For Personalized Medicine CPMC is the Gold Standard Study

Ok,

So I just wrapped up a meeting with some, well, nearly all of the most brilliant minds in Pharmacogenomics. Where was I? Yes, on the cover of USA Today's life section.....But where was I really?

Conference? No.

VC event? No.

I was at the Coriell Personalized Medicine Collaborative (CPMC) Pharmacogenomics Advisory Group meeting.

Yes, that sleepy 'Ol Cell Line joint in Camden New Jersey.

I am certain you all know about the CPMC now. But in case you have been sleeping.

Coriell is climbing the mountain, gaining collaborators, building camps. They are essentially doing all the hard work of study analysis so that you don't have to.

Brilliant if you ask me.

Who in the world has the time or money to cull data, looking for important findings?

Google funded "projects", Academic Programs and Not For Profits.

Who do you trust to give you unbiased reports?

NFPs.

Who is the NFP here? Coriell.

Are you curious what the CPMC does?

Why will CPMC win this battle? Even 23andSerge agree that CPMC is the gold standard

1. They have independent advisors and scientists

2. They have nearly all the best independent advisors and scientists

3. They have the support of the government, the community and oh yeah, the FDA isn't investigating them......

4. They have Mike Christman.

5. They have a team who believe in this moral imperative, not a pay check or stock options.

I vowed never to post what transpires at these meetings, but rest assured, it was truly academic heated debate with egos left at the door. This is precisely what you want when someone is going to tell you what your genetic material means for you.

The Sherpa Says: Coriell is on to something here. Something so valuable when the 1000 genomes and the rest of the genomes go public. Someone has to make sense of it all and study what it means......I am proud to be a part of it.

Reader's Points and Clarification.

Dear Sherpa, I am an avid reader of your blog and quite often marveled by your great writing style.

Today, however, I cannot resist to add another point to your list:
The sherpa says and might be right in saying so:
"7. The lack of medical training for genetic counselors
8. The lack of genetics training for medical professionals "

Dr. Look (me) would humbly like to add:

9. The (frequent) lack of medical clinical experience/training for human geneticists

Keep up the good work
Regs Dr. Markus P. Look,
Internist Bonn, GERMANY


Doctor Look,
Thank you so much for your comments. I would like to add that the street runs several ways. We have several shortcomings. In the United States in order for a geneticist to train in Medical Genetics (which is a 2 year program), you must first have 2 years of clinical experience in an ACGME accredited residency in just about any field. Most medical geneticists are pediatricians. This is a natural extension as the majority of classical genetic diseases start in childhood. However, there are a little under 100 geneticists trained in Internal Medicine. Approximately 1 in 10......

So I may agree that most medical geneticists are not Internists, but there are many who at least rotated through IM in medical school and elder statesmen who are internists who grandfathered into pediatrics. Much more clinical exposure than new graduates of genetic counseling programs....

But I do agree.....as genetics changes from a small sub specialty of pediatrics into pediatrics becoming a small sub specialty of genetics...we will most indubitably need more IM geneticists!

Linked together into a network preferably......

That's why I am up here at Yale.....

The Sherpa Says: If you don't know about the 24th specialty in medicine, how would you ever know how to refer to them? Looks like the ACMG needs to hire 23andMe's PR firm!

By Secretary or By Professional Report

A recent study caught my eye. Done by multiple centers.....

from the Division of Laboratory Systems,* Centers for Disease Control and Prevention, Atlanta, Georgia; the Wadsworth Center, New York State Department of Health, Albany, New York; the Albert Einstein College of Medicine, New York, New York; ARUP Laboratories and the University of Utah, Salt Lake City, Utah; the Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington; San Ramon Valley Primary Care, San Ramon, California; the Genetic Services Laboratory,** Sequenom Incorporated, San Diego, California; and the Department of Human Genetics, Mount Sinai School of Medicine, New York, New York.

What did they investigate? Simple....how genetic tests were orderded and how results were given. What really got my goat was the results.

First as a preface....the AMA in June put out a statement against DTC genetic testing Resolution 502, A-04. D-480.987 in case you want to check it out. This statement says:

Our AMA: (1) recommends that states restrict the performance of clinical and laboratory genetic testing to individuals under the personal supervision of a qualified health care professional......

Also in the AMA policy manual is E-2.131.....

Physicians who order genetic tests should have adequate knowledge to interpret information for patients. In the absence of adequate expertise in pre-test and post-test counseling, a physician should refer the patient to an appropriate specialist....

So with that backdrop I give you the study "Ordering Molecular Genetic Tests and Reporting Results. Practices in Laboratory and Clinical Settings."

To understand better the contributing factors to such compromised care, we investigated both pre- and postanalytical processes using cystic fibrosis mutation analysis as our model.

Ok this will be great! CF testing. When was the last time the OB went over pre and post test counselling for carrier status???? I can't wait to see the results...

