Genetic test may refine PSA or it may not!

I am going to read this article for the seventh time and get back to you this week.

In case you missed it, the PR Firm hired by DeCode pumped out a presser (press release), which I refuse to link to directly.....which essentially said

"Analysis of Four SNPs, in Tandem With Genetic Risk Factors Detected by the deCODE ProstateCancer(TM) Test, Yields Substantial Improvement in Efficacy of PSA Screening"

OK, 4 SNPs tells us whose PSA value is a bad 2.8 vs. good 5.8?

Or at least that's what the Kari S. tells us

"This is straighforward genetics with direct clinical utility." -Kari S. (Yes they rushed the release out with the misspelling of "straightforward")

Ok, so tell me, how has this straightforward genetic test performed in a prospective analysis?

What do you mean you haven't done that yet? So how can we have you assert that there is direct clinical utility?

We can't. Maybe you meant STRAY FORWARD?

Secondly, this study was carried out on Caucasian men, leaving African Americans, who often have earlier and more aggressive prostate cancer out in the dark.......

But what really got my Ire was when respected Tweeters started parroting this presser.........

Here is some high heat for us genome critics, read the study and read the presser. If the presser hypes the study, we should tear it apart and present the true facts for all to see on the internet.

Read and analyze the study, not the presser. I know we are all busy these days, but we owe that to our readers and the public. Hell, that makes us even better than a whole host of journalists who seem to quote Kari as if his opinion is the final take.

The Sherpa Says: On seventh read I will have a take on what these "SNPs that strengthen the predictive power of PSA" really mean.

23andKari, what the 99 USD subsidy means for Personal Genomics

Yes, Yes.....

Everyones' little heart is a-twitter for the subisdized cost of 23andSerge, now to be known as 23andKari (will tell you why soon) a whopping 99 USD. Which I had been saying is the correct price point for about 2 years now.

Yes, finally, something other than a blimp and million dollar parties will actually pull out the lurkers.....

Here's my take. There was a company in a galaxy far far away, Iceland. That was the toast of the town in 2004. Why? They were collecting genomes for a grand experiment. They were going to discover fantastic links to disease and sell access to the highest bidder.

While they did produce some great Nature papers......what happened to DeCode?

I think we all know.

23andKari has now emerged. The front end.....happy shiny ancestry and disease links.....

I have forgotten to mention that the FDA still hasn't finished working on these companies, have I?

The back end? A database of genomes to cull for disease links to be sold at the highest bidder?

Sound familiar??

In case you forgot, Kari did this with Gulcher and went belly up.......

And BTW, who owns that genetic data now? Is it getting resold?

Celera too?

Also in case you forgot, this is a rock bottom version of Navigenics game...How's that working?

I think 23andKari will actually survive. Why? Huge megacorporation investment. That's why.

GOOG et.al. own 23andKari now. Your data? Wrong! Theirs. Now that they are being investigated for antitrust in the EU, they have to move quickly on this phase......

I have said it before and will again. Why sell Manhattan for bobbles and trinkets?

Because it's cheap, that's why........Hell. IMHO, 23andKari should be paying you for your genome.

I hope the lab 23andKari is using is up to snuff this time.....after that whole sample swap issue, they are about to get a whole lot more volume.

The Sherpa Says: Democratization is about to go the way of Russia and it's oligarchs...

23andMe going infomercial style!

Dan Vorhaus points out the Plan B for 23andSerge!

Personally I love the irony of naming it "Plan B"

MSRP 499, but yours for the low, low price of 99 USD.

QVC, here we come!!!!

Respiragene Test and CT Screening for Lung Cancer?

I love personalized medicine.

I absolutely think it is beyond fantastic to be able to say to a patient "This is the drug for you"

Or, we need to screen for disease X because of Gene Y and your family history

But what I don't love is companies purporting the import of their special home brew test to do personalized medicine without any sort of data backing them up.

