Medicine as a data science

THE PATIENT WILL SEE YOU NOW
The Future of Medicine Is in Your Hands

Maybe the title is the most confounding factor of the new great book written by Eric Topol.  Once you have finished reading it, you'll be convinced that he set the expectations to high, ordinary people should develop certain skills beyond their capabilities to apply such concept. I would say that a greater part of the medicine is in your hands, not medicine at all. The rationale behind the book is that medicine digitization allows patients to know more about their disease and how to "manage" it in certain cases. The most important thesis is that future medicine has to be considered a data science. And this is exactly the impact of the digitization of diagnostic and treatment: pervasive application of Bayes theorem in clinical practice, using big data and analytics.(Remember my archimedes posts, surprisingly Topol forgot it).
The book includes many topics that those that follow this blog it would sound familiar, i.e. ch. 4 about Angelina Jolie and BRCA genetic tests, a must read. And chapter 5 is a journey on the new omics of the medicine, a topic that I have also covered in the blog.
Nowadays, Eric Topol is the writer that is able to capture what's going on in medicine and its impact on society. That's why this book is a key reference of our time and I strongly recommend it.

PS. If you don't believe me, check Forbes, NYT, WP, WSJ.
PS. The book is also an invitation to change the current academic programmes for life sciences universities. Better now than later.

The hype over genetic tests

Implementation of a companion diagnostic in the clinical laboratory:The BRAF example in melanoma

Analytical validity is one of the three steps for any assessment of genetic tests, combined with clinical validity and clinical utility. Understanding how this process affects specific tests is not that easy.Fortunately you can find a detailed explanation of one of them:the BRAF genotype analysis in tumor tissue samples for identification of melanoma patients that can benefit treatment with BRAF inhibitors.
Once you begin to read the article you'll understand the complexity of being precise in a test. This is the reason why if specificity and sensibility is uncertain, different methodologies are needed (check Figure 1).
But how to do it?. How to set up external controls of quality?. All these issues are covered in this article, that explains what's going on in practical terms. I'm concerned if due to such complexity, all "genetic test talent" is not concentrated in one site of the organization-hospital, and many departments and services -oncology or cardiology- are developing their own genetic tests. Somebody should block this option before it is too late.

European health regulator on holiday

After Canada, the first european country that has allowed recreational genetic testing is UK. Some weeks ago the Ethics Research Committee approved the commercialisation of 23andme test that provides 100 genetic reports. Wired says:

The £125 spit test kit is not a diagnostic test, but instead identifies genes that are associated with inherited conditions including cystic fibrosis, Alzheimer's disease, Parkinson's disease and sickle cell anaemia. It's not just health information that can be discovered within the results of the test though -- there is also the opportunity for customers to learn more about their inherited traits and genetic ancestry.

Why has the UK approved it and the FDA has restricted the same test in the US?.  Some months ago I explained that european legislation was outdated. Now the genetic testing firm has profited from bad regulation to enter into european market with CE mark. Does anybody know where the regulator is spending their holiday?

PS. While being  so easy to regulate recreational genetic testing under current false advertising rules, why is only the US doing that?. You should know that closer than you think similar tests are available for you. Where is the catalan health regulator?

PS. Why is the tax regulator not on vacation?

Emile Claire Barlow - Jardin d'Hiver

The uncertainty over genomics sequencing value in clinical decision making

Assessing Genomic Sequencing Information for Health Care Decision Making: Workshop Summary

"The value of genetic sequence information will depend on how it is used in the clinic", key statement that needs some elaboration. This is precisely what the IOM report does, you'll find in their pages the current situation about how genomics may impact in decision making. In chapter 5 you'll understand how an insurer decides about coverage of such tests according to 5 criteria:

1. The test or treatment must have final approval from appropriate governmental regulatory bodies, where required;
2. scientific evidence must permit conclusions about its effect on medical outcomes;
3. technology must improve net health outcomes;
4. the technology must provide as much health benefit as established alternatives; and
5. the improvement in health must be attainable outside investigational settings.

Unfortunately, if you start from the first one, you'll find a complete lack of references by governmental bodies on the approval of such tests. Therefore, I can't understand from the chapter how successful they are on such process.
While reading the book you'll increase your uncertainty about outcomes and value of genomic tests instead of reducing it. This was my impression. Let's wait for future good news, again.

