Thursday, July 29, 2010

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

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

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

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 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.....

Thursday, July 22, 2010

FDA Tuesday, Congress TODAY. More letters for DTCG.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Monday, July 19, 2010

FDA LDT meeting, bigger than just DTCG!

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

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

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

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

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

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

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"

Thursday, July 15, 2010

FDA and the DTCG company MashUp.

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

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

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

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

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

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

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

One has to ask first, will regulation stifle innovation?

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

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

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

A priori I would say yes. Always? No.

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

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

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

I would say:

1. Potential for human harm from use of innovation.

2. Misrepresentations of expected outcomes from using innovation.

3. Lack of innovation performance of stated use.

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

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

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

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

Will the FDA throw out traditional guidance here?


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?

Monday, July 5, 2010

Longevity Gene Study, The hype cycle must die!

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, 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?