This comes just DAYS after I said that their market is in England, NOT the United States.....

"After listening closely to Timothy Aitman of the Imperial College of London, it seems to me that the market for DTC is not in the United States.

It is in Jolly 'Ol England. "

One of my readers sent this to me today and I laughed and laughed.

Why?

I am filling out an abstract that I will present to the GAPPNET meeting in Michigan.

It is about media response and attitudinal change to these companies correlated to my blog posts......

So what does Jolly 'Ol Anne and Bloody Sergey plan to do for Londoners????

"Ms Wojcicki said that it would be especially important for companies like hers to work with doctors to interpret genomic information, as the costs of DNA sequencing fall further. It is widely predicted that it will be possible to sequence anybody’s entire genome for less than £1,000 within a year or two, to reveal genetic variations that influence disease risk and response to drugs."

Ahhh, now you want to work with doctors Eh? Maybe listening to Mari Baker a little???? Physician distribution centers......

OMG, Dietrich, did you tell them our plan????

Well, count me in. As long as you come on bended knee. I will hear what you have to say. But then you have to hear what I am to say as well........

I have been getting CPMC data, this is no different, except the lack of IRB, the potential of bankruptcy sales of my data, the pootential of google linking this data to my gmail account etc.

The Sherpa Says: After trying to replace doctors with algorithms and getting bashed up against a brick wall, I would be more than happy to help you do this the right way.....Unless of course, you eat pain for breakfast!!!!!

Re-Reviewing the National Academies

After listening closely to Timothy Aitman of the Imperial College of London, it seems to me that the market for DTC is not in the United States.

It is in Jolly 'Ol England.

Timothy seems to be very Pro-DTC and Dr. Khoury(CDC), Dr. Ganz (UCLA) and Dr Korn (HARVARD) seem to firmly believe that regulations are needed and that they should be treated as one in the same with "Any other Clinical Laboratory that is offering similar services"

Frederick Anderson asks, "How far does this go? Does this go to the interpretation or the testing? Or Both?"

It seems to me that this panel is Pro-Regulation.

Timothy BTW is just a presenter, not a member.

My guess, National Academies will conclude that the regulation of these companies currently is not up to par. In fact, they may conclude it is an area in dire need of further regulation. What will that mean?

The business models of these companies will shift towards research focus. OR, they will start medical practices. Which is sad that they run away from regulation as opposed to actually sacking up, taking the charge and doing it the best they can. Ah, such is the fickle problem with Venture Capital......why take that risk of regulations with other people's money. Understandable.

The Sherpa Says: I will cover the Alzheimers stuff later. It is not as exciting as you may think.....

Is it true?

Did Anne really dump Linda for Google?

Inquiring minds want to know.

I am looking forward to the next couple of weeks out of the DTC Genomics community.

IMHO, they were not that impressive at the IOM/National Academies meeting.

In fact, I came away with some significant questions which I am certaim the IOM will have as well.


First and foremost, "Tell me why you aren't practicing medicine"

No one here wants to stifle progress. But we don't think you need to break a dozen eggs before you get your omelette.

You would figure someone who had gotten a seat on the Board of the Foundation for the National Institutes of Health would have figured that one out.

Yes, that is correct.

She sits on the foundation board for the NIH!!!!

Once again I am amazed!

My Hypothesis is this.

Francis Collins has never come out abashedly against this type of testing. Why? He needs a Phenome Genome Metabolome study that can be run via the web. He is friends with Kari Stefansson, who knows how to do this. And NOW it appears Anne is on his Foundation's board. What a seriously crazy coincidence............

I do wonder what it takes to sit on that Board. My guess is that you have to have billions of dollars.

Because that is about all she has. B.S. from Yale (yeah, that and a 2.50 will get you a cup of joe), Company founded by her with her husbands money. But it is notable, that this young woman wields quite a bit of power now.

My guess, 23andme Francis and the NIH will sponsor the largest personalized medicine project to challenge the Coriell Personalized Medicine Collaborative.

Barack Obama will need a good will piece like this to erase the banter of health care and it will make everyone see how future oriented he is.

23andSergey win by getting access to the data, NIH wins by leveraging a huge tool which previously had stunted most large cohort studies, President Obama wins by changing the topic to something a little less controvesial (Unless you are an Eschatologist.....)

This will probably be announced in under a year.

The Sherpa Says: Yes 23andSergey, Drew was right, you will probably outlast all others because of your shear wealth. That doesn't make it right, or ethical, but in Washington it is what it is........

First Mari, Now Linda. Who's next?

First,

I wish Linda Avey all the best, eve though she stared me down in 2007 like I was some pariah doing awful things screwing up her plans for world domination.......

Second,
I wanted to point out that this is the second Woman CEO to "step down" to do other things in the personal genomics space.

The last was replaced by some guy named Lord.

I wonder if 23andME will get a guy named Jesus?

The public scoop From Kara Swisher Linda's email to the 23andme drones.

