Non-Clinician Misinterpretation of DTC Genetic testing

Ok,

In case you haven't all figured it out. Blogs are dead. Mine is too, sorta. I have less and less time to blog as my practice explodes. But there are some things that just merit a blog post.

I am on twitter, you can follow me there @genesherpas

But now I am on the Sherpa. Yes, the blog that nearly got me on 60 Minutes and definitely won me the hearts of USA Today to be interviewed...BTW the practice got super busy after that......

Today I want to talk about something more serious.

The FDA hearings have laid the course clear. Direct To Consumer Genetic testing will be regulated.

Why?

1 part potential harm

2 parts irreverence for laws and medical regulation

3 parts flagrant misrepresentation of what genetic tests can do.......

See Kari S. Disavowal of his company's stupid tag line.......

Today on twitter Shirely Wu @shwu retweeted something that was the picked up by @dgmacarthur..... great geneticist, but not a medical geneticist........

That was:

A thoughtful and eloquent case-study petition to keep genetic testing DTC:http://bit.ly/dL3qar from @celticcurse#FDADTC

The problem?

I respect Shirley a lot, but this article is not thoughtful, nor is it eloquent.

Instead it is full of misinterpretation and IMHO an ignorance of the role of genetic testing in hereditary hemochromatosis.....

In no way is HFE genetic testing required or indicated to pick up a person with hereditary hemochromatosis.

USPSTF says the harms outweigh the risks of genetic testing for screening

There are multiple genes involved in hereditary hemochromatosis only testing HFE and thinking you are "off the hook" is stupid.....

There are also modifier genes likely too.....

In other words, perhaps the cheerleaders for DTCG are misinformed about the true utility of this type of testing. Further, if they knew the literature, perhaps they would be less angry that the FDA(who know the data BTW) want to regulate against these types of misinformed claims that could lead to misinterpretation by consumers and end up fleecing their pockets for fools gold.

Let's take this little gem from @celticcurse

"A simple genetic test is all it takes to know if hereditary hemochromatosis, the most common genetic killer in America, is in your genes."

Bull$h!t buddy.....less than 30% of HFE variant persons ever develop the disease. Do me a favor, partner with a doctor to hack your health next time please......

In case you wondered, iron studies are the key to screening. I get them in every northern european or any family history of liver disease, gonadal failure, arthritis, etc......

But, the lab heads wouldn't know that. Which is why lab heads shouldn't release discoveries into the wild......

The Sherpa Says: This retweet blog post by CelticCurse is an eloquent reason WHY DTC genetic testing should be regulated for claims and use......regulate the medical as a medical test, let the ancestry buffs do their thing sans FDA. End of story guys.....

Unregulated DTCG saved my life.

Ok, so if Ellen Matloff hasn't flipped her bobbed haircut, 99245 without 60 min of MD care-insurance billing head yet, then this story will make her and the rest of the counselors who get mad when untrained MDs do BRCA testing flip out.

A woman's husband on DNADay takes advantage of 23andMe's rock bottom 99 USD fee. Clearly intended to double their database.....which it did

Only to have her HUSBAND open her results and

WHAMMO! You are a BRCA1 carrier! Mazel Tov! Not exactly the "fun" he had been looking for when he saw that flyer.....

Why does Myriad market to doctors? Their stance "We are missing a ton of BRCA mutations out there"

I agree.

So you would think I am happy that an unregulated DTCG testing company that the FDA pilloried finds a medically valid BRCA1 mutation that wasn't suggested by doctors.

Well, here's the shocker.

I am glad they found it.

Yes, thank god someone did before she had ovarian or breast cancer! If she would have, penetrance here is NOT 100% guys......

I am also glad that the woman who had the test was mentally stable enough and smart enough to seek professional help. I wonder what her husband and her do for a living?

