Monday, March 29, 2010

End of Gene Patents?

With the NY district court ruling in ACLU v USPTO/MYGN it appears clear that the bar for gene patents is super high and most will likely not reach it. Does this mean the end of gene patents or even just the BRCA1/2 patents?

No, but it is the beginning of slipshod sequencing and a whole host of labs testing for BRCA1/2 sequences. It is also the making of a SCOTUS case.

But here's why I think Myriad STILL is the gold standard.

A. They have the experience doing this testing
B. They have the infrastructure to handle national samples
C. They have the ability to analyze rare variants best. Why? They have the samples.....

That being said, could Quest or LabCorp begin BRCA testing? Yes and they would do a hell of a job.

One thing is for certain, Myriad will have a hard time justifying that 3120 USD price tag.

If you have MYGN maybe a short is in store?

The Sherpa Says: Myriad is how a genetics lab should be run, except for the outrageous price.

Wednesday, March 24, 2010

PGx in DTCG? Doesn't stand up to Useful testing.

HT Don Rule today as well as the ENTIRE Pharmacogenomics Advisory Group that I am a proud member of.

Don wrote this comment a few days ago

"I was curious about what SNPs the DTC companies offer so I wrote a little applet ( to compare them to the SNPs in PharmGKB. It turns out the the Cytochromes are particularly sparse."

Well Don, you are correct. Even more so, as we began to review SNP data it became crystal clear on Monday.

The reason I was pissed about 23andMe doing the CF testing is because they missed hundreds of potential carrier alleles. What was even more so angering when I realized, you could be "tested" by one of these DTCG companies for "Plavix Metabolism" and come up with the absolute wrong answer.

Imagine that. Most people turn to DNA for an "absolute call" but when you don't look for the right SNPs or all of the needed SNPs, you miss a whole bunch.

Quick story. I had this pulmonologist physician, an elder statesman, super smart, Ivy league trained come up to me and say "Hey Steve, can you help me out?"

He is a sleep doctor too. He said "I have been trying to test for this narcolepsy gene and I can't get the right answer"

I said "Sure Dr. X, what do you mean 'keep getting the wrong answer'?"

He Said

"Well I am looking for HLA DQB1 and they keep telling me about this HLA DR, I have sent this test 3 times now and still gotten no information about HLA DQB1."

I did a big 'ol face palm.

Instead it searched for an imperfect haplotype......

That's the problem. If you don't test for exactly what you are looking for, you will never find it. Nor will you have the correct clinical answer.

If you only test 2 SNPs for CYP 2C19, you will never be able to accurately predict what someone's metabolizer status is.

What people should be using to assess metabolizer status of medications is something like the DMET Plus with additional PCR or another platform. AmpliChip does a nice job, but we have to be serious when it comes to medical care.

You Cannot, I repeat Cannot take the advice from 23andMe when it comes to metabolizer status for Plavix.

Please, please, please listen to me. Even 23andMe states it on their post about Plavix

This DTCG test is not ready to be used in the clinic or even trusted to tell your metabolizer status. Right now, they are not testing enough SNPs for me to be happy with it and use it in the office.

Don't stop your Plavix! Instead go get a clinical pharmacogenomic test done by someone who understands the limitations of the labs.

That drunk who lost their keys is still looking under the lamposts because that is where the light is..........

That is a stupid way to do clinical pharmacogenomics.

The Sherpa Says: Pretending to be clinical without standing up to clinical rigor is a recipe for disaster. I await the lawsuit from in stent thrombosis for the poor sap that trusts 23andMe enough to stop their Plavix.

Tuesday, March 23, 2010

Why did P&G invest in Navigenics?

I kept beating myself up, trying to figure out why the largest food/products company in the world put money in Navigenics. Was it for nutrigenomics? Was it for the captive audience to market products to?

Until today, when I read in American Medical news that Proctor and Gamble BOUGHT MDVIP in December of last year! Man how did I miss that one?

"Terms of P&G’s acquisition were not disclosed. It was made by P&G’s FutureWorks unit, a new-business generator that’s intended to connect the company with external partners and expand P&G’s scope beyond its core businesses into new channels."

So, P&G is looking for the whole enchilada in personalized medicine here.

Too bad, Navigenics' tests are currently not useful. But maybe someday they will be......