"I’m leaving 23andMe and have begun making plans for the creation of a foundation dedicated to the study of this disorder. The foundation will leverage the research platform we’ve built at 23andMe–the goal is to drive the formation of the world’s largest community of individuals with a family history of Alzheimer’s, empower them with their genetic information and track their brain health using state-of-the-art tools. We’ve always planned to include Alzheimer’s in our 23andWe research mission…I’m just approaching it from a new angle."

It is becoming more clear.

With Linda gone, Google can now buy 23andMe.

Maybe make it a Google App???

Interesting, but it is with Anne's email that I am most curious......

"In the weeks ahead, we will outline a strategy for the company that we believe will make genetics a routine part of health care and will lead us to making significant research discoveries."

Holy Sh!t Google has found a way to do a 20 year cohort study in less than a month! Maybe the also have found a way to brainwash physicians into performing these tests? Have they partnered with Obama to have everyone spit in a cup with their census data and get barcode tattoos with their genomes linked to a central database at flag@whitehouse.gov or maybe BRAVENEWWORLD@Whitehouse.gov?

The Sherpa Says: Buh Bye Linda.......Hey Mari, how's that video game thing going? Well, She says the magic words "Build Physician Sales Channels" Must be Navigenics sees the reality of the market.

Some Confusion Exists

I have a great comment string going on with Daniel MacArthur over at his blog Genetic Future

I think there is some confusion going on here and I place blame on just about everyone in this space who has a mouthpiece.......

But mainly I lay blame on the marketing teams for the Direct to Consumer Genomics companies.

These companies have an interest in making you "think" that their products have some particular health relevance.

Otherwise, no one in their right mind would waste their time with these tests.......Other than the HUGE field of ancestry buffs like Blaine Bettinger J.D. (woohoo) We need clarity here.

From Daniel- "The American College of Medical Genetics is saying "Genetic tests of individuals or families for the presence of or susceptibility to disease are medical tests."

The fine print says:

"This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen"

Meaning

"The judgement of what constitutes an inclusive test is left up to the physician"

In my opinion, there are Green tests, Yellow Tests and Red Tests. I think Ryan Phelan sized this up pretty eloquently in 2007 at a conference I spoke at with her.

Red means - Stop, does this test need analytic/clinical utility/validity? Yes, Go ahead and regulate, these are clinically validated/used clinically for a long time, tests which have a use in medicine. If this test is claiming to do so but does not, then this too should be a cause of regulation.

Yellow means - Well, this could be used but maybe hasn't yet. I think of Age Related Macular Degeneration testing. They could have clinical applicability and haven't been put to use yet. This category may also include low odds ratio common SNPs here which indicate risk FOR disease.

You should have some caution when selling/regulating these tests. The biggest problem is that with evidence evolving over time the low ORs may actually be overturned or fall into the Red category.

They key point is what the test claims to do here.

Does it claim to tell you a risk for a disease via algorithm etc.?

If yes, then it becomes a Red test.

If it says in huge disclaimers, this test DOES NOT PREDICT DISEASE RISK, in plain and clear writing on every piece of its marketing then Yellow tests stay Yellow.

Green Tests - Have absolutely nothing to do with a person's health. These tests do not need medical regulations. Ancestry could be here. Eye color/ear wax/height.

But the moment it is used for medicine or medical procedures (PGD for these things, scary but possible) it then becomes a Red test.

ACMG is talking about Red tests. It is also saying, if you as a clinician think a Yellow test is actually a Red test, then it is a Red test.

Which I agree is confusing. But ACMG is not the US or State Governments. Nor is it the UK or anywhere else's government......It is a professional organization.

My take is simple. If there is a risk for public harm, the government should protect its citizens from that harm in a reasonable manner. I emphasize, reasonable manner. What Techies in the Silicon Valley view as unreasonable regulation may very well be extremely reasonable in the view of physicians and hospitals......

There is no reason to get all crazy here. The New York Times is right, until the government or state governments step in to protect the citizens of risk, it IS Buyer Beware when it comes to genetic tests.....

In my mind, genetic tests need to prove their worth in the field of medicine. They do this by medical science and clinical science studies.

Without these, they are useless noise.

So, should you be able to buy useless noise?

Go ahead.

But the moment the noise whispers in your ear "PSSST, I can tell you your risk for diabetes for 50 dollars" Its A$$ should be regulated.

I hope that clears things up. The problem here is that you have a company selling you noise mixed with clinically valid tests. They are the first company whose A$$ should be told to hold up and split the products.

Then you have a company selling you noise all the while "inferring" it is actually predictive and useful in medicine by getting Doctors to use it in medicine should also be regulated.

Blame Marketers and Spin Men, just like "Thank You for Smoking"

The Sherpa Says: If you apply the Red, Yellow, Green interpretation scale you will soon understand why all the confusion exists. And how that confusion can be cleared up.

National Academies skeptical at Best.

If you would like to watch the IOM conference you can check out day one here
My take away from the first day.

"Do you guys (DTC) know what you are doing?"

"I wonder what kind of research and the quality you can provide?"

"I can't believe you aren't regulated already."