A news report and "AACR Feature" highlighted precisely that. A test with no data......

From the article:

Researchers administered a gene-based predisposition test that incorporates 20 genetic markers associated with smoking-related lung damage and propensity to lung cancer along with clinical factors including age, family history and diagnosis of chronic obstructive pulmonary disease to derive a risk score on a 1 to 12 scale with higher scores correlating with higher risk.

Ok, new score with 20 markers, family history and age and clinical data....sounds reasonable. Has anyone else validated this tool????

Ahem. Crickets.....

“At scores of 6 or more … only 25 percent of otherwise eligible smokers would be screened but over half of lung cancers would potentially be detected, many in a treatable stage,” concluded Young and colleagues, who suggested that increasing the detection rate of lung cancer per number of patients screened could improve the cost-effectiveness of CT screening.

Ok, so did you get the jump? Did you catch it? "Who Suggested"

This guy who designed a genetic panel AND NEVER TESTED IT IN CONJUNCTION WITH CT CHEST SCREENING, is suggesting that using the test could increase the cost effectiveness of CT Screening, without one single solitary IOTA or shred of evidence of this.

This would be the same Dr. Young who found that genetic testing for a smoking cessation program likely doesn't have cost effectiveness or at best is uncertain.

Last year they were still researching this panel

Yet Respiragene is being held up as a great test!

One word that makes me suspicious is the word "Testamonials"

That word alone reminds me of the time I was bamboozled into going to multi level marketing events for proton pills and the like. You know, they all had lots of "Research" behind them.

Put simply, we do not know if gene screening PRIOR to CT Chest screening for lung cancer does any of the following things

1. Make CT Screening more cost effective

2. Personalizes medicine, targeting radiation to only those who need the test

3. Improves outcomes and detection rates of lung cancer.

That research is not available today. Nor will it be in one year.

My Advice, hold off on this one for now.

The Sherpa Says: Parroting an esteemed researchers OPINION as if it were scientific fact is a great way to get yourself in trouble and an even greater way to confuse the community! But it is the best way to get a test sold.

Pulitzer Prize Winner Amy Harmon hosting ethical dilemmas!

How do you face life as a 22 year old if you carry a genetic variant for an incurable illness that will most likely strike in middle age?

That's right,

Amy Harmon is hosting a fantastic course that will be starting November 15th. You better hurry up and register because space is limited and closing on the 14th of November.

What will be covered?

The course will have weekly live online sessions with the instructor as well as self-paced lessons filled with original content covering the weekly topics. All live sessions and course material can be accessed directly within the online course.

Prenatal testing can go into deep detail about an unborn baby’s prospects for the future. How much of this do we want to know? To share?

These questions and more will be addressed. If there is one thing I know. Amy is certainly a fantastic teacher, educator, and discussion leader!

I do miss conversations like those with her!

You too can have that kind of expertise. Register before November 14th!

I am certain you will enjoy this set of topics and have directed many people this way already.

The Sherpa Says: Family history picks up life threatening disease, DTCG tests probably not so much. That being said, what's the ethical quandry with either? Ask Amy and find out!

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

Family History Better than Navigenics/DTCG Shill for Cancer Genes?

Yes,

You heard it here. A recent study abstract and pressed about from my friend Charis Eng MD PhD, Clinical Geneticist, Internist and all around really smart lady spoke today about her findings of a head to head, DTCG vs Family History at discovering cancer risk.

You can watch the webcast about it here!

I actually sent some data Ken Offit's way about a similar thing way back when, Ken is yet another, really smart guy. He wasn't surprised. Nor was I when I heard Dr. Eng's findings.

First, Caveat Emptor

This is an abstract! Repeat after me......

What does that mean?

1. It is not peer reviewed fully

2. It is not published yet

3. It is preliminary data

This test was Navigenics Compass vs Family History in 22 females with breast cancer, 22 males with prostate cancer and 44 people with colorectal cancer.

