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.

I am glad we can all put this behind us. FDA rules on DTCG.

As you now may be aware. DTCG is considered a medical diagnostic according to the FDA. I look forward working with companies who may now allow me to use their tests for medicine.

The Sherpa Says: If we work together, we can deliver the best preventative and personalized care in the world!

Hey DTC genomics, Stay Private, Stay Alive, Go Public and Die

Today's lesson in start up business in the field of DTC Genomics is this.....

Stay Private and Stay Alive. IPO and doom yourself to a painful and public death.

Huh? Ah, yes our first DTC Genomics venture is going to be restructured to someone else and the thought experiment will become a reality.

"When a DTC Genomics bust, what happens to the data?"

Well, someone else can buy it, at a rock bottom price. Hell, the selling company can even violate YOUR TERMS OF AGREEMENT!

Daniel, posts a great email from some sucker who bought DeCodeMe......or maybe just an "Early Adopter"

" there has also been filed with the court an offer by Saga Investments LLC to purchase deCODE's Icelandic subsidiary, Islensk Erfdagreining (IE). IE, which is not declaring bankruptcy, carries out all of deCODE's human genetics work and and provides deCODEme."

So, Saga Investments, a private firm will be taking over in Iceland and likely will be handed the keys to a bunch of genotypes.....

"For this reason, we do not expect this to have any impact on your deCODEme account. As ever, our commitment at deCODEme is to keep you in the forefront of progress in understanding the human genome and what it means for you and your health."

What did this achieve? Well, it took the DTC DeCodeme out of the publicly owned realm. Which is probably a good thing. Let me tell you why.

Publicly owned companies shares are extremely liquid and can be crushed pretty easily, where as rich ol' moneybags (SergeandMe) can keep throwing money into the kitty and outlast this economic downturn and premature launch of these companies, hoping to innovate his way out of this money pit.

This reason is probably why DeCodeme went private and will likely give up control of their data. They need some sucker to keep pouring money into a boondoggle that has no exit for at LEAST the next 15 years if at all.

The moral of the story for start ups is "Stay Private, Lose Investor's Money, Live, Innovate (gulp)"

The Sherpa Says: Now I want to know how many people will file a class action against DeCode for selling the data? Any ideas? Because that could really make the genetic data an unwanted commodity.

Excuse Me? Harvard and Navigenics? WTF?

Ok,
So I was blown away when I read this juicy little tid bit from Genome Web.

NEW YORK (GenomeWeb News) – Navigenics and Beth Israel Deaconess Medical Center in Boston announced today that they will collaborate on training physicians in personal genomic testing.

Amazing! I had spoken with Mike Murray up there a while ago and have neen involved in his training curriculum with CMEs for providers. I have always interpreted his opinion on the DTC companies to be suspect of what the hell the companies are doing.

In fact when we, Mike and I presented together at the Association of Program Directors in Internal Medicine meeting in 2008 in New Orleans I assumed that their department as well as he didn't much support DTC genomic testing.

Which is why the BID move had me puzzled, so I emailed him. But I also read further.....

As part of the program, residents will be given the opportunity to have their own genomes analyzed through Navigenics' consumer genomics services.

"We believe that genetics and genomics will be critical to the future of health care," Mark Boguski, of BIDMC's Department of Pathology and the Center for Biomedical Informatics at Harvard Medical School, said in a statement. "Training our residents on the leading genetic services and technologies will be essential to this future."

Ahh, I see. It is not the Genetics department who is involved with this. It is the pathologists, you know, the physicians who look at microscopic slides and run the clinical laboratories who are behind this.........

This Makes all the sense in the world now, non clinical geneticists teaching doctors about clinical genetics and how to use a self-avowed NONCLINICAL, NONMEDICAL test to learn medical genomics.....

What the hell is Harvard thinking? I wonder if they received a nice endowment gift from the VCs who fund Navi????

So let me get this straight, Harvard Medical School sponsored Medical Residency at Beth Israel Deaconess is using a NONCLINICALLY validated test, from a company who states that the test should NOT BE USED FOR MEDICINE, to teach MEDICAL residents. To quote the plan

"Among the specific goals of the program are fostering an understanding of issues related to the evaluation of direct-to-consumer genotyping services and familiarizing physicians with the interpretation of genomic information and its correlation with personal medical and health information."

Have they lost their minds???? Shouldn't this be something that the clinical genetics department should be teaching? I wonder if Vance received a faculty position for this horse$h!t?

The Sherpa Says: I knew that this wouldn't come from the clinical genetics side. I hope they don't have any fingerprints on this one.....But my guess is Raju is involved in this one some how.....Now Harvard is confusing what is Important.

Watch Out Corporate Bloggers, FTC is on to you!

Now not only am I bashing corporate bloggers (Some may even call me corporate) Now the Federal Trade Commission has gotten into the game. It turns out that the FTC is on to the game of freebies for good blogging.

So to all of you who took free Navi or 23andMx or DeCodeme scans in hopes of them getting good press on your blog, you may have some issues. At least if you are in the US.....

From the Yahoo News

What some fail to realize, though, is that such reviews can be tainted: Many bloggers have accepted perks such as free laptops, trips to Europe, $500 gift cards or even thousands of dollars for a 200-word post. Bloggers vary in how they disclose such freebies, if they do so at all.

