Thursday, May 27, 2010

Personal genetics: DTC or DTMD?

Yesterday I ordered a book from Amazon called “Outsmart Your Genes” – this was prompted by a tweet from @genesherpas: 

Just got my copy http://www.outsmartyourgenes.com/ my Friend Brandon Colby MD's great work. It is a must read for all. That means AnneW too.

It wasn’t too expensive and it may be interesting – it also could be part of a slick marketing campaign, a few days previously a press release announced the launch of “Existence Genetics LLC, the world’s first predictive medicine company…”. With the website of the book linking to the Existence website, the twitter and facebook links, and so on, it does look like:

@dgmacarthur The "Outsmart your genes" book that @GeneSherpas is spruiking looks like extended ad for author's company: http://bit.ly/8Zanrd

We’ll see, I’ll update when I read the book, meanwhile I learnt some Australian slang as well…

First of all – there is nothing wrong with any of the above, it’s all fine and I have not much to say about the service offered by Existence Genetics (EG), I don’t know enough about it to comment. I am seriously interested in the service from a professional point of view – our aim at Eurogene is to bring such services to the practitioner in Europe – we have set up the software, systems and infrastructure to do so, to incorporate the genetics into the rest of the medical history, but we don’t develop our own genetic panels so EG could be interesting.

I’m also interested in the comparison between DTC such as decode and 23andme vs. DTMD (direct to medical doctor) like EG because a few days ago the regulatory waters were stirred up by the Pathway/Walgreen partnership (why that prompted it I don’t know – DTC via internet since 2007 = OK, DTC through pharmacy ≠ OK ?? Actually I fear it’s a knee-jerk response due to what in the UK would be called “tabloid pressure” on the FDA. But follow the link above to Genome Law Report, there you will find all you need on the current state of affairs). While I support some form of regulation / oversight (strong code of practice is my preference) but I also support DTC for easy access by anyone and full transparency.

The point is that the FDA may be jerked and lobbied into banning DTC and the only source of genetic health analysis would be through services like those of EG. The question is would that be better? There has been a lot of vocal opposition to the DTC services – they say that these are clinical services that need to go through a medical doctor. So is the EG service fine because it does go through a medical doctor, does it mean that the consumer/patient is protected by this relationship?

If I go to decode or 23andme I can see on the website a LOAD of information – the SNPs analysed, the references used to calculate the relative risks, the actual methods used in the calculations, and so on. They are both very transparent as far as what they are offering goes – and all this is available before I purchase. Which also means it is all available to anyone else to scrutinise, to error check and to validate, which is very important.

On the EG website there is very little information – no genes, SNPs, calculation methods or costs. I don’t know if they make available all the information on request – my request got this not too promising auto-reply:

Thank you for contacting Existence Genetics. While we do try to respond to e-mail inquiries, we are extremely busy and may not always be able to respond to all. Also, we are unable to answer any medical or health-related questions via e-mail.

Make sure to visit www.existencegenetics.com and www.outsmartyourgenes.com for more information and to sign up for our industry-leading Predictive Medicine Newsletter.

Thank you,
Soraya K. and The Existence Team

There are some pages from sample reports though. Here is a screen dump of a portion of the single page heart attack report:

Capture

 

And from 23andme:

image

One subtle but interesting difference: EG says this is YOUR risk while 23andme talk about population risks referring to people with similar genotypes. I prefer the latter style because that’s where the data come from, studies of populations, I’m not sure that it’s correct to state that this % is my actual risk given that my actual risk still depends on many unknowns (other genes and my lifestyle). That’s my opinion and I stand to be corrected if it’s wrong.

Another comparison is EG and Decode who both test for Alzheimers:

Decode:
The lifetime risk of your type: It is estimated that 39 of every 1000 males of European ancestry with your genotype variants develop this disease in their lifetime.
The average lifetime risk: On average, about 60 of every 1000 males of European ancestry develop this disease in their lifetime

Although there is currently no treatment available that can delay or stop the brain degeneration that causes AD, several drugs have been approved by the US Food and Drug Administration (FDA) that can temporarily slow worsening of symptoms for 6 to 12 months. As these drugs are mainly useful in the early stages of the disease, some individuals may choose to know their risk factors for the disease.

Individuals at high risk for AD may benefit from regular screening for early symptoms of the disease by their primary care provider. Early, active medical management, through available treatment options and utilization of programs and support services, can improve quality of life through all stages of the disease for diagnosed individuals and their caregivers.