The Sherpa Says: Navigenics is not the target. MDVIP was, so don't believe anyone who tells you otherwise...

Thursday, March 18, 2010

A moment of Clarity. Some DTCG is not bad.


Here is the G-d's honest truth. Not all SNP/DTCG companies are bad. What do I mean by bad?

Not all SNP/DTCG companies misrepresented that which is not medically useful as medically useful.

I look at Pathway and Counsyl for example. Fast followers looking to say what they do and mean what they say.

Some of these DTCG tests could be clinically relevant and useful. The problem I have, is that there is no point at which I can say, "Hey I just want the clinically relevant stuff!" No ear wax please.

I need that as a clinician. If I want a huge panel of say CYP450 tests, where do I go? there are some labs that do this and charge and arm and a leg. One company, who I used charged the patient thousands of dollars because insurance wouldn't pick it up.

That cannot ever happen again.

With the addition of these tests with some clinical value, there must be a value add of inexpensive and RAPID TAT (Turn Around time)

A classic example is my last post. Provided these tests become validated clinically, in a patient who can't give me her Gail risk information (tough not to, but it could be a real case) I would use that other panel

The same is true for BRCA founder mutations. Provided you won't drop it in some google database that they get served up mastectomy ads, some patients are afraid of needles and that is a barrier.

There are some very good things here. These good things are getting drowned out by some very bad things.

We can work together if you are willing to bend.

"The lack of really effective clinical utility and the existence of commercial interests increases the confusion though. It’s hard to sell something that is interesting, “fun”(?), quite expensive, but not actually that useful to the majority right now. Hard to sell means sometimes over the top marketing."

What medicine cannot tolerate is Over the Top Marketing. It leads to inaccurate statements. This is something extremely forbidden in certain states. In fact, some states don't allow advertising to patients at all, or there laws are so strict you couldn't say anything than

"Dr Murphy, accepting new patients, take insurance"

Why is this? It is to prevent false claims and promises. Doctors can't make money back guarantees. They can't make statements which are not based on fact in advertising. A lot of companies in a rush to get out young science and feed the hype cycle for grants and whatever have been all too guilty of this hype.

So when I get a comment from one of my readers who says (paraphrased)

"Hey all this bashing you do on DTCG is making us in the science end of the SNP reseach look bad"

It prompted me to say, hey, I wouldn't have to throw so much cold water on it if it weren't being hyped so much by DTCG.......

So I guess my point is simple.

Hey DTCG, your opportunity is to leverage your amazing platforms to launch medical services, TO and WITH physicians.

Keep the nonmedical exactly that, NONMEDICAL

Keep the Medical EXACTLY that, MEDICAL

People can benefit by knowing their 2D6/2C19/2C9/VKORC1.

But there are some hurdles to be overcome

1. How can I trust your results?
You have started by enlisting or creating CLIA certified labs, that is a good start. Maybe FDA cert would be nice. Not needed, but nice. There currently is only AmpliChip that is FDA approved....Would like others.

2. How can I know your interpretation is correct?
By using board certified molecular pathologists, I can get a comfortable feel for the fact that the results have been vetted by your specialist. This is muy importante!

3. How can I integrate the results into my EMR/PHR/etc.?
This is going to be super important. How can I save these results linked to patient care? Sure, some would pull paper and put it in the chart, others would prefer a pull in and link. You have to think how to do this.

4. What if the interpretation changes?
Will you take responsibility to contact Either the ordering physician or patient when a result changed? This will be important as we learn more about the nature of these genetic changes.

Doctor's rely on these 4 things from most labs that they use. The depend on these services to be provided professionally and accurately.

These 4 things are EXTREMELY hard to do. But NEED to be done if you really want to be a part of the medical community. But even if you don't, I think your customers deserve this sort of validation and service. Don't you?
Take the jump, create a medical arm. Work with us.

The Sherpa Says: This is what is needed. Medicinally used DTCG that is "Allowed" to be of clinical use. A new Terms of Service, just for doctors, with a validation process that is transparent. And a Marketing process which is truthful.

Wednesday, March 17, 2010

How can MDVIP use Navigenics Test for Medicine?

I have been harping on this say what you mean. Say what you do. Theme lately.

