1. Genetic Medicine

Category Archives: Genetic Medicine

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

Posted on by


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!

Posted on by


" 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.

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.

Posted on by

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.

Posted on by

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!

Posted on by

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

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.

Posted on by

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?

Longevity Gene Study, The hype cycle must die!

Posted on by

You know what I love. I love a good story.

Magic research discovers Longevity genes, now humans live to 900. Just like Methusaleh.

Great headline. Unfortunately, this may not exactly turn out what it was cracked up to be.

From the WSJ 1 July 2010

"Scientists discover keys to long life"

"By analyzing the DNA of the world's oldest people.......They expect soon to offer a test...."

Tranlsation, here is why you should read this story about this amazing discovery, because soon you can take a test to discover if you will live a very, very long time.

Ok, this assumes

1. The study is correct
2. The statistics are correct
3. The findings are replicated

What's worse about the article is that there isn't even One Iota of, this is a preliminary and needs to be backed up.

Instead!

Instead, they say

"The free test will be available through a public website maintained by the New England Centenarian Study"

Come An' Get It!

Well, the website doesn't have the free test. But I bet it had a million hits the day the WSJ article and the press hype came out.

One may ask, as I am now, Once the afterglow fades, what will be of this test? Further, will the paper now stand the test of scientific scrutiny.

Just this week, despite the hype machine again rearing its ugly head like it did with Time's invention of the year in '08 or the blimps and Oprah. "An Age Old Problem Solved"? Really Globe and Mail?......We are met with discourse and doubt

There are some issues with the paper. Some skeptical about the effect size. Other's, like myself are skeptical because the SNP chip used for controls and cases was not EXACTLY the same. This can at times produce noise and false positive variants....

I am going to ask the hype machine again. Before running with an AMAZING Story, Mr. Hotz and everyone else in the press. Please take the time to get both sides and an analysis of the study BEFORE publishing the story.

The Sherpa Says: I hope this does pan out though, it sure would be interesting to have an estimate, in this case 77% accurate if you would live to 100. I use family history for this and it is not as accurate as 77%. Who gets that number anyways?

No more 23andMe blog posts. The Sherpa has achieved his goals.

Posted on by


I am absolutely done talking about 23andMe.

Yes, you have heard correctly.

That doesn't mean I will stop watching what they are doing.

It means that I have coerced them into doing what's right. For now.

From the very beginning 23andMe had potential, heck Dr. Jeremiah Mahoney told me they came up to Yale to see them.

They must have not liked what Yale said, because they went further up the line and partnered with George Church.

Well, they def. didn't like what I had to say.

I had even conjectured about DTCG and what this landscape may look like and even warn about the shortcomings,
I had been pointing all of you to SACGHS to watch where this regulatory environment may go. The environment was heated with these companies going in.

So I knew I had to pay attention to what they were doing, especially the Google Backed company.....

First when these companies launch

1. I immediately point out 23andMe isn't using a CLIA certified lab which gives me grave concern over the seriousness with which they are doing testing. A-la Garage lab versus proper human sample processing.

2. I complain on Daniel MacArthur's blog about the obvious rookie blunder this company with no healthcare experience in leadership makes

Then 23andMe uses a CLIA certified lab

Second, I tell you that the states who have serious laws against DTC will shut down these companies quickly

Then they shut 'em down for a bit. And I gloat

Third

1. I complain that FDA needs to get their act together and in 2009 23andMe began doing absolute truly clinical testing with BRCA testing.

2. I point out the SACGHS feels the same way too and also complains to the FDA

3. I point out that 23andMe has no clinical clue what they are doing with PGx

Guess what? The FDA finally rules for regulation.

Lastly,

1. I complain about this research revolution akin to Tuskegee or other non IRB approved "research"

2. I point out that Google has off shore servers to hold this data free of US regulation.

3. I say that they are coercing subjects and offering discounts that wouldn't fly in an IRB

Today, they announce they have obtained IRB approval.

But I have my doubts as they have flaunted loopholes in laws And seem to point that out again today, or at least their blogger does.....