I wonder if they are college educated. I wonder if there demographic is anything like the majority of the United States.....probably not....Oh wait. Princeton Grad, Prior Google Grad, CEO....yeah sounds just like my cousin Billy in Dushore PA (FYI I don't have a cousin Billy) But Dushore is in BFE.....

I am not glad that everyone is NOT like Mrs. Steinberg or her husband. In the right hands and with easy access to health professionals this works, sometimes........That is why the FDA has stepped in. Not everyone lives like the Steinberg's

Without professionals and without a level head, this could be a problem.

But the news story re-emphasizes what is crystal clear. This is an unregulated company that delivered a medical diagnostic. This result then drove clinical decision making.

Seriously. The DTCG BRCA test is a medical test. I think the FDA gets that part. Despite what DTCG says.

The Sherpa Says: I am happy for this woman. We need more testing, I agree with Myriad. I also think CGCs should be out teaching doctors rather than letting pharma reps do it. In fact excellent CGCs like Ms. Matloff should never see patients and should instead teach doctors how to do cancer counseling everyday. That is what is needed here, more education given to those who need it. Because clearly the doctors who told Mrs Steinberg (I assume she is AJ) that she wouldn't "need" genetic testing despite the family history of cancer are likely in need of some schooling.

No more 23andMe blog posts. The Sherpa has achieved his goals.

I am absolutely done talking about 23andMe.

Yes, you have heard correctly.

That doesn't mean I will stop watching what they are doing.

It means that I have coerced them into doing what's right. For now.

From the very beginning 23andMe had potential, heck Dr. Jeremiah Mahoney told me they came up to Yale to see them.

They must have not liked what Yale said, because they went further up the line and partnered with George Church.

Well, they def. didn't like what I had to say.

I had even conjectured about DTCG and what this landscape may look like and even warn about the shortcomings,
I had been pointing all of you to SACGHS to watch where this regulatory environment may go. The environment was heated with these companies going in.

So I knew I had to pay attention to what they were doing, especially the Google Backed company.....

First when these companies launch

1. I immediately point out 23andMe isn't using a CLIA certified lab which gives me grave concern over the seriousness with which they are doing testing. A-la Garage lab versus proper human sample processing.

2. I complain on Daniel MacArthur's blog about the obvious rookie blunder this company with no healthcare experience in leadership makes

Then 23andMe uses a CLIA certified lab

Second, I tell you that the states who have serious laws against DTC will shut down these companies quickly

Then they shut 'em down for a bit. And I gloat


Third

1. I complain that FDA needs to get their act together and in 2009 23andMe began doing absolute truly clinical testing with BRCA testing.

2. I point out the SACGHS feels the same way too and also complains to the FDA

3. I point out that 23andMe has no clinical clue what they are doing with PGx

Guess what? The FDA finally rules for regulation.

Lastly,

1. I complain about this research revolution akin to Tuskegee or other non IRB approved "research"

2. I point out that Google has off shore servers to hold this data free of US regulation.

3. I say that they are coercing subjects and offering discounts that wouldn't fly in an IRB

Today, they announce they have obtained IRB approval.

But I have my doubts as they have flaunted loopholes in laws And seem to point that out again today, or at least their blogger does.....

"our research technically does not require IRB review."

So I guess I will have to keep posting until these guys stop skirting lines..............Nevermind

The Sherpa Says: Yes, why keep it up if they did what I asked? Because they will do it again, even if it takes an act of Congress. Why do I ask? To protect the patient and consumer from mega corporations whose interest is anything but patient empowerment.

Thomas Goetz has the wrong debate. FDA doesn't intend to restrict.

I think everyone in this space has been way off base as to what the problem is with FDA and Congress wanting to investigate the DTC Genomics companies.

The whole mindset is wrong.

What I hear from this debate is "It's my data, mine, mine, mine. Gimmee, Gimmee, you can't keep me from my data Big Brother!"


From Mr Goetz's Blog
"The controversy seems to have stirred the FDA to assert its authority – and that of physicians – over any and all medical metrics."