I am a board certified doctor who practices personalized medicine. I see patients and apply the principles or pharmacogenomics, risk prediction and prevention tailored to each individual patient. I do this by taking a 3 generation pedigree, using current clinical risk models and pharmacogenomic or other genetic tests when indicated. That's me.

I have this nagging pain about MDVIP, Ed Goldman and Navigenics.

Some MDVIP members are using Navigenics tests for medical risk prediction. Navigenics is ok with this because hey, they're doctors.

The contents of our Site, including any risk estimates or other reports generated by the Services (collectively, "Your Report") and any other information, data, analyses, editorial content, images, audio and video clips, hyperlinks and references (collectively, "Content"), are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis, or treatment.

The part I want to focus on is "Are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis or treatment"

It seems to me that this will be the more popular language in a Terms of Service for DTCG.
Notice that nowhere does it say, "This report is not intended to diagnose or treat"

I think that while it is nice to not say that, when in fact people are using it to diagnose, it is even goofier to say that it is not intended to substitute for a professional's diagnosis. Ok, so are you saying

1. This is not to be used for diagnosis/medical advice
2. This is to be used for diagnosis, but the professional's diagnosis trumps ours
3. This test is meant to be used by professionals to aid them in diagnosis and treatment

I am really confused here. Is this a medical test or not. Just come right out and say it!

The Sherpa Says: Say what you do, do what you say you do. Isn't that what the Common Framework of Principles is About?

SNPs for breast cancer risk? It Depends.

I hold in my hot little hands a copy of the NEJM, March 18th edition. In it there is an article which isn't even released yet.

"Performance of Common Genetic Variants in Breast-Cancer Risk Models"

Remember when we did this for heart disease risk? FAIL WHALE.....

Do you think it will happen again?

The Study

10 common genetic variants

I had to create a couple of pages on SNPedia for this list FYI.....

The Methods:
Cases and controls-WHI, ACS CPSII Nutrition Cohort, Nurses Health Study, Prostate/Lung/Colorectal/Ovarian Cancer Screening Trial, and Polish Breast Cancer Study.

Cases-Woman who had received diagnosis of invasive breast cancer.

Risk Models Used-A hybrid of the Gail model.....I.E. Not exactly the Gail Model.
1. First degree relatives with breast cancer
2. Age at Menarche
3. Age at first live birth
4. Number of Breast Biopsies

They acknowledge that they were unable to get atypical hyperplasia and Mammographic density. Both of which have improved Gail.

So, This Gail is a little hobbled and not the best predictive model.......

The studied models- 5 logistic regression models
I don't have the supplementary tables and methods yet.

The nongenetic model-Gail Model
The Demographic/Genetic Variant Count Model-included number of alleles.
The Demographic/Genetic Individual Variant-Accounted for individual effects of each SNP
The Inclusive Model-Gail, Genetics Demographics
The Demographic Model
And Random....

When we do these sorts of statistical analyses we look for a couple of things.

A. Number of people reclassified and how?
B. The Area Under the ROC Curve


1. The Inclusive Model Yielded and AUC of 61.8%
2. The Nongenetic Model yielded an AUC of 58%
3. The Genetic Individual Variant Yielded an AUC of 59.7%
4. The Genetic Variant Count Yielded an AUC of 58.8%
5. Breast Biopsy BY ITSELF Yielded an AUC of 56.2%

That is a 3.8% difference in Yield from Genes and without Genes integrated into the weaker Gail Model.

Lastly, they asked. Well, does this Inclusive Model do a good job of discrimination of High risk vs. low risk.

The Answer- It determines lower risk better than Gail. It does not determine higher risk better.

The authors of this study have stated that

"As in Diabetes and cardiovascular disease, the addition of the common SNPs added little to the predictive value of the clinical models. On the basis of theoretical models, Gail has shown that increases in the AUC similar to those observed here and not sufficiently large to improve meaningfully the identification of women who might benefit from tamoxifen prophylaxis or screening mammography"

Take Home

The addition of these factors only creates a minimal statistical increase that is of no useful clinical benefit.

The Sherpa Says: If the press says "gene tests fail to improve risk assessment" You can be assured that the DTCG industry is no longer the darlings. If instead they say "Improvement in risk model" well, then you have chance to woo them back! It Depends.......

