Monday, May 24, 2010

DTC Genomics reviewed in Genetics in Medicine

I just received the May issue of Genetics in Medicine, only 24 days late. But it caught my attention for several reasons.

1. The issue is covering Adult Topics almost exclusively this month

Granted this article was a single author MBA, it was notable at the work she must have put in to this review.


1st she did an extensive analysis of the service 23andMe, Navigenics, deCodeMe, Gene Essence. She assembled the 20 multigenically evaluated conditions, reviewed website data, and deep dove into the studies, average pop lifetime risk, loci, genes, SNPs, Quant risk assessment, and methodologies.

That sounds very similar to what the FDA is requesting to do. In their case with non publically available data as well.

2nd she did a complete locus analysis which is available here.


Analysis 1.
213 conditions covered by DTCG companies, with only 9 conditions covered by all identified companies. 15 addition covered by 4/5 companies.

Analysis 2:

Lifetime average risk values of the same populations.
It turns out that the companies provide different life time risks for the same disease in the same populations.

This is not a big deal to me if you wiggle 2-4 points. But some vary widely

Glaucoma 1% in Navigenics while it is 15 for deCodeme
Heart attack 42% for Navigenics and 21% for 23andMe in Men
Heart attack in women 25% in Navigenics while it is 7% at 23andMe
DVT 3 percent for Navigenics 12% for 23andMe

23andMe does not provide references for their lifetime risk data.

Heterogeneous SNPs and Loci Assessed

No big surprise here, it turns out each company has their own way to make a Big Mac, each has their own special sauce and pickles/onions and even their own sesame seed bun. Thus you get different SNP risks given to customers.

A total of 224 loci are covered 401 SNPs for the 20 multigenic conditions. Of the 224 loci, 115 are only covered by one company. 63 are reviewed by only 2 companies.

For 12 conditions covered by all 4 companies, only 9 SNPs were covered by all. These 9 SNPs represent ONLY 3% of the total SNPs covered by all 4 companies and 18% of all loci covered.

Heterogeneous quantitative risk assessment

Once again, different risk assessment methods rule the day at these companies. Just like if I were to use Reynold Risk instead of Framingham risk but at least I have some data to base my conclusion. We have none of that with the DTC company risk models......

He kept saying, It's My data. I kept saying. Fine, but the interpretation needs to be regulated.

I think we have a very decent reason why right here.

When you get a cholesterol of a blood pressure reading in the United States, you would hope the interpretation you receive is standardized in some way.

Further you hope at least the person giving you the interpretation of that data has some sort of licensing to assure quality and accuracy.

Unfortunately in this field there are many, many unknowns. This makes the risk prediction even less accurate. So it is no surprise these companies have widely variable assessments. But what does trouble me more, is the fact that they seem to not have done their homework with average lifetime risk populations.

That seems like they should be at least on the same page with this information. And why 23andMe has not listed reference articles for their quoted population risk is beyond me.

The Sherpa Says: Doctors go to medical school for 4 years, then go onto residency for 4-8 years and some do fellowship for another 2-5 years. And then we give risk assessment and diagnose and treat. Why do people forget that? Oh and we first operate under the principle of First Do No Harm. What doesn't Mr Goetz get about that?


Daniel said...

If we asked two doctors at random what the absolute lifetime risk of glaucoma was, what's the probability they would give the same answer? Even if they had time to read through the literature?

The fact that companies have different absolute risks down't necessarily mean they haven't done their homework; it may simply mean that the literature uses inconsistent definitions of the disease in question.

Eve Harris said...

This kept me awake until 2 am a few nights ago (your pissing contest, et al) I'm still reading Goetz and trying to understand him in context. I'm a supporter of so-called participatory medicine, but I'm not naive! When there's a profit motive and no oversight we're just asking for trouble. Thanks for speaking up

Steve Murphy MD said...


Exactly. Do we know what definition of a disease they are using? Further, is this medicine? You compared doctors with these companies in a very similar manner. Which means to me, in your mind they are doing the same thing. Is that true? Is this medicine?

Daniel said...