1. We found that although the majority of test requisition forms requested patient/family information that was necessary for the proper interpretation of test results, in many cases, these data were not provided by the individuals filling out the forms.

2. We found instances in which result reports for diagnostic testing described individuals as carriers where only a single mutation was found with no comment pertaining to a diagnosis of cystic fibrosis.

3. Remarkably, a pilot survey of obstetrician-gynecologists revealed that office staff, including secretaries, often helped order genetic tests and reported test results to patients, raising questions about what efforts are undertaken to ensure personnel competency.

If you have any question as to why OB/Gyns get sued more often than anyone else.....look no further than the results of this study!

The Sherpa Says: The real pickle is this. The American College of Obstetrics and Gynecology recommends that every pregnant woman get "screened" for cystic fibrosis mutations. So the OBs are forced to do this testing.....oh wait, no they aren't. They could actually refer patients. Or even better, they could hire a geneticist. But why do that when they could just have their secretary do that work? Scary stuff!!! This makes DTC look pretty warm and fuzzy.

OK for Journals but Cut From the LA Times

It is important for all of us to contribute to the literature and assure the success of new and upcoming journals. I want to point you in the direction of 2 of these journals published by Future Medicine in London.

I mention this because I just finished my manuscript for The Journal entitled Personalized Medicine. This is an excellent journal with a tremendous potential. I recently published here and intend to send a significant amount of my work its way. But what is most important about these journals, Pharmacogenomics and Personalized Medicine, is that they are giving an opportunity for younger scientists, physicians and stake holders a voice.

This is important especially because as we interview with reporters, there is no guarantees that it will end up in their article. BTW Anna, I loved the article. Anna Gosline wrote an LA Times article which she spoke with me about. Well, I guess Muin is a bigger name than me ;)

Everyone should read this article....It is excellent. And Anna, if you need some medical advice feel free to call us and you can be one of our cadre of Navigenics patients.

I have recently begun to realize the potential of pairing patient centered care with genomic medicine. By putting these two ideas together....we may have a winner. I think that these two parallel ideals may actually be synergistic. Put plainly, moving the care in a patient centered way that DOES NOT REMOVE the healthcare practitioner, but places them as the coach, enables patients to make better choices by understanding their genomic risk. First by taking a family history and secondly by using appropriate genetic testing. Just like Muin said.

Ok, now the gossip fix. Did anyone read the Sunday Times? Well Navigenics was in it. Slapping 23andMe in the face. From the article

The company has been authorized to sell the service to residents of every state except New York (Told you so), Ms. DuRoss said. New York residents must join a waiting list until state health officials license the company’s designated lab to provide services to New Yorkers.

Even if that regulatory hurdle had been cleared, Ms. DuRoss said she doubted that the company would have invited customers to provide saliva samples on the spot. “It’s a little awkward to ask people to spit in public,” Ms. DuRoss said. “It’s a very private thing.”

Woah!!! We (Navigenics) are classy and tactful, You (23andME) are classless. That's what it sounds like to me ;)

The Sherpa Says:
When my next article is published I will let you know. I hope it serves as a good compass. Speaking of compass, take a looksie at Daniel's post at Genetic Future....he seems to think these big corporate genomic companies will be fighting each other for quite some time....He may be right. Maybe they could read my article? Then they would realize what they needed to do. Differentiating themselves is definitely a start.

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!!!!

TCF7L2 Strikes again, This time it's the Finns

The Latest edition of Mendel's Garden is up at Scienceroll. If you haven't seen it, the Gregorian Rap All-Stars video is a must see!

It's official. I can say without any doubt that the gene TCF7L2 is somehow implicated in diabetes. Another whole genome association study was performed and results were published in the American Journal of Human Genetics.

The study which performed because there only exist a handful of genes that have been implicated in the genetics of diabetes. These include PPAR gamma, TCF7L2, KCNJ11, CPN10, FTO. And because GWAS is hot now. They selected 4 populations, all Caucasian. 200 Finns with diabetes and 200 without, similar numbers of Ashkenazi Jews, 100 soccer hooligans from Manchester and 99 affected Brits, as well as 100 Germans with diabetes and another 100 without.

What they found was not surprising. TCF7L2 SNPs rs7903146, rs7901695 and rs122255372 were all replicated as linked again with ORs of 1.6-1.7. They also found several candidate loci. None which were that impressive when attempted to be replicated.

So, what does this all mean? Well it means that there is an increased risk for diabetes if you have any of the aforementioned changes in your TCF7L2 gene. But how does that help us? Now that it is shown to be linked, we need some data on how to prevent diabetes in the carriers of altered TCF7L2.

Does anyone have good data on this?

The Sherpa Says: Sometimes I do eat humble pie. That being said, I will not recommend TCF7L2 testing for anyone. Importantly because there are several SNPs associated, not just the SNP that deCode tests for. There is more to this diabetes story than meets the eye.