Some Confusion Exists

I have a great comment string going on with Daniel MacArthur over at his blog Genetic Future

I think there is some confusion going on here and I place blame on just about everyone in this space who has a mouthpiece.......

But mainly I lay blame on the marketing teams for the Direct to Consumer Genomics companies.

These companies have an interest in making you "think" that their products have some particular health relevance.

Otherwise, no one in their right mind would waste their time with these tests.......Other than the HUGE field of ancestry buffs like Blaine Bettinger J.D. (woohoo) We need clarity here.

From Daniel- "The American College of Medical Genetics is saying "Genetic tests of individuals or families for the presence of or susceptibility to disease are medical tests."

The fine print says:

"This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen"

Meaning

"The judgement of what constitutes an inclusive test is left up to the physician"

In my opinion, there are Green tests, Yellow Tests and Red Tests. I think Ryan Phelan sized this up pretty eloquently in 2007 at a conference I spoke at with her.

Red means - Stop, does this test need analytic/clinical utility/validity? Yes, Go ahead and regulate, these are clinically validated/used clinically for a long time, tests which have a use in medicine. If this test is claiming to do so but does not, then this too should be a cause of regulation.

Yellow means - Well, this could be used but maybe hasn't yet. I think of Age Related Macular Degeneration testing. They could have clinical applicability and haven't been put to use yet. This category may also include low odds ratio common SNPs here which indicate risk FOR disease.

You should have some caution when selling/regulating these tests. The biggest problem is that with evidence evolving over time the low ORs may actually be overturned or fall into the Red category.

They key point is what the test claims to do here.

Does it claim to tell you a risk for a disease via algorithm etc.?

If yes, then it becomes a Red test.

If it says in huge disclaimers, this test DOES NOT PREDICT DISEASE RISK, in plain and clear writing on every piece of its marketing then Yellow tests stay Yellow.

Green Tests - Have absolutely nothing to do with a person's health. These tests do not need medical regulations. Ancestry could be here. Eye color/ear wax/height.

But the moment it is used for medicine or medical procedures (PGD for these things, scary but possible) it then becomes a Red test.

ACMG is talking about Red tests. It is also saying, if you as a clinician think a Yellow test is actually a Red test, then it is a Red test.

Which I agree is confusing. But ACMG is not the US or State Governments. Nor is it the UK or anywhere else's government......It is a professional organization.

My take is simple. If there is a risk for public harm, the government should protect its citizens from that harm in a reasonable manner. I emphasize, reasonable manner. What Techies in the Silicon Valley view as unreasonable regulation may very well be extremely reasonable in the view of physicians and hospitals......

There is no reason to get all crazy here. The New York Times is right, until the government or state governments step in to protect the citizens of risk, it IS Buyer Beware when it comes to genetic tests.....

In my mind, genetic tests need to prove their worth in the field of medicine. They do this by medical science and clinical science studies.

Without these, they are useless noise.

So, should you be able to buy useless noise?

Go ahead.

But the moment the noise whispers in your ear "PSSST, I can tell you your risk for diabetes for 50 dollars" Its A$$ should be regulated.

I hope that clears things up. The problem here is that you have a company selling you noise mixed with clinically valid tests. They are the first company whose A$$ should be told to hold up and split the products.

Then you have a company selling you noise all the while "inferring" it is actually predictive and useful in medicine by getting Doctors to use it in medicine should also be regulated.

Blame Marketers and Spin Men, just like "Thank You for Smoking"

The Sherpa Says: If you apply the Red, Yellow, Green interpretation scale you will soon understand why all the confusion exists. And how that confusion can be cleared up.

National Academies skeptical at Best.

If you would like to watch the IOM conference you can check out day one here
My take away from the first day.

"Do you guys (DTC) know what you are doing?"

"I wonder what kind of research and the quality you can provide?"

"I can't believe you aren't regulated already."

I think there are some really big issues here and there is some confusion.
Questions that remain to be answered..........
1. "Will these companies sell the customer/patient DNA/data?"
2. "Are these companies practicing medicine?"
3. "How do we quantify personal utility?"
4. "Will regulation really kill these companies?"
5. "What rigors and hoops will be required for these companies with research?"
6. "What will the GAO find about today's DTC companies?"

The best thing these companies have done is raise the need for answers and refined regulations.

The worst thing these companies have done is put customers/patients at risk for
1. genetic theft
2. harm via untrained physician
3. false predictions and false hopes
4. 3rd party harm

These companies should be behaving more responsibly, it is sad that they continue to market deceptively. It is also sad that they have not more carefully thought out their research aims. They clearly don't care about the chain of trust.

The Sherpa Says: I think the IOM and National Academies are skeptical at best. Which is the right attitude IMHO. DTC has a lot to prove and it hasn't done anything to do that yet.

NIH Draft Consensus Statement on Family History

The NIH conference on Family History came and went.

What were we left with?

A Consensus Statement.

What is the crux of it?

"The panel recognized that family history has an important role in the practice of medicine and may motivate positive lifestyle changes, enhance individual empowerment, and influence clinical interventions. The panel found that it is unclear how this information can be effectively gathered and used in the primary care setting for common diseases."


Well ladies and gentlemen. I can give you all sorts of anecdotal evidence. That being said, we are evidence driven creatures, so I suggest you give me a call and we set up studies in Primary Care practices with different family history tools.