The practice has grown to the degree that the Federal Trade Commission is paying attention. New guidelines, expected to be approved late this summer with possible modifications, would clarify that the agency can go after bloggers — as well as the companies that compensate them — for any false claims or failure to disclose conflicts of interest.

So what does this mean for the genomics blogging world? A ton. I remember many, I mean many bloggers getting free kits. I also remember many people writing glowing reviews. I also know that the corporate blogs have been "inferring" things about what a genome scan can and cannot do........

The Sherpa Says: Just another case of government coming in and regulating for the protection of its citizens. Because of their commoners inability to sift through bull$h!t and hype. Time will tell what these new powers will do to the blogging community. I wonder what it will do for Twitter??? Wouldn't the government save a lot of money if they just made marketing illegal?

The Genome Scan Dirty Little Secret

You know what I love, you take a company who is inferring that science IS clinical utility and then you hire them to perform interpretation on something that in it's current for is often uninterpretable......and then you sell that for something on the lines of 90-48, 000 USD.

My business is healthcare, my business is also risk prediction, but what my business is most is disease prevention......

My profession is physician, my oath is to do no harm and if I must harm, do so healing or palliating suffering....A noble profession to be sure.

But no one, I repeat no physician is leading the charge to do whole genome scans for risk prognostication.

Maybe for certain disease detection, but not for true risk prediction.

But, guess what? The business people are...... The business side of Genomics is all about getting "these little babies" into the hands of everyone......

Billions of people at 99 dollars a piece is a lot of money.....but the one thing that may hobble this model is what I like to call the dirty little secret of whole genome scanning.

You can read about it at my other posts
1. We have no clue what it really means.....Merry Christmas
2. Nature is So Wrong
3. Ok Guys, Seriously.
4. Rading the Medical Commons, A Pirate's Life for Me

Or you can let me recap. Currently DTC genomic companies are testing 1 million single nucleotide polymorphisms. We have in our body combined, 6 billion of these little nucleotides....

Sure the SNPs were safe, heck a SMALL minority had some science behind them.....but most were razzle dazzle and hyped by researchers to the press.....

Oversold and Overhyped.......If you thought that was something, wait to see the hype from the "Whole Genome" crowd.....

You see, even the most skilled, erudite, knowledgeable geneticist can be hobbled by the explanation of certain genomic changes......

A. If they changes often aren't in genes, then the biology needs to be elucidated, that takes years.
B. If the changes are in genes but that no one has seen before, how do you know what to predict will happen?
C. If we see a change which has been seen but has a wide variety of phenotypes, how do we explain the risk?
D. Most importantly, how do we modify disease risk based on genomic information for most of these things?????

My point is, you have disparate DTC companies calculating risks in different ways and even worse, recommending or "inferring" recommendations for lifestyle changes. Unfortunately, the quit smoking and lose weight isn't exactly "Science" or medicine, which is why they can get away with it.....

What about when a whole genome comes along at 30x coverage? Well, Illumina plans to do that and "outsource" the interpretation to these companies who are "interpreting" based on some very, very soft science already.

What in the hell do they plan to do with this whole genome interpretation?

In my mind these are the keys to get whole genome scan to utility.
1. Formalize some sort of standard interpretive algorithm AND THEN TEST IT CLINICALLY
2. Research the phenotypes which emerge from each and every genomic change out there.....Some like George Church plan to do this in the wide open....which may not attract the millions of people and dozens of years needed for this one....
3. Study the actions which will be proposed for each of the genomic changes to reduce disease risk or to treat disease.....

IFF you can get 5 common diseases captured with this, then you will have a successful system. But then the problem with this is what Illumina already knows...."you will be diagnosing disease and thus enter the realm of clinical test"

Which they have already prepared for by mandating physician ordering of their whole genome scan....

A long post I know......And a long way to go before this is useful at 99 USD per person.

The Sherpa Says: The incidentalome is just the beginning of the nightmare about to be unleashed with whole genomes.....

Consumer Genomics Spin

Thank God for Dan Vorhaus AKA @GenomicsLawyer on Twitter and a nice wrap up by Emily Singer

But like a groupie believing everything one reads, I want to caution those who attend that conference.

I heard major exaggerations and one might even say misstatements from the people presenting.......

The biggest one upset me. I am a fan of Jeff Gulcher's. I think he is a great guy. And his 1 in 100,000 story about finding aggressive prostate ca because of his SNP risk is very real. But, he claimed something which had been proven incorrect.

It had been proven incorrect months ago...... Maybe he did what DTC does best.....they imply things...... Jeff implied that their SNPs for CVD actually reclassify women's risk......

In order to prove that he would need a cohort and he would have to control for all other things AND he would have to have been studying this cohort for about 20 years.....which to my recollection has not happened with deCode.....

More importantly, the SNP they discovered was not found to add ANYTHING useful to the current classification system for risk of heart attack....

However, there is something which reclassifies approximately 40% of women and 17-20 percent of men......the Reynolds Risk Score, studied by Paul Ridker et.al. up at Harvard....

In this great example, clinical risk factors are combined with genetic factors, in this case Family History and it outperforms Framingham Risk Stratification........

