Follow up to Yesterday's WTF? Harvard, Navi? and Pfizer???

So I was thinking about all of this hullabaloo and how Beth Israel Deaconess flipped the script by using non-clinically validated, non medical tests to teach residents about medical genetics.....

Yes, that is pretty freaking preposterous in and of itself, but I have a deeper concern.....

"Beth Israel has launched the Personalized Genomics and Next Generation Sequencing Training Program, which includes a series of lectures, discussions, and presentations, aimed at promoting a better understanding of the personalized genomics field and next-generation sequencing technologies."

Ok, so my question is. Who will be giving the lectures?

Let me put this another way.....

"NewsFlash" (This is not true, however it is just as preposterous and written to illustrate a point)

Harvard Medical School has agreed to partner with Pfizer to educate young resident physicians about pharmacology.

Residents will receive a series of lectures crafted by Pfizer to help physicians understand the complexities of pharmacology. To help the young physicians a pharmaceutical specialist employed by Pfizer will take the residents out to dinner and give lectures crafted by Pfizer.

To further enhance the training, all physicians will be given free samples of viagra/modafinil to help them understand how the medication works

"We believe that pharmacology and pharmacogenetics 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 pharmaceutical services and technologies will be essential to this future."

(End Fake Story)

Do you get what I am saying yet, or are you such a blind supporter of DTC genomics to see the absolutely clear freaking conflict of interests here?

And for such a school which focuses so much on Conflicts of Interest, I am blown away that this program has not yet been shut down.....

You can email Mark Boguski at mark_boguski@hms.harvard.edu if you think this is as crazy as I do. Or maybe a phone call? 617-432-7375

The Sherpa Says: Do you see what I am getting at Mark? This is sketchy at best....

Great Job Mike! 2C19 meets the grade!

I was flipping through the internal medicine news yesterday when I saw a colleague. Mike Murray, Clinical Chief up at the Brigham who had given me some good advice re: being a fellow and academia......

He and a couple other internal medicine geneticists write a column called "Genetics in Your Practice"

Which is a welcome addition to what my wife and I (Both Internists) believe is one of the best print publications out there for keeping ahead of the curve with IM and subspecialties....

Well,
Mike wrote about Plavix, which, as you know, I have been all over since the studies came out in January showing significant differences in outcomes clinically with patients who cannot activate Plavix. Why was I all over it? Because it had met some criteria which I think will define what a good PGx test is......

I have as of yet failed to detail precisely what these criteria are.....It just so happens, Mike did a brilliant job of it.....So without further ado. Dr. Mike Murray, Internists, ID specialist AND geneticist defining the criteria....

From Internal Medicine News

So, what will bring a breakthrough application in pharmacogenetics? I believe that a true breakthrough into the mainstream will occur when the gene-drug pair has many or all of these characteristics:

▸ A widely used drug. There are currently some excellent examples of gene-drug pairs as models for the clinical application of pharmacogenetics; however, they happen to be with drugs used by only a small number of subspecialists. A true breakthrough application will need to be a widely used medication.

▸ An “essential” drug. Although we may eventually get to pharmacogenetics testing for almost all medications, a true breakthrough application will not be for a drug for which the application is usually elective (e.g., onychomycosis therapy) or for a drug that has equivalent substitutes inside or outside of the class (e.g., a diuretic for hypertension).

▸ Potentially severe consequences from use of the drug without pharmacogenetics guidance. The motivation for using a pharmacogenetics approach is mainly safety or efficacy. The breakthrough application will need to help the prescriber avoid morbidity or mortality associated with side effects or ineffective treatment.

▸ A narrow therapeutic window. Aminoglycoside antibiotics are classic examples of drugs with a narrow therapeutic window, where underdosing can lead to disease progression and overdosing can cause adverse effects.

▸ Pharmacoeconomic advantage. The application of new technology to guide gene-drug decision making will be more attractive for clinical uptake in instances where it offers cost savings.

▸ Straightforward genetic interpretation. Much of current genetic testing deals with complex interpretations of sequence data where variants unique to the individual patient have to be judged as causative, noncausative, or of unknown significance. In 2009 the most straightforward diagnostic genetic testing is based on screening for common variants that confer increased relative risk.