I think there are some really big issues here and there is some confusion.
Questions that remain to be answered..........
1. "Will these companies sell the customer/patient DNA/data?"
2. "Are these companies practicing medicine?"
3. "How do we quantify personal utility?"
4. "Will regulation really kill these companies?"
5. "What rigors and hoops will be required for these companies with research?"
6. "What will the GAO find about today's DTC companies?"

The best thing these companies have done is raise the need for answers and refined regulations.

The worst thing these companies have done is put customers/patients at risk for
1. genetic theft
2. harm via untrained physician
3. false predictions and false hopes
4. 3rd party harm

These companies should be behaving more responsibly, it is sad that they continue to market deceptively. It is also sad that they have not more carefully thought out their research aims. They clearly don't care about the chain of trust.

The Sherpa Says: I think the IOM and National Academies are skeptical at best. Which is the right attitude IMHO. DTC has a lot to prove and it hasn't done anything to do that yet.

IOM not webcast today. Why Not?

The IOM conference "Direct-to-Consumer Genetic Testing: A Cross-Academies Workshop" will not be webcast today? I wonder why not? Was it supposed to be and then submarined after Muin Khoury quoted an email I wrote him while he was presenting?

Why is there no webcast for this important conference today?

Maybe I am just a conspiracy theorist.

But I would like IOM and the National Academies to explain why the cover one day but not the second.

The second day by the way has some great topics


From the Agenda

Session 5: The Impact of DTC Genetic Tests on the Medical System

"If the medical system is no longer required to mediate genetic testing, how will the system cope with losing oversight (and reimbursement) of these services while retaining the full responsibility of caring for patients the services affect?"

Here is a little hint. Currently there is no mediation of this DTC testing, therefore you can see what is happening. Marketing hype, misinformation, inaccurate results, improper provision of the results, lack of follow up, no post services offered to BRCA mutation carriers.

Here's a mind bender, can you bill insurance legally for a ICD9 of Genetic Susceptibility to Breast Cancer from a 23andMx test for a 99245 on a HCFA form? Or is that insurance fraud?

To let these types of tests out in the wild, which we have, is only to introduce a lot of chaos which is not for the "Better" it is actually dangerous to the patient.

Now Back to the Agenda:

"Issues to Address:

Can we model the cost to the medical system of DTC genetic testing?

Reimbursement and DTC genetic testing – are insurance companies involved?
Do they have a role?

How can providers navigate DTC testing and results for patients in the clinic?

How do consumers react to DTC testing information, and what is the impact on their health behavior?"

Well, I would love to hear the explanations, but alas there is no webcast today!

Back to the Agenda

"Knowledge of DTC Genetic Testing Among the Public and Health Professionals"

I wonder if the public read the NY Times article yesterday ?

"It’s important to separate hope from hype,” Dr. Jennifer House, president of the March of Dimes, said at a recent meeting of its national communications advisory council. “Direct-to-consumer genetic testing is a buyer-beware market. Consumers need to be very, very cautious.”

Uh......haven't I been saying that for 2 years now? A little late to the sh!t party huh Dr House?

"At the moment, the reliability of most gene tests on all four criteria is questionable, Dr. Dolan said, adding that the “broad landscape of direct-to-consumer genetic testing is a slippery slope.”

You go Siobhan! Yet another one of Dr Marion's prodigies!

Yet, what Dr Khoury et.al. found is that 75% of doctors who were presented in the office with one of these DTC tests ALTERED care in some way.

What do Healthcare practitioners know about genetics? Very Little. What does the public know? Even Less. Which is why they are such an easy target to market to.

Back to the Agenda

"Cooperation or Competition – How Do Health Care and DTC Genetic Testing Coexist?"

They don't. Someone asked the guy from Pathway Genomics yesterday

"Do you think you are practicing medicine? If not, why not?"

That is the question here. Tell me Navi, 23andSergey, Pathway.........why aren't you practicing medicine?

You take a human biological sample, perform a test, run an algorithm and give a risk for disease. In what world is that not medicine?

Let me guess. "Uh we do those things, but what makes us NOT medicine is that we.....uh......
We uh...........we uh....DON'T CLAIM LEGAL RESPONSIBILITY FOR OUR ANSWERS"

The Sherpa Says: The IOM conference is going to be predictable, unless Google has dumped money into the Academies or the IOM......

NIH Draft Consensus Statement on Family History

The NIH conference on Family History came and went.

What were we left with?

A Consensus Statement.

What is the crux of it?

"The panel recognized that family history has an important role in the practice of medicine and may motivate positive lifestyle changes, enhance individual empowerment, and influence clinical interventions. The panel found that it is unclear how this information can be effectively gathered and used in the primary care setting for common diseases."


Well ladies and gentlemen. I can give you all sorts of anecdotal evidence. That being said, we are evidence driven creatures, so I suggest you give me a call and we set up studies in Primary Care practices with different family history tools.

Things such as the "SCREEN" screen versus a detailed 3 generation pedigree versus 1st generation.

It is pretty easy and inexpensive to set these studies up if you use current technologies.

What else did the panel say?

"For a systematically collected family history for common diseases to become an evidence-based tool in primary care clinical settings, substantial additional research will be needed."

