Wednesday, May 26, 2010

Breaking 23andMe's Terms of Service: Not just the patient's problem.

A blogger over at 5Am Solutions Blog is about to break 23andMe's Terms of Service.

"So I called my primary care physician's office and told the appointment-taker I wanted to discuss my 23andMe results with my doctor. She said 'ok' and scheduled an appointment for next week."

May I just add. It is not the doctor breaking the Terms of Service here. It is the customer by bringing it in to their doctor.

"BOOM! That patient coerced that doctor into malpractice liability.Section 3 of 23andMe Terms of Service: “The Services Content is not to be used, and is not intended to be used, by you or any other person to diagnose, cure, treat, mitigate, or prevent a disease or other impairment or condition, or to ascertain your health.”

The worst of this is that 23andMe ACTIVELY INSTRUCTS its users to violate this clause —not only personally, but to also implicate their medical doctors in crime.

And the doctor is trapped: he can respect the law and alienate the patient, or ignore the law and appease the patient."

Oh, wait. Maybe by using 23andMe I am now involved in their legal mess? Crap!

That being said, I just received the Counsyl results from one of my patients yesterday. Unlike being put in a risky position by the good folks at 23andMe, Counsyl is straight up clinical and useful.

I will be notifying the patient via secure email of his results and spending an hour going over it with him.

The Sherpa Says: 23andMe, just like others in the space have demonstrated a general disrespect of the precarious position they have put physicians in by using such crazy and convoluted Terms of Service to avoid regulations. But heck, why should they care about the hot water they put us in.

Monday, May 24, 2010

DTC Genomics reviewed in Genetics in Medicine

I just received the May issue of Genetics in Medicine, only 24 days late. But it caught my attention for several reasons.

1. The issue is covering Adult Topics almost exclusively this month

Granted this article was a single author MBA, it was notable at the work she must have put in to this review.


1st she did an extensive analysis of the service 23andMe, Navigenics, deCodeMe, Gene Essence. She assembled the 20 multigenically evaluated conditions, reviewed website data, and deep dove into the studies, average pop lifetime risk, loci, genes, SNPs, Quant risk assessment, and methodologies.

That sounds very similar to what the FDA is requesting to do. In their case with non publically available data as well.

2nd she did a complete locus analysis which is available here.


Analysis 1.
213 conditions covered by DTCG companies, with only 9 conditions covered by all identified companies. 15 addition covered by 4/5 companies.

Analysis 2:

Lifetime average risk values of the same populations.
It turns out that the companies provide different life time risks for the same disease in the same populations.

This is not a big deal to me if you wiggle 2-4 points. But some vary widely

Glaucoma 1% in Navigenics while it is 15 for deCodeme
Heart attack 42% for Navigenics and 21% for 23andMe in Men
Heart attack in women 25% in Navigenics while it is 7% at 23andMe
DVT 3 percent for Navigenics 12% for 23andMe

23andMe does not provide references for their lifetime risk data.

Heterogeneous SNPs and Loci Assessed

No big surprise here, it turns out each company has their own way to make a Big Mac, each has their own special sauce and pickles/onions and even their own sesame seed bun. Thus you get different SNP risks given to customers.

A total of 224 loci are covered 401 SNPs for the 20 multigenic conditions. Of the 224 loci, 115 are only covered by one company. 63 are reviewed by only 2 companies.

For 12 conditions covered by all 4 companies, only 9 SNPs were covered by all. These 9 SNPs represent ONLY 3% of the total SNPs covered by all 4 companies and 18% of all loci covered.

Heterogeneous quantitative risk assessment

Once again, different risk assessment methods rule the day at these companies. Just like if I were to use Reynold Risk instead of Framingham risk but at least I have some data to base my conclusion. We have none of that with the DTC company risk models......

He kept saying, It's My data. I kept saying. Fine, but the interpretation needs to be regulated.

I think we have a very decent reason why right here.

When you get a cholesterol of a blood pressure reading in the United States, you would hope the interpretation you receive is standardized in some way.

Further you hope at least the person giving you the interpretation of that data has some sort of licensing to assure quality and accuracy.

Unfortunately in this field there are many, many unknowns. This makes the risk prediction even less accurate. So it is no surprise these companies have widely variable assessments. But what does trouble me more, is the fact that they seem to not have done their homework with average lifetime risk populations.

That seems like they should be at least on the same page with this information. And why 23andMe has not listed reference articles for their quoted population risk is beyond me.

The Sherpa Says: Doctors go to medical school for 4 years, then go onto residency for 4-8 years and some do fellowship for another 2-5 years. And then we give risk assessment and diagnose and treat. Why do people forget that? Oh and we first operate under the principle of First Do No Harm. What doesn't Mr Goetz get about that?

Saturday, May 22, 2010

Thomas Goetz has the wrong debate. FDA doesn't intend to restrict.

I think everyone in this space has been way off base as to what the problem is with FDA and Congress wanting to investigate the DTC Genomics companies.

The whole mindset is wrong.

What I hear from this debate is "
It's my data, mine, mine, mine. Gimmee, Gimmee, you can't keep me from my data Big Brother!"

