Monday, August 31, 2009

National Academies and the IOM


Today and Sept. 1 the National Research Council and Institute of Medicine will hold a symposium to explore the health, policy, and ethical implications of direct-to-consumer genetic testing

AUDIO WEBCAST: Morning sessions on Aug. 31 -- covering the history and likely evolution of direct-to-consumer genetic testing, as well as the regulatory framework -- will be available via live audio webcast at http://national-academies.org.

Don't miss this. I am listening to Muin Khoury right now.

BTW, the best question was just asked. "Do you think you are practicing medicine and if no, explain why not?"

That is the crux of this whole DTC field. I have always thought, they are.......

The Sherpa Says: I will cover this and the NIH conference over the week.

Thursday, August 27, 2009

JAMA not so surprising, DTC genomics neither.

Ok,
Let's add fuel to this debate. Pharmacogenomic testing is CLEARLY a clinical laboratory test.
Seriously. In what world would this testing be used for anyting OTHER than the adjustment of medication?

You may be saying "But what about caffeine metabolism with CYP1A2?"

Ok, caffeine IS a drug, but it is available everywhere, so why shouldn't the people be allowed to have this test. Ok fair enough. But Theophylline is a drug which ALSO is covered by 1A2 and is NOT widely available.......

So here are my questions.

Should we regulate a test which COULD be used clinically?

What if there might be harm from using the test?

Should we regulate a test which has no purpose OTHER than clinical use which is being used for "Fun"?

What if there might be harm from improper interpretation and use of the test?

These are the questions which the government should ask itself. Why in the world is a BRCA test "for Fun"?

Why too is a CYP2C19 test which shows response to a medication and IS FDA approved in a certain type of kit not being regulated when it is a DTC test?

Does this make any sense to you?

So when one of these companies is playing on how they have CYP2C19 testing available in their "research" I wonder why in the hell, this non-IRB approved research is not considered clinical/medical???

Valid research like that in JAMA this week shows the real use of CYP2C19 testing in patients who are on Plavix.......

IN what world is that NOT a MEDICAL TEST? JUST LIKE BRCA1/2 MUTATIONS!!!

Tell me? Please. I am not the smartest guy on the planet, but you have gotta see what I see here.

There needs to be one of 2 things here. Either these DTC companies STOP offering clinical tests or they announce PLAINLY and Forcefully on their websites, marketing material, blogs, tweets, Blimps, Zeppelins, FU@k!ng cars, etc

"These tests SHOULD NEVER BE USED IN CONJUNCTION with medical care".

Otherwise, there needs to be a moratorium and analysis of what in the hell is going on here. I await the first lawsuit against the government for not protecting the public, because G-D knows the DTC people will run away and claim no responsibility in the harm caused by their deceptive marketing.

I am very disappointed that when the survey came out about the physicians inappropriately using these tests that the DTC companies didn't make public that the tests are NOT to be used for medical care.

What do you say?

The Sherpa Says: A little responsibility from a lady who wanted to dope up her child and her billionaire hubby would be nice to have don't you think?

Tuesday, August 25, 2009

NIH Conference and Lightning Bolts!

Did anyone get to see the first day of the NIH Conference on the State of the Science in Family History taking? I just found out Tom Morgan was on the panel. Tom was the clinical fellow at Yale while I was a medical student. What I couldn't figure out was how many of those board members were Internists.......

That being said, you can watch day 2 at 830 AM EST

I want to get back to my comment from yesterday. The proponents of not having a heavy hand with these "disruptive genomic technologies" (Personally I don't see how technology from the late 90s is disruptive, their words, not mine) have always couched this rationale by stating ultimately there was not a lot of real harm to be done by releasing these weak risk results directly to the consumer.

I have to agree, while scary and scientific, they were more likely to walk away confused. There was a small risk of harm coming from this information. Which I was slightly concerned about.

But my biggest concern was, what doctors would do with this information. I really didn't want these tests out there because often a clinician is not as nuanced with genetic tests and they often don't understand the difference between a useful and not useful test.