I agree, it is time we develop these tools as multifactorial shotguns which hit lots of targets. This IS what DTC is arguing that there puny little scans do. Without evidence Family History champions like myself run the risk of sounding like the marketing hacks out in Silicon Valley and PR firms like NYC.

That being said there are some evidence tools where Family History helps clinical classification. I think specifically of the Reynolds Risk and how it beat the Framingham

We should attack this one precisely the same way. Start by each individual risk calculator ADD family history and see what it does.

Then do a cohort study of practices which routinely perform 3 generation pedigrees and see how the incidence of diseases like diabetes, HTN and MI shake out.

That could be done over 5-10 years. Not a long wait to get some great evidence, if you ask me.

The Sherpa Says: The evidence may be weak for Family History as a Poly-Tool. But as a clinical marker in certain diseases it is ESSENTIAL.

PHG Foundation and my point.

A long time ago I had a post entitled "Beware Doctors Bearing Genetic Tests" back in April of 2007. It was an interesting post where I point out that this wonderful GI doctor who was IVY league trained completely hashed genetic testing for HNPCC.

I went on to explain the shortcomings with Internists in interpreting APC testing for familial adenomatoid polyposis coli. 1 in 3 misinterpret tests.....Wait till you see the DTC interpretation!

Everyone who gets all in a huff when I say that these DTC genetic tests should be regulated. But I am here to say there is a good reason for it, and it has nothing to do with the people getting the tests.......There is now threat of public harm.....

But first let me explain my frustration. Saturday I was on Twitter and Daniel MacArthur and I had a conversation, which he lead off by saying:

"@helixhealthct Just shows how arbitrary most medical care is anyway; not like it'll change the outcomes much.2:46 AM Aug 22nd from TweetDeck in reply to helixhealthct"

Which was in response to a PHG report on an article published in Genetic In Medicine [Kolor K et al. (2009) Genet Med 11(8):595].

Among the 1880 physicians sampled, 42% were aware of the tests(DTC Genetic tests) and, over the past year, 15% had at least one patient bring the results of such a test to them for discussion. Interestingly, of this latter group, 75% (212 physicians) indicated that the results had changed some aspect of their patient’s care.

Holy Crap! Really? 75% changed the care?

So it had me begging several questions.

1. Did the physician read the Terms of Service for the DTC test? "Not to be used to make medical decisions"

2. Did the patient read the Terms of Service when they brought this test to the physician.

3. How is the physician supposed to know that this is not a clinically validated genetic test?

4. How is the busy clinician to differentiate this test from other clinically valid tests?

5. Why did the patient bring the test to the doctor? Was it due to DTC marketing efforts?

I was pissed at Daniel. How dare he say what we as physicians do changes no health outcomes!

In some instances he may be right. In others I wondered how complaints may actually be neglected based on this "genetic test"

Did these 212 doctors know something I don't about the utility of this DTC testing?

I doubt it.

I am seriously concerned that the 3/4ths of the 18% had actually changed care based on a non-clinical based test. That, to me is Scary AS HELL!!!!!

Think on this for a second.....How many of these doctors will ignore chest pain complaints based on a low genetic risk?

Now think on this. How many doctors will unnecessarily order stress tests for patients who have no complaints and are "High Risk"?????

Either way you slice it, 3/4 of these doctors are acting incorrectly, or at least not according to evidence base.

This survey proved one thing to me. Doctors have no F^CK!n& Clue what they are doing with genomics!

Why should these tests be regulated?

1. Patients aren't following the terms of service, likely due to deceptive advertising

2. Doctors can pose a threat based on inaccurately using these tests

3. Over use of resources could end up being a big problem because of these tests.

4. The potential for public harm has now gone from silly consumer, to trained medical professional inflicting damage.......

The Sherpa Says: Like I said, beware doctors bearing genetic tests........and patients too.

Where from here?

This is the question I am asked so often.

1. We have the steady progress towards cheap genomes.
2. We have the biggest supporter of personalized medicine running the NIH
3. We have "some" clinical awareness of personalized medicine
4. We have the government aware of the shenanigans of some unscrupulous DTC advertising, etc
5. We have several milemarkers under our belts with genome science..... We are moving in the "right" direction, but where do we go from here

There are several areas we need to investigate. I would like to sum a few of them, both basic science and clinical. Basic Science first.

1. We need to understand precisely how gene regulation occurs in the face of certain common environmental exposures. Trans Fat, Tobacco Smoke, Alcohol, Stress. Is it RNA? Is it Methylation? What precisely is it? Maybe it is all of them and more. But the quicker we understand that, the quicker we can look for signs of these ill effects.....and stop them molecularly

2. We need a good CNV/Indel etc database. Toronto sure, I have heard that. But seriously. We need this and we need it now. Give me Normals, Give me abnormals, Give me phenotypes......This is a very key missing piece of the puzzle which neds to be completed in the next 2 years

3. Junk DNA investigation. This will come once we have a database like the one in Iceland......I am certain this will come. I think that next to nuclear fission, the investigation into the "junk dna" will prove to be one of the most fruitful works of governmental science. Yes, you can quote me on that one.