From Mr Goetz's Blog
"The controversy seems to have stirred the FDA to assert its authority – and that of physicians – over any and all medical metrics."

"To me, getting access to this information is a civil rights issue. It’s our data."

This is a straw man argument that has been set up to make regulating these companies seem unseemly and an invasion of privacy.

IT IS A DEAD WRONG ARGUMENT and I will not stand for it being perpetuated anymore.

This is not about getting access to your data.

Fine, you want a whole genome, go get it!

The FDA is not asking should people be able to go out and buy this.
It is asking several other questions.

1. Is Interpretation of biometric data considered medicine?

The answer here is certainly confusing. I think it rests solely with intent.

Do you intend to tell someone something about a disease they now have based on this biometric data that you analyzed?

If the answer is yes, that is viewed legally and medically as a diagnosis.
Which ultimately I think is medicine and falls under medical regulations.

2. Is DTCG analyzing biometric data and intending to give an interpretation of that data which indicates a disease a person has?

It depends on what you define disease as.

Most legal experts defer to the International Classification of Diseases

3. Should we regulate a system which has not given indication of their quality control if they are indeed intending to provide medical diagnosis?

4. Are these methods of obtaining human samples to derive biometric data for the intent of analyzing and providing information about disease considered medical devices?

This is precisely the argument and precisely what Congress and the FDA are trying to define.

So stop acting like a bunch of little kids running around because someone took your kool aid away!

If I hear another, "It's my data" whine again I will scream.

This is not about restricting access to biometric data.

Which by the way, some states do already.

Is an EKG biometric data? What about a cholesterol?

Probably, no one is stopping you from going out and buying a machine to obtain this data yourself.

But any doctor will tell you, it is the interpretation that can vary widely. As demonstrated by the multiple interpretations that Venter complained about

What they are intending to do is to prevent a third party from having NO ONE to answer to when providing interpretation of that very SAME biometric data.

The Sherpa Says: Regulation here will most definitely not stifle innovation as bad as a consumer death or class action lawsuit or lack of trust from consumers because of the aforementioned.

Thursday, May 20, 2010

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...

Wednesday, May 19, 2010

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.

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?


The Sherpa Says: First Do No Harm

Monday, May 17, 2010

Potential of genomic medicine, LOST

I was reading and often read Mark Henderson of the Times

The piece basically comes down to one conclusion.

We have no proof that most of this stuff is useful in any form.

This is something that I have been shouting from the roof tops ever since some self deluded socialite from Mountain View decided to say "Genetic testing is for fun"

Seriously DTCG. You knew this day was coming. You tried to play yourself off as hip, cool, sexy/ Yet at the same time to avoid regulation you played, not serious, not clinical, and in essence, not valuable.

I was deeply concerned about precisely this issue. By putting yourselves out there as an invalid in the clinical world, you cheapened the field and some of the tests that you offered.

Because of this conglomeration of useless with useful, the field of medicine and healthcare as a whole needs to create systems to sift between marketing and PR spin/hype from truth and medical utility.

Luckily in the US we have such a system EGAPP. We also have things such as the CPMC ICOB. But in England, they have no such official system.

What is even more troublesome is the lack of clinical utility of such tests and lack of funding to evaluate the utility. The problem with this rush to market the next GWAS is emblematic of this over hype cycle that exists in medical science.


Medical scientific discovery can or cannot be useful in medicine.

That is all.

Saying something promotes "Health" rather than treats,cures, prevents or diagnoses disease to avoid regulation confuses the public and unsophisticated venture capital. Which really makes me wonder if that is what you had intended in the first place........

What should have been said is "These tests have not been proven to prevent/diagnose/treat disease nor have they been proven to aid in healthcare"

But that probably wouldn't have sold many kits......Thus the problem with medicine, you can't just "fake it" with Time Magazine.......

What your "faking it" has done is created a hornets nest on both sides of the pond with governments scrambling to decide what matters.

"Caroline Wright, head of science at the PHG Foundation, said: “The heart of the problem is that we do not have enough data on whether these tests actually help patient care. We desperately need the equivalent of clinical trials for diagnostics."

Further, the UK doesn't have a team equivalent to EGAPP over here. Which BTW, K.O. if you are listening, I would love to be a part of..."I'm just saying......"

We need to ask ourselves as Andrew Yates points out, what results can we expect when the average death percentage over time in this country or any others is 100%

Will a flashy test keep you alive longer? Not if it has no clinical data proving that it does.

No amount of blimps and SoHo parties will prevent death or disease. Sorry.

The Sherpa Says: The Quake paper was their best shot of integrating this into clinical care and they are arguing about whether or not to put him on a prophylactic statin? Which BTW has no evidence behind it........Personally I think that shot was misfired......

Tuesday, May 11, 2010

GateKeeper? F! U!

Dan Vorhaus recently had a great post about the FDA coming in to carpet bomb DTC now OTCGenomics.

But what I am pissed off about is everyone using the term gatekeeper connoting a doctor required to do something.

What the FCUK do you think I am? A gatekeeper is a lot like a door man.

I don't get your bags.

I don't just open the door for you.

I am not profiting from the test that is ordered.