▸ Validated significance of gene-drug pair. There will always be varied levels of confidence in any data set; however, replication of significant correlation in more than one large, well-designed study will be the most likely to be associated with rapid clinical uptake.

This is precisely what Plavix is......And it is precisely why it will lead personalized medicine this year.......Not genome scans, not whole genomes, Plavix pharmacogenomics...... Mike, yet again, you have crystallized criteria which I often find nebulous......

The Sherpa Says: If we judge all tests by this criteria we would be better off.......Imagine how many less tests would be ordered. Bad for business, great for medicine......

Resistance is Futile

I was reading some peer review comments of an article I am submitting and it got me thinking.....How can we combat certain resistant to change mindsets? For example from the anonymized reviewer:


I strongly disagree that because there aren't currently sufficient numbers of genetics providers (even if you add up clinical geneticists and genetic counselors, as suggested above) that this means that the only solution is to move genetics into primary care. ...........




Ok, you can disagree.....but.....when you say this......


First of all, the demand for genetics services has not yet led to long waiting periods or other crises.

Ever tried to get into a cancer genetics or clinical genetics office in less than 1 month? More likely less than 3 months. That being said...even this reviewer acknowledged that there is not a massive amount of referrals.......

What number of trained genetics providers are needed and what are the barriers to educating, producing and hiring more and supporting their work?

Ahh....trade secrets that I will be publishing soon......





Can the authors imagine another group of specialists (for example, brain surgeons) deciding that there aren't enough knowledgeable brain surgeons, so primary care providers need to be trained (via a short course, perhaps) to do brain surgery?


The term is Neurosurgeon....and this argument is a fallacy..... They trained for 7 years and brain surgeons don't operate on Alzhemier's


I think statements about moving genetics into the primary care arena need to be much more carefully thought through and evaluated -- what are the outcomes likely to be associated with the suggested interventions??





Other than earlier pick ups in cancer predisposition, MI predisposition, adverse drug reactions, improved medication dosing, more cost effective utilization of care, less "loss of chance" malpractice....I could go on and on.....but I won't





The Sherpa Says:


This is the resistance we face ladies and gentlemen. Why do I have to learn something, just because there aren't enough specialists???? There is something called continuing medical education.......just because they didn't discover DNA when you were in medical school, doesn't mean you don't have to learn about it........Resistance is Futile....

When you know the Books are Cooked

I finally had a chance to sit down and review Genetics in Medicine for the month of June. Yes, I am a month behind.....leave me alone. I have been doing some other things for the last few weeks........So take it easy on me.....

Have you ever had the feeling that the results of a study need replication? Especially because the results do not match up with clinical reality. What am I talking about?....Wylie Burke's study on how many PCPs have ordered a genetic test. There is an age old adage that on self-report tests for anything....you will get 2 answers.....80-85% and 15-20%.....By that I mean, most physicians don't want to say they do something all the time, or none of the time.....By that I mean, most physicians lie on self reports.....even when anonymized....

This is why I saw malarky on this study, recently published....

Methods: Survey of a random sample of 2000 primary care physicians in the United States (n = 1120,

62.3% response rate based on eligible respondents) conducted in 2002 to assess what proportion have (1) ever ordered a genetic test in general or for select conditions; (2) ever referred a patient for genetic testing to a genetics center or counselor, a specialist, a clinical research trial, or to any site of care.

Results: Nationally, 60% of primary care physicians have ordered a genetic test and 74% have referred a patient for genetic testing.

Approximately 62% of physicians have referred a patient for genetic testing to a genetics center/counselor or to a specialist, and 17% to a clinical trial.

Minority-serving physicians were significantly less likely to have ever ordered a genetic test for breast cancer, colorectal cancer, or Huntington disease, or to have ever referred a patient for genetic testing relative to those serving fewer minorities.

Conclusions: Reduced utilization of genetic tests/referrals among minority-serving physicians emphasizes the importance of tracking the diffusion of genomic medicine and assessing the potential impact on health disparities.

OK, Wylie, you are an excellent physician scientist, but you know this to be intrinsically garbage. If even 30% of PCPs referred just one patient for services, then the entirety of the genetics community would be rapidly overwhelmed.

