Tuesday's Doc! Getting bamboozled in Genomics.

Warning! If you don't want to hear me go off on the Public Relations and Journalism field, click away now!!!!!

Now!!!

Seriously, now.


For centuries advertising and journalism have existed. In fact there relationship has been one of symbiosis. Think about, papers can't print without money, the money often doesn't come from subscribers, it comes from advertisement's..........

This is one of the big reasons why papers are dying.

Online Media Outlets just keep seeing the money flow in though......... Why pay to get marketed to? That is essentially what the savvy news reader is saying.....which is why they have turned away from newspapers and turned towards blogs and twitter......what used to be the gold standard of journalism is now being exposed as a piece of paper for rent to the highest bidder, couched in some official looking headline....

I am afraid the same may happen to blogs and twitter........But this game is not new, the advertising industry has a whole army called "Public Relations" which is designed to do just that, sucker a pressured journalist into "copying" a Press release into an article and send it out "AS IF" it were news.....

What really turned the public's attention towards this really, really big scam? Blogs........ Yes, blogs.

The very thing I am writing now.

Why do I know this?

Because I saw it happen........ In 2007 when I started blogging, I was the only, I repeat only voice dispelling the HYPE behind DTC genomics..... The press had been infiltrated by the PR crazies.......

Article after article about how fantastic this would be, without ANY other input from the professional genetics side........or if it was, it was a zealous Ph.D. without any clinical context.......

Drew mentioned the news cycle in most fields with a backlash, that often happens pretty slowly, but with Blogs, it is now sped up.........

It turns out that the PR crazies, in an attempt to keep the good times rolling on crappy products and services which don't sell themselves, but instead need millions of PR dollars have turned their eyes to another target......

Yes, the very target that can dispel their hype........luring them with giveaways and maybe even financial rewards..........That is right, Bloggers and Twitterers......

You who write are now the target.....Please tell me you already knew this....... For every PR bastard that I have to filter out of my inbox, to every free fruit drink or textbook I have to throw away, I see it more clearly........ If more bloggers than not are duped by these PR crazies, the blog may actually go the way of the newspaper........

Think about it.

PR has to spend billions a year on newspapers, but they can buy YOU off for a 300 USD SNP kit, or a TOUR of their client's facilities......

It has happened to me. I have been wowed by some wonk running one of the genomic companies. And if it could happen to super cynical me, imagine how many more it could as well.....Don't believe it?

All you have to do is read this NYT piece (I know, I just bashed newspapers) about PR's new target...... The FTC realizes this.

They are going to start cracking down on this type of relationship in a way they never could have with the newspapers. Why?

Newspapers have lawyers and money, unlike the lowly bloggers. Just ask me how much it has cost to keep this blog going.........time and heartache......and J.D.'s

Which is why I commend people like Blaine Bettinger J.D. who has put on his tweets involving Pathway Genomics, the disclosure that he is a consultant for them.....

I am going to stay away from any paid advisory roles in any of these for profit companies, yes I was offered a medical directorship/advisorship for 2 new startup DTC genomics companies, but I knew I couldn't do it......I would have to scrap my blog, no matter how "The Right Way" they did these things, my credibility would erode, just like the journalists who I no longer read in the WSJ and NYT.......

Luckily, most often, the reporters who publish PR swill are junior anyways.......but in blogging, it could be some of the biggest names.....

So today when I get an email from one of the fathers of genome exploration asking me why I didn't talk about 23andMx's Blimp escapade......I explain that the press can do that, besides, the incestuous way in which the Zepplin, not a blimp came to be was because of pure insider deals, which I am not shunning, but am not going to promote it either........

HT Martian Genetics

From the NYT:

Gone are the days when snaring attention for start-ups in the Valley meant mentions in print and on television, or even spotlights on technology Web sites and blogs. Now P.R. gurus court influential voices on the social Web to endorse new companies, Web sites or gadgets — a transformation that analysts and practitioners say is likely to permanently change the role of P.R. in the business world, and particularly in Silicon Valley.

So I guess it is just a case of build up your friends/followers list, so you can cash in on them by marketing to them.......just like a salesman would.......

The Sherpa Says: I will never sell ads, shill for profit companies, or tell you anything but my god's honest opinion about personalized medicine and DTC genomics. There has to be someone out there willing to do it..........because PR is gunning for us now and we can't let the blog medium turn into a marketing op rather than a vehicle for truth.