EG:
Your lifetime risk 54%
Generic lifetime risk 17% [misread this as genetic at first, confused me!]
This is equal to a 220% increased risk
Clinical significance: This potential disease is very important to your health & wellness
Actionability: Preventive measures have been shown to help prevent or delay onset/progression of this disease [and it lists these as protect head from trauma, low animal fat diet, increase exercise, red wine, statins, aspirin, yoga]

Note: the founder Brandon Colby, talks about Alzheimer in a Huff Post article:

Predictive medicine's strategy in defeating Alzheimer's is straightforward: first, we use genetic screening to identify those individuals who are at increased risk; second, for those who are at increased risk, we use further genetic analysis to determine the most effective forms of prevention; and third, we institute these genetically tailored preventive measures throughout the person's life, starting as young as possible. With a simple, relatively low-cost test requiring only some saliva (no needles, no blood), we can now predict who is at risk for Alzheimer's and what will be the most effective methods of prevention against it.

Hmmm…I would really like to see the articles that are the basis of this Alzheimer prevention.

There are many questions, but first of all I would like to not get into definitions about “is it medicine” or not – that’s been gone over so many times it’s become a sterile and distracting occupation. The overall question that the FDA and others want to sort out is should decode and 23andme et al. be able to continue to offer their services DTC or should they need to be delivered to the consumer via a medical doctor. Further – should the decode and 23andme services be strictly controlled as medical devices with lengthy, costly pre-market scrutiny and FDA approval required before selling (which would effectively put them out of business)?

1. Decode and 23andme provide details of how they calculate risks, EG does not provide much information at all but makes much stronger claims and promises.

2. Should EG be subjected to the same scrutiny as 23andme etc., has it been required to submit the same sort of information requested by the FDA of the DTC companies, or does going via MDs make the service immune from this?

3. Can the EG service be freely sold in New York or California without having to go through the approval steps necessary for the DTC companies?

4. How much will the EG service cost me and what information will be supplied – will I get the results of all the SNPs on the proprietory “Nexus Gene SNP” for which there is no information on the website?

5. What is the scientific basis for the EG “Disease Matrix technology” and “Reflex Analysis” ? How have the algorithms been validated?

And so on. To be clear I am not saying that the EG service is poor, wrong, bad, or whatever – I don’t know, I can’t know, there is no way of finding out as far as I can determine. Let’s say that they are very good - that the service is excellent and life saving – great, but that’s not the point. EG may be good but the next DTMD service may not be, and we would not be able to tell. If all personal genetics were delivered DTMD would that be OK for the critics of DTC, is that what they demanding? If it were all DTMD then would there be no reason for the FDA to get involved as it has done recently? Would it have all stayed under the radar screen?

If that is the case then I sincerely hope that the future is not restricted to DTMD – this is the situation in Germany, the paradox is that going down this route actually reduces scrutiny, quality control, transparency and will lead to the marketing of dubious products and services (like in Italy – through medics only for a mere €700 plus doctor fees you can buy Nutrigenecode, 50 anonymous SNPs, then you buy the magic supplements. It sounds good though because “it’s prevention and will save you loads of money in future doctor fees” plus DNA really is the “fountain of eternal youth” – so there).

Those who call for health related genetic tests to go through medics need to demonstrate how restricting the services to the EG type model is really better, because that is not at all apparent from the information available. Strong regulation can have serious damaging and harmful consequences if not done properly – see this Genetic Future post from Daniel MacArthur for a good review.

Really I don’t think we need to tie ourselves in too many knots over this regulation stuff – 90% of the problems would disappear with a good code of practice, transparency and the recently proposed NIH genetic test registry.

I hope that the FDA will see the possible futures and allow us all to continue to pay our money and make our choice.

13 comments:

  1. Great comprehensive & balanced post Keith!

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  2. I am still reading this book and will post heavily on this once I am done. I suggest people buy it, read it and then form their own opinion. I don't like absolute numbers for risk, but I do like the idea of panels for diseases and in fact am working on similar things with some Genomics companies now.

    Still, for a doctor to say this is useful in the office makes the claim for, this is medicine and medical testing.

    Which, BTW doesn't always have to be through physicians, but should be regulated as tightly as any other device or medication.

    Your thoughts?

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  3. Thanks Michael

    @Steve
    Some regulation yes, how tight it should be is difficult, it's moving too quickly. Panels are potentially good but if they needed pre-market review what happens when a new SNP is added or the advice is updated? Does it need to go through another review? It's unworkable, look how far things have changed just in the last 3 years.