I would bet that those tests sent off were Factor V Leiden tests for hypercoaguability work up(Now considered fairly worthless tests post clot)

There is no way 74% of PCPs even know a geneticist to refer to. This study is so flawed and I am embarassed to see it actually passing peer review. Who in there right mind would believe any of these data.

74% is awfully close to 80%....this is a fishy smelling study and I am blown away that it got published.

How did I know that they probably didn't sense the anomaly I did? Because they are all PhD's not a single community based doctor in the bunch......

Damn!

The Sherpa Says:

If you believe this study, then I have a bridge to sell you.........Further proof, you can't always believe what you read....Not much has changed in 5 years since the NEJM study, so I doubt that this study is true.

Senator Kennedy's Cancer Family History

Dr Lubin, my partner at Helix Health of Connecticut asked me this question.

"Am I the only one to think about this? Ted Kennedy Junior had Osteosarcoma. His other son Patrick had a Spinal Tumor (I'd love to see the path on that). Ted Senior has a Glioma.....Likely GBM. In addition, his daughter had lung cancer at 43 (Was she a smoker?) and breast. So what this tells me is that the Kennedy family may have Li-Fraumeni or Li Fraumeni Like."

Well, perhaps we should call Dana Farber. Why? Because, Dr Rosenthal over there does not seem to be impressed. from the Globe:

Dr. David S. Rosenthal, former president of the American Cancer Society and the medical director of the Leonard P. Zakim Center for Integrated Therapies at the Dana-Farber Cancer Institute, said that while he is not familiar with the details of the Kennedys' medical history, he considers it "unlikely that the cancers are related." Given the young age at which some of the Kennedys' cancers occurred, and the fact that they were found in different organs, it is unlikely, but not impossible, that there is a common genetic thread linking them.

Hmm, let's see what a little GeneTests search can do. BTW the article was written by a Dana Farber genetic counselor.

Disease characteristics. Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with soft-tissue sarcoma, breast cancer, leukemia, osteosarcoma, melanoma, and cancer of the colon, pancreas, adrenal cortex, and brain. Individuals with LFS are at increased risk for developing multiple primary cancers.

Hmmmm....

Genetic counseling. LFS is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the disease-causing mutation. Predisposition testing for at-risk family members is available in families in which the disease-causing mutation has been identified.

Two forms of Li-Fraumeni syndrome are recognized: classic Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL).
Classic LFS is defined by the following criteria:

A proband with a sarcoma diagnosed before 45 years of age AND

A first-degree relative with any cancer under 45 years of age AND

A first- or second-degree relative with any cancer under 45 years of age or a sarcoma at any age [Li & Fraumeni 1969].

LFL shares some, but not all of the features listed for LFS.

Warmer.....

Birch's definition of LFL [Birch et al 1994]:

A proband with any childhood cancer or sarcoma, brain tumor, or adrenal cortical tumor diagnosed before 45 years of age (Ted Junior) AND

A first- or second-degree relative with a typical LFS cancer (sarcoma, breast cancer, brain tumor, adrenal cortical tumor, or leukemia) at any age (Ted Sr) AND

A first- or second-degree relative with any cancer under the age of 60 years (Daughter age 43)

Well Harvard. Looks like you were scooped by Helix Health of Connecticut.......

To the Kennedys, feel free to call for a full evaluation with Dr Murray up there, if someone at Harvard hasn't had the sense to send you already!

276 pages of pure reality!

Have you read it? Come on.....You didn't. Well, you are missing out. Back in 2004 I started watching the Secretary's Advisory Committee on Health, Genetics and Society. But even more importantly I began watching back meetings that were webcast, including the SACGT. I studied the players in the field, the advisors, the government. I began to notice trends and agendas.

This is why I saw all of the regulations coming. I began emailing members, speaking with advisors, and learning how and when all of the issues would arise and then be solved. Then in 2005 I began to develop the business plan for Helix Health of Connecticut.

The safest climb to the summit is with trained genetics professionals like the ones we have. The riskiest is D-I-Y. The SACGHS is against D-I-Y...notably this 276 page report goes into this in fine detail.

Highlights include

Are Genetic Tests Special?