Smoke or $h!t gets in your eye!

A recent study was brought to my attention by a great reader. I highlight it here, not because it is going to change personalized medicine, but because it illustrates some key points.

The study is entitled: "Responses to Online GSTM1 Genetic Test Results among Smokers Related to Patients with Lung Cancer: A Pilot Study" Cancer Epidemiol Biomarkers Prev 2009;18(7). July 2009

This study interested me for several reasons, the first of these was that it involved a hotly debated environmental detoxification gene which has been tested for by numerous nutrigenetics companies for years now.

The second reason it interested me is because it dealt with a population who knows that there family can get cancer when exposed to smoking. I have always wondered for years why there are these families out there who have multiple members with lung cancer, yet everyone in the family seems to keep on puffing.

Are these families full of ignorant people who can't put 2 and 2 together despite years of public health campaigns? Are the genetically or environmentally predisposed to smoking? Does the family have some weird death wish set of genes?

I have always wondered why they do what they do. This study evaluates precisely these families....

It was published on GenomeWeb and on several blogs as well as several news outlets with titles like:
1. Online Genetic Testing Appears to have Benefits
2. Study Suggests Online Genetic Test May help Smokers Quit
3. Possible Benefit From Online Genetic Testing For Lung Cancer

What they did: They identified relatives of Patients with stage IIIB/IV lung cancer who were receiving care in the Thoracic Oncology Clinic at the H. Lee Moffitt Cancer Center and Research Institute were identified. So in essence, patient who have pretty bad cancer, their relatives....who likely know that it is a bad cancer.

They tested the relatives for GSTM1 genotypes. Which is pretty interesting to me, because as the study admits, the Odds Ratio for Lung cancer in this null population is 1.15 to 1.17. essentially as close to one as you can get......

Which means that this association is pretty freaking weak......

So in essence they are going to clinically LIE to the person tested and tell them they had a higher risk.

Oh and BTW, they only analyzed 44 people.....Hardly a useful sample size, especially when 96% were white.....and 22% were college educated, hardly the 23andMx population......

What they found.
1. Smokers with the at risk profile GSTM1 nulls, remembered at 6 months that they had a "higher" risk.
2. Smokers with the normal risk, forgot that more often.....roughly 50% remembered that they were at "lower" risk
3. Both parties "believed" the test results equally........
4. There were NO SIGNIFICANT DIFFERENCES in uptake of the smoking cessation services between those who received the GSTM1-present and GSTM1-missing test result.......
5. At the 6-month follow-up, the proportion of smokers in each group who reported medication use did not differ significantly.
6. Perceived risk for cancer was the SAME in both groups
7. There were no significant differences over time in confidence in ability to quit smoking between the GSTM1-present and GSTM1-missing relative smokers.


"This observational study was not sufficiently powered for nor was it a study aim to assess smoking cessation as an outcome."

Obviously as it only had 44 participants in it........ So I am freaking left asking myself "Where in the HELL is the benefit?"

There are a ton of limitations which prevent this article from even being a study. It is an observation of a very, very small cohort......I consider this as statistical NOISE.........

But, the authors try to save themselves by stating "However, these limitations need to be balanced against the strengths, which include this study being the first, to our knowledge, to offer genetic testing for a common gene variant online."

Are you serious? Strengths? Maybe Strength, but I think that there is other research currently going on involving online genetic testing.

Maybe not published, but there is ongoing......

Some important points that I take from this paper........
1. DTC Genomics has a huge PR machine that will trick papers into writing bull$hit headlines and false claims....I.E. you cannot trust a single thing published in the lay press about genetic studies EVER!!!!!

2. How does a study with 44 people get noteworthy accolades for proving that essentially a single gene variant, weak association, does nothing in terms of empowering patients.....IFF you accept that this study wasn't just noise......

3. The DTC companies offer THOUSANDS of these little polymorphisms......if the people with normal results can't remember that they are at "REDUCED" risk from ONE, how can we expect people to remember THOUSANDS.....BTW, this is essentially like telling a patient that if they eat a ONE cheeseburger from McDonalds on Tuesday July 16th that they are at risk of a heart attack in the next 5 years......Statistical Bull$hit with ZERO Veracity

4. People will cling to the tiny shred of suspect evidence of the 6 of 44 who quit smoking.......% had the GSTM1-Null genotype, which if you look at statistics is likely pure chance as 50% of the pop is NULL.......Hmm whats the odds of 5/6 being null....I can't believe they even mentioned this in their paper.....What a crock!!!!!