"To me, getting access to this information is a civil rights issue. It’s our data."

This is a straw man argument that has been set up to make regulating these companies seem unseemly and an invasion of privacy.

IT IS A DEAD WRONG ARGUMENT and I will not stand for it being perpetuated anymore.

This is not about getting access to your data.

Fine, you want a whole genome, go get it!

The FDA is not asking should people be able to go out and buy this. It is asking several other questions.

1. Is Interpretation of biometric data considered medicine?
The answer here is certainly confusing. I think it rests solely with intent.
Do you intend to tell someone something about a disease they now have based on this biometric data that you analyzed?

If the answer is yes, that is viewed legally and medically as a diagnosis.
Which ultimately I think is medicine and falls under medical regulations.

2. Is DTCG analyzing biometric data and intending to give an interpretation of that data which indicates a disease a person has?

It depends on what you define disease as.

Most legal experts defer to the International Classification of Diseases

3. Should we regulate a system which has not given indication of their quality control if they are indeed intending to provide medical diagnosis?

4. Are these methods of obtaining human samples to derive biometric data for the intent of analyzing and providing information about disease considered medical devices?

This is precisely the argument and precisely what Congress and the FDA are trying to define.

So stop acting like a bunch of little kids running around because someone took your kool aid away!

If I hear another, "It's my data" whine again I will scream.

This is not about restricting access to biometric data.

Which by the way, some states do already.

Is an EKG biometric data? What about a cholesterol?

Probably, no one is stopping you from going out and buying a machine to obtain this data yourself.

But any doctor will tell you, it is the interpretation that can vary widely. As demonstrated by the multiple interpretations that Venter et.al complained about

What they are intending to do is to prevent a third party from having NO ONE to answer to when providing interpretation of that very SAME biometric data.

The Sherpa Says: Regulation here will most definitely not stifle innovation as bad as a consumer death or class action lawsuit or lack of trust from consumers because of the aforementioned.

Attention Lab Directors!!! The FDA is coming!!!

I have been mentioning this several times to several VC firms and to several small companies. If your business plan or investment does not have a section devoted to getting FDA approval, you will soon see that business do 1 of 3 things.

1. Be sold to a commercial lab who can get FDA approval quicker

2. Become extinct

3. Struggle to create a plan to attain FDA approval and be 6 months to 1 year later to launch.

Why am I saying this today????

Did anyone look at the NY Times yesterday?

Quest admits problems with the Vitamin D test???

On Good Morning America Diane Sawyer said "I didn't know that the tests which my doctor ordered are not FDA approved"

Translation: A huge amount of public demand on an already strapped organization to regulate and assure the quality of laboratory testing, just as they do drugs and food.

This plays perfectly in President elect Obama's plan to create an interagency organization for regulating these and other IVDMIA tests.

Meanwhile, the F.D.A. is considering increasing its role in regulating diagnostic tests. Now, test kits sold to labs, hospitals and doctor’s offices must be approved by the agency. But tests developed and offered by a single laboratory, like the Quest vitamin D test, do not.

I am jumping on this as I read a report from one of our Yale laboratories which says

"THIS TEST WAS DEVELOPED AND ITS PERFORMANCE CHARACTERISTICS DETERMINED BY THE LABORATORY. TESTS DEVELOPED AND USED BY INDIVIDUAL LABORATORIES ARE NOT SUBJECT TO FDA APPROVAL........

Well, that is going to change. And I predict it will happen very, very soon. Especially now that there is public awareness that people were getting false negative Vitamin D results because the FDA doesn't regulate home brews......

Imagine all the people who could have been taking supplements. Especially as more literature comes out about Vitamin D deficiency being linked to all sorts of diseases....Including heart disease...the biggest killer in the United States....Yikes.