When considering whether genetic testing is different from other laboratory tests, it is important to understand the viewpoint known as "genetic exceptionalism," the perspective that genetic information is unique among health-related information and therefore deserves special considerations and protections. Proponents of this perspective usually point to the following features of genetic information as being distinct from other types of health information:

• It can be used to make predictions about an individual’s health future.
• It does not change throughout a person’s lifetime.
• It has the potential to reveal information about family members.
• There are instances in which it has been used to discriminate against individuals or selected populations.

But.....

....... a nonexceptionalist approach has been taken with respect to Federal health privacy protections. The Federal Health Information Portability and Accountability Act Privacy Rule, which became effective in 2003, treats genetic information as equally sensitive as other medical information and provides the same level of protection to genetic and other types of personal health information. Recent policy recommendations encourage movement away from genetic exceptionalism.

That Being Said....

The Committee is concerned by the gap in oversight related to clinical validity and believes that it is imperative to close this gap as expeditiously as possible. To this end, the Committee makes the following recommendations:

A. FDA should address all laboratory tests in a manner that takes advantage of its current experience in evaluating laboratory tests.

B. This step by FDA will require the commitment of significance resources to optimize the time and cost of review without compromising the quality of assessment.

C. The Committee recommends that HHS convene a multistakeholder public and private sector group to determine the criteria for risk stratification and a process for systematically applying these criteria. This group should consider new and existing regulatory models and data sources (e.g., New York State Department of Health Clinical Laboratory Evaluation Program). The multistakeholder group should also explicitly address and eliminate duplicative oversight procedures.

D. To expedite and facilitate the review process, the Committee recommends the establishment of a mandatory test registry as noted in the following recommendation.

The Sherpa Says:

I will go into this report in more detail later. But If I was Google......This would be mandatory bed-time reading...Looking at these snippets it is clear. The barrier to entering the testing business is about to get MUCH, MUCH bigger. Playing nice with the government will only get you so far.

They're HEEEERE!!! Navigenics in New York

Well in a move to trump NY or a business plan that does include physicians. Navigenics will Launch April 8th in NYC!!!

That's right

From a counselor's email sent by dnanyc@navigenics.com

Dear xxx,

Navigenics invites you to be one of the first people in NYC to experience first-hand a leading-edge approach to health and wellness.

Navigenics is launching its first genetics service April 8th. We truly believe this company will revolutionize the way we think about our health. Our first service, called the Navigenics Health Compass, tests for genetic risk markers for 18 actionable common conditions—cardiac disease, several cancers, Alzheimer’s among them—and arms you with specific information on how you can mitigate your individual risk for developing each condition, including personal genetic counseling sessions and customized health and wellness content. To celebrate the launch of our first service, we are coming to New York City for two weeks in April (April 8 – 17) to host a series of exciting and informative events. We will be installed at a SOHO location, and I encourage you to join us for some of our events. (Please see the calendar invitation below.)

Please help us celebrate this transformation for medicine: from a “sick care” model of “wait and see” to the emergence of early risk detection. The time has come to empower individuals with the opportunity and knowledge to take preventative steps, and a hands-on approach to their family’s health and wellness!

All the best,
The Navigenics Team

RSVP@navigenics.com

Now it will be interesting to see how their competitors 23andMe and deCodeMe react. Our practices stand ready to pick up the pieces and serve as an information source for both patients and physicians who have lost their compass, or just want to learn about this new technology.

The Sherpa Says:
I'll be there. How about you? To all my physician freinds, give me a call and I can explain what the hell is going on.... You should go to these events....Seriously, they look pretty impressive

The Sherpa Silenced

I know that it has been a long time since my last post. During this time I have been interviewing geneticists, networking with some major league all stars in the fields of nutrigenomics, personalized medicine and pharmacogenomics. So I ask for all of your forgiveness.

First let me state that it has been a great little breather that has got me re-invigorated to keep up the work of a Gene Sherpa.

Second, let me tell you how great it is to live in an age where the work which giants in the fields of medicine and genetics can now be applied broadly to medicine. But, with that benefit comes the danger of charlatans and hucksters.