Tuesday, March 16, 2010

The Argument Against DTC Genomics Marketing and such

Keith Grimaldi and Daniel MacArthur and Andrew Yates and I have a little bit of confusion. I think we are arguing over 2 different points.

First, Keith, Daniel and Drew need to go read a paper I authored entitled

"In Need of a Reality Check" published in the May 2009 Nature Biotech Journal.

I think many people have misunderstood our messages. So to be simple.

A. Keep the Medical, Well, Medical.

1. Medical Genetic tests that are to be used clinically should have clinical input
2. Medical Genetic tests should be regulated according to the laws of each state/country
3. DTC Genomic tests come in several flavors. The DTCG Medical tests should be Medical.

I have been championing this one for a LONG time. The arguments for this are pretty clear

1. Without clinical input, selling medical tests without an understanding of their use on a FIRST HAND basis is a bad business plan. Also, the risks of a non physician over marketing these tests as to be used for too many things or used before the science pans out could harm the consumer. Think OvaSure......

How? Via false advice and guidance, delivered not by a physician, but by a website.
Who takes accountability and liability for this? The answer no one. Thus, the chain of trust is broken and the patient is left no recourse.

2. Medical Genetic Tests should be regulated by the laws of the country/state/province of use.

Why? Well, if we don't agree to follow laws, we are lawless. How does being lawless benefit the consumer/patient? How does it build trust? It doesn't, thus, EVEN IF the laws are "stupid and outdated" those who break the law, break the trust required for such special testing and care.

3. Medicinally used genetic tests, whether DTCG or not, should be represented and treated as Medical Tests.

Why? This goes back again to quality control and tests. This also goes back to trust. If a patient is encouraged to use a medicinally used genetic test, they should have the confidence that it meets medical quality and that the lab follows that are required for medical tests.

Am I wrong? I challenge someone to give me 3 good reasons why these rules should not be followed. And they cannot use "We are slowing innovation" "It is inevitable" or "You are rent seeking doctors" Why? these are stupid arguments that you will need to prove beyond a shadow of a doubt. Why? When patient safety and trust is one the line, you better be DAMN sure of your stance.

B. The marketing of these current DTCG tests in not keeping medicinally used tests in the medical realm. They should immediately correct this course.

1. Marketing message confusion leads people to equate nonmedical tests as medical. This results in the customer/patient. relying on non-standard of care tests.

I use here the example of Dane Jasper an SV entrepreneur who said he could save "25 bucks" buy relying on 23andMe's CF test instead of going to a trained professional to have testing done.

2. Simply stating your tests are "nonmedical" does not make them "nonmedical" especially if they have a long history of being used medically.

May I skip getting licensed in a state if I say I do "nonmedical" medicine? May I give you coumadin "OTC" if it is to not be used to diagnose or treat a condition? No, I may not. Can someone OTHER than a pharmacist/doctor get access to medications? Not in the US.

They do this to avoid charlatanism and people putting other people at risk. In this case, the risk is a "nonmedical" diagnosis of CF carrier state, or a "nonmedical" misdiagnosis of no CF carrier state.

3. Marketing "NonMedical" Medical tests as cool and hip

A. Turns off doctors from using useful tools
B. Makes the valued noble profession of medicine appear, trivial, akin to Paris Hilton.

Please stop this now.

The Sherpa Says: This is too long to have in a post. I am drafting a paper on this subject now. But you first should read "In Need of A reality Check" in Nature Biotech.

Sunday, March 14, 2010

BRCA testing by 23andME is the same as Myriad Genetics.

February 2009 23andMe entered into clinical medical testing of DNA variants which are the exact same variants Myriad Genetics tests for. There is only ONE use for this test. That is a clinical use. When these results are obtained clinical counseling is the standard of care for delivery of these results. Not a flashy webportal......

Minimizing the seriousness of a medical test looked just as awkward by us in the first video as it should be by showing it on a blimp or at a cocktail party or highway billboard sign.....All things that Linda Avey and Anne Woj decided to have their company do....

The Sherpa Says: Misha is correct, Medical Geneticists painted themselves into a corner by harboring in the rare disease port. This allowed people who have no G-dDamn business in medicine, to play doctor at parties and on the internet!