Things such as the "SCREEN" screen versus a detailed 3 generation pedigree versus 1st generation.

It is pretty easy and inexpensive to set these studies up if you use current technologies.

What else did the panel say?

"For a systematically collected family history for common diseases to become an evidence-based tool in primary care clinical settings, substantial additional research will be needed."

I agree, it is time we develop these tools as multifactorial shotguns which hit lots of targets. This IS what DTC is arguing that there puny little scans do. Without evidence Family History champions like myself run the risk of sounding like the marketing hacks out in Silicon Valley and PR firms like NYC.

That being said there are some evidence tools where Family History helps clinical classification. I think specifically of the Reynolds Risk and how it beat the Framingham

We should attack this one precisely the same way. Start by each individual risk calculator ADD family history and see what it does.

Then do a cohort study of practices which routinely perform 3 generation pedigrees and see how the incidence of diseases like diabetes, HTN and MI shake out.

That could be done over 5-10 years. Not a long wait to get some great evidence, if you ask me.

The Sherpa Says: The evidence may be weak for Family History as a Poly-Tool. But as a clinical marker in certain diseases it is ESSENTIAL.

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.2:46 AM Aug 22nd from TweetDeck in reply to helixhealthct"

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.

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.........

The Doctors are OK with this?

Yesterday in "The Times" a nice article was posted about the revolutionary way in which doctors will receive education about CLINICAL genetics, this time it is from NonClinical Scientists......

At the tune of 4.5 Million British Pounds!

This may work with CGCs, oh wait, they don't do much of anything in the UK system.

What about clinical geneticists?
Who?

Ok, scientists it is......

So I can just see it now.

A busy NHS practice, patients out the door, flu shot here, flu shot there and in rolls the "Scientist"

Clinician-"Oh hi, you must be the genetics guy sent from the government. Have a seat, I'll be right with you"

4 hours later

Scientist-Sitting nicely, waiting

Clinician-"Ok, lets chat over lunch"

Scientist-"Glad to be here, Let's talk about what a chromosome is"

Clinician-Scarfing down a sandwich "Ok, that was great, gotta go. I am double booked. See you in a few"

4 hours later

Scientist-Sitting Nicely, waiting

Clinician-"Sorry about that, I had a sickie and then the crazy lady....G-d where did the time go?"

Scientist-"See you tomorrow?"

Clinician-"You bet, I feel better prepared already"

As nice as this one is, I have already tried it with a clinical geneticist who actually can create billable events and see patients........ I am not so certain that going to the doctors will help as much as being on their iPhone or on a hotline.......

The Sherpa Says: When climbing the mountain for the first time, it is best to chat with someone who has been there before.....Muin and Franics, I hope you are paying attention here.

Crazy Friday, Awesome Call, Tru Blocks the Sherpa

I was amazed the first time I met Francis Collins, longtime a hero of mine, Francis was gracious and kind when I met him. I also share a common bond with him. Francis' Intern at UNC was a guy by the name of Jim Sabetta, one of my instructors....


That being said, before I started HH, I watched webcast after webcast of the SACGHS. This was 2005 and 2006 I'm talking about. I did it because it was research. But I saw a guy on there who inspired me, who had such a sense of reason that the whole group respected. His name is Muin Khoury.....and I just met him Friday!

It turns out we also have people in common. But more importantly, we have a healthy respect for family history in common...... This guy and his team at the CDC have been researching Family History tools and the state of the science of family history pretty aggressively. This team is a heavyweight in the field and I am blown away by what they are doing.

Why?

It is the cheapest whole genome, phenome, metabolome scan we have today. The best part is that it covers multiple people with just one take!


They are actually researching the role effect of family history on behaviors and diseases! Something which NEEDS to be done, just like it does for SNP sandcans. Except of course, Family History costs nothing.....and has some good data already! Their FamilyHealthware methods have just been released! I will cover this further in depth in another post....

I am a little ad that I didn't get invited to GAPPnet, but am very excited to see what this conference in August on the state of the science in family history will bring.....More on this later


"Update" of TruGenetics.

While I WAS optimistic that a physician was at the helm of this company, I was reminded once again that we can be shady as well. It turns out, Dan Vorhaus AKA Genomicslawyer, read the fine print of the consent form. HT Daniel MacArthur too! It turns out Free is not so Free. Its now out that if you consent, you give the green light to TruGenetics sharing your results with companies and that your data goes into a database for "research" OK, that's strike one and strike 2......


The high heater came when I was following the COO of TruGenetics on Twitter......I challenged some of thet things he had said, like I do @Lindaavey @23andMx @Navi......But unlike those companies that stand up and defend themselves and agree to spirited debate with me.......@Achamedian the COO of TruGenetics "blocked" me!

Strike three TruGenetics.

You are out! I am deeply disappointed that you wouldn't debate me. It shows your TRU-Colors, to run and hide and also hide the fact that you are taking people's DNA for compensation of about 299 USD...... Not impressive. Nor is your call rate and error rate of 5%...... I guess you get what you pay for, when of course that product isn't hyped by large PR firms...


The Sherpa Says: Don't sign up for TruGenetics and if you do, at least you now know that they have a shady COO who runs from the questions and from the Sherpa!