But to state that their tests perform the same or even to insinuate this, well, that's just intellectually dishonest and I wouldn't expect that from Jeff......which means he "must have been mistaken"


So today I look forward for more exaggeration at CGS as I call in to the ICOB meeting for the Coriell Personalized Medicine Collaborative......I implore others to follow Dan @genomicslawyer and look for the same.

The Sherpa Says: We must always listen with a critical ear to what is said by people with money or power or both......

rs2200733 ok, now what?

I am busy pouring through all sorts of association studies which I had let sort of slip through my fingers. I have been cue'ing a lot of these and only in the last few days have been able to get to them. Most of the SNP that the press put out there now seems to be dying off pretty nicely.

Although there are bits of useful data out there, most is just noise......but one of the SNPs which caught my eye was rs2200733 studied in Icelandic, Italian and other Caucasian populations with a small replication in an Asian population as well......What does rs2200733 predispose to?

Atrial Fibrillation. A condition that can lead to unannounced strokes, syncope, and heart failure (at times) Atrial fibrillation is the most common arrhythmia in the United States.

About 2.3 million Americans have atrial fibrillation (Go, 2002). Men have a 50% higher incidence than women at any age (Benjamin, 1994). Among individuals 50 years of age and older, the prevalence is higher for Caucasian individuals than African Americans.

The prevalence of atrial fibrillation is 0.1% for individuals under age 55 and 9.0% for individuals over the age of 80 (Go, 2002). HT CPMC.....

Here's why I am revisiting it? It popped up on my screen as a SNP with a study which purported an Odds Ratio greater than 2...... In my mind, no SNP should be even looked at without having this.....why?

Well, most clinical scenarios have
1. Good risk prediction tools already, as with the 9p21.3 issue
2. No true benefit of presymptomatic detection, i.e. no effective prevention (Parkinson's)
3. No ability to guide therapeutic decision making..... This is true in 99% of cases, aside from pharmacogenomics that is.......


So why am I looking again at rs2200733? Because this may actually be a case where I think it may augment my other clinical tools of prediction......Maybe.

Why only maybe?
A. Most of my patients get annual physicals with annual EKGs.....and often AFIB manifests with symptoms....
B. Most of the patients with AFIB are elderly and in the studies some indicate earlier AFIB pops, some don't which may be confounding in the study
C. Most of the people with AFIB that I see report a family history of some sort of arrythmia, most often AFIB.....

That being said, there is a population <10% who end up with No family history, Present Early and present with a stroke....It is rare, but does happen.....so I naturally would want to watch that population more than not......But does that mean I should do "More" for them?

In the age of Comparative Effectiveness, I may not be allowed to..........There is no ICD9 code for genetic predisposition to Atrial Fibrillation......

But maybe people would pay more than the 20 dollar copay for care???? Probably not that often, but maybe.....And for what? A home monitor to be hooked up on them 24/7?

It turns out

DeCode sells a test with this SNP, Is on the Affy and Illumina Chips, I.E avail for 23andM- and Navi.............
None of these are actually valid clinical tests yet though.....Similar to other "clinical" detection tools we have today.

So what I am going through is in essence mental acrobatics while I await a company to do a study which proves that there is some benefit and some action to be taken here.......

The Sherpa Says: While a promising SNP is out there, it is just that a promising SNP. Most of these things won't affect me clinically for another 5 years. I wonder what the public will do with this data? Will they go see a doctor? Who ultimately would be asking the same question I am.....and waiting for the same data

Why Is Healthcare so Expensive?

If you want to have any insight into how complex and horrible the medical system is, then you need to set aside 24 hours and read this.

If you pay someone to create these sorts of manuals, you should be paying someone to read them.....otherwise, who will follow the rules?

The short answer. No One.

That is why President Obama is auditing doctors at an alarmingly higher rate than has occurred in the past. No one is following the rules......even the insurers that make the rules.

How in the world do we expect to fix a system mired in this much red tape?

Oh.....don't worry. The INTERNET will fix it........yeah right......

The Sherpa says: How can the government focus on effectiveness without focusing on the effectiveness of its policies and procedures? They can't. Which is why audits are up this month.

2009, Kansas is going Bye Bye!

Ok, So last year I closed with a joke from Francis Collins, who by the way, I predict to be the next head of the NIH....

The Joke?

"There is this woman who is married to a research geneticist......... He keeps telling her how great their sex life WILL be."

That certainly was the hype from 2008. As we finally begin to wash ourselves off from the greatest hype and over-selling ever committed in Genomics, we may be a little skeptical...Even the FDA has now jumped on the regulation bandwagon. That's ok. But please don't dismiss Personalized Medicine as dead. Trust me, We've only just begun....

To prove this works.....

First, I am proud to announce that Helix Health of Connecticut is the newest member of the Personalized Medicine Coalition. In addition, I will be serving on their Clinical Science Committee. I am excited for the meeting on Feb. 12th!

Second, I look forward to developments from Coriell. I am told that their "disruptive move" by offering patients a Genome SNP scan at no cost, shook up 23andMe, encouraged Navigenics to partner with Scripps on a "similar" study and Caused Kari to Scream with fits of four letter expletives at a recent NIH/CDC conference.....

Why at no cost as opposed to the study funded by Navigenics and Scripps, which charges participants? They feel (and rightly so) that no one should ever have to pay for research which is being implemented through them. Yes, true they are non-profit. But have you ever seen BMS, Pfizer or Novartis charge patients for drug research????? It just doesn't make sense.