Friday, March 12, 2010

The FDA, 2c19 and the ACC

Did anyone see the FDA issuance of the better warning that as many as 14% of patients will not benefit from Plavix/Clopidogrel?

Did anyone see the cold shower being poured on by the press and the cardiologists?

Christopher Cannon Assoc. Prof at Harvard says:
The ACC will need to develop protocols, "Thus a real conundrum"

He then says "I expect mass confusion in response to this FDA warning"

Well Chris, It's not as if we haven't been shouting from the rooftops about this for over a year now.......

"The test costs about 500 USD according to Courtney Harper PhD, Director of the FDAs division of chemistry and toxicology devices. But cost isn't the only issue."

Which BTW is false 23andME is cheaper......But wait, isn't that medicine?

"The time to get a result varies. It may be a few hours to a day or two, or other labs may take a few weeks"

This is absolutely true. It takes me 3 weeks for a test from Quest. I am certain that there has to be some lab to do it quicker.......

BUT, the FDA has only approved AmpliChip for this testing.....

This sounds to me like the FDA needs to approve some kits and PDQ with the ACC meeting coming up like,

My guess

1. The ACC will address and release its prelim algorithm

2. The ACC conference will have even further data regarding this released.

3. The last step is to FDA in some kits to do this test, quicker and more standardized.

We need a company that can direct us to

So the question, why all the cold water on this killer app? Well, because it is getting lumped in with DTC genomics, which is feeling a backlash from hype and failed promises. Or trying to play medicine.
As well as a flat disregard for medicine. So when the press and the healthcare providers are against you, you can feel it.

But this is what I have been frustrated about all along. I saw this coming. Doctors blowing off PGx thinking it is SNPChip Hype. Journalists pouncing on overpromising and intellectually dishonest DTC Genomics companies.....

This is why I was so mad about the blimp.

When something really awesome comes around, people are burned out from Open Bars......

The Sherpa Says: Let's really do this. Genomics and PGx IS medicine. Let's say it proud, Let's ay it loud. Quit screwing around to avoid regs. Let's how the world how we can use this to help mankind!

........DTC Genomic Medicine?

Back in February of 2009 23andMe/Serge decided to do testing for genetic founder mutations.........

Yet they claimed it wasn't medicine and should not be used for medicine.

BRCA Ashkenazi Jewish founder mutations offer information that can confer an elevated risk of Breast, Ovarian, possibly melanoma, Pancreatic and maybe blood cancer.

There really isn't any other thing that these tests can be used for other than medical decision making and diagnosis. The diagnosis would be Genetic Risk for Cancer. There is a medical code for it in the International Classification of Diseases 9th Edition. In fact there are multiple codes. The v84.0 super family of codes.

Granted this presentation was a bit manic and the iPhone volume control was horrible (turn down your speaker volume). But the point is clear. Either founder mutation testing is a medicine or it is not.

You cannot have it both ways. Say what it means. If that means your state requires physician consultation or ordering, do it.

If it doesn't, well, I strongly recommend you receive that healthcare provider service.

Thursday, March 11, 2010

The problem with Comparative Whole Genomics......

I have been having this debate with a good friend and mentor.

I think Complete Genome Comparison could be a Killer App.

He thinks it could be a legal and scientific nightmare.

I think he's right.

Let's really think about this for a second. If history has anything to say about human behavior we need look no further than the secrecy with which gene sequences were hunted.

Hell, even Science makes mention of it several times. The Article "Data Hoarding Blocks Progress in Genetics" might be a good read if you are interested.

Guys like Daniel MacArthur over at Genetic future point out some good points about the difficulty in making sense of all the noise that exists in genomes. But the problems go even further than that. Hell, CNV can differ in IDENTICAL TWINS!!!! Say Wha?

So what do we have to say about this? Phenotype and comparison are kings. Databases of "normals" and disease afflicted need to be developed. They need to be curated, they need to be "shared"

Ahem, excuse me? Did you say "shared?"

Yes, I did say shared.

Exec/USGOVT/BGI/UK/Etc- "Well, sure we would like to give that idea more credence and study it. And the implications it may bring. Would you be so kind as to forward your attorney's information so that our attorneys can consult with yours in order to bankrupt you and send you away with you radical thinking?"