They, like most of the public, view genes as discrete pieces of heritable material. Thus genetic reductionism "The Gene for Ankylosing Spondylitis=HLAB27" for DVT, MTHFR, etc. etc. I think you get my point. If you have any questions, you can just look at all the inappropriate HFE testing that went on for years and still goes on......

So when this report in Genetics in Medicine came out, I gasped when I read it.

What interventions were done? What care was changed by these doctors?
It is not so much that there were only a few doctors who had been engaged by patients, it was what they did WHEN engaged.

If this technology will become more widespread, what will the doctors do? I don't think it wise that we are releasing this testing into the wild where physicians can actually harm patients. The potential in this space is very, very scary. I can only imagine what resources will get over utilized or under utilized.

Why should the public be punished for physician shortcomings? I am not certain, but which punishment is worse? Lack of access to your genome OR lack of access to someone qualified to understand what the hell it means or doesn't mean.

There is a definite threat to public safety here.

How can we fix it? I think the first step is to all have the DTC companies be mandated to place labels like the cigarette makers stating that this testing "IS NOT TO BE USED FOR MEDICAL DECISION MAKING"

Secondly, I don't think marketing with the intention of inferring that it can be used medically is doing anyone any favors, and I would say that if you were harmed by the doctor relying on a nonmedical test you should sue the doctor. Which is precisely the position DTC Genomics loves to be in.

It is NOT THEIR BAD! But when you look at the marketing how can you not feel it IS THEIR BAD.

Now that we have some evidence that physicians are acting on clinically useless information, we have to protect those who could be harmed.

END OF STORY.

The Sherpa Says: These tests should have a moratorium on the DTC genetic testing until we can educate physicians and other healthcare practitioners. It's not like these companies are making record profits or anything, hell one went belly up just the other day. Isn't public health about protecting the public's health?

Monday, August 24, 2009

PHG Foundation and my point.


A long time ago I had a post entitled "Beware Doctors Bearing Genetic Tests" back in April of 2007. It was an interesting post where I point out that this wonderful GI doctor who was IVY league trained completely hashed genetic testing for HNPCC.

I went on to explain the shortcomings with Internists in interpreting APC testing for familial adenomatoid polyposis coli. 1 in 3 misinterpret tests.....Wait till you see the DTC interpretation!

Everyone who gets all in a huff when I say that these DTC genetic tests should be regulated. But I am here to say there is a good reason for it, and it has nothing to do with the people getting the tests.......There is now threat of public harm.....

But first let me explain my frustration. Saturday I was on Twitter and Daniel MacArthur and I had a conversation, which he lead off by saying:

"@helixhealthct Just shows how arbitrary most medical care is anyway; not like it'll change the outcomes much.Which was in response to a PHG report on an article published in Genetic In Medicine [Kolor K et al. (2009) Genet Med 11(8):595].

Among the 1880 physicians sampled, 42% were aware of the tests(DTC Genetic tests) and, over the past year, 15% had at least one patient bring the results of such a test to them for discussion. Interestingly, of this latter group, 75% (212 physicians) indicated that the results had changed some aspect of their patient’s care.

Holy Crap! Really? 75% changed the care?

So it had me begging several questions.

1. Did the physician read the Terms of Service for the DTC test? "Not to be used to make medical decisions"

2. Did the patient read the Terms of Service when they brought this test to the physician.

3. How is the physician supposed to know that this is not a clinically validated genetic test?

4. How is the busy clinician to differentiate this test from other clinically valid tests?

5. Why did the patient bring the test to the doctor? Was it due to DTC marketing efforts?

I was pissed at Daniel. How dare he say what we as physicians do changes no health outcomes!

In some instances he may be right. In others I wondered how complaints may actually be neglected based on this "genetic test"

Did these 212 doctors know something I don't about the utility of this DTC testing?

I doubt it.

I am seriously concerned that the 3/4ths of the 18% had actually changed care based on a non-clinical based test. That, to me is Scary AS HELL!!!!!

