Respiragene Test and CT Screening for Lung Cancer?

I love personalized medicine.

I absolutely think it is beyond fantastic to be able to say to a patient "This is the drug for you"

Or, we need to screen for disease X because of Gene Y and your family history

But what I don't love is companies purporting the import of their special home brew test to do personalized medicine without any sort of data backing them up.

A news report and "AACR Feature" highlighted precisely that. A test with no data......

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????

Ahem. Crickets.....

“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.

Last year they were still researching this panel

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.

Pathway Genomics IS a lab. Not an algorithm.

Today an article came out in BioIT world about Pathway Genomics. (Sounds Eerily like Amway)

With a tagline like, "Your Future, Only Better" I thought that maybe they were like Vanilla Sky or some Total Recall like service. I could only guess how in the world they could offer a better future through a SNP scan.....

Yes another DTC Genomics/SNPscan Company in the game. Hopefully they will accept regulations and not try to manipulate the laws. I hope that they act responsibly with the data and samples. I hope that they will be transparent and honest.

FROM Bio-IT

"In common with other consumer genomics firms, Becker oversees an editorial team to review criteria from the latest peer-reviewed genome association studies. That team includes Victoria Magnuson, who trained with Francis Collins and John Todd and is an expert in type 2 diabetes genetics. “We are putting together a white paper that will eventually be on our website that describes our criteria,” said Becker. “We’ve tried to be pretty conservative as to what is acceptable, validated research versus preliminary research markers.”

Mostly, I hope that they put people with clinical experience into positions of management and decision making. Because if they don't, they will be making the same mistakes as 23andSergey.

Fast follower? Probably. But is fast what is needed here? No, I would say slow and methodical is the best way to be in this business. Which is why DeCodeMe may ultimately win in the end. That is unless they go off the deep end and push clinical tests from recent discoveries without validation......

Oh wait, they already did that........

So to Pathway I say, good luck. My guess is that your tests will cost 75.95 USD very, very, very soon.

The Sherpa Says: Your future, Only better. Damn, I am glad you are around Pathway (Sounds eerily like Amway) because I have no ability to make my own future better without you.

HT Dan V.

No Gene is an Island

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

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

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

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


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

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

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

"No Gene is an Island"

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In My Inbox........

I think maybe the government of Germany has been receiving the same emails as myself. You see, in case you missed it, Germany is banning Direct To Consumer testing of DNA. This is something that I have been covering for almost 2 years now.....not the Germany thing but the whole regulation of what could be construed to be the practice of medicine.

Why do I think Angie Merkel has been getting the same emails as me? Well, take a look at my inbox-

"There is a new comment on the post "How to Fake a DNA Test".http://www.eyeondna.com/2008/04/13/how-to-fake-a-dna-test/

Author: Scooter Jones Comment:If someone wants to fake a DNA test would it work if he put someone elses saliva, sperm or blood in his mouth prior to being tested.?"

A while back I said that people could potentially "fake" a DNA test, planting DNA at a crime scene, etc.

It turns out 'Ol Scooter is trying to figure out whether Sperm, Blood or Spit is the best way to go......Too Bad he doesn't know that it's awfully tough to "spit" sperm or blood into a vacutainer tube.......

Maybe he could just bid on one of those Whoel Genome Scans that KNOME is offering.........too late :(

These DTC companies better hurry up before the US does the same thing as Germany's law

"Under the law, genetic tests can only be carried out by a doctor and require the full consent of all parties involved.

In addition it prohibits the use of genetic testing for indications of a predisposition to illnesses that appear only later in life, such as breast cancer or diseases of the nervous system."

The Sherpa Says: With guys like Scooter out there, it makes a lot of sense to follow Germany's line. These days we seem to be pro-regulation anyways......... I think I hear Agent Smith at the door now.....