He has me convinced (a tough thing to do) that the level of collaboration amongst human geneticists and Venture Capitalists might not be exactly the level of their physician brethren....

What happens when you get access to a database, but not "all of it"

Who pays? Who benefits? Who gets rights of discovery? Who pays the Nosferatu? (sorry Dan)

With Sequencing as a Service, do you have these problems licked? Probably not.

So when Daniel points out every geneticist afflicted with a disease feel good discovery, there are about 100 nightmare scenarios of chasing down rare variants that turn out to be nothing except a good excuse to burn through 10 million dollars........

I begin to say, well how can we pick that up quicker? Comparative Whole Genomics.

Great, which database do I start with? Do I have to use 20 or 200 databases? How can I afford such work? Which one of the 200 won't make a play legally to own my discovery?

Ahh, yes. It is a good time to be a genome centric attorney. But a nightmare to launch a business where you depend on someone else's database.........

The Sherpa Says: Yes, sugar plums, ponies and lemon drops for as far as the eye can see for Genomics! I hope Andy will bring this back to earth........Or maybe Glenn Close can show us where the fruit punch swimming pool is?

Tuesday, March 9, 2010

What a difference a year makes

It has been one year since I commented on 23andMe's foray into clinical medicine. I was frankly blown away that such a move would be so blatant without integration of health care practitioners.

I also was blown away that Myriad wouldn't sue the ever living bejesus out of 23andMe. A year later, no lawsuit. I am still surprised about this one. Don't you have to demonstrate protection of your patent to keep it?

Maybe Google/23andMe are paying a VIG to Myriad? I don't know, but it hasn't shown up on Myriad's SEC reports yet......

Why was I so surprised? Well, a few months after 23andMe launched the service AND Myriad did not sue, MYRIAD WAS SUED.

I began to wonder if not suing Google/23andMe was a sign of weakness. I was certain Myriad would then shut down the DTC Genomics BRCA testing.

To date, they have not.

This begs the question, does Myriad think they do not have a case and would lose against Google, thus strengthening the case against them by the ACLU? If that is truly the case and we will begin to see judicial activism in patent removal, well, then we could be in for an EXPLOSION of genetic testing labs out there, each doing their own thing, their own way.

An article in Nature Medicine by Brendan Borrell, does an excellent job of discussing the potential backlash and issues related to DTC Genomics and patent holders. They took the tech line. "Should we really be charged to look in the mirror?" Well, do you have to buy a mirror to look in it? FAIL

The question is: "Will other patent holders see themselves as vulnerable by allowing DTC Genomics companies to test for THEIR patented genetic markers?"

This could prompt a huge wave of lawsuits against these fledgling DTC Genomics companies. Normally, companies sue to shake down, scare away competition and make money or at least protect patents. What we could see is lawsuits designed to crush these young companies in an attempt to scare off the ACLU

By Myriad NOT suing 23andMe, we may have opened up a new wave of patent paranoia and fear. When that happens companies often turn to the courts to scare away competitors and people hell bent on their (patent) destruction......(ACLU)

It will be interesting to see what this year holds for the Gene Patent......

The Sherpa Says: I would love to hear Dan Vorhaus or Gary Marchant's or Barbara Evans' opinions on these things.........

Thursday, March 4, 2010

Just 4 million? What 23andMe is worth.

So by now I am certain everyone in the DTC genomics world has seen this BNET story

From the Story

"Is it really the best time for 23andMe, a leader in recreational genetic testing to be handing $4 million to an executive officer? That’s the news from their SEC filing. The official explanation is the $4 mm was a payback to a company officer for a loan, with the money coming from the company’s series B financing, which included an investment from Google. "


I have flayed them for playing doctor even begged my associates in the past to as well.

Listen, if anyone has a beef with these guys. I do. They had this thought to replace physicians, which is a foolish way to think. You cannot replace doctors. Just empower them. Which is what should have been done here, but instead they were too busy playing Doctor on Oprah and GMA......

But the question "Are these guys going under?" is a foolish question. Drew was right. They are not going under. They, just like ACORN are changing faces to try anew........

The industry is morphing here. They see that the only sustainable solution is partnered with health care practitioners is a smart way which benefits all, but most importantly, the patient....

The Sherpa Says: The question should be, "What is this 4 million dollars for?"