I am going to read this article for the seventh time and get back to you this week.
Tuesday, December 21, 2010
Tuesday, November 30, 2010
Posted by Steven Murphy MD at 5:49 AM
Wednesday, November 24, 2010
Thursday, November 18, 2010
From the article:
Researchers administered a gene-based predisposition test that incorporates 20 genetic markers associated with smoking-related lung damage and propensity to lung cancer along with clinical factors including age, family history and diagnosis of chronic obstructive pulmonary disease to derive a risk score on a 1 to 12 scale with higher scores correlating with higher risk.
Ok, new score with 20 markers, family history and age and clinical data....sounds reasonable. Has anyone else validated this tool????
“At scores of 6 or more … only 25 percent of otherwise eligible smokers would be screened but over half of lung cancers would potentially be detected, many in a treatable stage,” concluded Young and colleagues, who suggested that increasing the detection rate of lung cancer per number of patients screened could improve the cost-effectiveness of CT screening.
Ok, so did you get the jump? Did you catch it? "Who Suggested"
This guy who designed a genetic panel AND NEVER TESTED IT IN CONJUNCTION WITH CT CHEST SCREENING, is suggesting that using the test could increase the cost effectiveness of CT Screening, without one single solitary IOTA or shred of evidence of this.
This would be the same Dr. Young who found that genetic testing for a smoking cessation program likely doesn't have cost effectiveness or at best is uncertain.
Yet Respiragene is being held up as a great test!
One word that makes me suspicious is the word "Testamonials"
That word alone reminds me of the time I was bamboozled into going to multi level marketing events for proton pills and the like. You know, they all had lots of "Research" behind them.
Put simply, we do not know if gene screening PRIOR to CT Chest screening for lung cancer does any of the following things
1. Make CT Screening more cost effective
2. Personalizes medicine, targeting radiation to only those who need the test
3. Improves outcomes and detection rates of lung cancer.
That research is not available today. Nor will it be in one year.
My Advice, hold off on this one for now.
The Sherpa Says: Parroting an esteemed researchers OPINION as if it were scientific fact is a great way to get yourself in trouble and an even greater way to confuse the community! But it is the best way to get a test sold.
Thursday, November 11, 2010
How do you face life as a 22 year old if you carry a genetic variant for an incurable illness that will most likely strike in middle age?
Amy Harmon is hosting a fantastic course that will be starting November 15th. You better hurry up and register because space is limited and closing on the 14th of November.
What will be covered?
The course will have weekly live online sessions with the instructor as well as self-paced lessons filled with original content covering the weekly topics. All live sessions and course material can be accessed directly within the online course.
Prenatal testing can go into deep detail about an unborn baby’s prospects for the future. How much of this do we want to know? To share?
These questions and more will be addressed. If there is one thing I know. Amy is certainly a fantastic teacher, educator, and discussion leader!
I do miss conversations like those with her!
You too can have that kind of expertise. Register before November 14th!
I am certain you will enjoy this set of topics and have directed many people this way already.
The Sherpa Says: Family history picks up life threatening disease, DTCG tests probably not so much. That being said, what's the ethical quandry with either? Ask Amy and find out!
Posted by Steven Murphy MD at 5:59 PM
Wednesday, November 10, 2010
Here are the top ten reasons why in its current state, direct to consumer or otherwise, genomic testing for cardiovascular disease risk is dead in the water
1. Family History Risk paints a far better picture and IT IS FREE
2. Reynolds and Framingham risk paint a more accurate picture
3. An independent panel has reviewed 58 variants, 29 genes, and gave the thumbs down.
4. The highest increased risk from any of these tests is 30%, Fam Hx can be as high as 500%
5. Kif6 was just shot down as a useful marker.
6. Clinical Utility has not been evaluated in ANY of these tests.
7. Spit Parties don't lower cholesterol
8. The FDA is hunting down these type of crazy claims!
9 . Topol's heart attack gene didn't pan out, why would these?
10. A recent 23 gene panel failed to make the grade as well.
Let me be crystal clear.
I am glad that the number one reason for ordering a DTCG test was curiosity and not true medical concern in the "early adopters"
But I am concerned that may not be the case for the next wave. I am concerned they will take these genetic tea leaves and use them.
The problem, most of these tests are disproven or will be in the next couple of years.
Loose associations with small increased risks sounds a lot like fortune telling or phrenology. Or hell, even birth order....
Someday we will have good predictive models, 10-15 years from now. But NOT Now! Do you hear that VC country, SV, NYC, Hedgies?