The Sherpa Says: Just because it is published in a journal doesn't make it Good Science. Hell, it doesn't always make it Science at all.......Shame on the press and the bloggers who hyped this piece of garbage.......

No Gene is an Island

This is a saying I have been using for about 4 years now.
When someone asked about testing for HFE and why we don't do it as the first screening step anymore.....

They often looked at me confused.....I then bring up the case of sickle cell disease.

Most doctors have seen a sickle cell patient in the hospital.......They may have even seen a family in the hospital, brother and sister, Son and Mother......but what most don't know is that the majority of sicklers never go into the hospital.....

That's when I ask, what is the mutation that the son and mother have? The answer Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position.


Now what about the patients who never come into the hospital?

Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position.

Why is that? I answer my question as they have lots of guesses....

"No Gene is an Island"

You see, there are several things linked to the development of the adverse outcomes with sickle cell disease. Environment, Modifier Genes, Epigenetics (which ultimately is environment) I could go on from there........but suffice to say, genes can only provide us a small answer into the majority of diseases......

Drug metabolism, is a very different story at times.....

I then go on to say that there are very, very few diseases for which severity of disease or even disease itself is attributable to JUST one gene........ Or frankly to JUST ONE MUTATION..........

The body is a set of systems and by being super reductionist and looking at one gene or one mutation versus another, we ultimately end up missing the boat and making a big deal out of something which is not so big a deal......

Or we apply something which may be clinically valid but have little clinical utility.......

Even worse, we take something which has wonderful analytic validity and to use it clinically, with a huge waste of money and a huge waste of resources........ This is the case with DTC.

Some may argue that we should allow people to waste their money on anything they want. I tend to agree with this.

However, what should not be tolerated is false claims and manipulation of claims without scrutiny.

In addition, something which meets the definitions of medicine, should be held to that standard......plain and simple........ Taking human tissues/samples and using them for research requires an IRB, taking human tissues and using them to predict risk of disease IS MEDICINE..........and should be regulated as such......

There are a whole host of laws which regulate how a doctor can advertise, why are we not applying them to these companies who are performing such analysis?

But more importantly, why are these companies the only people educating the public. And doing a very slanted and manipulative job here......

No Gene is an Island......thus no SNP is the end all or be all of risk.....It is much more complex than that.

Which is why I say "Family History is the cheapest and most clinically useful Whole Genome analysis"

The Sherpa Says: Someone is watching these claims, I hope you come here to debunk their junk.

The Infer Game

What really gets me upset is that marketing people infer something but don't outright make a claim.

They do this because to make a claim which isn't true is grounds for the FTC to investigate you, but if you "infer" something, you don't make the claim.... Why do I jump on this?

Because I don't play "infer" for my patients.

In fact, health information and healthcare is too important to "infer" anything. You cannot manipulate peoples' trust in you....

Either we can justify via science and current medical practice or we cannot. Why let people dangle in the wind with false information.....

But this little game is nothing new. Vitamin hucksters and weight loss supplements play this "infer" game too.....so I guess the DTC genomics companies want to be seen as Hucksters....otherwise, why infer something which isn't true......

This went on with Navi's most recent blog post

It is possible that the Factor V mutation also confers a selective advantage to people who carry one copy, but scientists just aren’t sure yet.

If you carry the mutation, you can take steps to prevent becoming ill as a result. And, if you meet someone else who carries the mutation too, it’ll be a little like finding a long-lost brother or sister! Somewhere back in the human genetic family tree, the two of you have a “Factor V” ancestor in common.

The inferring that goes on is that there is some treatment that can prevent clots in these patients with Factor V Leiden. The truth is, there is no treatment to prevent these clots whose benefits outweigh the risks........

I already made this point with 23andMx's goofy CEO Anne Wojicki who made claims in a similar fashion on Charlie Rose the other night....

Pay attention closely, if the FTC doesn't jump in and investigate these companies' suspicious practices.........I will be surprised......very surprised....

Are you pissed at the inferring game too? Well, you too can voice a complaint to the FTC....

The Sherpa Says: DTC genomics companies are lucky that their product doesn't cause arrythmias, sudden death, liver failure or loss of smell.......But even if they don't their marketing claims certainly still do stink......