The Sherpa Says: This is a good thing. I promise. Yes it may burden the FDA and HHS and CMS and all the little labs looking to jump into diagnostics, but in the end, it will start to restore the public's trust in healthcare....which is something we sorely need!

Uh Oh......the FDA sets the bar

In an editorial from the Lancet,

Medical groups have expressed doubts about the validity, effectiveness, and clinical usefulness of direct-to-consumer genetic testing. More harm than good is done, for example, by false reassurance from unproven genetic tests or by unreliable information that could lead patients to terminate a pregnancy or seek surgery.

These are the concerns from the field and they may be valid. They may also not be valid. Let's examine each:

1. Doubts about validity-

What exactly is valid? Is valid the genotype? Is it the validity of the phenotype which the genotype is said to "predict" Is it the validity of the studies which back up the test? In the case of genotype, I would say the test is valid. In the case of the 2 others...it clearly is not.

2. Doubts about effectiveness-

Effectiveness in what? Predicition? Prevention? Guidance of therapy. On all of these counts, the doubts of effectiveness are valid.

3. Doubts of clinical usefulness-

Well, what IS clinical usefulness? Is it, the ability to derive a new use/diagnosis from a test result? Is it the ability to put into action a clinical plan to prevent or treat disease? If it is either of these, the data is not there for most DTC tests....But I also have said that clinical usefulness could just be the ability to plan for future risk or future care. In this case predisposition testing for Alzheimer or Parkinson Disease may be useful......depending on the test and its clinical evidence....To answer this question a genetic test needs:

A. A clinical study showing predictive outcome. I.E. in a prospective manner, that would be very nice. Especially if I am to tell a patient how likely they are to get this condition and when....

B. Some clinical data showing outcomes in treating patients with genetic predisposition. I.E. in the case of the BRCA1 or BRCA2 genes.

C. Some clinical data showing that an intervention on persons with a certain SNP or mutation, prevents the prior expected outcome.

Even if we had none of these things......some may say "Why not let people buy this sort of information to do with it what they wish" That is not clinically useful. It may be socially useful, but some have real questions about that as well...

In my humble opinion, this buyer beware is a very libertarian/conservative view. Which may or may not be so bad. Unless we have harm being done to citizenry.

So, is harm being done?

Some would argue no. Others argue yes.

But these data revolve around clinically valid tests. Most importantly, almost all medical societies are against DTC testing b/c of possible harm. But some argue that these motivated genetic test subjects wishing for DTC testing, self select to minimize the harm....which could be the case. But that assumes the tests are actually valid.

So what happens when the tests do not meet the criteria above? Well, no one knows the answer. But there are a ton of ethicists who are arguing against such testing. Why is this important?

Well, put simply. Medical Ethicisists most often fall along the lines of patient autonomy. In fact alot of people debate about this principle seeming to be absolute. So if most ethicists think the patient should have ultimate choice in their care, why are they against DTC testing???? Good question.

So here we are, in a position with not much data, and we won't likely have it for several years. We have ethicists who put patient autonomy first, against DTC testing. We have doctors, against DTC testing. We have government against DTC testing. Now, with the recent FDA warnings to labs promoting tests without evidence, the writing is on the wall.

“Because you do not have marketing clearance or approval from the FDA, marketing OvaSure is in violation of the law,”

That could just as easily be any other genetic test marketed to physicians or consumers. The FDA has weighed in and DTC is likely to be in its sights. Despite their detractors, the FDA is unstoppable here.

So, the answer is simple....we all have to await clinical data and trials for a clinical tool. Is that such a stretch? Is that such a bad thing? Well, it very well may be if your investors are on your case. Or if you need to pay your bills and your university salary is paltry. Or it may be if you have a mortgage whose rates are climbing? I hope you see what I am saying.....money clouds medicine, most importantly genomic medicine.

The Sherpa Says: In a time when Wall Street has a black eye from its fraud and scandal let's not let Genomic Medicine get punched too. It already has too many detractors....