10 year exit strategy. Not 2 not 8. So stop hyping this bull$h!t and go invest in Gold or Commodities or something for the love of god!
The Sherpa Says: Did you hear the one about the research geneticist? He keeps telling his wife how great their sex life WILL BE! Someday we will have this tool, let's try not to burn out and cynicize the public yet.....HT Francis Collins
Friday, November 5, 2010
Wednesday, October 27, 2010
Thursday, October 21, 2010
Thursday, October 14, 2010
As the FDA debates what they should do, Barbara Evans at the University of Houston Law School and Amy L. McGuire of the Center for Medical Ethics and Health Policy at Baylor College of Medicine in Houston, also includes, Canadian legal expert Timothy Caulfield and Wylie Burke, M.D., of the University of Washington School of Medicine post some guidelines for regulation of DTCG/LDT genetic testing.
I love this sort of handicapping.
You have absolutely brilliant people posing ideas for regulations. I have read a ton. There are those from industry insiders, Ones from industry "Advisors", Ones from politicians who receive funding from industry, Ones from academic centers that do LDT testing. Ones from bioethicists...
But I have paid attention to the mixed group that includes pragmatist Wylie Burke and Barb Evans
In an article I just read from Science published October 8th. They propose rules for DTCG, but I am certain they also would work for LDT.
What they propose is a "sliding scale of potential harm"
Which is sort of what I had been saying for years, which perhaps is why it rings true.
If this is for earwax type, let it go to market, if it is for medically related decision making, probably needs some regulation.
The proponents for a wild west DTCG (WWDTCG), which BTW includes a "registry" say
"Well, there is no proof of harm or risk"
I say, well, this is not about psychologic risk.
Instead, it is about medically actionable risk.
I say this because recently, Kif6 testing has fallen into question, despite a company promoting these tests to physicians.
The test is marketed as a "Statin response" genetic test.
Can you imagine how many people were started on statins? Well, 250,000 tests had been ordered. Even if 10% were started it would be nearly as many people as DCTG 23andMe have tested.
The real problem here: Pharmacogenomics tests are not something you hide, you ask your doctor to use these results. Unless you are a doctor, you can't use these results to dose medications.......
That is a real risk. Despite what WWDTCG proponents say.
Another risk, BRCA testing. I cringe at the thought that a doctor would use 23andMe results and only those results to infer carrier status of BRCA 1/2
The same goes for CF carrier status.
These DTCG medical tests aren't recreational. These companies added these tests because NO ONE wanted to pay hundreds, hell thousands of dollars to find out these risks.....
In a business decision, they fell short of looking at the medical risks.
So yes, a sliding scale of regulation is likely coming. But not because of Wylie, because of the FDA.
It is obvious. Again, medical testing will be regulated as medical. Ear Wax as ear wax. Will LDT be forced to go through pre-market review? Probably not if they can only be ordered by licensed professionals.....
It's not a form a rent seeking, it is a form of guidance and protection for consumers. That's why physicians are licensed and malpractice covered.
Yes, yes. Someday everyone will have these genomes done and everyone will be educated enough to know what they mean. And all humans will have medical education and we can replace the oligarchy of physicians and the tyrannical healthcare system once and for all........
But until that day, we will have to rely on trained professionals who don't have their retirements tied to their company's new genetic test......
The Sherpa Says: Handicapping of the FDA by the Sherpa. If it has any medical utility it will be regulated as either Class II or III. If only ordered via physician it will more likely be Class II. If not, will need Class III.
Posted by Steve Murphy MD at 6:51 PM
Friday, October 8, 2010
Wednesday, October 6, 2010
I have a lot of friends and readers who have emailed me over the month.
The recurring comments: "Has the DTCG field run you off of your blog?"
The answer: "Uh No"
Why I have I stopped blogging so much? For multiple reasons.
1. DTCG has been put on the Radar of the FDA and Government. I have nothing more to say about that.
2. Journalists and Genomics aficionados have been correctly pointing out the hype behind some tests. Most notably lately with the ADHD stuff, which BTW should not have been put out there in the press....Maybe, I need to blog more.....
3. My practice and patients have really taken up my time. I am working to apply personalized medicine daily. Because that is what is needed. We need to show the public and the press how it is done on a daily basis.
I will be back soon, to dissect shotty science and poor clinical studies. But for now, our boots are on the ground and we are climbing the mountain....
See you soon!
Posted by Steve Murphy MD at 6:44 PM
Tuesday, August 31, 2010
Apparently a BMS (I.E. Plavix maker) funded study investigated this
We hypothesized that the benefits of clopidogrel as compared with placebo would be decreased in persons who carry a loss-of-function CYP2C19 allele and increased in carriers of the gain-of-function *17 allele.