Pharmacogenomics Rising

Just recently released, LabCorp will study the role of polymoprhisms in cytochrome p450 2D6 and women's response to breast cancer. Which is good news for physicians like myself who would gladly use this test if their were some good data. Unfortunately, some think it is ready right now for prime-time....

Which leads me to the next topic. In the November edition of the American Journal of Human Genetics there is a systematic analysis of something called Variants of Uncertain Significance. You see, the problem that DTC testing companies don't want to tell you is that sometimes an answer only confuses things. More importantly, these things called VUSs require significant follow up. You have to double check databases and see if the genetic changes found in yourself are also found in a significant amount of those tested. And if those tested have manifested disease. In BRCA it is breast or ovarian cancer. But what happens when you pay for testing and come up with a VUS? Who translates the data? A form? A phone call?

So what is the outcome of this study? It seems that VUS are more likely to have problems if they were located in splicing sites, in the protein coding regions, or in the highly conserved areas of the gene....Makes some sense. But, you will not know the answer until you have enough patients...Which means continuing follow up....Not exactly the most scalable solution.

Lastly, Dr Bettinger comments on the ancestry article I commented on earlier.

The Sherpa Says: Would we take the tests if we knew that it may not give us an answer.......or if it gave us an answer we weren't ready to find out. What if we weren't prepared to handle what we found out? That's the role of the genetic counselor. They are there to protect us from ourselves......Or help us find what we are looking for...

NYT and WSJ cover Myriad's campaign

I have been silent on this for too long. Why? I was awaiting the review by my attorneys. The last thing I need is another threat of litigation. Why litigate? Because, critics like myself and the esteemed Ellen Matloff from Yale :) have been telling physicians that testing for BRCA ain't like checking a sodium.....or even better a pregnancy test.

Why can you get a pregnancy test over the counter? Because its results are crystal clear. The FDA has requirements for OTC testing. This whole issue was raised with at home HIV testing. The issues were portrayed here.

The interesting questions poses include these.

What test characteristics favor possible approval of an OTC home-use HIV test?

• The test is simple to use compared to other types of HIV tests and earlier versions of rapid HIV tests, suggesting that untrained persons will be able to perform the test properly.
• The test does not require special storage conditions.

The most interesting one was......

• Informational materials supplied with the test are sufficient to provide adequate information to potential users on performing the test and to substitute for live counseling.

Now my question is....has it even been proven that written materials substitute for adequate face to face counseling? Never for BRCA testing. So why does it take evidenced based medicine to prove a drugs efficacy? Well, partially because the FDA's evaluation is not about efficacy. It is about danger to the patient. Is there danger in not getting cancer screening if your BRCA test is negative? (Which BTW is not an appropriate counseling answer to the patient)

Yes, I do agree with Hsien. Direct to consumer advertising is a great way to introduce new products. Like the iPOD.

"Advertising serves to bring new products to our attention and to stimulate interest as well as the desire for more information. In the case of genetics and genetic testing, I would venture to say that all of us need to learn more, not less."

But the best way to learn about breast cancer risk is by being able to ask question to a knowledgeable, trained, health professional. How do we learn more about genetics? Take a freaking class, don't try to do self counseling for G-d Sake. Has anyone seen the Edward Jones commercial where the surgeon is telling a guy sitting at his kitchen table how to do surgery? Over the phone the surgeon asks "Did you sterilize the field?.....Good now with your kitchen knife make a 3 inch incision.........."

This is the type of thing that DTC testing is trying to get you to do. Patient empowerment aside, I don't let my patients prescribe their own meds. I even guide them on vitamins that they take. Did anyone see the expose on the Vitamin Shoppe's vitamins containing abnormally high amounts of lead. It was on Good Morning America a couple month's ago.

Well as the post was entitled the NYT and the WSJ had article on this yesterday. The ad campaign is telling you to go see you internist, OB/Gyn, or family practitioner. Guess what none of them have had training regarding this topic. There are less than 100 internist/geneticists in the country and even fewer OB's and FP's. According to the WSJ

Myriad says it is developing a program to school primary-care doctors about the test. Dr. Critchfield said the company is focusing on primary-care doctors, oncology specialists and tertiary-care centers, along with genetic counselors, "to get the message out."

