UK House of Lords report on genomic medicine: implications for DTC genetic testing

The UK House of Lords Science and Technology Committee has published the long-awaited report (PDF) from its inquiry into genomic medicine.

Mark Henderson at The Times has been busy today, putting out three excellent pieces on the report: a summary of the major implications, an opinion piece pushing the need for the health service to respond quickly to the arrival of genomic medicine, and a lengthy blog post praising the report and providing his views in more detail. 
I find little to disagree with in Henderson's coverage, and certainly agree with his overall opinion of the report: this report is a careful, balanced analysis of the major issues facing health systems as they move into the era of genomic medicine. Since most of the problems the UK is facing in coping with this transition will also be issues for other developed countries, governments and health agencies around the world would be well-served by printing out a copy of this report and taking its major messages seriously.
I'd recommend reading all three of Henderson's pieces for the broader context of the report (and particularly for the implications for health services). Here I want to focus on the report's implications for the area closest to my interests: the direct-to-consumer genetic testing industry.
My position on the regulation of the direct-to-consumer genetic testing industry is pretty simple - good regulation of the industry would:
  1. Ensure that companies provide high-quality genetic data to consumers, along with simple and accurate descriptions of the predictive value of the tests performed;
  2. Ensure that information about testing companies is placed in public databases that allow consumers to make a thoroughly informed choice between genetic testing providers; and
  3. Not prevent customers from gaining free access to any part of their own genetic information if they want it, or position clinicians as the absolute gate-keepers to such information. 
Based on what I've seen so far, the committee's recommendations are a step in the right direction for point 1 and 2, and don't seem to violate 3, so I'm reasonably happy with this section of the report.
The inquiry heard from a number of quite eminent witnesses who provided both positive and negative views on the genetic testing industry - sometimes from the same person. For instance Ron Zimmern, Executive Director of the PHG Foundation, described DTC genetic testing as providing "totally useless information", but also argued "that companies should not be prevented from selling DCTs and ... that he could 'see nothing in a free society to suggest that we should stop people from knowing that they have a two per cent higher risk of asthma or a four per cent lower risk of heart disease".'

Professor Peter Donnelly, who led the massive Wellcome Trust Case Control Consortium study of the genetics of common diseases, was more unambiguous in his support for the DTC industry: 

Donnelly ... spoke positively about DCTs and suggested that they might be the best way to ensure that technology develops to a point where it becomes useful for public healthcare. They would also be beneficial for the small number of individuals who had a high risk of developing a disease due to the additive effects of having several low risk gene markers. He thought that DCTs were the first step to a service that would eventually be incorporated into routine clinical practice.

In the Appendix of the report is a lengthy description of Donnelly's presentation to the inquiry, where this argument is elaborated:

While most individuals would have an average risk for most diseases almost
everyone would be at very high risk for some diseases. Professor Donnelly
estimated that 95 percent of people would be in the top five percent of genetic risk
for at least one disease, 40 percent of people would be in the top one percent of
genetic risk for at least one disease and five percent of people would be in the top
0.1 percent of genetic risk for at least one disease. 

[...] It may therefore be useful to think of genomic tests, including
those sold "direct to consumers", as a tool for individuals to identify the diseases
for which they had the highest genetic risk, based on current knowledge.