What was the result? Family History placed far more people in the proper high risk category. 8:1

Family History put 22 people in the appropriate High Risk Hereditary Category, DTCG only one.

Further, it looks to me that the Navi "Gene" Scan missed several high risk patients who actually had MMR mutations (I.E. Genetic Cancer).....D'Oh.

First off, this is like a case study. But it signals a HUGE shortcoming of DTCG. False reassurance.

I have been beating this over the head for 3 years now! These tests that have "medical" relevance need to be couched with proper medical guidance.

I told Mary Carmichael of Newsweek this!

This stuff is medical data and I Told Thomas Goetz of Wired this!

Even the WSJ has gotten it!

There are huge shortcomings in the current offering of DTCG tests and those offering medical information need to be regulated as medical. This is a classic case in point of potential and REAL missed cases.

Not Good.

That being said. It is November AKA Family History Month. You should absolutely take your family history and bring it to your doctor. If they don't know what to do with it, call us. We do.

The Sherpa Says: No surprises Charis, I saw this with some DTC cases I have had, passed it on to Ken who passed it on to NIH and The IOM. This is the huge problem with hype and over promise. It always fails to deliver, unfortunately in this case at a great risk to consumers.

For Personalized Medicine CPMC is the Gold Standard Study

Ok,

So I just wrapped up a meeting with some, well, nearly all of the most brilliant minds in Pharmacogenomics. Where was I? Yes, on the cover of USA Today's life section.....But where was I really?

Conference? No.

VC event? No.

I was at the Coriell Personalized Medicine Collaborative (CPMC) Pharmacogenomics Advisory Group meeting.

Yes, that sleepy 'Ol Cell Line joint in Camden New Jersey.

I am certain you all know about the CPMC now. But in case you have been sleeping.

Coriell is climbing the mountain, gaining collaborators, building camps. They are essentially doing all the hard work of study analysis so that you don't have to.

Brilliant if you ask me.

Who in the world has the time or money to cull data, looking for important findings?

Google funded "projects", Academic Programs and Not For Profits.

Who do you trust to give you unbiased reports?

NFPs.

Who is the NFP here? Coriell.

Are you curious what the CPMC does?

Why will CPMC win this battle? Even 23andSerge agree that CPMC is the gold standard

1. They have independent advisors and scientists

2. They have nearly all the best independent advisors and scientists

3. They have the support of the government, the community and oh yeah, the FDA isn't investigating them......

4. They have Mike Christman.

5. They have a team who believe in this moral imperative, not a pay check or stock options.

I vowed never to post what transpires at these meetings, but rest assured, it was truly academic heated debate with egos left at the door. This is precisely what you want when someone is going to tell you what your genetic material means for you.

The Sherpa Says: Coriell is on to something here. Something so valuable when the 1000 genomes and the rest of the genomes go public. Someone has to make sense of it all and study what it means......I am proud to be a part of it.

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.

Barbara Evans is Right! Sliding scale of regulation.

As the FDA debates what they should do, Barbara Evans at the University of Houston Law School and Amy L. McGuire of the Center for Medical Ethics and Health Policy at Baylor College of Medicine in Houston, also includes, Canadian legal expert Timothy Caulfield and Wylie Burke, M.D., of the University of Washington School of Medicine post some guidelines for regulation of DTCG/LDT genetic testing.

I love this sort of handicapping.

You have absolutely brilliant people posing ideas for regulations. I have read a ton. There are those from industry insiders, Ones from industry "Advisors", Ones from politicians who receive funding from industry, Ones from academic centers that do LDT testing. Ones from bioethicists...

But I have paid attention to the mixed group that includes pragmatist Wylie Burke and Barb Evans

In an article I just read from Science published October 8th. They propose rules for DTCG, but I am certain they also would work for LDT.

What they propose is a "sliding scale of potential harm"

Which is sort of what I had been saying for years, which perhaps is why it rings true.