"our research technically does not require IRB review."

So I guess I will have to keep posting until these guys stop skirting lines..............Nevermind

The Sherpa Says: Yes, why keep it up if they did what I asked? Because they will do it again, even if it takes an act of Congress. Why do I ask? To protect the patient and consumer from mega corporations whose interest is anything but patient empowerment.

Ok, Spam Botted! Prasugrel PLUS 2C19 PM has better outcome.

Posted on by


Alright, so I just found out that I posted a spam bot post. Not from a nice student named Ashley.

Instead what I will post is a subgroup analysis of TRITON TIMI 38. The subgroup analysis? 2C19 PMs and Prasugrel.

Great clinical question-Did the PMs (poor metabolizers) on Prasugrel fare better than the PMs on Plavix.

The obvious answer:
Duh, of course yes.

But Always we need some science and statistics here.

Individuals with a CYP2C19 reduced-metabolizer genotype were estimated to have a substantial reduction in the risk of the composite primary outcome (cardiovascular death, myocardial infarction or stroke) with prasugrel compared to clopidogrel (relative risk 0.57; 95% confidence interval [CI], 0.39 to 0.83).

Ok, so we should screen for PMs? Probably.

What about every other result?

What about the EMs?

For CYP2C19 extensive-metabolizers (EM) ( approximately 70% of the population), however, the composite outcome risks with prasugrel and clopidogrel were not substantially different (relative risk 0.98; 95% CI, 0.80 to 1.20).

The Sherpa Says: We should AT LEAST be identifying the PMs and placing them on Prasugrel. This subgroup analysis shows increased risk while on Plavix. Primum Non Nocere.

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

Posted on by


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!

Posted on by


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?

Posted on by



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......

5 Days after the Quake Critique

Posted on by


I want to know, when everyone got all upset with my review of the Quake paper and bashed me on this blog. Why?


Why did no one post on the Viewpoint put out in The Lancet exactly 5 days after my review?


I will keep this brief, as I will be speaking precisely on this topic on Thursday at the Consumer Genomics Conference.

Maybe no one read the viewpoint?

Today I was able to read the

It echoes every single thing I have been saying for the last 2 years. Not that any of this is news for those of us in "the know" But it is confirmation that people who include a DIRECT Advisor to 23andMe agree with my stance.

However, there are some things in the paper that I disagree with.

1. "The author assumes that because of the rapidity of cost decline with WGS (whole genome sequencing), that it will be used more and more in Medicine."

I disagree.
Payors, Clinical validity and Exposure to malpractice risk will determine the uptake in the clinic
2. "Reduced sequencing costs seem likely to cause a rise in WGS"

I disagree.
Perhaps in research this will be the case, but for customers, who are now staring down the barrel of an FDA investigation, House of Reps investigation, they may think twice. No matter what Oprah has to say.

3. "even if that information averaged only 3 min per disorder, this process would take more than 5 hours of direct patient contact, after many hours of background research"

I disagree.
The average time per disorder would be at least twice that, meaning ten hours of direct patient care. Which on my clock is about 4000 USD, at least.

4. "As academics, we often assume that information is good and more information is better. but more information can sometimes be counterproductive"

I agree whole heartedly.
I know many excellent academicians who say "Garbage in, Garbage out" or "Information is just that, but Noise is Garbage"

The Sherpa Says: We need to bite things off a piece at a time. That is the problem with whole genomes. People will need to be revealed information in a staged fashion WITH SKILLED CLINICIANS. Nice to see Russ B Altman MD et.al., advisor to 23andMe agree with what I have been saying over the last 3 years now.

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

Posted on by

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.

DTC Genomics reviewed in Genetics in Medicine

Posted on by

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.

Methods:

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.

Results

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?

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

Posted on by


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 et.al 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.

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

Posted on by


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?

23andSerge

The Sherpa Says: First Do No Harm

How Bad Can a House Investigation be for DTC Genomics?

Posted on by


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...

Potential of genomic medicine, LOST

Posted on by

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.

Why?

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......

  1. Genetic Medicine