Non-Clinician Misinterpretation of DTC Genetic testing

Ok,

In case you haven't all figured it out. Blogs are dead. Mine is too, sorta. I have less and less time to blog as my practice explodes. But there are some things that just merit a blog post.

I am on twitter, you can follow me there @genesherpas

But now I am on the Sherpa. Yes, the blog that nearly got me on 60 Minutes and definitely won me the hearts of USA Today to be interviewed...BTW the practice got super busy after that......

Today I want to talk about something more serious.

The FDA hearings have laid the course clear. Direct To Consumer Genetic testing will be regulated.

Why?

1 part potential harm

2 parts irreverence for laws and medical regulation

3 parts flagrant misrepresentation of what genetic tests can do.......

See Kari S. Disavowal of his company's stupid tag line.......

Today on twitter Shirely Wu @shwu retweeted something that was the picked up by @dgmacarthur..... great geneticist, but not a medical geneticist........

That was:

A thoughtful and eloquent case-study petition to keep genetic testing DTC:http://bit.ly/dL3qar from @celticcurse#FDADTC

The problem?

I respect Shirley a lot, but this article is not thoughtful, nor is it eloquent.

Instead it is full of misinterpretation and IMHO an ignorance of the role of genetic testing in hereditary hemochromatosis.....

In no way is HFE genetic testing required or indicated to pick up a person with hereditary hemochromatosis.

USPSTF says the harms outweigh the risks of genetic testing for screening

There are multiple genes involved in hereditary hemochromatosis only testing HFE and thinking you are "off the hook" is stupid.....

There are also modifier genes likely too.....

In other words, perhaps the cheerleaders for DTCG are misinformed about the true utility of this type of testing. Further, if they knew the literature, perhaps they would be less angry that the FDA(who know the data BTW) want to regulate against these types of misinformed claims that could lead to misinterpretation by consumers and end up fleecing their pockets for fools gold.

Let's take this little gem from @celticcurse

"A simple genetic test is all it takes to know if hereditary hemochromatosis, the most common genetic killer in America, is in your genes."

Bull$h!t buddy.....less than 30% of HFE variant persons ever develop the disease. Do me a favor, partner with a doctor to hack your health next time please......

In case you wondered, iron studies are the key to screening. I get them in every northern european or any family history of liver disease, gonadal failure, arthritis, etc......

But, the lab heads wouldn't know that. Which is why lab heads shouldn't release discoveries into the wild......

The Sherpa Says: This retweet blog post by CelticCurse is an eloquent reason WHY DTC genetic testing should be regulated for claims and use......regulate the medical as a medical test, let the ancestry buffs do their thing sans FDA. End of story guys.....

Consumer Genetic Testing for heart attack risk? Worthless!

Here are the top ten reasons why in its current state, direct to consumer or otherwise, genomic testing for cardiovascular disease risk is dead in the water

1. Family History Risk paints a far better picture and IT IS FREE

2. Reynolds and Framingham risk paint a more accurate picture

3. An independent panel has reviewed 58 variants, 29 genes, and gave the thumbs down.

4. The highest increased risk from any of these tests is 30%, Fam Hx can be as high as 500%

5. Kif6 was just shot down as a useful marker.

6. Clinical Utility has not been evaluated in ANY of these tests.

7. Spit Parties don't lower cholesterol

8. The FDA is hunting down these type of crazy claims!

9 . Topol's heart attack gene didn't pan out, why would these?

10. A recent 23 gene panel failed to make the grade as well.

Let me be crystal clear.

I am glad that the number one reason for ordering a DTCG test was curiosity and not true medical concern in the "early adopters"

But I am concerned that may not be the case for the next wave. I am concerned they will take these genetic tea leaves and use them.

The problem, most of these tests are disproven or will be in the next couple of years.

Loose associations with small increased risks sounds a lot like fortune telling or phrenology. Or hell, even birth order....

Someday we will have good predictive models, 10-15 years from now. But NOT Now! Do you hear that VC country, SV, NYC, Hedgies?

10 year exit strategy. Not 2 not 8. So stop hyping this bull$h!t and go invest in Gold or Commodities or something for the love of god!