Great Job Mike! 2C19 meets the grade!

I was flipping through the internal medicine news yesterday when I saw a colleague. Mike Murray, Clinical Chief up at the Brigham who had given me some good advice re: being a fellow and academia......

He and a couple other internal medicine geneticists write a column called "Genetics in Your Practice"

Which is a welcome addition to what my wife and I (Both Internists) believe is one of the best print publications out there for keeping ahead of the curve with IM and subspecialties....

Well,
Mike wrote about Plavix, which, as you know, I have been all over since the studies came out in January showing significant differences in outcomes clinically with patients who cannot activate Plavix. Why was I all over it? Because it had met some criteria which I think will define what a good PGx test is......

I have as of yet failed to detail precisely what these criteria are.....It just so happens, Mike did a brilliant job of it.....So without further ado. Dr. Mike Murray, Internists, ID specialist AND geneticist defining the criteria....

From Internal Medicine News

So, what will bring a breakthrough application in pharmacogenetics? I believe that a true breakthrough into the mainstream will occur when the gene-drug pair has many or all of these characteristics:

▸ A widely used drug. There are currently some excellent examples of gene-drug pairs as models for the clinical application of pharmacogenetics; however, they happen to be with drugs used by only a small number of subspecialists. A true breakthrough application will need to be a widely used medication.

▸ An “essential” drug. Although we may eventually get to pharmacogenetics testing for almost all medications, a true breakthrough application will not be for a drug for which the application is usually elective (e.g., onychomycosis therapy) or for a drug that has equivalent substitutes inside or outside of the class (e.g., a diuretic for hypertension).

▸ Potentially severe consequences from use of the drug without pharmacogenetics guidance. The motivation for using a pharmacogenetics approach is mainly safety or efficacy. The breakthrough application will need to help the prescriber avoid morbidity or mortality associated with side effects or ineffective treatment.

▸ A narrow therapeutic window. Aminoglycoside antibiotics are classic examples of drugs with a narrow therapeutic window, where underdosing can lead to disease progression and overdosing can cause adverse effects.

▸ Pharmacoeconomic advantage. The application of new technology to guide gene-drug decision making will be more attractive for clinical uptake in instances where it offers cost savings.

▸ Straightforward genetic interpretation. Much of current genetic testing deals with complex interpretations of sequence data where variants unique to the individual patient have to be judged as causative, noncausative, or of unknown significance. In 2009 the most straightforward diagnostic genetic testing is based on screening for common variants that confer increased relative risk.

▸ Validated significance of gene-drug pair. There will always be varied levels of confidence in any data set; however, replication of significant correlation in more than one large, well-designed study will be the most likely to be associated with rapid clinical uptake.

This is precisely what Plavix is......And it is precisely why it will lead personalized medicine this year.......Not genome scans, not whole genomes, Plavix pharmacogenomics...... Mike, yet again, you have crystallized criteria which I often find nebulous......

The Sherpa Says: If we judge all tests by this criteria we would be better off.......Imagine how many less tests would be ordered. Bad for business, great for medicine......

23andMx looking to cook the books in CA with SB 482

Daniel MacArthur and I have been noticing something and he decided to cover it today, which is why I have decided to provide a counterpoint here....Also GenomeWeb published on this. SB 482 is a bill I glossed over in a post in the past and was recently interviewed for in the San Jose Mercury News.......

Daniel leads this as 23andMx leading the regulatory push.....but this is more insidious than that. This is 23andMx trying to cook the books and create laws which exempt them from the stringent regulation which they should receive......

I told this to the newsies over at San Jose on Sunday, so I am going to post this today......

It turns out that this bill SB 482 essentially exempts DTC companies from facing the harshest regulations that medical providers/labs have to face

From Daniel
"In other words, 23andMe is pushing to have companies purely providing analysis of genetic data regulated separately from those doing the actual laboratory testing. Since 23andMe out-sources its testing to an external laboratory, this would exempt the company from some regulatory requirements. The move follows some fairly serious regulatory controversy over direct-to-consumer testing in California a year ago."

Which I predicted BTW....... But in all seriousness, these portals to lab services view themselves as NON MEDICAL entities, that is the crux of this argument, and by passing this bill it would set legal precedent as being non-medical and not facing medical regulations......

But that bill should fall flat. Why? Because it is written with a false logic. I am about to explain the correct logic............