What struck me was the benevolence of Dr Critchfield, who in the NYT article

Dr. Critchfield said Myriad waited nearly five years to start the new campaign to give more time for health care providers to learn to handle genetic testing. “We are in a far different place today than we were then,” he said.

The Sherpa Says: Well Dr Critchfield, you are incorrect. Clearly he has no clue or doesn't want to sour the internists' palate. OB's regularly fail to recognize at risk and not at risk groups, so do internists. As for the newest batch? I just tested primary care residents at a major academic center and only 30% recognized that a BRCA test was NOT indicated. Maybe that's what Myriad is looking for? If you want the literature I have quoted, send me an email and I will be more than happy to forward it on. As for the 8 month wait, Helix Health of Connecticut is open for business and seeing patients in less than a month!!!

American Society of Human Genetics speaks out on DTC testing

After a wonderful conference call with some friends regarding the future of personal genomes, I was heartened to see ASHG put out a statement on Direct To Consumer (DTC) testing. Here is what these learned individuals say.

Currently, DTC genetic testing is permitted in about half the
states2 and is subject to little oversight at the federal level. In July
2006, the Government Accountability Office issued a report documenting
troubling marketing practices by some DTC testing
companies,3 and the Federal Trade Commission (FTC) issued a
consumer alert cautioning consumers to be skeptical about claims
made by some DTC companies

While DTC testing also encompasses paternity and ancestry testing,
this policy statement addresses solely those genetic tests that
make health-related claims or that directly affect health care decision
making.

For a test to be of good quality,
the laboratory performing it must be able to obtain the correct
answer reliably, meaning that it detects a particular genetic variant
when it is present and does not detect the variant when it
is absent. A test’s accuracy is referred to as “analytic validity.”
Further, there must be adequate scientific evidence to support the
correlation between the genetic variant and a particular health
condition or risk—the so-called clinical validity.

Currently, the federal government exercises limited oversight
of the analytic validity of genetic tests and virtually no oversight
of their clinical validity.

Several complaints have been filed and
are pending with the FTC about a specific DTC genetic-testing
company, and the FTC recently issued a consumer alert warning
the public that “some of these [DTC] tests lack scientific validity,
and others provide medical results that are meaningful only in
the context of a full medical evaluation.”

So there in lies the problem. They have several solutions.

Recommendations
I. Transparency
To promote transparency and to permit providers and consumers to
make informed decisions about DTC genetic testing, companies must
provide all relevant information about offered tests in a readily accessible
and understandable manner.

a. Companies offering DTC genetic testing should disclose the
sensitivity, specificity, and predictive value of the test, and the
populations for which this information is known, in a readily
understandable and accessible fashion.

b. Companies offering DTC testing should disclose the strength
of scientific evidence on which any claims of benefit are based,
as well as any limitations to the claimed benefits. For example,
if a disease or condition may be caused by many factors, including
the presence of a particular genetic variant, the company
should disclose that other factors may cause the condition
and that absence of the variant does not mean the
patient is not at risk for the disease.

c. Companies offering DTC testing should clearly disclose all risks
associated with testing, including psychological risks and risks
to family members.

d. Companies offering DTC testing should disclose the CLIA
certification status of the laboratory performing the genetic
testing.

e. Companies offering DTC testing should maintain the privacy
of all genetic information and disclose their privacy policies,
including whether they comply with HIPAA.

f. Companies offering DTC testing and making lifestyle, nutritional,
pharmacologic, or other treatment recommendations
on the basis of the results of those tests should disclose the
clinical evidence for and against the efficacy of such interventions,
with respect to those specific recommendations
and indications.

The Sherpa Says:

I am still waiting for the data from Salugen/Luxor...........hmmm I wonder why? Wake up people, this field is filled with snake oil salesmen!!!!