Coriell is at its heart a Medical Research Institute. My hope is that Helix Health of Connecticut will learn to be the same. A patient-centered genomic healthcare instutute.

We are also looking forward to several other announcements likely to come out in the month of January.

As for the rest of the field, things are progressing nicely. Some of the barriers we have discovered are finally being ascended. See, Cue4, Generation Health and another company I had done some work with.....

But, without further ado.......

Finally, what you all have been eagerly anticipating.

The Sherpa's Predictions for 2009.

Mind you they come in 3 groups. Highly likely, Possible and Ridiculous

Highly Likely:

1. Francis Collins will become the director of the NIH and collaborate with Kari from Iceland to create a national database of genomes. This is the only way to jumpstart personalized medicine. My feeling is that Kari knows how to do this, is a friend of Francis, and Obama is likely to give him the greenlight on this, despite public sentiment....

2. We will see our first lawsuit for a pharmacogenomic cause. My colleague over at ASU, Gary Marchant says it will only take one and the flood gates will open. The lawsuit will be based on something called "Loss of Chance" doctrine. The theory goes, "did you cause the patient to lose a chance at a better health outcome?" If the answer is yes, well then you can be sued. This recently has been the case for delayed diagnoses in several states (24 to be precise). All it takes is one smart, enterprising, hungry attorney to go after this....I can see it now.

Plantiff's attorney(PA) "Doctor, who is the FDA?"

Doctor(MD): "The US Food and Drug Administration"

PA "and what do they do?"

MD: "FDA provides safety information on drugs and other FDA-regulated products, and allows for adverse event reporting."

PA: "Would you use a drug that was not approved by the FDA?"

MD: "No"

PA: "Doctor, would you mind reading this label?"

MD: "…genetic variations in the CYP2C9 and VKORC1 enzymes may influence the response of the patient to warfarin.” In the “Dosage and Administration” section, it states that lower initial doses should be considered for patients with genetic variations in CYP2C9 and VKORC1."

PA: "Doctor, what is the genotype of the defendant Mr. X?"

MD: Silence....

PA: "Doctor?"

MD: "I do not know"

PA: "Doctor, why do you not know everything you need to know about a patient PRIOR to giving this deadly rat poison"

MD: Silence

PA: "Doctor, is there evidence showing that patients with poor metabolism would need a lower dose than the one you prescribed Mr. X?"

MD: "Yes, but......"

PA: "But what doctor? Why would the FDA put something on the label if there wasn't solid evidence behind it?"

PA: "furthermore, if you knew your patient had a liver problem with metabolizing the medication, would you give the dose you gave to Mr. X?"

MD: "Well, hepatic dysfunction is (cut off by attorney)

PA: "CYP2C9 genetic mutations ARE hepatic dysfunction doctor"

I think you get where I am headed. In economic lean times, people will try anything....and this sure is like the Statue of Liberty play. It WILL score a touchdown, that's why people still run it.

3. We will see George Church's Exome project results and they will certainly confuse all of us as to what it really means. We may even see a broken ladder?

Possible:

1. We will have an X-Prize winner. If PacBio and the black box known as Complete Genomics work out, this will be ready by November 2009. Seriously.....now, to sort out what the hell it means......We need a database, someone to actually take liability (Unlike the chickeSh!^ companies today), and someone to counsel on this.....do you really think 2700 people is enough???? That is only a cool 111,533 people per provider......at 2 hours per evaluation that is only 223,066 hours of work, only 9294 days of straight work, or 25 years straight!.....give me a freakin break NSGC/ABMG/ABGC/ACMG!

2. Mr. Stoicescu sues KNOME for a 345,000 USD refund. It could happen, the oligarchs lost a ton of money last year. I am sure he could use the money back in exchange for Complete Genomics Genome evaluation.

3. Oprah will have a third hoax on her hands as she discovers her genome scan was bogus. 3 strikes and your out Oprah!

Ridiculous:

1: Mark Cuban will buy the rights to 23andMe's database. If I have at least one thing, it is tenacity.....this one will happen

2: A new technology called next-next-next-next gen sequencing will debut and have your genome done in 15 minutes. They will say the technology will be ready for prime time in 2 years.

3. The United States will fracture into 6 territories controlled by Russia, Mexico, China, Canada....I think I played this game in the 1980s.

The Sherpa Says: Happy New Year! May the new year be as good for you as it already has been for me. Here's to personalized medicine in 2009!!!!!

Sherpa's Batting Average for 2008.

I make some pretty outlandish predictions on this blog, including Francis Collins will become director of the NIH.....I am not afraid to be wrong. If I see a trend or a problem, I call it. What has gotten people's attention is that I tend to be right more often than I am wrong....at least for now.....

I start out every year with some of these predictions, so I figure, why not look at the one's I made last year in 2008

As I looked into my magic 8-ball/Complete Genomics Scanner. Which came true? Here are the predictions:

1. Jim Watson will die.
Well, only a few base pairs off on this one. The legend Victor McKusick did pass, God rest his soul.....Damn that 10x coverage.

2. Mark Cuban would buy the rights to 23andMe's genome database.....I knew he would do something dastardly.....only it was not genome stealing.....it was insider trading..

3. The X-Prize would be won by a little known start up........At that time I thought Pac Bio would be ready to launch.....Guess I was wrong....