4. Systems biology. This is one of those areas where we will eventually realize the Greeks were right with phlegmatic systems vs bilious systems.......

Now onto the top 3 Clinical Science targets

1. A complete revamping of the current risk stratification system. What do I mean? We need to develop a process for efficiently introducing genotypic risks into current clinical risk stratification. We need to evaluate the with and without and change in AUC......
1b. We need to evaluate the role of integrating family history in some risk stratification models. I know Dr. Khoury/Scheuner et.al are working on these things, but it sure would be nice to have odds ratios and RRs/HRs for adverse drug outcomes, common autoimmune disease risks, COPD, Alcoholism, Suicide, etc. types based on fam hx integrated with current models.

2. Pharmacogenomics......end of story, we need more science here for more drugs. There is not nearly enough clinical study weight on outcomes. I understand why from the Pharma end, but the US government cannot ignore its utility, especially with the pain they feel from Medicare part D
This area has tremendous promise, but has not seen the will from genetics departments, mine looked at my cross eyed when I wanted to do a PGx study. There has to be a will in basic medical science departments like pharmacology and cell biology to understand the processes and polymorphism which really screw up a drug's effect.....or really enhance it. And there has to be a will in clinical departments to study the outcomes with different therapies based on genes.....

3. I want to know what behavioral outcomes are likely with knowledge of one's family history risk versus genome scan risk vs both together vs with no knowledge.

These are some low hanging fruit that could get accomplished and probably already are........

The Sherpa Says: These are not stretch targets, these are do-able things in the next 5 years or so. If we can accomplish most of these, we will be well on our way to evidence based personalized medicine, which is where we need to be........

Family History, State of the Science

The NIH/CDC is hosting a conference next week. I conference I wish I could go to, but alas, I will be DOING family histories on my patients that week.

The conference will be held at the NIH in Bethesda. This is an NIH state of the science conference about Family History and its usefulness.

I for one, am very glad that the government is trying to address this super important issue. It is beyond due for an evaluation.

Why?

With the cost of a genome going to drop to 5000 USD by the late fall (trust me), we will soon see another level of DTC and Clinical lab set offering the genome as a predictive tool.

There are several reasons that Family History beats a Genome (For Now)
1. Phenotypic data of family history represents complex interplay of genes and environment

There is no way that a simple genome will be able to give us the story of how a human will develop. That is predicted by environment and genes, which are successfully covered by..... A family history.

2. 5000 USD is still more than what it costs to obtain a family history.

By the time the software tools are released, we will see that social networking and the internet will transform the costs of family history next to nothing. Which is still a long way to go for the genome scans.

3. We have no clue what most of the genome data means.

Indels or CNVs or SNPs, we have no freaking clue what most mean, we do know what a heart attack at 40 means.......

4. Even if we had everyone's genome scans, we would still need phenotypic data and pedigrees.

What's the one thing we do when we have an intellectually delayed child with an abnormal CMA/CGH? We test the parents. Looking for THEIR phenotypes to make sense of the genome mess.

Look, people always give me reasons why the genome is important and a family history is useless.
I've heard them.

-"We don't speak with that side of the family"
-"My father lived with his uncle, because his father died (secretly running the empire as Darth Vader)"
-"I was adopted by Bail Organa, only to find out I have a lost twin brother"

There is one thing that will always be certain over time, there will be some screwed up family dynamics making it difficult (BUT NOT IMPOSSIBLE) to obtain an accurate family history.

That being said, it is still often useful to capture those who you can. And still less expensive.

I look forward to the briefings from this conference, and Muin, if you are listening, I would love to have the link to the webcasts.... Oh wait, they have that too! Sweet.

If you can't be there, you can get the information you seek!

Once again, we need a state of the science on genome prediction, not a consensus statement a real eval of the state of the science. When placed side by side with the state of the science for a family history, we will soon see why family history is the preferred screening tool and will likely to continue that way, perhaps in conjunction with a genome scan, but genomes will NEVER replace family history.

The Sherpa Says: The press better be at this conference and report on Family History. And to the founders of Geni.com, you missed on this one when Tindall presented to you. Or maybe you just are going to steal the idea.........

Something off my chest........Health care will never be fixed by Lawyers

I rant and rave about genomics and about hyping of genetic tests but today I have a bigger issue. That issue is plain and simple.


Healthcare is FCUk3D up.



I run a successful personalized medicine practice, just recently we started taking health insurance. The demands from handling billing and copays from insurers AND medicaid has not been that cumbersome. Why? We only see 10 patients per doctor per day.

When you start seeing more than that it creates all sorts of problems.

Like manpower requirements that start to exceed 100-200k per doctor.......

If you have less doctors for more patients, the equation is simple.

Rationing of physician care.

That is what will happen when you cut 400 million dollars of Medicare money. Oh wait, I mean 500 BILLION dollars......

Do I think that the Lawyer serving in congress will ever solve those problems?
No.
Do I think that the very few doctors in congress will fix this problem?
No.