The Sherpa Says: Did you hear the one about the research geneticist? He keeps telling his wife how great their sex life WILL BE! Someday we will have this tool, let's try not to burn out and cynicize the public yet.....HT Francis Collins

Unregulated DTCG saved my life.

Ok, so if Ellen Matloff hasn't flipped her bobbed haircut, 99245 without 60 min of MD care-insurance billing head yet, then this story will make her and the rest of the counselors who get mad when untrained MDs do BRCA testing flip out.

A woman's husband on DNADay takes advantage of 23andMe's rock bottom 99 USD fee. Clearly intended to double their database.....which it did

Only to have her HUSBAND open her results and

WHAMMO! You are a BRCA1 carrier! Mazel Tov! Not exactly the "fun" he had been looking for when he saw that flyer.....

Why does Myriad market to doctors? Their stance "We are missing a ton of BRCA mutations out there"

I agree.

So you would think I am happy that an unregulated DTCG testing company that the FDA pilloried finds a medically valid BRCA1 mutation that wasn't suggested by doctors.

Well, here's the shocker.

I am glad they found it.

Yes, thank god someone did before she had ovarian or breast cancer! If she would have, penetrance here is NOT 100% guys......

I am also glad that the woman who had the test was mentally stable enough and smart enough to seek professional help. I wonder what her husband and her do for a living?

I wonder if they are college educated. I wonder if there demographic is anything like the majority of the United States.....probably not....Oh wait. Princeton Grad, Prior Google Grad, CEO....yeah sounds just like my cousin Billy in Dushore PA (FYI I don't have a cousin Billy) But Dushore is in BFE.....

I am not glad that everyone is NOT like Mrs. Steinberg or her husband. In the right hands and with easy access to health professionals this works, sometimes........That is why the FDA has stepped in. Not everyone lives like the Steinberg's

Without professionals and without a level head, this could be a problem.

But the news story re-emphasizes what is crystal clear. This is an unregulated company that delivered a medical diagnostic. This result then drove clinical decision making.

Seriously. The DTCG BRCA test is a medical test. I think the FDA gets that part. Despite what DTCG says.

The Sherpa Says: I am happy for this woman. We need more testing, I agree with Myriad. I also think CGCs should be out teaching doctors rather than letting pharma reps do it. In fact excellent CGCs like Ms. Matloff should never see patients and should instead teach doctors how to do cancer counseling everyday. That is what is needed here, more education given to those who need it. Because clearly the doctors who told Mrs Steinberg (I assume she is AJ) that she wouldn't "need" genetic testing despite the family history of cancer are likely in need of some schooling.

Reporter Mary Carmichael, will she do it? Newsweek and DTC Genomics!

" I don't even know if that was a hammer that got dropped on their heads. More like a piano."
-Anon Quote re: DTCG and Congressional hearings....

When Ms. Carmichael approached me to answer a burning question for her. She got an answer alright, more like a diatribe and then and answer.

In case you didn't know, Mary is a writer for Newsweek and is thinking about doing a DTC genetic test kit. In fact, she bought the kit and it is staring her in the face. FYI, she's not in New York, where such activity is illegal, she is in Boston, where it is encouraged......

She is taking opinions from just about everyone in the biz. And, yes, she has a comments section for all those Yahoos who feel left out.......

My recap here is what Newsweek wouldn't put in their print, but as you know.....I am more than happy to put here for my readers enjoyment......

Hi Mary,

You think you are set and ready to get, DTCG'd. Just hold on a second. I think you need to really think about what you can and can't learn from this sort of testing. Some say nothing, others say these little babies hold the secrets that the government is trying to keep from you, other say Google's overlords are plotting to steal your children's DNA.

I want to know, have you thought about it? What can you and what can't you learn? Since I have seen probably more patients with these types of tests than just about any clinician out there, I can tell you what the patients ask and what I tell them.

1. You will not learn what you will die from.

Yes, this is true. As a physician who has counseled and seen patients who have brought me their 23andMe, et.al., one thing is clear, patients ask about what this means they may die from.

This test won't tell you that, in fact most tests won't tell you that, whether ordered via Amazon or through your doctor. This test may show some scientifically linked risks for disease, but again, they won't tell you what you are going to die from.