4. Oprah will have her genome sequenced.....Pretty pleased to say I was spot on.

5. Obama too........maybe not until 2009 when he comes to visit Helix Health of Connecticut....

6. Academia will start to market personalized medicine..........Duke, Harvard, Mayo, Scripps, Mount Sinai, UCSF, Stamford, Wisconsin, Ohio State all joined the ranks. I wonder why Yale is not there????

7. GINA will be passed........Thank god this one's in the books!

8. One of the DTC companies will be sued.....Well, you can always count on California to regulate something....NY too..

Welcome to the Big Leagues of Healthcare my VC brethern!

9. Navigenics would launch and use telemedicine. Man was I wrong....instead they tried to pass themselves off as medicine despite stating in their terms of service you cannot use this for healthcare decisions.......Yet MDVIP is....so how does that work??? Oh, you pay 2500 USD....got it.

So, where did I stand.....

Absolutely Correct:
4 of 9, if you count legal proceedings from a state as getting sued......

Close to correct:

1 of 8, McKusick dying is pretty damn close to Watson.....Damn that magic 8 ball....

Dead wrong:

4 of 9, Well........you can't guess them all. But I was right when it mattered most, which is more than I can say for A-Rod!

A near .500 Average will get you paid pretty well in the MLB. And most definintely will get you paid well in the world of Venture Capital.....or Wall Street.

The Sherpa Says: When you spend as much time climbing as I do, you see a lot of climbers come and go.......One thing is for sure, that Mountain never goes anywhere.

We have a lot of climbing left to do in 2009, we haven't even finsihed the approach!

We have no clue what it really means....Merry Christmas

The scene, a roundtable of geneticists reviewing a case.

Geneticist 1: Well, some one (Non geneticist) astutely ordered genetic testing for condition X before we saw them. When we saw them we ordered a Chromosomal Micro Array (CMA) and a karyotype....

Geneticist 2: Well, did you ate least think of condition X?

Geneticist 1: Not really, it was pretty atypical for condition X so we thought we might find something with a CMA.

Geneticist 3: You'll certainly find things with a CMA. Now what the hell you will do with those rare deletions and duplication is another topic.

Geneticist 4 and Training Geneticist 5: "Chuckle, Chuckle"

Geneticist 1: Well, while we were waiting for the CMA, we were notified by the patient's family, they have condition X....

Geneticist 2: Wow, I would have thought it was Condition Y based on your presentation which would have been picked up on CMA.....

Geneticist 1: Well, we did pick up something on CMA...

Geneticist 5: Let me guess, a rare unknown duplication

Geneticist 1: Correct, how did you know???

Training Geneticist 5: 50-50 shot.

Geneticist 2: So now what will you do.

Geneticist 1: Same thing we always do. Test mother and father, if they're "normal" we will say it is a benign event......

Training Geneticist: Too bad we can't say "We have no clue what it really means....Merry Christmas"

Close scene....

Today this is happening at an alarming rate in clinical genetics services in academic centers everywhere.....

Here's the catch.....It will only get worse before it gets better, and it will take a very long time or 10 million people to make it better.

We really have no idea what is in store when we start looking at all these genomes....My guess is that even the smartest geneticist will be rendered a bumbling idiot at least 10 times in the next decade.....

The Sherpa Says: A smart entrepreneur finds solutions to this and many other problems that wil stem from this crazy genomic data......and when Francis becomes NIH director, the US will turn into DeCode/Iceland, it is the only way to figure this stuff out.....too bad the public isn't ready for it.....Franics is no Kari and the US is no Iceland....Merry Christmas!

Raiding the medical commons!!!! A pirate's life for me.

I just got back from Disney World the other day.....What a great trip.....my take is that if you keep believing and work hard enough your dream will come true....or at least Disney wants you to think that's true.....But I have a little problem......how can anyone believe without some evidence?....You can, but then it is not belief, it then becomes faith. Faith is belief with the absence of proof.....

Unfortunately, that is how alot of blind individuals see personalized medicine....Too bad they are dead wrong. There is proof. For Pharmacogenomics all one has to do is scan the pharmacology literature.....but that's tough for scientists to do, even tougher for doctors, and toughest for genetic counselors...but it exists.....just take a look at the nearly 4000 papers published on CYP 2D6....

Unfortunately, Time did not name Pharmacogenomic testing, invention of the year. Instead they chose Personal Genome Scans.......While a unique technology (sort of) this type of testing requires further study. Several colleauges will be speaking at a conference of heavy hitters in the space. The conference sponsored by the CDC and NIH will examine the role of these scans....They need to especially as Muin Khoury noted that only 3% of all genomic studies addressed questions related to clinical integration or outcomes....Scary Statistic for sure, but how can we expect lab physicians and scientists to understand clinical intergration?

From the site

This 2-day workshop, cosponsored by CDC and NIH, will explore the type of scientific foundation that is crucially needed to make the promise of personal genomics a reality. The workshop participants will explore how the integration of genomics into personalized health can follow an evidence-based process. The process for using genomic applications in personalized healthcare (e.g. pharmacogenomics, early detection markers, testing in clinical trials) is being discussed.

It starts on December 17th and ends on the 18th.

I have sent some speakers case presentations that we have experienced evaluating these scans. All confidential mind you, but some are pretty interesting.....