I am saving your f'ing life.

Stop calling me GateKeeper and call me what I am.

Doctor. Sworn to save your life.

Last post edited by Drew

"Clinical Assessment Incorporating A Personal Genome"

The clinical assessment was incomplete.

It was missing the following items

1. A Physical Exam
2. A Complete Pedigree with ethnicity
3. Appropriate Clinical Laboratory testing
4. A Full Social History


D minus.

Adjusted for curve a good solid B minus

But ultimately, this novel approach is clinically unfeasible.


The manpower alone required to perform this "clinical" analysis is unsustainable for 300 Million people.

Monday, May 10, 2010

Personal Genomes in Clinical Care. Quake paper Falls Short!

With all due respect to the scientists involved in analyzing Stephen Quake's genome in clinical context.

You did a major league $h!tty job.

No offense.

I can only assume this based on what you reported in the lancet paper.

Start by asking yourself.

"Is Stephen healthier because of what that genome and clinical assessment added to his care?"

I am speaking precisely on this topic at the Consumer Genomics Conference on June 3rd at 830 AM. So I will hold off on all my arguments....But,

The Paper
even says

"We noted that most of the sequence information is difficult to interpret, and discussed error rates"

Ummm, ok. Nice counseling session.

"patients with whole genome sequence data need information about more diseases with a wide clinical range"

Perhaps that person could actually be a physician, maybe a generalist?

"For this we offered extended access to clinical geneticists, genetic counsellors and clinical lab directors"

Nice! Joubert's is not Gilbert's is not Plavix. Thanks for stopping by.

I did appreciate that your paper calculated pretest probabilities. Unfortunately these were based on a pedigree which had no ethnicity and incomplete clinical data.

1. No Glycohemoglobin to evaluate for diabetes risk or maybe even diagnose it
2. No Iron Studies to evaluate for Hemochromatosis, yet you state genes may set him up for it.
3. No documentation of a physical exam including DRE for prostate hypertrophy/cancer or PSA
4. No dietary history? No Smoking history? No social history?

Shall I go on?

You show increased risk for Diabetes post test as well as prostate cancer, obesity, CAD, MI, Asthma, NHL, RA (no ESR/CRP/CCP?)

You projected an increased risk for 7 and decreased for 8. Yet no Assessment of MCI etc in Alzhemiers disease? My god, you did a stress test in an asymptomatic patient who exercises daily.

"Although the methods we used are nascent, the results provide proof of principle that clinically meaningful information can be derived about disease and response to drugs in patients with whole genome sequence data"

Translated: We made up a system and used novel DNA results to hypothesize about disease risk using research fellows, computer programs an excellent cardiologist (Not a GP) and an Echo machine.......But we skimped on the physical exam, use of primary care doctors, complete blood counts and other clinically useful testing and procedures.

I admire your efforts, but

A. You have missed the boat in using not all the tools at hand
B. By being Genome-centric, we miss the clinical picture.

"Although no methods exist for statistical integration of such conditionally dependent risks, interpretation in the context of the causal circuit diagram allows assessment of the combined effect of environmental and genetic risk for EVERY individual"

Translation: Nothing exists statistically to evaluate disease interaction and how it may increase risks of interlinked disease.

Ask yourself, "What have we done to make Stephen Quake healthier from this test?". Other than hype the use of a genome clinically?

This paper was all genome and NO CLINICAL ASSESSMENT!

The Sherpa Says: The only thing of note that is important here is the CYP2C19 data.......
I have seen abnormal CGH data in a child with severe developmental delay come directly from a high functioning mother who was a power litigator. The genome scan as it stands now is noise. It also requires a full team a month to intepret. Clearly not ready for medical prevention or prognostication, sorry.

Thursday, May 6, 2010

Coriell Personalized Medicine Collaborative rising

This evening I want to write about something amazing I recently was able to participate in. It was the first meeting of the Pharmacogenomics Advisory Group. This group, chaired by Issam Zineh is pretty amazing. Let me tell you why.

1. Members of PAG have been involved in pharmacogenomic studies involving most if not all current markers
2. They include members/contributors of PharmGKB, FDA, AAPS award winners, Howard MacLeod, I could go on and on.....and one lowly blogger and clinical personalized medicine specialist.....
3. The group was willing to engage in active criticism of each other and of ideas. That is the key to a great advisory group.

While we see the dropping costs of genotyping going further and further with some quoting a 10k genome by June's end, it is becoming crystal clear that the test is not the product. The test is a razor handle. Seriously. It will be given away free. But the question is, what will we do with it.

Coriell is aiming to answer some of these questions and is engaging in ethical research. Coriell is the cohort study that we will turn as we turn to Framingham. When the next decade closes we will sit back and laugh at how all of the VCs dumped money into supposed 1000 gene tests that gave nearly useless results or results that couldn't be used for what they needed to be used for by Terms of Service......

At the same time, we will see how a sleepy little institution in Camden NJ, known for holding cells became a powerhouse in the Personalized Medicine Movement by holding patient lives and medical data......with a little help from their friends........

The Sherpa Says: If you haven't joined the CPMC, you should. They are climbing the mountain skillfully