The assumption is, that by only running an algorithm on biodata and giving a risk number, you are not practicing medicine.....nor is it running a laboratory....

Thus they don't need healthcare regulation or medical lab regulations.....but they are dead wrong.....

The first myth: Running an algorithm on biodata and giving a risk estimate is not medicine.......

Answer: IN FACT it IS medicine, the AMA guide book for Current Procedural Terminology acknowledges that this IS medicine and it should be coded with the number 99420 of the evaluation and management code..... I run something called a reynolds risk calculation on patients. It is a computer algorithm found at www.reynoldsriskscore.com. Give it a shot, you will see it is very similar to a DTC genomic test. I bill and get paid for providing this medical service......

The Second Myth: Because we don't run the test, we shouldn't be responsible for CLIA regulations. We are not a laboratory.....

Answer: This company actually accepts ownership for the sample and provides specimen handling which is delivered to an analytical facility.....By merely handling the specimen they need to be considered as part of the healthcare unit, or apply for CLIA exemption. Any handling of any specimen can be billed for and should be regulated as such..... Not the shipper, the company/person/lab who takes ownership of the specimen.....

Lastly,

I was on twitter last night when I saw this ugly retweet come from the account at 23andMx RT @dane: @23andMe BTW, you saved me $25 for a CF test - used my and spouse's 23 results instead. Thx! (via @23andMe)

Which raised eyebrows from myself and Daniel

"@23andMe For once I agree with (Steve) - implicitly promoting your chip as replacement for a validated CF test is a risky move.about 19 hours ago from TweetDeck"

I basically said that this is the type of shennanigans coming from a company who isn't being regulated.

If they were, this insinuation that using a 23andMx test for a clinical use, would never bubble up.....but it did.

And I am willing to bet the twitterer for 23andMx isn't medical at all....... Which is once again why, oh why SB 482 needs to be shot down immediately....

I am glad the ACLU is on this, but the AMA, The ACMG and the NSGC need to be all over this bill too........

As you can see from the edits, this bill was initially proposed as a healing arts bill, which is what it is....... But even with that, 23andMx has no use for YOUR laws.......

The Sherpa Says: 23andMx deleted that tweet, so at least they understand that what they are doing WAS and still is wrong......

Anne Wojicki, First Benadryl doping, now Factor V

I was actually watching the Charlie Rose interview with the 23andMx ladies....When Charlie Asks what the advantage of 23andMx is.

Anne and Linda both say "The problem with the GWAS is that you aren't followed over time. You get one shot and people can't give you further information"

What Anne and Linda are saying is: The Coriell Personalized Medicine Collaborative is the gold standard, we are merely trying to monetize something they are doing for FREE.


In addition, we are not IRB approved and are unethically doing this business, which is ultimately research. Which IS being done by a Not For Profit Medical Institution, Who is charging nothing I.E. FREE, and we would like to do what they are, but charge you 399 and have the right to sell your data......

Oh and did we mention that Google just put another 2.6 million into our bank accounts?????

But probably the funniest thing Anne had to say was at minute 18 of the clip on the PGP site..... Anne says "It's early, but there is a lot of interesting and valuable data in there (the genome scan)"

She then goes on to say "For Instance, there is a genetic marker for Blood Clots called Factor Five Leiden. Charlie, I am certain you must travel a lot. Wouldn't you like to know if you were at risk for these clots?"

That is when it hit me, for the 3000th time.

A.Neither of these ladies is in medicine
B. Neither of these ladies are PhD scientists
C. Neither of these ladies understand what it really means to be carrying out this type of study.

Hence

1. NO IRB
2. Promoting Factor V Leiden testing despite evidence to the contrary and a HUGE AHRQ report
3. Doping up their kid for transcontinental flights with benadryl!
4. She even said you might want to take medications for Factor V Leiden! OMG!

Why is the world listening to these silly ladies????
Why aren't they listening to themselves?

They both plainly stated, Coriell is the best study and that they want to be Coriell, without ever mentioning the name Coriell.

But the best line in the ENTIRE interview came when she said "With budgets these days, you may or may not end up flying economy class these days........." Charlie quips "WHEN WAS THE LAST TIME YOU FLEW BUSINESS CLASS?"

The Sherpa Says: There you have it, 23andMx's leadership endorsing Coriell's study. For FREE, not 399 USD. Oh and with an IRB and without Google.......