As an aside, You will die from something. Everyone dies. Even those transhumanist singularity punks die. No amount of knock off stem cell clinics will help with that one. Even the G-Damn Buddha dies. In fact someone off'd him with rotten food....

2. You will not learn what diet is right for you.

Again, you are getting DTCG'd. But if you were getting some of the Nutrigenomics tests I would tell you the same thing, There is no magic diet currently based on 23andMe data or any other genetic data. We do know some people may benefit from some types of diets to lower cholesterol and lose weight, but the science to accurately predict genes and diet is not ready to bring to market, no matter what Proctor and Gamble tell you....

Second aside, Isn't funny how the GAO bashed these nutrigenomics companies in 2006 and they are still out there slinging there proton pills. Goes to show how much force the FDA or any other organization has to control commerce......I wonder what happens to the first batch who refuse to buy health insurance.....You can buy things that give you cancer or an erection, why not DTC tests? Properly regulated of course......

3. You will not learn if you are of the lost tribes of Israel.

True, your hot little hand will get a hold of a J Haplogroup analysis, but even the ancestry experts will tell you, this is a small window into heritage. Only 50% of the Cohanim have the Cohen Modal Haplotype. Is it a start? Yes, maybe a hint. But no SNP test offered by 23andMe will rule that out or in as J.E. Ekins et al stated. It requires extended STR testing.

Ok, my buddy, who shall remain nameless as he is at Camp in PA for his kids right now had a patient come to him adamant she was of the royal lineage of the Czar (Russia). She paid a bundle to have her mito DNA checked.....Guess what? She wasn't........

P.T. Barnum once said
"You can fool some of the people all of the time; you can fool all of the people some of the time, but you can never fool all of the people all of the time." But what he forgot to say is, some people are fools all of the time......

What will you learn?

Good Question Mary.

1. You may learn you are a carrier of a medically relevant condition.

For all intents and purposes, the lab used by 23andMe is CLIA certified, which means its results for positive carrier tests are just as valid as those ordered by a doctor (in some instances). But remember, this test is better at ruling in than ruling out as it often misses carriers in genes such as CFTR for cystic fibrosis. So if they say you are NOT a carrier, don't trust the results. And if it say you are you can always double check with a doctor.

Mary, this is a medical test. And should be held to the same standards as other medical tests.

2. You may learn you carry a rare mutation putting you at significant increased risk of breast or ovarian cancer.

23andMe tests for 3 mutations in BRCA1 and BRCA2 which could put your risk of breast cancer as high as 85% over your life. Are you ready for what to do with those results if you had them?

Mary, this is a medical tests and I advise you to have some clinician back up when reviewing these results. Even if they are negative, that doesn't rule out a BRCA mutation. This test is confusing and should be regulated as a medical test.

3. You may learn you cannot metabolize medications properly.

23andMe tests for medication metabolism using the same genetic markers as found in other medical tests. Again, they use a CLIA lab, so you may be able to trust their poor metabolizer status. But are you taking Plavix Mary? Tamoxifen? Does it really matter for you now? Or ever?

The whole thing about Pharmacogenomovigilence is that ideally everyone would have a panel of these useful genotypes before dosing medications. But based on the soon to be available rapid turn around time here, we could do these in some labs overnight. The big question here is, is the DTCG test enough of a test to trust clinically?

I am not so certain as they miss certain SNPs and rare mutations that are important.
The Sherpa Says: Ok, Mary. You want it, you got. If you buy a test, you've got a guy just a few Acela Stops away who can help sort out the madness for you.......Clinically of course.....That is, if I haven't convinced you otherwise.....

Answer to GenomicsLawyer's Question. What the FDA will do with DTCG.

Dan Vorhaus JD on his blog says "The path of least resistance may be to simply agree with the FDA....The viability will depend on how the FDA intends to categorize the specific product...."

I agree, these companies have big choices to make. If it is any indication, Counsyl (full of smart people) and now, Pathway Genomics (full of smart people) have both decided to go the route of Medical test.

Perhaps it is because they think the burden will cost less to investors than fighting the "Man"

Well, in guessing what the FDA will do, it is always best to see what they have done to a "similar" product. In this case, they have a great product that is very similar. That would be the FDA's approval of AmpliChip.