If this is for earwax type, let it go to market, if it is for medically related decision making, probably needs some regulation.

The proponents for a wild west DTCG (WWDTCG), which BTW includes a "registry" say
"Well, there is no proof of harm or risk"

I say, well, this is not about psychologic risk.

Instead, it is about medically actionable risk.

I say this because recently, Kif6 testing has fallen into question, despite a company promoting these tests to physicians.

The test is marketed as a "Statin response" genetic test.

Can you imagine how many people were started on statins? Well, 250,000 tests had been ordered. Even if 10% were started it would be nearly as many people as DCTG 23andMe have tested.

The real problem here: Pharmacogenomics tests are not something you hide, you ask your doctor to use these results. Unless you are a doctor, you can't use these results to dose medications.......

That is a real risk. Despite what WWDTCG proponents say.

Another risk, BRCA testing. I cringe at the thought that a doctor would use 23andMe results and only those results to infer carrier status of BRCA 1/2
The same goes for CF carrier status.

These DTCG medical tests aren't recreational. These companies added these tests because NO ONE wanted to pay hundreds, hell thousands of dollars to find out these risks.....

In a business decision, they fell short of looking at the medical risks.

So yes, a sliding scale of regulation is likely coming. But not because of Wylie, because of the FDA.

It is obvious. Again, medical testing will be regulated as medical. Ear Wax as ear wax. Will LDT be forced to go through pre-market review? Probably not if they can only be ordered by licensed professionals.....

It's not a form a rent seeking, it is a form of guidance and protection for consumers. That's why physicians are licensed and malpractice covered.

Yes, yes. Someday everyone will have these genomes done and everyone will be educated enough to know what they mean. And all humans will have medical education and we can replace the oligarchy of physicians and the tyrannical healthcare system once and for all........

But until that day, we will have to rely on trained professionals who don't have their retirements tied to their company's new genetic test......

The Sherpa Says: Handicapping of the FDA by the Sherpa. If it has any medical utility it will be regulated as either Class II or III. If only ordered via physician it will more likely be Class II. If not, will need Class III.

Kif 6, Genetic Findings = Useful Medicine 1 in 1000 times

Way back in 2008 I mentioned an article, which I hoped would pan out. Or at least I hoped it would point the way to a model of PGx research which would be followed by pharma and alike to find associations to help us target the right medication for the right patient.

While the similar model followed through with Plavix, the initial study did not.

Which is why when the Berkeley Heart Lab guy came last week, I told him I would not be testing for Kif6. It had not been replicated in further GWAS.

Heck, I don't even use the 9p21.3 test......Why?

A VAP cholesterol panel, a HsCRP, a family history and a blood pressure can help me predict risk much better.

The problem and backlash facing DTCG and DTMD genetic test purveyors is

the 'Ol "Your million dollar major study now rushed to market has just been refuted"

Yes this happens in biomedical science and in medicine ALL THE TIME.

Bed rest for MI anyone?

Low Dose Dopamine?

I could go on and on, but I won't

Put simply, the majority of the genome is NOT ready for clinical medicine or clinical decision making.

It won't be for 20 years.

That doesn't mean there aren't some things we can use.

1. BRCA1/2

2. MMR genes

3. CYP2C19

4. CYP2D6, sometimes.....

5. SCD genes

6. Counsyl universal carrier screening

That is why the FDA is all hepped up about DTCG and even DTMD.

If a gene test comes to market that purports disease risk it had better be studied for at least 5 years before it comes to market.

Post market surveillance did not protect all those patients on Statins, "just because" of Kif6 risk.

Get it? These tests can lead to incorrect medical decisions....

Which can lead to risk.

Yes, even the DTCG tests can fool doctors and patients.

The Sherpa Says: If 2008 was the year of the GWAS, will 2011 be the year of the overturned GWAS?

A Whole Month Off, for Good Reason!