What did this team study?
we examined the efficacy and safety of clopidogrel as compared with placebo according to genotype status among patients in two randomized trials: the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, in which patients with acute coronary syndromes were enrolled, and the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) A, in which patients with atrial fibrillation were enrolled.
Ok, so they took 2 different populations and bundled them into the same article....
The 2 studies?
CURE-randomized, double-blind, placebo-controlled trial comparing clopidogrel (at a dose of 75 mg per day) with placebo — both in combination with aspirin — among 12,562 patients with acute coronary syndromes without ST-segment elevation.
ACTIVE A- was a randomized, double-blind trial comparing clopidogrel, at a dose of 75 mg per day, with placebo — both in combination with aspirin — for reducing the risk of stroke among patients with atrial fibrillation and at least one additional risk factor for stroke who were not eligible for warfarin therapy.
What did they find? No difference between Poor Metabolizer and Wild Type in secondary and primary outcomes.
So are we wrong with our studies showing 2C19 genotype matters in outcomes?
1st the authors note why.
1. One possible explanation for the divergence between our findings and those of previous studies involving patients with acute coronary syndromes is the difference in the rates of PCI with stenting. Only 18.0% of patients in the CURE population included in our study underwent PCI, and only 14.5% underwent PCI with placement of a stent, as compared with more than 70% in previous studies
2. We cannot definitely exclude the possibility of an interaction in the subgroup of patients who receive stents, particularly those who receive drug-eluting stents, which were not in use at the time of the CURE trial.
3. the ACTIVE A genetic data set contained fewer participants and outcome events than did the CURE data set and therefore had less statistical power.
The ACTIVE A trial to assess the hypothesis was powered at 45% to detect a difference, thus it is a worthless study and should not be included in this analysis.
While I agree that a placebo group may be useful. It is not needed to assess a difference between people using Plavix with normal Plavix metabolism and Poor metabolism. In fact it may even confuse the situation as it introduces further confounding factors not genotyped or phenotyped out.
The authors disagree
First, the inclusion of a randomized placebo group in our analyses reduces various sources of confounding, such as potential pleiotropic genetic effects or population stratification.
Well, did they test or assess for pleiotropic genetic effects? No.
Further, by introducing a study COMPLETELY underpowered to observe and eval the hypothesis into this article, it ONLY creates a false image of scientific validity.
The authors disagree
Third, we observed consistent benefits of clopidogrel, irrespective of CYP2C19 genotype, in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations.
Again to quote the article
Among patients with atrial fibrillation in ACTIVE A, our study had much lower power (45%) to detect a similar interaction.
So why did they include the POORLY POWERED study?
" in two different patient populations, which validates our findings and suggests that they could be generalizable to other populations."
While I laud the effort to have Randomized and Observational versus retrospective efforts. I think we have to be very careful in our study design to make sure
1. We are properly powered to observe differences.
2. That we assess pleoitropic effects, rather than claim to control for them mysteriously.
The Sherpa Says: Why include the second study? It is improperly powered, further the CURE study did not include Drug Eluting Stents! Why? Plavix goes generic in 2011. They did this to save the market......Expect more screwy studies published in NEJM etc. As PGx gains traction, contrarians and Pharm will always fight it.....
Thursday, August 5, 2010
I just was threatened by Daniel MacArthur over at GenomesUnzipped that he was about to delete my comments.
He called it trivial. I think he is missing the tremendously simple point.
Why is the FDA mad as hell? Medical Claims.
Hell, they even told Mary Carmichael in the interview.
Alberto Gutierrez = AG
"AG: The concern is with everything."
"AG: The law requires us to clear devices or approve devices BEFORE they go into the marketplace when they make medical claims"
This to me is crystal clear. Make a medical claim. Get regulated.
Which is interesting. Because I would say some of what DTCG did was, infer medical claims without making outright claims- silly games . I happen to think that is a shitty way to sell something. But heck it is a way to create a discussion rather than instant regs.....
"AG: The question with 23andMe has been whether their claims were medical or not. The original claims they were making were very much on the edge."
"AG: We actually told them that WE(FDA) thought they were medical claims, but it was at least possible you could argue that they were not"
Do you get it? The judge thought they were medical claims, but let the company proceed. Giving it just enough rope to hang itself.......
The question here is clear. What is a medical claim?
Which boils down to: What is medical?
I can tell you what I do as a doctor.