A friend of mine in Canada argues about the holes in this platform, but unfortunately it is the only FDA approved platform.

You can read the letter for the FDA approval here

This was cleared in 2005! I wonder if the DTCG companies ever looked at AmpliChip as a model before?

In the letter it is clear, microarray technology used for drug metabolism prediction is considered a Class II medical device. The letter indicated that this applied not only to AmpliChip, but also to similar devices.

It also does not waive premarket submission.

Both of these are very important points in how the DTCG groups evaluate their future business models and potential market.

The Sherpa Says: Why Conjecture? Just look at what the FDA decided for AmpliChip. It will be a similar template.

Cellulite On Your Bod? Blame your genes! Or market 'em!

Could I go on a huge rant about 23andMes mess up and how it was discovered by a customer rather than LabCorp or 23andMe?

Yes. Would it be useful?

No.

Why?

I need to save my rants, and any doctor will tell you, labs screw up all the time.
It is something we are used to thinking.

So much so, that a knee jerk answer for a lot of doctors is to repeat a test if the results are so far out there.......

So, my rant today will be directly placed at the rocket scientists who dreamed up CelluliteDX

"The CelluliteDX Genetic Test is only available for sale through participating physicians' offices. If you would like to learn more about the CelluliteDX Genetic Test and receive a Welcome Package to establish your office as a CelluliteDX Genetic Test provider, please contact us Monday through Friday between 8 a.m. and 5 p.m. Pacific Standard Time or e-mail anytime"

Ok, this is the problem that the DTCG community has and I do too.

Doctors may be using crappy tests as a marketing ploy to drive patients through the door. Well, some DTCG does market crappy tests to drive customers through their portal too. But this one takes the freaking cake.....today

This test which BTW is the ACE genetic variant testing has a full page called "Science" where you can read about this brain trust.

200 patients, 200 controls, the offering......

"A physician using the CelluliteDX Genetic Test for Moderate to Severe Cellulite, can predict that a patient who tests positive has approximately a 70% chance of developing Nurnberger-Muller grade 2 (or greater) cellulite."

The science: Is there a paper on this? Seriously? A gene for cottage cheese butt? Awesome! You've gotta love Italians and there passion for the A$$

"the multivariable-adjusted odds ratios for cellulite were 1.19 (95% CI: 1.10-1.51; P <> 1.19 huh?

How is that 70% increased risk? Would love to see that please. No, seriously, tell me how. This is why Congress jumped. What Doctor in their right mind would offer this test?

The Sherpa Says: This is why we need education of physicians and the public here. Hullo? FDA, maybe they should get a letter too?

DTC Genomics adjusts for regulations. 23andCGC?

In a blatantly obvious, why the hell werent they doing that in the first place? move.


23andSerge acknolwedges, finally, that they ARE Providing clinically important work. Duh,

Since the website won't let me copy the presser, I will quote, with my own translation through business BS speak.

"23andMe customers now have the option to speak with a board certified genetic counselor"

-Translation, we realized that by testing BRCA mutations we put people at risk and needed some back up from someone who knows what the FCUK they are doing opposed to a VC billionaire babe and ruby on rails programmer kids.

-Because, frankly, we don't want to get sued or go to jail......Like Liz Dragon......

"We chose Informed because they were the leading independent genetic counseling provider"


-Translation, we alienated/pissed off the entire rest of the FCUKING community by saying they were stupid. Thus these were the only guys who would work with a company getting ready to be pilloried by Congress

IMHO, Informed are a great service, we are modeling genetichub after them, but... No one else would work with them on this. NO ONE, or so I am told......

"We wanted to be sure that the information our customers receive would be completely objective"

-Translation: We didn't want to have egg on our face when the geneticists said, "Well Andre, that finding essentially means nothing to your long term health and happiness"

"Customers who want a more thorough review of their family and medical histories can chose the Comprehensive Clinical Genetic Counseling"


-Translation: Yes we know we have been pushing this "It's not clinical" thing, but let's face it, no one is buying it. So we said Clinical, yes we did. See Henry, we are trying Congressman. See. Please no pre-market review.