I have a lot of friends and readers who have emailed me over the month.

The recurring comments: "Has the DTCG field run you off of your blog?"

The answer: "Uh No"

Why I have I stopped blogging so much? For multiple reasons.

1. DTCG has been put on the Radar of the FDA and Government. I have nothing more to say about that.
2. Journalists and Genomics aficionados have been correctly pointing out the hype behind some tests. Most notably lately with the ADHD stuff, which BTW should not have been put out there in the press....Maybe, I need to blog more.....
3. My practice and patients have really taken up my time. I am working to apply personalized medicine daily. Because that is what is needed. We need to show the public and the press how it is done on a daily basis.

I will be back soon, to dissect shotty science and poor clinical studies. But for now, our boots are on the ground and we are climbing the mountain....

See you soon!

Plavix and 2C19 BrewHahHah

Yes,

I am a little slow

Yes,

It has been a long time.

But,

I am back. With a serious hankering to smash some studies. I already pooh pooh'd the Migraine SNP study on Twitter, but the Plavix stuff.....That deserves a blogpost.

To quote a famous caridologist and friend

"If Plavix really didn't work for 30% of patients, why don't we see more in-stent thrombosis?"

Translation: Your science is nice, but how does it fly in the real world?

I have to tell you, at first I couldn't answer. It was a great question. Do a full third of people have that severe failure?

The obvious answer is NO. If 1/3 rethrombosed, we wouldn't be using Drug Eluting Stents.

So what is the answer:

Apparently a BMS (I.E. Plavix maker) funded study investigated this

We hypothesized that the benefits of clopidogrel as compared with placebo would be decreased in persons who carry a loss-of-function CYP2C19 allele and increased in carriers of the gain-of-function *17 allele.

What did this team study?

we examined the efficacy and safety of clopidogrel as compared with placebo according to genotype status among patients in two randomized trials: the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, in which patients with acute coronary syndromes were enrolled, and the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) A, in which patients with atrial fibrillation were enrolled.

Ok, so they took 2 different populations and bundled them into the same article....

The 2 studies?

CURE-randomized, double-blind, placebo-controlled trial comparing clopidogrel (at a dose of 75 mg per day) with placebo — both in combination with aspirin — among 12,562 patients with acute coronary syndromes without ST-segment elevation.

ACTIVE A- was a randomized, double-blind trial comparing clopidogrel, at a dose of 75 mg per day, with placebo — both in combination with aspirin — for reducing the risk of stroke among patients with atrial fibrillation and at least one additional risk factor for stroke who were not eligible for warfarin therapy.

What did they find? No difference between Poor Metabolizer and Wild Type in secondary and primary outcomes.

So are we wrong with our studies showing 2C19 genotype matters in outcomes?

Probably not.

1st the authors note why.

1. One possible explanation for the divergence between our findings and those of previous studies involving patients with acute coronary syndromes is the difference in the rates of PCI with stenting. Only 18.0% of patients in the CURE population included in our study underwent PCI, and only 14.5% underwent PCI with placement of a stent, as compared with more than 70% in previous studies

2. We cannot definitely exclude the possibility of an interaction in the subgroup of patients who receive stents, particularly those who receive drug-eluting stents, which were not in use at the time of the CURE trial.

3. the ACTIVE A genetic data set contained fewer participants and outcome events than did the CURE data set and therefore had less statistical power.

My take

The ACTIVE A trial to assess the hypothesis was powered at 45% to detect a difference, thus it is a worthless study and should not be included in this analysis.

While I agree that a placebo group may be useful. It is not needed to assess a difference between people using Plavix with normal Plavix metabolism and Poor metabolism. In fact it may even confuse the situation as it introduces further confounding factors not genotyped or phenotyped out.

The authors disagree
First, the inclusion of a randomized placebo group in our analyses reduces various sources of confounding, such as potential pleiotropic genetic effects or population stratification.