    The claims need looking at as do the methods to calculate risk - these have been thoroughly scrutinised for the DTC companies, blogged about, written about in scientific journals and have generally been found to be pretty rigorous. That's the confidence that transparency brings (and it shouldn't really be necessary to buy a book to get more info). If 23andme or decode made strong claims about being able to prevent Alzheimers I'm sure that they would have been heavily criticised, unless they showed the evidence (which may exist, but as far as I know does not). This is where the genetic testing registry would be a huge benefit.

    One disappointment though is that the genetic report is not integrated directly with other patient parameters. This is a missed opportunity by EG. Using a standalone genetic test to determine risk of heart disease etc, in the absence of considering family history, lifestyle, behaviour, diet, etc - is not very useful at the individual level. You know that, have said it often, and it has been widely demonstrated. Yes the doctor can integrate it, but really, how many would know how to? I'm sure Dr Colby and colleagues can, but how many others? In my experience of meeting many many medical doctors over the years and talking about exactly this, it's not many and it is the area where they need help. My opinion is that these patient details should all be included into the report, that's where the practitioner delivered service has real value, that really is medicine, I mean useful medicine - otherwise I'm not even sure it's much more than information (but I reeeeaaaallllyy don't want to get into that debate, I think we are OK there now).

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  4. Great post! Transparency is the most important issue in this field, for both DTC and DTDM. I think that DTDM services are less transparent because they are done by phyisicians, who have always been possessive with their informations. Moreover, they don't need to be transparent, because people usually trust them a priori, because "My doctor said so". I think that there should be some kind of regulation, so that every company or physician who wants to perform a genetic test has to clearly state which are the methods used.

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  5. Wait, so Existence's tests are direct-to-MD and the Terms of Service *still* say they're not for diagnosis/treatment?! Then what's the point of requiring the MD to order them?

    http://www.existencegenetics.com/policies.html

    "No Diagnosis, Treatment, Etc.: Nothing on the Site should be used for medical diagnosis or treatment. Any information we provide should not be considered complete, nor should it be relied on to suggest diagnosis or treatment for a particular individual. Material on the Site should not be relied upon for personal, medical, legal, technical, or financial decisions. EXGE does not practice medicine and so Material should not be used in place of a visit with or advice from your doctor or other qualified health care professional. You should always get the advice of your doctor or other appropriate health care professional if you have any question about diagnosis, treatment, prevention, mitigation, or cure of any medical condition, phenotype, disease, impairment, or status of your health. Opinions, advice, statements, and other information on the Site may be from others and are not necessarily those of EXGE. If you have any health care related questions, please promptly consult your physician or other qualified health care provider."

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  6. Important words

    "Nothing on this site"

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  7. What steps are being taken by the FDA to make sure patients don't go to a doctor for their genetic data and return home infected with a bad case of identity theft or genetic discrimination? Let's hope "do no harm" in the US extends to genetic data privacy.

    I hope cash payment for anonymous genetic data remains an option.
    @dnatimes

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  8. Great post!! Not sure I'd be as nice to EG. I dug around their website for information on their “Nexus Gene Chip", “Disease Matrix technology” and “Reflex Analysis" and came up empty handed. It seems to me that the information they are providing is purposefully ambiguous and vague, which implies (at least to me) that none of it is currently ready for the market or it's all (or mostly) snake oil.

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  9. Keith,

    Thank you for your post. You made some excellent points and I wanted to write to let you know that we appreciate your insight and have added content to our website to answer some of the questions you proposed.

    We did receive your email and I do apologize for not responding sooner. In your email you mentioned that our service looks promising in terms of integrating it with Eurogene’s service. As VP of Corporate Development, I would be happy to work with you to enable Eurogene to be able to offer Existence Genetics’ Genetically Tailored Technologies, including our Nexus gene chip.

    In response to some of the issues you outlined in your blog:

    -Yes, we do provide the physician who ordered the test with access to the list of genes and genetic variants that are used in assessing the information contained in the report. Similar to the list of references we provide, the list of genes and genetic variants is not included in the main body of the report because our medical advisory board decided it would be a distraction from the foremost goal of our reports – the straightforward conveyance of genetically tailored prevention information. While this is a different methodology than has been used before, in our beta testing we have found that this type of separation helps significantly with the understanding and adoption of the preventive information. To see this policy outlined on our site, you may visit:http://existencegenetics.com/geneticreports.html#3

    - As with almost all companies that perform genetic testing and/or genetic analysis, the exact list of genetic variants assessed is not public information. While it is true that the DTC companies provide people with information about variants utilized to arrive at the information presented for each disease, they do so only after their analysis as part of the genetic report (this info is only included in the report after the person has used their service).