This is why we need more Gene Sherpas. I am now putting out a plea to all of those who wish to harness genetics for health and longevity, those who wish to have science behind their clinical decision making, those who have a keen business sense and the ethics to make you shudder when you see what is being sold, those who wish to learn more about the future of genetic and medicine.....please email me and we will collaborate and create wonderful things to protect our patients, friend and families from the onslaught of false claims, dummied up studies and infomercials which will soon spring up all over the place.

Lastly I would like to direct your attention to the Institute of Medicine's (IOM) Report called "Nutrigenomics and Beyond: Informing the Future-Workshop Summary" I have spent a significant amount of my time reviewing it and trying to glean what it spells out.

A little about the IOM. It was establish in 1970 to attract elite physicians and scientists to examine national policies regarding health of the public. It issues statements all the time including those on direct to consumer testing.

The report summarized states that the science is not quite there....In addition there is much hype but also much hope. Dr Fineberg, President of the IOM closes with this statement.

"IS it possible that over time we can identify what ultimately must be the common biological pathways through which all determinants of disease or health must ultimately exercise their effect?.......Is it not possible that nutrition science -bridging as it does, everything from human behaviour, cultural values, all the way through to nutrigenomics and metabolomics and so on--might not be the crossroads for such a grand unification theory for health and disease"

The Sherpa Says: Once again, Nutrigenomics is not ready for prime time, otherwise Dr Fineberg would have said "Nutrition science is the grand unification theory" Another scientist stated that "Nutrigenomics is a in a very fragile paradigm...there are very few success stories" So please, tread lightly when someone sells you a diet based on blood type, body shape, or genetics......

Why Can't We Be Friends?

A recent study in the New England Journal of medicine implicated a gene called FTO (Fatso) in increased risk of obesity. If you had one copy, then you had a 33% increased risk of being obese. 2 copies? 67% increased risk. On average people with FTO weighed 7 pounds more.

It is true that we know of some increased risk due to genetics. However, a study published this week in the NEJM suggests perhaps your friends may play a larger role than your genes.

In this study, if you listed someone as your friend, and your friend became obese during the time they were studied, then your risk of becoming obese would be 171%. Much greater than the risk of carrying 2 copies of FTO.

What about the 6 degrees of separation effect? Wht if it was a friend of a friend? Well they found that the increased risk was less than that of FTO's effect. However, there still was increased risk.

The Sherpa Says: This study was performed on the famed Framingham Heart Study offspring. They attempted to control environment by evaluating neighbors. It does turn out that there is no relation between neighbors and obesity.....Unless they are friends...This tells us that social networking is an indicator of risk of disease. Intuitively this makes sense. Smokers hang together, as do illicit drug users, and perhaps as this study shows over-eaters. Why can't we be friends? Because you are fat.

WBUR posts on coumadin and Personalized Medicine!

Despite the heavy Boston accent,

On WBUR Carol's worries regarding Coumadin and Personalized Medicine hit home to millions of patients everywhere. This is an excellent example of the press' coverage of my specialty. Dr Sam Goldhaber a physician at Mass General talks about the promise of pharmacogenomic testing in blood thinning and avoidance of its horrible side effects.

Lastly they interview the Pope of Personalized Medicine

Francis says "Is this the scenario we want personalized medicine to enter?"
"The public thinks that this is snake oil (i.e. Direct to consumer testing and nutrigenomics)"

In addition Dr Collins talks again about the 2 Betty's and the potential to miss diagnose and have horrific outcomes.

The Sherpa Says: "Save Betty!!!" We must take the time to educate everyone about the promise and pitfalls of personalized medicine. In My Humble Opinion, the only thing to move physcians will be the slew of lawsuits that happen after we publicize our great outcomes at Helix Health of Connecticut.

Harvard Honoring the Sherpa!

Today I was asked to be on the faculty of Harvard's famous Continuing Medical Education conference in the Genetic Basis of Adult Disease. I am extremely honored to be a part of this distinguished faculty. This year's conference will be held October 12-14th. The last conference topics and website are still up and I am certain the new one will be shortly. I highly recommend it for all physicians looking to become Sherpas or at least to stay up with the breakneck pace of genetic discovery in medicine. Several topics include:

• Genetic Causes of Heart Failure
• Genetics of Lipid Disorders
• Genetics of Cardiovascular Disease
• Genetics of Common Psychiatric Diagnoses
• Genetics, Lung Cancer and Treatment Responses
• Genetics of Gastro-Intestinal Diseases
• Barriers to the collection and use of the Family Health History in Primary Care

So who should attend this great conference?