Well, did they test or assess for pleiotropic genetic effects? No.

Further, by introducing a study COMPLETELY underpowered to observe and eval the hypothesis into this article, it ONLY creates a false image of scientific validity.

The authors disagree
Third, we observed consistent benefits of clopidogrel, irrespective of CYP2C19 genotype, in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations.

Again to quote the article

Among patients with atrial fibrillation in ACTIVE A, our study had much lower power (45%) to detect a similar interaction.

So why did they include the POORLY POWERED study?

" in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations."

While I laud the effort to have Randomized and Observational versus retrospective efforts. I think we have to be very careful in our study design to make sure

1. We are properly powered to observe differences.
2. That we assess pleoitropic effects, rather than claim to control for them mysteriously.

The Sherpa Says: Why include the second study? It is improperly powered, further the CURE study did not include Drug Eluting Stents! Why? Plavix goes generic in 2011. They did this to save the market......Expect more screwy studies published in NEJM etc. As PGx gains traction, contrarians and Pharm will always fight it.....

What is medical testing? Why it matters for DTCG survival.

I just was threatened by Daniel MacArthur over at GenomesUnzipped that he was about to delete my comments.

He called it trivial. I think he is missing the tremendously simple point.

Why is the FDA mad as hell? Medical Claims.

Hell, they even told Mary Carmichael in the interview.

Alberto Gutierrez = AG

"AG: The concern is with everything."

"AG: The law requires us to clear devices or approve devices BEFORE they go into the marketplace when they make medical claims"

This to me is crystal clear. Make a medical claim. Get regulated.

Which is interesting. Because I would say some of what DTCG did was, infer medical claims without making outright claims- silly games . I happen to think that is a shitty way to sell something. But heck it is a way to create a discussion rather than instant regs.....

"AG: The question with 23andMe has been whether their claims were medical or not. The original claims they were making were very much on the edge."

"AG: We actually told them that WE(FDA) thought they were medical claims, but it was at least possible you could argue that they were not"

Do you get it? The judge thought they were medical claims, but let the company proceed. Giving it just enough rope to hang itself.......

The question here is clear. What is a medical claim?

Which boils down to: What is medical?

I can tell you what I do as a doctor.


I diagnose, treat, cure, palliate, prevent human suffering and advance human health.

If you are making claims to do any of those things, I would call it medicine.


This is very important to understand and I hope you VC are listening........

Diagnose, Treat, Cure, Palliate or Prevent human suffering.......and advance human health.

Words matter. Did you notice I didn't say disease. Because what's today's disease may not be tomorrow's.

And Vice Versa....

Is a priest a doctor? Well, they used to be.

Is a counselor practicing medicine, well, I would say yes, they are in the healthcare arena

Yes, it is now sinking in. That huge pit in your gut. The millions invested trying to game the system that is millenia old........


It will not work. DTCG has just proven that. And, do you think the vitamin industry has a chance over the next decade?

No.

I will begin the deep dive into the FDA comments shortly. But rest assured, I just gave you some insight into what medical really means......

The Sherpa Says: There Daniel, there you have it. I have told you what medicine is. Now if you wish to argue against that go ahead bub.......

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.....

Another Ho Hum for SNPs, FGFR2 and breast cancer risk.

The setting: Salvage of SNPs for Breast Cancer risk prediction published in JAMA yesterday.

The study: Women, 10306 with breast cancer mean age of Dx 58, 10393 sans breast cancer.

Outcomes:
1. Highest OR is 1.3 to predict Estrogen Receptor (ER) Positive vs ER negative with rs2981582 and 1.24 for rs3803662
2. The rest of the results were so suspect that the authors didn't include them in the abstract

"Certain Established risk factors for breast cancer have similar or even greater effects on breast cancer incidence that the differences seen here" -The Authors about this study's predictive model.

Bottom line: What good is a predictive SNP analysis of ER+ vs ER- if you can do that with pathology most of the time?