The Sherpa Says: Well 23andMe, I am proud you came around. Too bad it only took an FDA review and being called to testify before congress before you "acted" in the best interests of your customers. 3 years later and I can say it. I told you so......

How Bad Can a House Investigation be for DTC Genomics?

Ok, so you've been summoned to Congress to testify

It won't be that bad if you know what you are in for. So let's review.

1. A chart listing the conditions, diseases, consumer drug responses, and adverse reactions for which you test;

2. All policy documents, training materials, or written guidance materials regarding genetic counseling and physician consultations, including documents regarding what conditions, diseases, drug responses, or adverse reactions trigger the need for genetic counseling or physician consultation, and documents governing communications with consumers regarding individual genetic testing results;

3. All documents relating to the ability of your genetic testing products to accurately identify consumer risk, including:

a. internal and external communications regarding the accuracy of your testing;

b. documents describing how your analysis of individual test results controls for scientific factors such as age, race, gender, and geographic location;

c. third party communications validating the association between the scientific data your company uses for analyzing test results and the consumer's risk for each condition, disease, drug response, or adverse reaction as identified by the results of an individual test; and

d. documents relating to proficiency testing conducted by your clinical laboratories.

4. All documents regarding your policies for processing and use of individual DNA samples collected from consumers, including:

a. policy documents and protocols regarding collection, storage, and processing of individual DNA samples;

b. policy documents and protocols relating to protection of consumer privacy; and

c. documents regarding collected DNA sample uses other than to provide individual genetic counseling to a consumer, including documents relating to third-party use of collected DNA samples.

5. All documents regarding compliance with the Federal Food, Drug, and Cosmetic Act and

U.S. Food and Drug Administration (FDA) regulations.

And you should have that to them in about 2 weeks.

What could be so harmful?

If you know anything about the history of such investigations, they are mostly a dog and pony show that ends up in one of a few options.

1. Public Pillorying that leads to a slap on the wrist and a consumer base who doesn't trust you anymore (See Toyota)

2. A massive class action lawsuit from some enterprising attorneys who review the publicly available documents that the House requests via Freedom of Information.

3. The Congress forces you to behave like normal society rather than a bunch of radicals trying to take over the world.

4. Some clone company sees all your internal documents via a Freedom of Information Act, copies the good, removes the bad and launches in like 6 months.......

5. Someone goes to jail, perp-walk style.

Since 5 is not realistic, I think we can expect some combination of 1-4 for these companies.

The worst outcome is probably Number One here.

The consumer base already doesn't trust Google/23andSerge

Navigenics already has a distribution network, but if the physicians don't trust the test, they won't order it.

Pathway will have a bump in the road and no retail launch.

Number 2 could hurt too, especially Ms Wojiciki who could get personally named in the suit as well as investors like Dyson.

If I was the lawyer, those are the deep pockets I would be after. Navigenics is owned by P&G now and their corporate counsel will likely shield them.

Pathway has probably the least customers to be exposed to such a lawsuit, unlike 23andSerge's 30k

Number 3 stinks for the "Research Revolution, Che Style" but probably won't hurt Navigenics or Pathway.

Number 4 is a definite reality. I have already heard that scuttlebutt on the street.

So, I ask. Is getting companies to behave responsibly and acknowledge that some of what they are doing is medical testing so bad? Ryan made the move. Very smartly Ms. Phelan. I knew she would.

The Sherpa Says: This certainly is a nice distraction from Tar Balls and Toyota...

Couldn't you have picked a better Gene Set Berkeley?

I admire UC Berkeley for pushing the envelope. They have been doing it for decades. Encouraging risk taking, and defying stereotypes

But when I read about their summer research project I cringed.

We are going to test students' ADH and tell them whether or not they can process alcohol properly.......

Excuse me?

Ok, I get it, poor metabolizers will cut down on drinking so much, The UC saves on risk management insurance, win for the administration and win for the educators who will then "teach" about the findings......

What about that party-hardy freshman who has that timid roommate? well, the roommate just found out that she can process alcohol "just fine"

@KTVU news at 11. UC Berkeley student found dead after party.