Internal Medicine Docs
Family Physicians
Genetic Counselors
Registered Nurses
Nurse Practitioners
Physician Assistants

I was at the conference last year and am excited to be behind the podium this year. Please mark your calendars!!!!

Personalized Medicine. Coming To A Hospital Near You!

The Houston Business Journal today reports on a ground breaking ceremony for Baylor College of Medicine.

"The soon-to-be Baylor Clinic and Hospital will be constructed at Old Spanish Trail and Cambridge Street in the Texas Medical Center area.

The campus will include an adult hospital, outpatient clinics, faculty offices and research space. The fully integrated health care facility, which will focus on personalized, gene-based medicine, will be open for business in 2010.
The Houston-based school also said its "Best Minds, Best Medicine" fundraising campaign is nearly half way to its $1 billion goal for clinical, research and education projects."

Baylor is best known in genetics circle as the place you send your CMA/CGHs. Personally, this is a great accomplishment. They now join the ranks of TGen, Mount Sinai, Duke, Mayo, Michigan State and Harvard in planning and implementing "Personalized Medicine Departments/Hospitals"

The problem I see is: Whom will talk with the primary care physicians in a language they can understand? Surely these patients will get genetic guided therapies and hopefully get some excellent counseling, but will the PMD have the knowledge to understand what was done? What about the patient. Will there be an educational program directed at clinic physicians? Where do non-clinic patients get their care? Will the summary reports be at a level the PMD can digest?

The Gene Sherpa Says: All this planning is great, but can we have something Right NOW?

Archon X-Prize Here We Come

This week in the Proceedings of the National Academy of Science an article entitled:
"Single-molecule mass spectrometry in solution using a solitary nanopore" was published.

Why is this mouthful of words important? Well, the future of genetic testing and sequencing is going to change and this is the likely direction. This pore, created by a bacteria (Staph Aureus) is only 1.5 nanometers. For appreciation, the human hair is 10,000 nanometers. What I think is ironic is that the enzyme used to create the pore actually gives staph its ability to really make us humans sick. The technique used is remarkable...I don't know if anyone has seen a tandem mass spec before. But it usually takes up the size of a lab table. This procedure could actually be accomplished on a microchip!!! This study is a proof of concept study done in Ohio and Brazil which demonstrates the fidelity of molecule size prediction. I am sure there will be more to follow.

In addition Harvard has gotten into the game of nanopore sequencing and will likely be the world leader. But this is no surpirse. They have been in this nanopore game since the early 2000s (did I just say that?) The rough estimate for launch in this project has just gone from 7 years to 3.

The biggest problem clinicians have with genetic testing is it often takes too long with some of the quickest results taking longer than 6 hours. Nanopore sequencing could give answers in less than 2 hours. This would allow a physician to dose medicines, change treatments, identify disease in a much more reasonable window of time.

Do I see nanopore sequencing being used in the ED? Not quite yet, but the pharmacogenomic implications for personalized medicine are huge!!!!

Thanks Jason for putting this on the Radar Screen back in March.

Genes for Heart Attack Risk/Prostate Cancer Risk

This week in the American Journal of Human Genetics 2 articles about genetic risk for heart attack are published. The findings raise hope of future therapeutic targets and identification of risks. The first study implicates the KALRN gene and an intronic(noncoding) SNP. This polymorphism(change in a gene) was found in almost all Caucasians with early heart attack. What does this mean? Very little so far. The results need to be replicated... But more importantly this gene operates in a totally different system than cholesterol in creating atherosclerotic plaques! The second study is more limited in scope and is less important for pan-ethnicity and only applies to French Canadians.

The news is just as exciting for African Americans as new studies implicated and corroborate other findings that a gene polymorphism could be responsible for up to 2/3rds of prostate cancer in this ethnic group. This set of data may lead to early detection or even prevention. This is the goal of all Personalized Medicine specialists....including myself!