PS. Summary of the report:
"Clinical use of DNA sequencing relies on identifying linkages between diseases and genetic variants or groups of variants. More than 140,000 germline mutations have been submitted to the Human Gene Mutation Database and almost 12,000 single nucleotide polymorphisms have currently been associated with various diseases, including Alzheimer’s and type 2 diabetes, but the majority of associations have not been rigorously confirmed and may play only a minor role in disease. Because of the lack of evidence available for assessing variants, evaluation bodies have made few recommendations for the use of genetic tests in health care."

The hole for genetic testing market entry

Technology Assessment on Genetic Testing or Molecular Pathology Testing of Cancers with Unknown Primary Site to Determine Origin
Update on Emerging Genetic Tests Currently Available for Clinical Use in Common Cancers

AHRQ has just published two reports of interest. The first is devoted  to assess the evidence on the analytical validity, clinical validity, and clinical utility of commercially available genetic tests for identifying the tissue of origin (TOO) of the cancer in patients with cancer of unknown primary (CUP) site. The second describes genetic tests that have applications in the common solid tumors (breast, lung, colorectal, pancreas, etc.) as well as tests that are used in hematologic cancers (leukemia, lymphoma) and are already available in clinical practice.While the first is an assessment, the second is informative.
There is still a third report to be released and meanwhile NRD explains its conclusions. Having selected 11 prognostic tests, only around half had evidence supporting their prognostic accuracy or clinical validity. Therefore the question is always the same: why these tests without evidence are on the market? Why have they been approved by the FDA?. There is a big regulatory hole to fill in.

False advertising

The concern over consumer protection is growing with new health technologies. This is not new, you may think. However the lawsuit by FTC against Genelink for misleading claims is the first case in a genetics testing company. Genelink said that they analyzed your DNA and afterwards send back nutritional supplements customized to your personal genome. The regimen, the company promised, was good for diabetes, heart disease, arthritis, insomnia and other ailments.On request by FTC, they were unable to confirm such promises.
Since you may find a similar test on the corner of the street, once again my question is: where is the regulator?

PS. Some months ago, was the FDA who asked 23and me to stop selling its genetics test kit.

PS. On DTC genetic tests, a good article.

Courts as market makers

Recent decision invalidating Myriad patents has had immediate results. The market of genetic tests on breast and ovarian cancer has new entrants. The price of the test has decreased 40% (!) in just four months after the resolution. More entrants are expected in the next future for more tests.
The question is still the same, is there any clear cost-effectiveness analysis available for such tests? Why homebrew tests (LDT) are beyond any regulation? Does any regulator care about all this issues?. The answer is: up to now, we can't see any efforts. Patents create artificial monopolies, courts may create markets when invalidate patents,  but patients are concerned about health improvement and value. In an asymetric information environment, the regulator can't take permanent holidays. Overdiagnosed population doesn't necessarily mean healthier population.

 Forbes Healthcare Summit 2013

Insurance Companies Enter A New World

Genome sequencing mess

Since the world is more complex than it used to be, it is our duty to prevent any further complication. However sometimes some individuals forget it. The anouncement of sequencing genome for 100.000 citizens in UK last December raised controversy and BMJ right now publishes a head to head on this issue.
This blog has remarked many times that if effectiveness of any benefit is undemonstrated, then value is uncertain and potential harm of its application exists.
The summary of the position against sequencing is the following one:

If we sequence individuals’ DNA and tell them that they are genetically predisposed to be slightly more at risk of common diseases, we may be doing them a great disservice, demotivating them from behaving sensibly. And the private sector will see a marketing opportunity for all sorts of clinically unnecessary and potentially damaging screening, with further negative and unintended consequences. Possessing the technical ability to do something new is not an immediate justification for going ahead with it, especially in such an ethically complex area. Good medical practice requires tests to answer a specific question with a reasonable expectation of results being interpretable and useful. Currently, whole genome sequencing in healthy individuals has nothing to offer clinically because most of the data generated are meaningless; the maxim first do no harm still holds.