But trust me, there are way more lawyers than doctors in Congress, so I am extremely doubtful.
No Offense GenomicsLawyer.......

Why?

They are not the people who are experiencing the problems.

Maybe the doctors were, but they aren't now.

The solution will come from doctors/nurses/patients who are involved in the system already...... currently.......

To think otherwise is foolish.
And to drown out the protesters, intimidate them and hide from town halls is also foolish.

Both parties in this argument are dead wrong.

They are having the wrong argument.

The average primary care doctor gets paid about the same as they did 10 years ago. Does that make sense?
Costs go up. Rent Goes up. Medical Supplies cost more. And insurance pays less and less, Including Medicare, who pays routinely 1/2 to 1/3 of what private insurers pay.

As a doctor, Don't like what you get paid? Switch Insurers.
But you won't be able to do that under a universal plan.

As a patient? Don't like what your insurance paid for? Switch insurers. Pretty simple, unless of course you have preexisting conditions.......

The system is a mess, not because of what we pay doctors or hospitals or whoever.

The system is a mess because there are a whole lot of sick people out there......More sick people than healthcare practitioners equals shortage of attention.

Shortage of attention leads to worse care and more labs and more procedures. Shortage of attention leads to increased malpractice costs, risks and fears...... Want to fix the system?

Encourage more doctors to go into primary care, make their liability risks less, create technology so that they can "fire" their overhead this will create increased revenues for doctors without raising pay.

But please, don't ration care because we are too busy and too risk averse to do it on our own.

Enable the professionals to do it by giving them time to think about their patients...... This system will never get fixed by lawyers.......never.

Medicine is a thinking man/woman's game, not a sweatshop.....why ask us to run sweatshops? The American people deserve better than that......

The Sherpa Says: What good is personalized medicine if the doctor can't take the time to personalize it for the patients??? You tell me.

The Doctors are OK with this?

Yesterday in "The Times" a nice article was posted about the revolutionary way in which doctors will receive education about CLINICAL genetics, this time it is from NonClinical Scientists......

At the tune of 4.5 Million British Pounds!

This may work with CGCs, oh wait, they don't do much of anything in the UK system.

What about clinical geneticists?
Who?

Ok, scientists it is......

So I can just see it now.

A busy NHS practice, patients out the door, flu shot here, flu shot there and in rolls the "Scientist"

Clinician-"Oh hi, you must be the genetics guy sent from the government. Have a seat, I'll be right with you"

4 hours later

Scientist-Sitting nicely, waiting

Clinician-"Ok, lets chat over lunch"

Scientist-"Glad to be here, Let's talk about what a chromosome is"

Clinician-Scarfing down a sandwich "Ok, that was great, gotta go. I am double booked. See you in a few"

4 hours later

Scientist-Sitting Nicely, waiting

Clinician-"Sorry about that, I had a sickie and then the crazy lady....G-d where did the time go?"

Scientist-"See you tomorrow?"

Clinician-"You bet, I feel better prepared already"

As nice as this one is, I have already tried it with a clinical geneticist who actually can create billable events and see patients........ I am not so certain that going to the doctors will help as much as being on their iPhone or on a hotline.......

The Sherpa Says: When climbing the mountain for the first time, it is best to chat with someone who has been there before.....Muin and Franics, I hope you are paying attention here.

Go See a Gastro Doc

I am so blown away at the desperation (def: recklessness arising from despair) of the DTC companies. Recently my iPhone has been flooded with all sorts of clinically inaccurate information designed to make people think that something miraculously has changed with DTC genomics tests.

A change so impressive that it now appears as if you can actually do something about the results.

The best is a video now on Navi's website

2 sisters on the site taking about their results......likely plants......

The transcript includes these misleading words.......
Sister 1: We both tested "High" For Colon Cancer!

Sister 1: But the Crohn's disease was "really high" on my results. Which is interesting because, I didn't know we had that disease in our family......

Sister 2: It is a disease that is 75% genetic but 25% controllable by environment and diet

Sister 1: So I am making an appointment now to go see a "Gastro Doc"

Explain this to me, how in the hell are they getting away with such a flagrant use of insinuation that they tested for the exact 75% genetic part of Crohn's.... AND who the hell says it is 75% genetic but 25% controllable?

What does that exactly mean?

Chalk another piece of false advertising claims up to the geniuses at Navi......Good job Denise.

Let me know how that call with the FTC goes......and clean up your twitters.

Inferring that you can find out your risk for colon cancer with a gene test is false as well.... I am not going to even comment on their partnership with the Toronto Clinic other than to say that this will likely be the move of these companies prior to the US regulation hammer falling.....

They (DTC Genomics) will all move to foreign markets like Canada, Asia and maybe even Africa. Because the EU and likely the US will have had enough of their false claims and shenanigans.....

This video and the tests have tricked this ASYMPTOMATIC woman into going to see a specialist, for what I don't know....I can't wait to see the GI doctor's face. Assuming of course this wasn't just a bull$h!t marketing video that wasn't real.