Most of the people at this meeting agree that the role of genome scans and primary healthcare remains in the realm of the primary care physician. But we all know the limitations they have.

1. Education on genetics and genomics

2. Limited Time Schedules

3. Ability to order and get these tests and their care paid for.

4. Lack of clear studies demonstrating clinical utility

Dr Wylie Burke writes in JAMA last week about this topic "An Unwelcome Side Effect of Direct-to-Consumer Personal Genome Testing: Raiding the Medical Commons" In it she posits that the incidentalome that is unleashed will waste healthcare dollars in investigations that are unwarranted, based on meager risk estimates...She may be right. She may also be wrong....But there is only one way to know this.....we have to study how genetic information such as genome scans is used in the clinic.....

Helix Health of Connecticut is in prime position to do just that. Starting at the end of this month we will....I can't tell you how now....but it will change the way genetic research is done. It is time to move out of academia and into the field....That's where we are headed. Armed with a physician a counselor and the internet! Together, not exclusive of each other.....

The Sherpa Says: I am back with a vengeance! I am about to blow the doors off of this Genome Scan land.....With the help of some other Sherpas! Oh did I forget to mention that we are all connected now???? For me, I do believe it will come true.

Nature is so Wrong!

Nils over at SciPhu has decided to stop posting about DTC and his stance. Why would such a great scientist/blogger decide enough is enough? Nature made him do it...Huh? Yes Nature and its eloquent arguments about personal genomics......

From Nils

"I have voiced opinions on this too, but have decided to desist more arguing (for a while) after reading this editorial in Nature biotechnology"

I am going to deconstruct the arguments in Nature right Now!

1. We need to move from late to early diagnosis

It is virtually impossible to conceive of a sustainable form of healthcare that operates as the current systems in industrialized nations do. At present, healthcare is based on the late diagnosis of disease and the division of diseases into a few categories based on some overarching gross similarities. And it firmly places physicians as the central gatekeepers of information.

So this argument says.....That in the current system...

1. Doctors cannot do early diagnosis

2. Patients should be responsible for early diagnosis

3. The current system is not adapting to early diagnosis

Why is this nature argument a fallacy?

1. Doctors have been doing earlier and earlier diagnosis.....Ever heard of Pre-Hypertension or Pre-Diabetes? These conditions are getting detected at earlier and earlier stages, physicians ARE doing a better job of finding this out.....

2. Patients can interpret laboratory tests and should because we don't have enough healthcare providers to interpret the data......Huh? Ok, so I propose that we have 2 levels of care, the one level in places like Harlem where it is an under served community. We have a patient take a blood test and then have the patient interpret the results. Heck we could give them a computer and Internet.......Good luck! Oh and the other system where doctors and other healthcare practitioners decide to practice and deliver care.....Nice argument.....

Patients should not be responsible to defend themselves in a court case because they can't afford an attorney, they shouldn't be responsible to design their own homes because they can't find an architect, Hell, there is even H&R Block for people's taxes.....Why are we trying to cut out healthcare professionals because costs are high? I say costs are high because we don't have enough professionals...instead we have coders and healthcare administrators............Would you expect a patient to interpret a liver biopsy? What about an X-Ray? So why in the hell would you say they should interpret their own genetic information? Garbage argument.....

3. Huh? The system is adapting to early diagnosis and adherence to standards of care. Ever heard of PQRI? What about JCAHO and the preventable outcomes evaluation? The system is working to prevent errors and diagnose early.......Just b/c it's not enough doesn't mean you destroy the system.....

2. To do this we need find ways to utilize the potential unleashed by large scale analysis of genetic-material.

The healthcare of the future, on the other hand, if the technical potential to provide personalized medicine is ever to be realized, will probably require a greatly expanded emphasis on diagnosis and monitoring, early and subtle intervention, monitoring of the impact of intervention, and gradual adaptation of treatment with the evolving physiology, metabolism and lifestyle of the individual.

So this argument says that we don't have enough people to monitor the care of patients, so we scrap that system and put everything in the hans of the patient.....over the internet I suppose. There are 3 things wrong with that.

1. What happens when a patient mis-diagnosis him/herself? What happens when the ignore the "Service engine soon" light? The same people avoiding healthcare now are precisely the ones who have diabetes diagnosed at a late stage, or the patient who comes in 5 days after his heart attack.

2. What's to say the the Internet will motivate that person to change? Doubtful at best.....Patients need professionals to monitor their health....end of story...no system can serve all.....even crazier.....who maintains privacy of that patient?

3. Even crazier....who does a patient sue when the diagnosis is missed???? The system?

Nature's solution?

3. But, the medical professionals and healthcare systems do not currently have the capacity to adequately respond.

Faced with this huge expansion of data on ‘my’ health, it will simply not be affordable to maintain our dependence on medical gatekeepers, whether they are physicians or genetic counselors, without individuals taking a much greater responsibility for their own wellbeing. Whether the medical establishment likes it or not, it will be too cumbersome and too expensive to conduct personalized medicine if all diagnostic-to-therapeutic decisions depend on doctors.

Ok, mythbuster number 3.....the amount of data relevant to a patient's care and health WILL NOT CHANGE THAT MUCH IN THE NEXT DECADE!!!!!