Although the inquiry also heard from critics of DTC genetic testing (such as the notorious skeptic Helen Wallace of GeneWatch UK, who predictably called for a ban on all DTC genetic tests), the more balanced view of experts such as Donnelly led the panel to make two fairly reasonable recommendations regarding regulation of the nascent DTC testing field:
  1. The development of a voluntary code of practice for DTC genetic testing companies, including a requirement for companies to place information about their laboratory accreditation and testing standards in the public domain, and guidance regarding the provision of pre- and post-test counselling;
  2. The creation of an online registry hosted by the Department of Health that lists this information about DTC genetic testing companies, and also describes "the extent to which the DNA sequence variants used ... have been validated in genome-wide association studies, and shown in prospective trials to have utility for predictive genetic testing."
Which is almost exactly what I hope to see in terms of regulation of this field. The only area I disagree is in the voluntary nature of the code of conduct, but there's also a third recommendation that may provide heftier regulation of industry standards: the report proposes that all genetic tests, including those provided direct-to-consumer, should be reclassified from "low risk" to "medium risk" within the current EU In Vitro Diagnostic Medical Devices Directive. That reclassification would seem to carry with it some non-trivial paperwork for genetic testing companies to justify their tests (see the hideous flow-charts at the bottom of these pages), but I'm currently unsure exactly how onerous this procedure is. 
Hopefully this re-classification treads the fine line of protecting customers from outright scammers while not hindering legitimate genetic test providers with unnecessary bureaucracy - I'd invite anyone with a solid understanding of the Medical Devices Directive (which I completely lack) to add their thoughts in the comments.
A final thought: I may have missed it, but there seems to have been little attention paid in the report to the potential overlap between disease gene testing and more "recreational" services such as the immensely popular genetic genealogy industry. Companies often offer both of these services simultaneously (e.g. 23andMe), but even "pure" ancestry testing carries a risk: genetic variants that appear to be perfectly benign ancestry markers today may turn out to be associated with disease at some point in the future (a probability that rises proportionately with the number of markers tested). In addition, ancestry tests do carry the risk of discovering potentially emotionally unsettling findings such as non-paternity; and a false revelation of non-paternity is potentially far more harmful than a false revelation of a 15% increased risk of psoriasis.
Does that mean that ancestry testing should be regulated just as stringently as directly disease-relevant genetic testing? Under the wording of the report (which seems to treat "genetic testing" as a monolithic entity) that would probably be the case; and perhaps that's not such a bad thing. Apart from the dangers quoted above (which are admittedly unlikely to affect the vast majority of genetic genealogists), I'd argue that providing basic information about the laboratory validity of genetic genealogy tests and their accuracy in determining patterns of relationship or deep geographical ancestry is not an unfair hurdle for testing companies.
Anyway, I think this report should at the very least stimulate some constructive discussion about the future of the DTC genetic testing industry; whether it actually leads to the appropriate regulatory changes is, of course, another matter entirely.

More like this

The brief Golden Age of direct-to-consumer genetic testing - in which people could freely gain access to their own genetic information without a doctor's permission - may be about to draw to a close. In a dramatic week, announcements of investigations into direct-to-consumer genetic testing…
OK, so this GenomeWeb Daily News article is approximately four centuries old in internet time (i.e. around a week), but it's worth going back and reading. I've previously argued at length that although personal genomics currently offers little in the way of useful, predictive health information,…
An excerpt from an article I co-wrote for Xconomy with Genomics Law Report's Dan Vorhaus - link to the full article below. Are you ready for consumer genetics? Is your government? Recent announcements of federal investigations into the budding direct-to-consumer (DTC) genetic testing industry…
(This is an edited excerpt from an op-ed piece I just wrote for Xconomy, posted here as I think it provides some nuance on my views on regulation of genetic testing that was lacking from my post last week. Some context for new readers: a Congressional investigation into the direct-to-consumer (DTC…

The first Times article you cite, states (with my emphasis):…

In the past few years, the costs of reading DNA have fallen so sharply that many scientists predict it will be possible to sequence any individualâs entire genetic code for less than £1,000 within a year or two. Research has also revealed hundreds of genetic variations that affect peopleâs risk of disease, or their response to medicines. The committee, chaired by Lord Patel, said that while it would be several years before this information allows the accurate prediction of disease, several medical applications are already practical or not far away.

While the examples given (dividing type 2 diabetes into sub-diseases, and measuring the known warfarin dose response SNP) are sensible, it is not clear that "accurate prediction of disease" is possible, let alone achievable.

For example, two recent papers, using rather similar data, come to completely opposing conclusions:

Clayton DG (2009) Prediction and Interaction in Complex Disease Genetics: Experience in Type 1 Diabetes. PLoS Genet 5(7): e1000540 concludes that, for most diseases, the discovery of all disease susceptability loci would not give great predictive power.

Lu Q, Obuchowski N, Won S, Zhu X, Elston RC (2009) Using the Optimal Robust Receiver Operating Characteristic (ROC) Curve for Predictive Genetic Tests. Biometrics. 2009 Jun 8 on the other hand conclude that:

With the discovery of more disease risk variants, and eventually their interactions, we might be able to form a predictive genetic test [for type 1 diabetes] that could be implemented in clinical use.