"Indeed or estimate of.....in the top fifth for polygenic risk score is similar to that for women in developed countries with one first degree relative with breast cancer" -The Authors about the less than useful polygenic risk model they created when compared to family history

Heck even the authors admit, this stuff is great......For studying pathogenesis, but NOT FOR CLINICAL USE TO GUIDE PREVENTION PROGRAMS!!!

The Sherpa Says: Again, "You would be in the high risk of pretty much getting it".........Not a good way to do medicine or guide consumers guys.....

FDA Tuesday, Congress TODAY. More letters for DTCG.

I read with great interest Dan Vorhaus' post on the new letters sent to DTCG companies this week.

While it seems to me that these letters were probably planned beforehand, they may indeed be just trying to batch the "Publicized" I.E. Venture funded DTCG with the private funded DTCG. BEFORE, congress has a chance to sit down with the Big Money DTCG.....

I also disagree with his take that the FDA has worsened its position of trust with the LDT companies via these letters. In fact, what is going on as I speak with more LDT directors of labs, they are mad as hell. They are mad that these DTCG companies came in and screwed everything up in their nice little universe of LDT.

If anything, the FDA letters represent an effort to show clinically useful and ordered LDTs that they are siding with them and against the microcosm known as DTCG.

I think the Congressional Hearings on DTCG will prove the same here.

Back in 2007 when these companies launched, I expressed concern on my blog. I was concerned that these DTCG companies, which wanted to initially play down their clinical role, NITDOC loophole, would actually make the whole field look silly and create public distrust. I even predicted that this movement to "flip" a company I.E. "Create a revolution" may even lead to the death of personalized medicine

Unfortunately, that is exactly what has played out. At least the distrust part and definitely the confusion part. It appears the FDA is extending a lifeline to LDTs ordered by physicians and trying to amputate the DTCG arm of LDT.

LDT companies can either turn on the DTCG companies and devour them, thus saving themselves from onerous regulation or they can stay silent on DTCG at their own peril. This will be interesting to see how it all plays out.

One thing is for certain, what DTCG says or presents to congress will likely give lots of cannon fodder to the LDTs being used and ordered by clinicians and patients.....

Congress already has fodder to attack DTCG, they have been collecting it for a month. Wha? Those letters basically say "Give us everything. Tell us everything about how you funded and ran your companies. Tell us how you fixed your screw ups or didn't. We want it all. Emails, Texts, etc."

The Sherpa Says: This is not LDT vs FDA, this is Clinical LDT vs DTCG LDT vs FDA and The US Government. I think that if they fight it will be very ugly here. Congress needs to ask 1 question "Do you think you are doing medical testing? If not why not?"

Addendum: Video Sting from the GAO presented at the conference shows.

They are not only doing medical testing, they are giving medical advice.......




This industry is about to get blown up from the inside to protect the Clinically Useful and Valid labs. Those labs are about to feel the pain of a 2000 sample validation process......

FDA LDT meeting, bigger than just DTCG!

At the FDA public hearing today, I began to hear a collective groan. The groan was from the LDT community that provide tests that are actually in clinical use today. You, see, this hearing is much more about LDT than it is about little 'Ol DTCG.

DTCG in fact was the perp walk that allowed LDT to now fall under question. For years, Home Brew labs up at Yale and Harvard and GeneDx and I could go on and on, went unscathed from FDA regs. Why? The tests were used by so few people and the case for harm was pretty weak.

Despite all of this, the FDA is now awoken and realizing it was asleep at the wheel here while the wagon train was being run by the Music Man! You can tell from the agenda that there is one thing at stake here........the future of nearly ALL genetic testing.

If you look at the list of speakers it was a hodgepodge of diagnostic labs, testing advocacy groups, consulting firms that bring biopharma through the pipeline and something called OMBU. WTF is OMBU?