I diagnose, treat, cure, palliate, prevent human suffering and advance human health.
If you are making claims to do any of those things, I would call it medicine.
This is very important to understand and I hope you VC are listening........
Diagnose, Treat, Cure, Palliate or Prevent human suffering.......and advance human health.
Words matter. Did you notice I didn't say disease. Because what's today's disease may not be tomorrow's.
And Vice Versa....
Is a priest a doctor? Well, they used to be.
Is a counselor practicing medicine, well, I would say yes, they are in the healthcare arena
Yes, it is now sinking in. That huge pit in your gut. The millions invested trying to game the system that is millenia old........
It will not work. DTCG has just proven that. And, do you think the vitamin industry has a chance over the next decade?
I will begin the deep dive into the FDA comments shortly. But rest assured, I just gave you some insight into what medical really means......
The Sherpa Says: There Daniel, there you have it. I have told you what medicine is. Now if you wish to argue against that go ahead bub.......
Tuesday, August 3, 2010
" I don't even know if that was a hammer that got dropped on their heads. More like a piano."
-Anon Quote re: DTCG and Congressional hearings....
When Ms. Carmichael approached me to answer a burning question for her. She got an answer alright, more like a diatribe and then and answer.
In case you didn't know, Mary is a writer for Newsweek and is thinking about doing a DTC genetic test kit. In fact, she bought the kit and it is staring her in the face. FYI, she's not in New York, where such activity is illegal, she is in Boston, where it is encouraged......
She is taking opinions from just about everyone in the biz. And, yes, she has a comments section for all those Yahoos who feel left out.......
My recap here is what Newsweek wouldn't put in their print, but as you know.....I am more than happy to put here for my readers enjoyment......
I want to know, have you thought about it? What can you and what can't you learn? Since I have seen probably more patients with these types of tests than just about any clinician out there, I can tell you what the patients ask and what I tell them.
As an aside, You will die from something. Everyone dies. Even those transhumanist singularity punks die. No amount of knock off stem cell clinics will help with that one. Even the G-Damn Buddha dies. In fact someone off'd him with rotten food....
Second aside, Isn't funny how the GAO bashed these nutrigenomics companies in 2006 and they are still out there slinging there proton pills. Goes to show how much force the FDA or any other organization has to control commerce......I wonder what happens to the first batch who refuse to buy health insurance.....You can buy things that give you cancer or an erection, why not DTC tests? Properly regulated of course......
Ok, my buddy, who shall remain nameless as he is at Camp in PA for his kids right now had a patient come to him adamant she was of the royal lineage of the Czar (Russia). She paid a bundle to have her mito DNA checked.....Guess what? She wasn't........
P.T. Barnum once said
"You can fool some of the people all of the time; you can fool all of the people some of the time, but you can never fool all of the people all of the time." But what he forgot to say is, some people are fools all of the time......
What will you learn?
Good Question Mary.
Mary, this is a medical test. And should be held to the same standards as other medical tests.
Mary, this is a medical tests and I advise you to have some clinician back up when reviewing these results. Even if they are negative, that doesn't rule out a BRCA mutation. This test is confusing and should be regulated as a medical test.
The whole thing about Pharmacogenomovigilence is that ideally everyone would have a panel of these useful genotypes before dosing medications. But based on the soon to be available rapid turn around time here, we could do these in some labs overnight. The big question here is, is the DTCG test enough of a test to trust clinically?
I am not so certain as they miss certain SNPs and rare mutations that are important.
The Sherpa Says: Ok, Mary. You want it, you got. If you buy a test, you've got a guy just a few Acela Stops away who can help sort out the madness for you.......Clinically of course.....That is, if I haven't convinced you otherwise.....
Thursday, July 29, 2010
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 of.....in the top fifth for polygenic risk score is similar to that for women in developed countries with one first degree relative with breast cancer" -The Authors about the less than useful polygenic risk model they created when compared to family history
Heck even the authors admit, this stuff is great......For studying pathogenesis, but NOT FOR CLINICAL USE TO GUIDE PREVENTION PROGRAMS!!!
The Sherpa Says: Again, "You would be in the high risk of pretty much getting it".........Not a good way to do medicine or guide consumers guys.....
Posted by Steve Murphy MD at 6:09 AM
Thursday, July 22, 2010
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......
Posted by Steve Murphy MD at 5:30 AM
Monday, July 19, 2010
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.
Posted by Steve Murphy MD at 6:34 PM
Thursday, July 15, 2010
Posted by Steve Murphy MD at 5:31 PM
Monday, July 5, 2010
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?