The Sherpa Says: Want to know about Crohn's disease? Don't think that a few genes can give you disease or that we even know how to modify the environment enough to prevent it. I know for sure that eating some carrots, onions and peppers sure as hell ain't gonna prevent it.....I hate marketing lies. And these guys do it ALL the time.

Genetic Variation in Different Cell lines? That's News?

Ok, So I have to get something off of my chest.

Has anyone heard of a segmental NF patient?
No?
Maybe because you have never done clinical work?

What about the fact that even Monozygotic twins have different CNVs and epigenetic changes?
That's new to you too?

Well, HOLY $H!T is this gonna rock your world.

Blood cells and cells in the Aorta have different SNPs!
Wow!

""The usual dogma is that your DNA is the same all over the place," senior author Morris Schweitzer, an endocrinologist and lipidologist with McGill University and the affiliated Lady Davis Institute for Medical Research at Montreal's Jewish General Hospital, told GenomeWeb Daily News. But, he said, his team's work suggests that isn't the case."

Who the hell taught this guy that? That's so 1990s......

Do you mean that I could have different SNPs in my spit than in my brain? Yes!

Now what about in my blood and in my sperm? Yes again!

This is the thing I love about all these simpletons out there.

Just because we have different genetic material doesn't make the research bull$H!T. The associations are there, we just may not know exactly what the hell they mean. Nor may we actually find a pathway just because of SNP tests and GWAS.......

To ascertain true disease cause we need disease tissue, plain and simple. That has been the problem whcih has plagued psychiatric and alzheimer's genetics for years.......

I can see it now "23andSergey Research Revolution" Sign up for this GWAS where we biopsy the brains of depressed people.

It wouldn't exactly meet IRB standards, which is why I think Sergey's Angels could be the only people to pull that one off........

But seriously, what I am taken a back by is the fact that all of these purported genetic experts are suprised that SNPs are different in different tissue types. In what world would that NOT be the truth?

Maybe a world that Venture Capital was pitched to, but that ain't reality and it may not even be that big a deal.

BUT, a lot of "Smart" people have been misled if they actually assumed that SNPs were stable between tissue types.....

The Sherpa Says: A little bit of clinical work would go a long way for the people in the lab.......

TruValue is coming. Valuation of GMG......

Valuation, it is a fickle beast. I love this post from AskTheVC.com

Valuation – especially for early stage companies – falls in the category of “more art than science.” While buyout investors who are acquiring companies with meaningful cash flow streams love their multi-sheet Excel models with 37 pivot tables, most early stage VCs can do valuations on a napkin (or – if they are good at simple math (e.g. addition and subtraction) – in their head.) In the early stages three things drive valuation: (a) ownership dynamics, (b) market terms, and (c) competitive deal dynamics.

Remember Again - this is art - there is no scientific way to really value three guys and a powerpoint slide or a web service with 10,000 subscribers of which 250 are active (although no one can prove that only 250 are active.)

Which brings me to my next point. How do you value a service which has an undisclosed amount of users, immense governmental regulation, and a company who is moving to offer the service for free?

The Art would say, unless you are going to sell the data to someone AND have that contract in hand......it is pretty much B.S.

I am surprised Pathway launched simply because of this reason.

Which makes me wonder, do these companies have contracts to sell YOUR genetic data? Did they disclose to you who they have contracts with?

Which also makes me wonder about this whole research revolution. What's so revolutionary about it? Maybe how they don't use independent reviewers to approve the research and monitor the safety of the participants? Aside from Nazi Germany and Tuskegee, that is pretty much a revolutionary concept....

One thing is for certain, the company which says takes us seriously as we charge you 2500 USD for Gornish has seen the light.

Take their recent Twitter posts

"Navigenics Health Compass: $499 until August 31st. Take control of your health. Use promotion code COMPASS-LTO-26225 http://bit.ly/11FvS2

and

New price on genetic testing http://bit.ly/oRsLF

So one has to be asking yourself, when market segmentation doesn't work and Big Blimps don't work and Celebrity endorsement doesn't work and super cool bubble conferences don't work what is the value of this and how does the public view it? The value or perceived value must be on the users themselves OR their data..........

I personally wouldn't pay any amount of money to give a single drop of spit to these companies UNLESS I could profit from their companies and the data they sell. Maybe after the companies offer free testing, they will next try to give you dividends for the investment of DNA?

It could happen. Why? 1 year ago asked attorneys about doing this grand Genome Phenome Metabolome study and if we could give people who participate shares in the company....... The lawyers freaked out. Which is precisely why it sounds just like the thing 23andSergey would do.....and in the end Navi would follow in their footsteps........ Just like they are doing now.

I have been asked why I dislike these companies and distrust them.

1. They give geneticists and genomics a bad name by hyping inaccuracy
2. They are screwing with the public perception of genetics and personalized medicine
3. The infer clinical value and don't offer it
4. They purposely avoid regulations put in place to protect people
5. They have given absolutely NOTHING back to the field of genetics or medicine
6. They are doing "research" on human subjects without protecting them

I could go on and on here, but I will save it for now.....

I like to close with a great quote, edited for Genomics purposes.