Think on this for a second.....How many of these doctors will ignore chest pain complaints based on a low genetic risk?

Now think on this. How many doctors will unnecessarily order stress tests for patients who have no complaints and are "High Risk"?????

Either way you slice it, 3/4 of these doctors are acting incorrectly, or at least not according to evidence base.

This survey proved one thing to me. Doctors have no F^CK!n& Clue what they are doing with genomics!

Why should these tests be regulated?

1. Patients aren't following the terms of service, likely due to deceptive advertising

2. Doctors can pose a threat based on inaccurately using these tests

3. Over use of resources could end up being a big problem because of these tests.

4. The potential for public harm has now gone from silly consumer, to trained medical professional inflicting damage.......

The Sherpa Says: Like I said, beware doctors bearing genetic tests........and patients too.

Thursday, August 20, 2009

Tarceva, Iressa and EGFR screening.

No Duh.

Can't believe I missed this yesterday. In the NEJM there is an article talking about Tarceva therapy (Very Expensive) and that it targets lung cancers that have EGFR mutations. So if you don't have those mutations, why would we expect you to benefit from these expensive drugs first line?

Wha?

Ok let me explain.

Read this first

Iressa and Tarceva are EGFR tyrosine kinase inhibitors, which interfere with cancer cells' ability to multiply. People with certain mutations respond. In fact, I heard Mike Murray talk about the Lazarus response to Iressa which was published back in 2004

We tried a novel treatment and found that in certain tumor types, those with EGFR mutations, deletions in exon 19 and L858R primarily had better response to treatment with these TK EGFR inhibitors.

So, now we have what is a prospective trial assessing the utility of genotyping for therapy. This trial took 3 years to complete.

In addition, there was another study published which showed a head to head trial of toxic IV chemo versus targeted molecular therapy in a group highly likely to have EGFR mutations. Guess what they found? Yup, better outcomes with EGFR TK inhibitors and best outcomes in those with EGFR mutations......

They found:
Gefitinib is superior to carboplatin–paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib.

The data are stunning. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin–paclitaxel.

But the subgroup findings are where this personalized medicine approach had the most teeth with again, a very, very expensive drug.

In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001),> the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin–paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001).

This will be music to the comparative effectiveness gurus ears. Have an expensive drug? Test first to see if it works. Then give it........

Brilliant.

The Sherpa Says: We need more studies like this in many, many more fields. They will come, I am certain of that, which is why I am where I am.........

Where from here?


This is the question I am asked so often.

1. We have the steady progress towards cheap genomes.
2. We have the biggest supporter of personalized medicine running the NIH
3. We have "some" clinical awareness of personalized medicine
4. We have the government aware of the shenanigans of some unscrupulous DTC advertising, etc
5. We have several milemarkers under our belts with genome science..... We are moving in the "right" direction, but where do we go from here

There are several areas we need to investigate. I would like to sum a few of them, both basic science and clinical.
Basic Science first.

1. We need to understand precisely how gene regulation occurs in the face of certain common environmental exposures. Trans Fat, Tobacco Smoke, Alcohol, Stress. Is it RNA? Is it Methylation? What precisely is it? Maybe it is all of them and more. But the quicker we understand that, the quicker we can look for signs of these ill effects.....and stop them molecularly

2. We need a good CNV/Indel etc database. Toronto sure, I have heard that. But seriously. We need this and we need it now. Give me Normals, Give me abnormals, Give me phenotypes......This is a very key missing piece of the puzzle which neds to be completed in the next 2 years

3. Junk DNA investigation. This will come once we have a database like the one in Iceland......I am certain this will come. I think that next to nuclear fission, the investigation into the "junk dna" will prove to be one of the most fruitful works of governmental science. Yes, you can quote me on that one.

4. Systems biology. This is one of those areas where we will eventually realize the Greeks were right with phlegmatic systems vs bilious systems.......