"Well, it all started when she found her genetic test results meant that she could handle alcohol just as well as I could"-Dead Student's Roommate

Couldn't they have picked a better gene?

What were they thinking? I dunno, maybe they were blinded by Time Magazine. Well, the good news is that all Berkeley Freshman will all be entered in a drawing to receive a free test from, Guess Who?

23andSerge

The Sherpa Says: First Do No Harm

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 (http://snpweb.cloudapp.net/#/PharmGKBSNPs) 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.

Quest, where he had sent the blood, did not test for HLA DQB1

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.

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.

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 et.al.

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.........

You can't have it both way. Either scared your genome is sold off or not.

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.......

Long QT Syndrome, location matters

I just saw a family who had Long QT with a KCNQ1 mutation ripping through them. Which is why I loved this email I received from one of my long time readers the day after I saw them.

Closer Look at Genetic Testing in Long-QT syndrome

One of my favorite lines from this paper was

"Nothing tests the tools of clinical risk prediction quite like sudden death."

Ummmm......Uh Huh.

They go on to say

"The difficulties encountered in the clinical application of genetic data, even in inherited conditions such as the long-QT syndrome (LQTS), in which the transmitted risk of sudden death is several hundred-fold greater than that in the general population, highlight some of the hurdles that must be overcome if DNA diagnosis is ever to transform cardiovascular medicine. "

The reader then went on to send me a release from ScienceDaily

But I should probably give you some background.

Long QT syndrome is a condition where the electrical activity in your heart is faulty. In fact, the conduction system has dangerous delays that can lead to dangerous heart rhythms which cause sudden death.

It is so serious that in every single patient I see, I ask "Has anyone in your family died suddenly or in their sleep? Has anyone had any crib death? Any sudden unexplainable car accidents?"

This is my lay screen for Sudden Cardiac Death (SCD).

Long QT is one of the causes of SCD. The rate is about 1 in 2000 or so. In 10% of people roughly, the first symptom is sudden death. This can be due to exertion, stress, auditory triggers.

A multicenter study was performed to evaluate genetic "noise" in 1400 controls and approximately 400 subjects (Far more than the Norovirus resistance gene for 22andSerge)

What did they find? They found some noise......of course.

This noise was present in about 4% of controls. This is surprisingly low in my estimate......

What else did they find? They found a genotype/phenotype correlation. Which in Autosomal Dominant disease is also no big surprise. Which likely will be augmented with modifier genes.

What is the "noise rate" for other genes? That, my friend is a good question.

What is noise? It could be anything we haven't classified as for certain pathogenic or benign. For BRCA we call these changes "Variants of Uncertain Significance" or affectionately known as VUSes

The VUS rate for BRCA is anywhere between 10 and 15 percent. Which is why I was so surprised about the LQTS study. Heck, there are more than 2 genes involved in LQTS

So why is this noise such a big deal? As we reach the precipitously dropping cost of the genome, we will be able to have a whole bunch of noise......

In fact, I think it will take us at least 20 years to sort out that noise. Add on layers of epigenetics and we may have another 20 years.......

Why so glum? We do have pretty valid clinical testing for Sudden Cardiac Death. It works, MOST of the time. Whole Genome Scanning?

Well, that may be a different story. I have harped on the Incidentalome several times on the blog, but this bears repeating.........

" If practitioners pursue these unexpected genomic findings without thought, there may be disastrous consequences. First, physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements. Second, patients will be subjected to unnecessary follow-up tests, causing additional morbidity. Third, the cost of genomic medicine will increase substantially with little benefit to patients or physicians (but with great financial benefits to the genomic testing industry), "

-Zak Kohane

"Mathematicians modeled sequencing the whole genome. As they get up to sequencing 10.000 people they find that the fraction of the population with a false positive result skyrockets up to 60%. What does this mean? Well, we have to carefully select who we test. Or better yet we need an immense database of "Normal Variants". At a minimum we will need 1000s of "sequence specialists" or "computer sequence analysis programs" to evaluate and decide if the "work up" is indicated or not. Personal Genomics is very complex, even more than personalized medicine."

-Steven Murphy in 2007

The Sherpa Says: In Genomics, there is going to be a whole lotta maybes........which in case you are curious, computers handle very poorly....