"The Silicon Valley is a system, Neo. That system is our enemy. But when you're inside, you look around, what do you see? Businessmen, Marketers, Hyped Scientists, Programmers. The very minds of the people we are trying to save. But until we do, these people are still a part of that system and that makes them our enemy. You have to understand, most of these people are not ready to be unplugged. And many of them are so inured, so hopelessly dependent on the system, that they will fight to protect it."

Have an idea, hype it, put it on Oprah, and hope the hell the sheep buy it........ I have a bad feeling about this. The public is awakening from the slumber here and it is likely that the usual VC stunts are not working......... Uh....Oh........Genomics for free, at a price.

The Sherpa Says: All the tricks the matrix pulls, all of the bamboozling, Ahh Gornish Helfn.

Pathway Genomics IS a lab. Not an algorithm.

Today an article came out in BioIT world about Pathway Genomics. (Sounds Eerily like Amway)

With a tagline like, "Your Future, Only Better" I thought that maybe they were like Vanilla Sky or some Total Recall like service. I could only guess how in the world they could offer a better future through a SNP scan.....

Yes another DTC Genomics/SNPscan Company in the game. Hopefully they will accept regulations and not try to manipulate the laws. I hope that they act responsibly with the data and samples. I hope that they will be transparent and honest.

FROM Bio-IT

"In common with other consumer genomics firms, Becker oversees an editorial team to review criteria from the latest peer-reviewed genome association studies. That team includes Victoria Magnuson, who trained with Francis Collins and John Todd and is an expert in type 2 diabetes genetics. “We are putting together a white paper that will eventually be on our website that describes our criteria,” said Becker. “We’ve tried to be pretty conservative as to what is acceptable, validated research versus preliminary research markers.”

Mostly, I hope that they put people with clinical experience into positions of management and decision making. Because if they don't, they will be making the same mistakes as 23andSergey.

Fast follower? Probably. But is fast what is needed here? No, I would say slow and methodical is the best way to be in this business. Which is why DeCodeMe may ultimately win in the end. That is unless they go off the deep end and push clinical tests from recent discoveries without validation......

Oh wait, they already did that........

So to Pathway I say, good luck. My guess is that your tests will cost 75.95 USD very, very, very soon.

The Sherpa Says: Your future, Only better. Damn, I am glad you are around Pathway (Sounds eerily like Amway) because I have no ability to make my own future better without you.

HT Dan V.

Why SB482 is bust. I am amazed by smart people.

If any of you were on the receiving end of my email blast, bear with me. I have a few points to make this morning. A coupla weeks ago, June 24th to be precise.......23andSergey reposted a tweet which really got my attention......


The original tweet was "@23andMe BTW, you saved me $25 for a CF test - used my and spouse's 23 results instead. Thx!"

The user is a really super smart CEO of a company.

After Daniel MacArthur and I protested, 23andSergey pulled down the post........Normally not a big deal, but then came a tweet for me which really had me even further convinced of some issues with DTC

"@hh Really, how so? Our fertility doc says "either of you been tested as a carrier of CF?", yes, both know status via our @23andme."

Do they really know?

No. Truth be told, the delta508 mutation is not exactly the gold standard for carrier screening.....and what the hell? Carrier screening? Isn't that medicine?

Which brings me right down to it........State Bill 482 in essence says that these DTC genomics companies aren't really doing testing. They are only applying a mathematical algorithm to determine risk...........

Could you please tell me what algorithm is used to say you are or you are not a delta508 carrier in the CFTR gene?

Here's another question.

What algorithm are you using to tell people whether or not they have Ashkenazi Jewish Founder Mutations in BRCA genes?

The answer is, they are speaking out of both sides of their mouth. These companies are intellectually dishonest and are looking to pull a fast one here.......and their lack of care for customer or patient safety and health is amazing.

When they pulled that CF retweet, did they post a tweet which says "23andSergey services are not to be used for medicine, and carrier screening is part of medicine"
The short answer.

No.

The long answer, why turn away a customer base who is inferring that it can be used?

I was quoted at the bottom of a San Jose Mercury News article the other day I am an Internist BTW.......

But my point is this, in the world of scandal in politics and lack of transparency, shouldn't we be asking why a company who wants to do this research revolution but won't have an IRB, a company who wants to "Be regulated" buyt by their own rules, a company who has deep ties to a company whose bailiwick is data mining and archiving, a company who performs medical type tests and infers that they can be used as such (despite the fine print)......shouldn't they be held to some sort of standard here?

Are we in the field of genetics so desperate for attention that we let these companies slide in their own laws and their own rules? Do all ships really rise with the tide? We need to ask ourselves here, is this sort of quick shiftiness and legal manipulation ok for the field of genetics?

What sort of trust does it inspire to know that the laws regulating companies were written by the companies. Less than 10% of all congressmen and senators were ever doctors (for my curious detractors).

Why does the medical field come under fire? Lack of trust. Do we really want another chink in our armour?

Does the entire field of genetics and its amazing discoveries want in its midst a company who is willing to manipulate data, lawmakers and ethics to survive?

What does that say about the field? How desperate are we?

What does accepting them say about us?????