But you could greatly overwhelm the system by introducing bogus bits of information that have absolutely nothing to do with health outcome.....Don't believe me? Did you read the incidentalome written in JAMA. Russ Altman and Zak Kohane (advisors to 23andME wrote this)

Here's the excerpt:

Genomic medicine is poised to offer a broad array of new genome-scale screening tests. However, these tests may lead to a phenomenon in which multiple abnormal genomic findings are discovered, analogous to the "incidentalomas" that are often discovered in radiological studies. If practitioners pursue these unexpected genomic findings without thought, there may be disastrous consequences.

First, physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements.

Second, patients will be subjected to unnecessary follow-up tests, causing additional morbidity.

Third, the cost of genomic medicine will increase substantially with little benefit to patients or physicians (but with great financial benefits to the genomic testing industry), thus throwing the overall societal benefit of genome-based medicine into question.

They said it...so why are the advising a company which puts all that data out there???? Good question.....

The Sherpa Says: Because the system can't handle the data we should throw out the interpreters of the data????.....Listen.....this isn't Cobol you freaking chuckleheads! This is years and years of scinetifically proven medical physiology, biology, and healthcare which doesn't just get replaced with a better model.......We may Augment....but never completely replace....until the evidence tells us what we are doing is incorrect we shall continue with what we have.

Genetic Test or Family History? Which Matters More?

I would say that when used in combination a 3 generation family history and appropriate genetic testing are probably the best tools we have to identify risk for and diagnose genetically linked disease.

So what matters more to patients? What risk means more? The results of a genetic test OR their family history. Hsien Lei touches on this briefly at Eye on DNA, but the interpretation she provides is not exactly what the article said or studied.....What article? Well the one I am about to tell you about...

Published in the Archives of Pediatrics and Adolescent Medicine this week an article entitled:

"Parents’ Concern About Their Own and Their Children’s Genetic Disease Risk"

The article sought to study:
To evaluate the effect of the genetic risk information source (family history vs genetic test results) on parents’ concern about their own and their children’s genetic disease risk.

In lay terms, which mattered more and carried more weight when "assessing" risk by a parent....family history OR genetic testing.....

Hsien interprets this Family History of Disease Scares Parents More Than Genetic Test Results .... I wouldn't say scares......I would say concerns.....or means more to them.....

Fear was not studied in this analysis......Concern was....

The Method:

Parents first received a vignette about their hypothetical genetic risk, randomized as either a family history assessment or genetic test results. Next, parents received a vignette about their youngest child’s hypothetical genetic risk, similarly randomized.

The Vignettes:

Imagine that you have family members with a disease that causes severe symptoms in adults. Having this “family history” means that (you/your youngest child) has a 30% chance of developing this disease. A 30% chance means that 3 out of 10 people will develop the disease.
“How concerned are you that (you/your child) might develop this disease?”

AND

Imagine that (you/your youngest child)gets a genetic test result that says he/she has a 30% chance of developing a disease with severe symptoms in adults. A 30% chance means that 3 out of 10 people will develop the disease. “How concerned are you that (you/your child) might develop this disease?”

So this clearly is a high risk gene 30% likelihood is about what the risk is for Ovarian Cancer carrying a BRCA gene mutation. "Roughly" for my CGC readers who like ranges......

The Results:

Parents were more likely (twice as likely) to be concerned about their own disease risk when
the risk estimate came from a family history assessment vs a genetic test result (odds ratio, 1.96; 95% confidence interval, 1.44-2.68).

But here's where it gets interesting.......Patients perceive the risk of their child's as the same as their own.....clearly not a mendelian concept or even a genetic concept......Even more interesting was the fact that despite this being the case 73% of the time, the other 27% actually were concerned that their child's risk was HIGHER than their risk......

Ah.....you have to love denial!!!!!

Conclusion:

Positive family history of disease generated greater concern about parents’ own risk of inherited
disease than did genetic test results.

The Sherpa's Conclusion? People don't know what the hell they are doing when analyzing genetic risk. Nor do they know what the hell they are doing analyzing multifactorial disease risk in pedigrees....

So I ask you....."Should we expect them to?" Isn't this the exact reason why we have geneticists and genetic counselors? Our job is to interpret family histories and genetic test results....in the doctors' case they interpret full medical history, perform physical examination and review of systems and evaluate other lab values oh, and medication history too.......

Why should we expect patients to know or understand these concepts? Oh, I know why.....because we are trying to thrust onto themselves the diagnostic and interpretive responsibilities in some crazy screwed up way to save costs for the American Healthcare system.....By doing non-clinically valid DTC testing which will be pushed down our throats by Time magazine and the PR firms of the silicon valley DTC firms.....

Or at least that's what some one in this field told me......Personally, if you want to save healthcare costs....fire the coders, HR departments, compliance people, essentially fire everyone who doesn't lay their hands on a patient or handle their lab specimens.........That's where the fat is.....it is NOT in direct care.....

The Sherpa Says: Pedigree analysis, Bayesian Interpretation, Molecular Biology and Genetics are not taught in high school...why In the hell should we think everyone will be able to use DTC testing, which doesn't even throw family history into the mix......Silly....real silly......Stick with your Sherpa.....don't try to climb mountains on your own.....

Daniel Ballon Off Course with DTC testing!

I read an interesting article in the SF Chronicle today. It was entitled State off course on 'personal genomics' Authored by Dr. Daniel Ballon PhD...