Restless Legs and deCODE

In the New England Journal of Medicine next week there will be an article on yet another study done at deCODE. Their model may be that of the next wave of pharma companies. Personally, not a bad model, but imagine Pfizer sending press releases on all of their Phase one data. It would result in a lot of "white noise" that may or may not have some future health news. That seems to be what is going on in Reykjavik. At least they are getting their money's worth for the Icelandic genome.

In this study the research team conducted genome-wide scans of nearly 1,000 Icelanders and 188 Americans. A new chip technology was applied along with genome wide association methods. This approach allowed Drs. Rye and Stefansson to probe more than 300,000 small regions (single nucleotides) distributed across the entire genome for differences more common to RLS sufferers as compared to population-based controls.

The expedition was to find a gene linked to Restless Leg Syndrome. Sleep is often interrupted in these patients and can lead to a terrible lifestyle. There is a high prevalence of this disease in North America and Europe. Seemingly a Caucasian disease it was natural to look for this linkage in the Icelanders.

Here's what my Head Genomic Counselor had to say:
"They found an intronic SNP in the BTBD9 gene that has an OR of 1.7 for PLM (heterozygotes) and an OR of 2 – 4 for homozygotes for the A allele (vs. the wild type G allele).
The interesting thing is that it seems to be associated with PLM alone and RLS with PLM, rather than RLS without PLM.
They replicated the association in three independent patient groups – two in Iceland and one in the US. Seems like a good study from a design perspective."

What does that mean? Let me translate. The searched the genome of these Icelanders for genes linked with restless leg syndrome versus periodic leg movement disorder in sleep. RLS is a common neurologic disorder which involves both sensory and movement components. Identification of the genetic under pinnings in RLS has been difficult because of several confounding variables including other medical conditions. Periodic limb movements in sleep are a component of RLS. These movements can also be absent in the presentation of RLS.

The group found and replicated a non-coding change in a gene called BTBD9. This gene was also correlated with depleted iron stores. RLS has been long linked to iron deficiency and this makes this whole study "seem" to be correct.

The Sherpa Says: All this is fine and Dandy, but what clinical use will this finding hold. Personally, I feel that this is a confusing issue. The predisposition test would let us know something that we currently cannot prevent. Testing for this???? I wouldn't recommend it. But I am certain they will market this test just like the risk for atrial fibrillation. Not a bad model over there......too bad it could lead to misguided healthcare in the wrong hands. Why? Because who would tell you to take a blood thinner, just because you have a predisposition to atrial fibrillation? Only those doctors looking to get sued........

SACGHS and DTC testing

The SACGHS met this month and alloted 15 minutes to the CDC presentation on awareness to DTC tests. The CDC funded three states to study awareness of DTC testing as well as utilization of DTC testing. They also performed a national study. The presentation reviewed this data and of note there were some intersting findings

1. Only 0.6% of the national population has used DTC tests (BTW that's 1.8 milllion people)


2. 14% of the US population is aware of DTC testing


3. 73% of those who were aware, heard through the media


4. Yet over 60% who used the tests were directed by DOCTORS!!!!!!

In addition a survey was administered to physicians. This DocStyles study had 555 physicians who were aware of DTC testing. Of Those

1. Only 4% of MDs report >10% of their patients asking for DTC testing


2. And an amazing 93% of physicians report <1%>
   
3. 96% of physicians report Journal Articles as the most trusted source for Genetic Testing Information. ONLY 6% report that other health professionals are a trusted source for Clinical Testing! (Does this include CGCs or Geneticists?)


4. The majority of info physicians receive on DTC testing is from the media, not Journals.

The Sherpa Says: There are some limitations with the public studies. One thing is for sure.....The media has a powerful lock on distribution of this information. Did you hear that Mr Murdoch? I am truly scared that the physicians do not find other physicians knowledgeable or trustworthy. YIKES!!!!