Now onto the top 3 Clinical Science targets

1. A complete revamping of the current risk stratification system. What do I mean? We need to develop a process for efficiently introducing genotypic risks into current clinical risk stratification. We need to evaluate the with and without and change in AUC......
1b. We need to evaluate the role of integrating family history in some risk stratification models. I know Dr.
Khoury/Scheuner et.al are working on these things, but it sure would be nice to have odds ratios and RRs/HRs for adverse drug outcomes, common autoimmune disease risks, COPD, Alcoholism, Suicide, etc. types based on fam hx integrated with current models.

2. Pharmacogenomics......end of story, we need more science here for more drugs. There is not nearly enough clinical study weight on outcomes. I understand why from the Pharma end, but the US government cannot ignore its utility, especially with the pain they feel from Medicare part D
This area has tremendous promise, but has not seen the will from genetics departments, mine looked at my cross eyed when I wanted to do a PGx study. There has to be a will in basic medical science departments like pharmacology and cell biology to understand the processes and polymorphism which really screw up a drug's effect.....or really enhance it. And there has to be a will in clinical departments to study the outcomes with different therapies based on genes.....

3. I want to know what behavioral outcomes are likely with knowledge of one's family history risk versus genome scan risk vs both together vs with no knowledge.

These are some low hanging fruit that could get accomplished and probably already are........


The Sherpa Says: These are not stretch targets, these are do-able things in the next 5 years or so. If we can accomplish most of these, we will be well on our way to evidence based personalized medicine, which is where we need to be........

Wednesday, August 19, 2009

Family History, State of the Science


The NIH/CDC is hosting a conference next week. I conference I wish I could go to, but alas, I will be DOING family histories on my patients that week.

The conference will be held at the NIH in Bethesda. This is an NIH state of the science conference about Family History and its usefulness.

I for one, am very glad that the government is trying to address this super important issue. It is beyond due for an evaluation.

Why?


With the cost of a genome going to drop to 5000 USD by the late fall (trust me), we will soon see another level of DTC and Clinical lab set offering the genome as a predictive tool.

There are several reasons that Family History beats a Genome (For Now)
1. Phenotypic data of family history represents complex interplay of genes and environment


There is no way that a simple genome will be able to give us the story of how a human will develop. That is predicted by environment and genes, which are successfully covered by.....
A family history.

2. 5000 USD is still more than what it costs to obtain a family history.

By the time the software tools are released, we will see that social networking and the internet will transform the costs of family history next to nothing. Which is still a long way to go for the genome scans.

3. We have no clue what most of the genome data means.

Indels or CNVs or SNPs, we have no freaking clue what most mean, we do know what a heart attack at 40 means.......


4. Even if we had everyone's genome scans, we would still need phenotypic data and pedigrees.

What's the one thing we do when we have an intellectually delayed child with an abnormal CMA/CGH? We test the parents. Looking for THEIR phenotypes to make sense of the genome mess.

Look, people always give me reasons why the genome is important and a family history is useless.
I've heard them.


-"We don't speak with that side of the family"
-"My father lived with his uncle, because his father died (secretly running the empire as Darth Vader)"
-"I was adopted by Bail Organa, only to find out I have a lost twin brother"

There is one thing that will always be certain over time, there will be some screwed up family dynamics making it difficult (BUT NOT IMPOSSIBLE) to obtain an accurate family history.

That being said, it is still often useful to capture those who you can. And still less expensive.

I look forward to the briefings from this conference, and Muin, if you are listening, I would love to have the link to the webcasts.... Oh wait, they have that too! Sweet.

If you can't be there, you can get the information you seek!


Once again, we need a state of the science on genome prediction, not a consensus statement a real eval of the state of the science. When placed side by side with the state of the science for a family history, we will soon see why family history is the preferred screening tool and will likely to continue that way, perhaps in conjunction with a genome scan, but genomes will NEVER replace family history.

The Sherpa Says: The press better be at this conference and report on Family History. And to the founders of Geni.com, you missed on this one when Tindall presented to you. Or maybe you just are going to steal the idea.........

Tuesday, August 18, 2009

Finally Francis!