However, a subtile strategy has emerged recently. The Wellcome Trust will  finance with 3.2 m € a pilot study in London to analyse 97 cancer predisposition genes starting in 2014. It's not by chance, it coincides with Angelina Jolie double mastectomy recent news, and the patent expiration in 2014 of BRCA genetic tests. Is this a philantropic affair? or market access strategy?. The answer is yours.

PS. Beware of nonprofit foundations working for profit. This is a succesful strategy for market access when regulatory constraints have been set up and transparency rules apply. In such cases free lunches exist suspiciously,  but in the long-run they always disappear, and the social cost is enormous.

PS. A call to challenge "Selling Sickness"

PS. Save the date Sept 10-12 to prevent overdiagnosis.

Economics of genomics

The Economics of Genomic Medicine - Workshop Summary

Just imagine for a while that you are concerned about economic implications of genomics and you invite a distinguished professor of genetic medicine - James Evans- to the introduction of a workshop at IOM. Instead of more is better, he sends a cautious message to the audience. And beyond the potential and valuable applications for those that are already ill,  he openly critizises the current trend towards the use of genetic tests for the healthy:

Assessing the risk of common diseases through whole genome analysis of a healthy person has received the most attention, but this attention “is somewhat misplaced,” Evans said. Currently, assessment of genetic risk alleles has “rather feeble predictive power” because the increased risks tend to be small. “From a clinical standpoint I don’t know what to do with patients who are at a 1.3 relative risk for colon cancer,” said Evans. “Am I going to hurt them by doing more intensive screening, or am I going to help them?”

"I know what almost everybody in this room is going to die of,” said Evans. “We are going to die of heart disease or cancer. . . . We are all at high risk for these maladies regardless of our [genomically determined] risk. And many at decreased risk for heart disease will still die of heart disease. So we are all going to benefit from interventions that lower heart disease. We don’t really need to target people. It doesn’t do anyone much good to tweak our estimation of an individual’s relative risk for common diseases which we are all at high absolute risk of developing anyway."

 “The old adage that an elephant for a nickel is only a bargain if you have a nickel and you need an elephant applies here. I am not sure most of us need that elephant. Even if free, perceived low cost is an illusion, because the misapplication of medical tests—and make no mistake, whole genome sequencing is a medical test—is very expensive,”

A clear message for geneto-enthusiasts and marketeers. Cost-effectiveness of genetic testing starts with assessing if they are effective. If not, any economic analysis is useless . This is obvious, but we do need to repeat it, just in case.

PS. Must read, Reinhardt's blog.

PS. A report to understand the financial markets' mess and why recovery is far by now.

Veure-les passar

El tema segueix sobre la taula. El debat sobre les proves genètiques i com regular-les preocupa a la FDA i encara que ja ha dit que cal aplicar els mateixos criteris que als subministraments mèdics (medical devices), hi ha molts dubtes sobre els detalls.

Els de Genomics Law Report expliquen el que ha passat a les compareixences recents. Si n'esteu interessats feu-hi una ullada.
Les preguntes clau:

Should the agency require proof of analytical validity, clinical validity and/or clinical utility prior to approving a particular test and, if so, what standards of proof should be required?
Should the agency regulate tests SNP-by-SNP, claim-by-claim or test-by-test, and what should be done to prepare for the inevitable arrival of tests based on whole-genome sequence data?
Should the agency oversee the labeling and advertising claims offered by companies in association with such tests?
Should the agency require companies to collect and submit data regarding the post-test benefits and harms and the actual (as compared to intended) uses of their tests?
Should the agency impose requirements on companies to prevent unauthorized testing, protect data privacy and limit companies’ ability to share genetic information without their customers’ consent?

While these questions, and countless more, will be critical to the development of sensible genetic testing regulation, one question clearly generates more and more emotional responses than any other:

Should regulators require some or all genetic tests to be routed through a clinician, or should tests be made available directly to consumers who desire them?

I mentrestant per aquí, les veiem passar...i ens costen una pasta...

PD. El gran Ferran Torrent representa una alenada d'aire fresc els diumenges, tant en directe a Rac1 com els comentaris a ARA. Cita Josep Renau: "Quan arribes a València i et menges una paella o una sípia t'oblides de la lluita de classes". I mentrestant els de FT ens recorden que "Valencia is burning"