Tomorrow is more of the same. Of course Wadsworth was there to represent some sanity in this process, thank god. But my big Gestalt from today's action is:

1. The FDA firnly believes it is time to get its act together in regulating genetic testing

2. The Genentech complaint from December 2008 really struck home with the FDA

3. The FDA regulates tests, not labs.

What does this mean.

Well I can tell you this. The FDA will regulate LDT and follow some line that it already has with things like AmpliChip.

I can also tell you, the LDT house is huge and a few little revolutionaries in DTCG have brought the entire house down. I am surprised that the genetic testing industry and academic labs didn't see this one coming. So many I know in the space were always pro DTCG, I warned them precisely against the regulatory scrutiny which LDT would face given "Oprah, Dr. Oz, Blimps, Open Bars and Trump"

They said, nawh, we are ok in this space and serve a need, why regulate us? I think in Genetech we just found the answer. How can we hold a corporation to a different standard than an academic lab? How can we hold a big company to a different standard from a small company? How can we justify that to the public? More importantly, to the court?

The answer: They can't.

The Sherpa Says: I don't think I could stand another moment of the FDA conference tomorrow. Instead I will play on loop C3PO saying "Please don't deactivate me"

FDA and the DTCG company MashUp.

I know I said I would stop writing about 23andSerge. I will, but I am still going to write about what I think may go down next week in D.C. Land.

As you may know, I am a big supporter of classifying DTCG tests in certain ways

1. If the company has purported some sort of health benefits or decisions regarding medical care for a test, then it should be classified as a medical device and regulated as such. Class II or Class III

2. If a DTCG test does actually have medical implications for treatment, diagnosis or prevention, regardless of what a company says, this should be a Class III subject to premarket review.

3. If a DTCG test has nothing in the way of health implications or diagnosis, treatment or prevention it should not be considered medical.

If 3 should become item one or 2 based on new evidence, then it should be regulated as item one or 2.

What do I think should happen here with the FDA and DTCG? Well, it depends.

One has to ask first, will regulation stifle innovation?

If you ask me, most of this rhetoric is merely legal polemic. Very similar to how the Pharma companies complain about regulation. I have seen very scant evidence on the horrible effect it has on health or longevity.

In fact most of the "evidence" on regulation seem to come via law school papers and angry blog posts and twitter feeds.

But to get at the heart of this issue facing regulators we need to ask a follow up. Is innovation a good thing?

A priori I would say yes. Always? No.

I challenge anyone to prove to me that some innovation hasn't led to bad things or bad outcomes. "Magic Mineral" anyone? Or how about derivatives trading?

Assuming that not all innovation is good, we can see the role of regulation to prevent the harm of bad innovation. Is that such a bad thing? The general pubic doesn't think so. A poll in May finds that 72% of Americans trust the job the FDA does. They also are wayin favor of regulation of innovation in the space.

Now the FDA needs a litmus test for genomic innovation to define their regulation. What defines bad innovation?

I would say:

1. Potential for human harm from use of innovation.

2. Misrepresentations of expected outcomes from using innovation.

3. Lack of innovation performance of stated use.

I think in some ways, certain DTCG companies have had 2 and 3.

Number One is a potential in some peoples minds, but I have clinical examples that were presented by K.O. a year or 2 ago.

Unfortunately for the FDA, they have some lines and categories already which can create some rigidity in their guidance. And may not apply the scale I use.

But, it is just a construct. Similar to the one I presented before.

Will the FDA throw out traditional guidance here?

No.

They will follow the construct listed here, no matter how many people rant and rave at the DC meeting. Why?

I just told you. The public wants innovation in healthcare regulated. Which leads me to my next question. What do you think congress will do?

The Sherpa Says: We have to stop ranting about how the world will end if this tiny little field with the "unproven" ability to transform medicine sans clinician has to face regulatory scrutiny. Instead, we have to ask, is this a good innovation now? How will we make it a good innovation? Can we?