I know which side I'm on - discovering you have twice the risk of something rare is not very interesting: see rule 12 of the excellent A Worrier's Guide to Risk, and an interpretation of an 18-fold increase in risk caused by the common rs9272346 AA genotype from SNPedia's entry for anonymous caucasian NA07022, picked up from an earlier post - but you could also check out the NEJM Perspective piece :

Kraft P, Hunter DJ (2009) Genetic Risk Prediction â Are We There Yet? NEJM 360:1701-1703

With respect to the comments of our Executive Director Dr Ron Zimmern, I should clarify that the key point is that there is no objection to companies selling "totally useless information" in the form of pointless or unvalidated genetic susceptibility tests - PROVIDED that consumers are able to easily access information that reveals test performance and clinical meaning (if any) of such tests.

Our evidence given to the House of Lords inquiry therefore called for evidence relating to test performance (or lack of it) to be transparent and publicly available, whilst proposing that "funders of health services, and clinicians, should be discouraged from using tests that are not backed by appropriate clinical evidence" (see

Without really thinking about this, I had assumed Donnelly's calculations were the fruit of intensive analysis of the rich data source that is the WTCCC:

While most individuals would have an average risk for most diseases almost everyone would be at very high risk for some diseases. Professor Donnelly estimated that 95 percent of people would be in the top five percent of genetic risk for at least one disease, 40 percent of people would be in the top one percent of genetic risk for at least one disease and five percent of people would be in the top 0.1 percent of genetic risk for at least one disease.

[...] It may therefore be useful to think of genomic tests, including those sold "direct to consumers", as a tool for individuals to identify the diseases for which they had the highest genetic risk, based on current knowledge.

Not a bit of it - a colleague points out that it is simple probability - in a distribution, someone must be at the top, someone at the bottom, and "if genetic risks were independent and we consider 50 diseases, the percent of people in the top 5% in at least one disease would be

100 * (1 - 0.95^50)

which is 92.3%. For the top 1% we get 39.5% and for the top 0.1% we get 4.9%."

Which makes me think the second paragraph quoted is not a logical conclusion of the first, but a fairly nuanced position statement - that the predictability of genetic tests may be becoming good enough to be worth knowing about.

However, not everyone present bought into this: the Discussion that followed Donnelly's presentation (p107) begins:

One participant gave the view that discussions on clinical management run the risk of being hijacked by genetic enthusiasts who overemphasised the importance of genetic factors and genetic testing. Other conventional and possibly more important factors in disease aetiology and management, such as lifestyle, social factors and family history could therefore be disregarded.

That Donnelly's position is nuanced is shown by his second conclusion, which can be seen as a refutation of Steve Jones' challenge as to the purpose of GWAS - although the session being quoted was held on 19th March 2008, about a year before the Steve Jones story kicked off:

while there was ongoing uncertainty regarding the clinical utility of genomic tests for disease prediction, the most important outcome of this new research may be in advancing understanding of the molecular causes of disease development, which was already providing new leads for ways in which to prevent and treat common diseases.

Hey Neil,

Great points, and very useful links - I'd strongly second the Kraft paper as an excellent and worthwhile read.

There's definitely a danger that the predictive value of genetic tests will be over-hyped, and I think we can all agree that integrating these tests with both family history and environmental risk factors will be essential for generating meaningful predictions. Telling someone that their SNPs suggest a lower-than-average risk of lung cancer is rather pointless if the person is also a heavy smoker with a strong family history of cancer. Obviously this makes risk predictions more difficult, though.

As for Donnelly's pre-emption of Jones' critique (which was really just an unattributed echo of David Goldstein's NEJM opinion piece); I suspect GWAS researchers started carefully honing this defense as soon as the WTCCC results made it clear that GWAS would find lots of risk variants, but provide fairly trivial clinical predictive power. The "but we found new pathways!" defense does have some genuine truth to it, but it's only really employed because the "but we can now predict disease risk!" defense obviously doesn't hold any water...