This is exactly what we have all been waiting for. Someone, one of us, one like us who has now gotten a hold of the National Institutes of Health. Thank the Lord!

For those atheists among you, I want to assuage your fears. Christians can perform great science too.
Francis has and will continue to. I am so very happy for this pretty amazing occurrence.

From the WSJ.

Collins, 59 years old, served as director of the NIH’s National Human Genome Research Institute from 1993 to 2008 and oversaw the international collaboration known as the Human Genome Project. That project, completed in 2003, determined the sequence of the three billion base pairs that make up human DNA.

Moreover, it spurred the field of genomics and the dream to personalize medicine for individuals based on their genes. His nomination is being applauded by organizations like the American Heart Association and Personalized Medicine Coalition, who laud his “landmark discoveries of disease genes.”


Tell me, how many winners of the Presidential Medal of Freedom have led the NIH?

Francis had this vision from the very beginning, merge genetics with environment. Nature or Nurture?

Yes, and that is why he is an ideal NIH director. He will bring comparative effectiveness research into the personalized medicine realm and has the insight to understand the answer can often be "Both"

A long time supporter of what we only saw as obvious, yet others not so much, his wisdom and insight only stands to benefit the United States tremendously.

Bravo Francis!


The Sherpa Says: Whatever your opinions on genetics, genomics, medicine, you have to admit Francis is one hell of a great leader.

Tuesday, August 11, 2009

Something off my chest........Health care will never be fixed by Lawyers


I rant and rave about genomics and about hyping of genetic tests but today I have a bigger issue. That issue is plain and simple.


Healthcare is FCUk3D up.



I run a successful personalized medicine practice, just recently we started taking health insurance. The demands from handling billing and copays from insurers AND medicaid has not been that cumbersome. Why? We only see 10 patients per doctor per day.

When you start seeing more than that it creates all sorts of problems.

Like manpower requirements that start to exceed 100-200k per doctor.......

If you have less doctors for more patients, the equation is simple.

Rationing of physician care.

That is what will happen when you cut 400 million dollars of Medicare money.
Oh wait, I mean 500 BILLION dollars......

Do I think that the Lawyer serving in congress will ever solve those problems?
No.
Do I think that the very few doctors in congress will fix this problem?
No.

But trust me, there are way more lawyers than doctors in Congress, so I am extremely doubtful.
No Offense GenomicsLawyer.......


Why?

They are not the people who are experiencing the problems.

Maybe the doctors were, but they aren't now.


The solution will come from doctors/nurses/patients who are involved in the system already...... currently.......

To think otherwise is foolish.
And to drown out the protesters, intimidate them and hide from town halls is also foolish.


Both parties in this argument are dead wrong.

They are having the wrong argument.


The average primary care doctor gets paid about the same as they did 10 years ago. Does that make sense?
Costs go up. Rent Goes up. Medical Supplies cost more. And insurance pays less and less, Including Medicare, who pays routinely 1/2 to 1/3 of what private insurers pay.

As a doctor, Don't like what you get paid? Switch Insurers.
But you won't be able to do that under a universal plan.

As a patient? Don't like what your insurance paid for? Switch insurers. Pretty simple, unless of course you have preexisting conditions.......

The system is a mess, not because of what we pay doctors or hospitals or whoever.

The system is a mess because there are a whole lot of sick people out there......More sick people than healthcare practitioners equals shortage of attention.

Shortage of attention leads to worse care and more labs and more procedures. Shortage of attention leads to increased malpractice costs, risks and fears......
Want to fix the system?

Encourage more doctors to go into primary care, make their liability risks less, create technology so that they can "fire" their overhead this will create increased revenues for doctors without raising pay.


But please, don't ration care because we are too busy and too risk averse to do it on our own.

Enable the professionals to do it by giving them time to think about their patients...... This system will never get fixed by lawyers.......never.

Medicine is a thinking man/woman's game, not a sweatshop.....why ask us to run sweatshops? The American people deserve better than that......

The Sherpa Says: What good is personalized medicine if the doctor can't take the time to personalize it for the patients??? You tell me.