He raises some interesting points that I would like to highlight.

Why would a state that regards itself as progressive and high-tech act to censor what we can know about ourselves? Though regulators may shut down unscrupulous firms, the services offered by Navigenics and 23andMe meet the highest standards of accuracy, validity and reliability. The laboratories employed by both companies are fully licensed and trusted by researchers around the world.

First off....it didn't start that way with 23andMe.....Also, I just found out they came to Yale Genetics in '06 looking to database people and their samples.......hmmmmm

California is progressive, but it is still a state which believes that government should help protect its citizenry, and this is likely why it acted. There were some really bad players out there....now that the well funded firms could hire legal defense to open back up, they have....those less funded buggers shut down.....who was more scrupulous.....I couldn't tell....but who was more funded I certainly could tell.......

I Highlight "the services offered by Navigenics and 23andMe meet the highest standards of accuracy, validity and reliability."

Simply because we need to ask what these three words are that Ballon PhD throws around as if they are the gold standards.....

Accuracy? Of what? Of what your genetic code is? If that is all they are providing, then maybe this is the most important thing...but if they start providing risk estimates....then that accuracy, I am afraid is terribly flawed and often not agreed upon by physicians or a host of scientists...So if we are judging that accuracy.....we have a big goose egg there....

Validity? Of what? A valid genotype? What is an invalid genotype (Well, that's what the natural born were called in Gattaca) Are the genotype results valid? I would say yes....the same as they are accurate.....in the genotyping realm this IS the same thing. But I think Ballon PhD is trying to get you to believe that the interpretation IS what's valid......For the majority of medical estimates (Which BTW IS medicine, I don't care what anyone says about that) their estimates are not valid.....validity used as an adjective describing assertions, arguments, conclusions, reasons, or intellectual processes that are persuasive because they are well founded. In this case that validity would be scientific or medical......most of these SNPs fail on both counts....therefore Dr Ballon.......DTC just laid another big fat goose egg.....strike 2!

A great example includes the fact that there are more failure of replications in SNP data, than replications......

Reliability? of what? The genotype? Isn't that the exact same thing here when we are dealing with As, Cs, Gs, and Ts? Are the letters what they say they are and can you trust that you will get the same letters every time? I hope so......But if you are talking about the reliability with which you can trust the interpretation reports.....once again I say you fail......why? The science isn't there to create a reliable report on most of these SNPs......So again.....Strike 3....

Don't believe me......look at the last month and the SNPs in 9p21 a region argued that is highly linked to heart attack.

1. linked to Irish heart disease

2. Failed to replicate in the Dutch

3. Replication in the Chinese

4. Now linked to Alzheimer's Disease if you believe it........

So which is correct? More importantly.....will testing this help us risk stratify any better? Will it help us treat any better? Will it help prevent disease? None of these questions have been answered scientifically yet.....Not a single one! No where is this mentioned in regards to validity, accuracy or reliability....yet these reports include risk assessments...based on these SNPs!!!!

He then makes this absolutely bogus argument....

If residents must obtain permission to see their own bodies, however, why can they look in the mirror without approval from a licensed cosmetologist?

Well, if I needed to put my eyes in a tube, ship them off to a lab, and the lab would need to tell me what I saw......I would say yes, that lab should be licensed.....

But, listen Mr. Biased, your statement tells me that your "Insight" is clearly skewed and biased

Unlike cosmetologists, doctors have a powerful lobby in Sacramento, and these technologies directly threaten their profits. Personal genomics aims to empower the individual, not line the pockets of an elite medical establishment.

So let me get this straight...

1. The doctors have more of a lobby than the billions of dollars in tech and in Google.

2. DTC testing doesn't line any one's pockets? Oh wait.....it lines the pockets of....oh wait, these companies are still bleeding cash......And BTW what doctor should you skip seeing because you have one of those new fangled scans....skipping doctors appointments is a bad thing.....that is one of the reasons why California stepped in.....b/c most patients are willing to trust an unvalidated SNP scan when it tells them they are healthy.....

3. These technologies threaten doctors profits?????? Have you ever seen a billing code for bogus SNP scan...insurance would never pay us to interpret this data......So no dipping into our paying patient populace......Sorry, another false argument....

Lastly, here's a myth buster for ya Mr Ballon....

You say

For example, it is currently impossible to know the hundreds or thousands of tiny genetic variations that help explain why someone loves roller coasters or horror movies. If 10,000 people join an online network for thrill seekers and start comparing their genetic profiles, the variations they share will be obvious.

10,000 patients wouldn't even come close to enough data to draw any meaningful conclusions regarding this highly variable phenotype of thrills.....SORRY......So stop making the public think it will.

So I ask all reporters.....if you are going to put this swill out there and hope it stands up as an argument......I say, think again.....

Daniel R. Ballon is a fellow in technology studies at the Pacific Research Institute in San Francisco. Contact us at insight@sfchronicle.com.

The Sherpa Says: Dr. Ballon needs to go to medical school or maybe just spend some time with the clinicians and scientists actually working on personalized medicine.....rather than hang with his Spit Happy crowd in the Silly Con Valley. Mr. Ballon, you stick to Cell Bio and I'll stick to Healthcare.......sound reasonable???? Sometimes business regulation is necessary, I think we see that crystal clear now.