    -We actually do integrate non-genetic factors into our analytical process whenever research has shown that the risk of a phenotype for a specific allele or genotype is dependent upon a definable non-genetic factor, such as smoking status, BMI, age, etc. We’ve updated our website to make sure this is now clearly conveyed – the info can be found here: http://existencegenetics.com/genechip.html#3.

    Existence Genetics believes that both genetic and non-genetic factors are incredibly important for the ascertainment of risk and we are always looking for ways to integrate additional non-genetic information when scientifically and clinically possible. While we do integrate in some non-genetic factors now, we expect this evolve significantly over the next few years. We also understand that it is important for health care providers to interpret any genetic report with non-genetic risk factors in-mind and we’ll be promoting this concept with the providers we work with.

    -We have also updated our site with information about the risk assessment process including whether a specific algorithm is used. That information appears here: http://existencegenetics.com/genechip.html#2

    -Each panel ordered assesses a large number of phenotypes, and each phenotype will be assessed using our Disease Matrix and Reflex analysis technologies, which allows Existence to be able to provide genetically tailored prevention information to the ordering health care professional. In-order to convey the concepts of these technologies, we have made sure to put up a large number of examples with different views.

    I do greatly appreciate your comments and feedback and the entire Existence team looks forward to making sure our predictive medicine services have as much beneficial impact upon the health care industry as possible.I hope that our updates to our website convey our willingness to quickly respond and be receptive to constructive feedback.

    Thank you,
    Soraya
    Existence Genetics

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  10. Sorry for the second post but I forgot to mention that if a physician qualified to provide our services has questions about specific genes and/or genetic variants prior to ordering a specific panel then we are happy to provide them with this panel-specific information. Therefore, it isn’t necessary to order the service in-order to receive the genes and genetic variants assessed but we do not release this information on our website as we, just like all other companies, consider this intellectual property that took years and a tremendous amount of time and resources to compile, organize, and define – and then utilize to invent the Nexus gene chip.

    Thank you,

    Soraya

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  11. Soraya

    thanks for the comments and clarifications which are helpful.

    I can understand the reluctance to release the genes/SNPs on the Nexus chip - it's a common fear that it would leave you vulnerable to being copied - in fact it is relatively simple to reproduce a gene chip but still the fear is unfounded. What is hard to copy is the many person-years of work that goes into the translation of the the genetic results into meaningful clinical decision making information.

    You're situation is different from the DTC genetics companies since you go through doctors, however you do market DTC and transparency will always help you.

    You have an opportunity here. Although you are not really "the world’s first predictive medicine company", you are still an early entrant and have the possibility of helping to set standards & become one of the reference, responsible, serious and trustworthy companies in the field. You can achieve this by releasing perhaps more information than you feel comfortable with but which nevertheless shows what and who you are. Besides, by the time any competitor has made any use of your information your service will already be upgraded and improved, it's such a fast moving field.

    You should at least be ready to release information to the proposed NIH genetic testing registry if and when it appears. You are confident about your services, make us all confident as well - any competitor that copies you will eternally be playing catch-up, you don't need to worry about them.

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  12. Hi Soraya,

    As with almost all companies that perform genetic testing and/or genetic analysis, the exact list of genetic variants assessed is not public information. While it is true that the DTC companies provide people with information about variants utilized to arrive at the information presented for each disease, they do so only after their analysis as part of the genetic report (this info is only included in the report after the person has used their service).

    This is simply false: the more reputable personal genomics companies (e.g. 23andMe, deCODEme) do freely provide customers with a demo data-set that includes all assayed variants.

    This list is absolutely crucial for consumers to be able to make fully informed decisions about purchasing a test. I fully agree with Keith that the commercial disadvantages of doing so are exaggerated.

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  13. Count me as one who does not agree with Soraya's assertion that the measured genetic variants need not be publicly disclosed.
    More to the point, I think that secrecy about which genetic variants are utilized is a strategy more likely to be used to prevent comment/criticism on the veracity of the associated health risk and prevention claims than to prevent the end-user from experiencing distraction from conveyance of genetically tailored prevention information. In the end, this could cause an otherwise good genomics company more trouble than disclosing the information and staying ahead of the competition in other ways.

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