You may have noticed I've avoided your whole "is it medicine" question. It's because I think it's largely irrelevant; the question isn't whether DTC fits into some definition of medicine cooked up by protectionist clinicians, but whether it's likely to do harm to consumers. The evidence so far points to the answer there being negative.

In the absence of demonstrable harm, and the presence of some benefit to consumers (however marginal), the onus is clearly on the regulation proponents to prove their case. You are dismally failing to do so.

Steve Murphy MD said...

No Daniel,
You have avoided the argument because you know that I am correct. This is medicine/medical testing. In the US There are laws which already govern medical devices/labs/services. This is done to keep confidence in the medical field as well as ensure public safety.

That is why you are avoiding this debate. Harm or no harm is not the issue. Medicine or not is. I think you know the answer.

I am not gonna play in this harm game you guys and bioethicists want to play. That is not the issue. Medicine and services associated are regulated whether you like it or not. This is a medical service, they were the moment they did BRCA testing and PGx testing.

That is why the FDA is involved, because the government of the US thinks it is medicine too.

Steve Murphy MD said...

Lawyers and congress make the laws. Last time I checked, the US government has rarely had any physicians in it and instead is and has been largely dominated by lawyers. So stop using that inflammatory protectionist physician bullshit here. It is pure and utter garbage. Do you think any doctor wants a monopoly on "early adopters"? Even if they did, the government has next to no physician in it. So please stop yet another strawman attack. Do you hate doctors? I am beginning to think that a majority of people taking your stance do. Frankly, just wait till you need us. Then you won't be so harsh on us.

Keith Grimaldi said...

Daniel said "You may have noticed I've avoided your whole "is it medicine" question. It's because I think it's largely irrelevant"

Steve disagrees and says "Harm or no harm is not the issue. Medicine or not is... Medicine and services associated are regulated whether you like it or not"

Steve you say that these DTC genomics services need to be performed via medical practitioners, right?

Probably we can agree that DTC genomics include medical services and probably most will agree that this could benefit from some sort of oversight/regulation.

Certainly we can disagree though that just because they may be medical services means that they cannot be provided DTC. Just like many other medical items and services are. That's why the "is it medicine?" question is irrelevant and the "could it be harmful if delivered DTC?" question is relevant.

I don't think many in the debate are against some form of oversight - even at the extreme libertarian end. Regulation is not the big issue - extent of control is.

How can you say harm is not the issue? It's the most important issue throughout medicine and controls who does what. I can get some DTC medical advice from health websites, some medicines OTC from the supermarket. For some treatments I will need to see my GP. If I need major surgery my GP is not allowed to do it and needs to refer me to a specialist surgeon. Etc (until I need the specialist services of a priest...)

The decision on control is always based on harm vs. benefit. If all "medicine" required a medical doctor then the denial of direct access to medical information, medicines and services, DTC, would be a cause of great harm. Imagine if I had to go to a doctor before getting a plaster and antiseptic cream after cutting myself - instead I benefit from performing medicine and surgery on myself.

It's "First do no harm" not "First do medicine" isn't it?

Steve Murphy MD said...

The issue of harm is that currently there is little empiric evidence of harm. There is potential harm, but because so few people have done this DTCG testing we have no realized it yet.

Doctors do medicine, clinical labs do medical testing, medical device makers make medical devices.

Before we can apply current regulations we need to define what DTCG services are. Remember, Primum Non Nocere is medicine's pledge, not corporations like BP or 23andMe.

That is why we can't move forward until we define DTCG laboratory services. This is precisely where we get stuck in the logic.

Can corporations sell things that harm? Try cigarrettes, alcohol, twinkies, Big Macs. Shall I go on?

They are held to a different standard than medicine, which is why the sliding scale of harm allowance is seen.

If these companies went to doctors in the first place we Would have our answer. They did not, thus the conundrum that the FDA and Congress have to sort out.

Just because you say it's not medical, doesn't make it so.

Once we solve that issue, then we can address the Harm issue.

Keith Grimaldi said...

I didn't say it's not medical - it may be it may not be. But just because it may be does not mean it needs to go through doctors first. Why should it? Not all medicine goes through doctors either first or ever.

Doctors do medicine
Nurses do medicine
Pharmacists do medicine
Supermarket assistants do medicine
I do medicine

So what if genetic testing is medicine? It doesn't mean it cannot be DTC. It's not necessary to ban it all now while we decide if it's medicine or not.

It's really not difficult, or even a conundrum, it's very straightforward. Let's define it as genetic testing, look at the content of the service and look for potential harm and benefits in any aspects of it (ancestry, parentage, health, whatever). Look for evidence of harm as well (there are >100,000 who have done DTC testing by now, going back to before 23andme etc - no evidence of harm yet and given the number and passion of it's opponents I bet the lack of evidence is not for the want of trying to find it).

Let the FDA or whoever try "evidence based" debate and then apply the appropriate levels of oversight/control. Tobacco, alcohol, medicines, junk food - all are regulated to some extent and all are available DTC (but not all to all consumers).

Steve Murphy MD said...

I am not saying that ALL DTC needs to go DTMD. I have said that clinical testing should go through physicians.

I think that debate is best left up to each state. NYS says yes, NC says no, so there ya go.

But if this is Medical, it should receive the appropriate federal and state medical regulations as any other lab in that country/state would.

People have to stop putting this "Solely through medical doctors" strawman argument out there.

No one, I repeat, no one has said that all DTCG should be solely through MDs.

Should clinical test be ordered by clinicians? Probably, but as I said before, each state has a different take.

Daniel said...

Hi Steve,

Do you think any doctor wants a monopoly on "early adopters"?

Of course not. But they want to make sure they have unfettered market control once genomic medicine moves beyond the early adopter crowd.

Even if they did, the government has next to no physician in it.

Right, and I'm sure the AMA has no lobbying sway whatsoever.

Do you hate doctors? I am beginning to think that a majority of people taking your stance do. Frankly, just wait till you need us. Then you won't be so harsh on us.

Some of my best friends are clinicians (no, seriously).

I don't hate doctors, nor do I see them as useless. When I have a nasty infection or need some part of my body removed, you can bet I'll be relying on a doctor.

But when it comes to modern genetics, doctors currently aren't the most qualified people to interpret my data, and I resent their attempt to impose control over that process despite their clear incompetence in the field.

If you want doctors to be the ones interpreting genome-wide data, train them so they know how to do it. Until you're finished, don't act all shocked when people prefer to be able to get their interpretation from people who actually have some clue what they're doing.

Steve Murphy MD said...


"I don't hate doctors, nor do I see them as useless. When I have a nasty infection or need some part of my body removed, you can bet I'll be relying on a doctor."

Daniel, do you think that is all we do. Save your A$$ when you are sick? That is the old model of medicine.

Besides, you just crapped on

1. Psychiatrists
2. Physiatrists
3. Clinical Geneticists
4. Pathologists


That typical "Grey's Anatomy" view of doctors cheapens the field of cognitive medicine. Which us Cognates have been bitching about for years.

Personally, I think you, Daniel are the best to interpret your own genome.

But I think Kim Kardashian or Paris Hilton might be suited going to a doctor, several times.

I am not saying we do it better. I am saying we have a way of dumbing things down to a "non-scalable" system that cannot be replicated by SV.

I am not saying all Genomic testing needs to go through doctors Daniel. I am saying one thing and one thing only

If it is a medical test, regulate it as such according to the laws of the state/country etc.

If it is not a medical test, prove it.

If it is a medical test, prove it.

You and I both know, the majority of the genome scan is a lot like getting a lab test with 1000 levels. There is gonna be false positives. There is also going to be lab errors. In the case of the whole genome, at least 6000 per genome I bet.

So if you are going to give people this data and expect that they will use it medically, wouldn't you like a medical expert involved in that?


Joe said...

I would definitely want a qualified interpretation of my genetics by people that know what they're doing... which is why I would stick with a company that is focused on that approach - like Navigenics.

I would believe that the raw data would be the same from 23andMe, but I would very likely have my private data compromised or be led on red-herring chases with unproven research interpretation.