When asking your physician is not enough

23andMe and the FDA

Some weeks ago I explained the FDA "closure" of DTC genetic testing business. NEJM analyses with detail the rationale behind such policy:

The goal of the FDA and 23andMe (as well as all clinical geneticists, testing laboratories, and the entire genetics industry) should be to ensure that genomic information is both accurate and clinically useful. Clinicians will be central to helping consumer–patients use genomic information to make health decisions. Any regulatory regime must recognize this reality by doing more than simply adding the tagline on most consumer ads for prescription drugs: “Ask your physician.” That is insufficient guidance unless your physician has ready access to a clinical geneticist or genetic counselor.

European regulation is 15 years old and the new directive is still being discussed. It will not be applied for at least 3 years. Meanwhile, do you know who is protecting us from inaccurate and clinically useless information?

When science and regulation don't talk to each other

An Evidence Framework for Genetic Testing

National Academy of Sciences and Food and Drug Administration don't talk to each other. At the same time that NASEM publishes a report on how to assess genetic testing, FDA clears genetic testing for 23andme without any precise assessment, for the following tests:

• Parkinson’s disease, a nervous system disorder impacting movement
• Late-onset Alzheimer’s disease, a progressive brain disorder that destroys memory and thinking skills
• Celiac disease, a disorder resulting in the inability to digest gluten
• Alpha-1 antitrypsin deficiency, a disorder that raises the risk of lung and liver disease
• Early-onset primary dystonia, a movement disorder involving involuntary muscle contractions and other uncontrolled movements
• Factor XI deficiency, a blood clotting disorder
• Gaucher disease type 1, an organ and tissue disorder
• Glucose-6-Phosphate Dehydrogenase deficiency, also known as G6PD, a red blood cell condition
• Hereditary hemochromatosis, an iron overload disorder
• Hereditary thrombophilia, a blood clot disorder

Meanwhile NASEM recommends a decision framework for the use of genetic tests in clinical care:

1. Define genetic test scenarios on the basis of the clinical setting, the purpose of the test, the population, the outcomes of interest, and comparablealternative methods.
2. For each genetic test scenario, conduct an initial structured assessment to determine whether the test should be covered, denied, or subject to additional evaluation.
3. Conduct or support evidence-based systematic reviews for genetic test scenarios that require additional evaluation.
4. Conduct or support a structured decision process to produce clinical guidance for a genetic test scenario.
5. Publicly share resulting decisions and justification about evaluated genetic test scenarios, and retain decisions in a repository.
6. Implement timely review and revision of decisions on the basis of new data.
7. Identify evidence gaps to be addressed by research.

If you want further details, check Mathew Herper blog. My first impression after reading it is that this move, paves the way for recreational genetic testing. An approach that should be completely banned by legislation. If FDA has done so, let's wait for what it may happen in Europe where the regulator is still planning a change of the regulation in 2022!!! Meanwhile, the door is open (to the worst for citizens).

New album by Txarango. Enjoy it!

Les expectatives de CRISPR (2)

 The Genetic Age: Our Perilous Quest to Edit Life

Avui presento una breu recensió amb IA d'un llibre que va del mateix que ahir, edició genètica. Coincideix en el temps amb el cas de 23andme, una empresa pionera que es troba prop de la fallida després de la fuita de dades genètiques més gran que hi ha hagut. Trobareu articles meus sobre l'empresa al blog.

"The Genetic Age: Our Perilous Quest to Edit Life" de Matthew Cobb, explora la història i les implicacions de l'enginyeria genètica, des dels seus orígens fins a les tecnologies més recents com CRISPR. Aquí teniu un resum dels temes clau tractats al llibre:

● Orígens i Descobriments Clau: El llibre comença amb els experiments pioners d'Avery i els seus col·legues que van demostrar que l'ADN és el material genètic. També es discuteixen els descobriments de les endonucleases de restricció, com EcoR1, que permeten tallar i manipular l'ADN, i la tècnica del clonatge gènic.

● Biohazards i Asilomar: Un punt central és la conferència d'Asilomar de 1975, on científics van acordar una moratòria sobre certs experiments de recombinació d'ADN per tal d'avaluar-ne els riscos. El llibre descriu els debats sobre la seguretat i l'ètica d'aquesta tecnologia emergent, així com les tensions entre els científics i la comunitat política. A més, destaca la importància d'establir protocols de bioseguretat per prevenir la propagació de material genètic perillós.

● Desenvolupament de la Biotecnologia: Es mostra el naixement de la biotecnologia comercial a partir de la tècnica del clonatge gènic. S'explora com les universitats i les empreses van començar a col·laborar per desenvolupar productes basats en l'enginyeria genètica, com la insulina. Es menciona que es van patentar processos de clonació de gens i hi va haver batalles legals per aquestes patents.

● Teràpia Gènica: S'analitza el desenvolupament de la teràpia gènica, amb els seus alts i baixos. El llibre aborda els desafiaments i els fracassos, així com els avenços recents que han portat al tractament de certes malalties genètiques .

● CRISPR i Edició Genòmica: El llibre examina la descoberta i el desenvolupament del sistema CRISPR-Cas9 . Es detalla com CRISPR es va convertir en una eina poderosa per a l'edició genètica , i les implicacions ètiques i socials de poder alterar fàcilment l'ADN. També es discuteixen els experiments amb embrions humans utilitzant CRISPR , així com els debats sobre la modificació de la línia germinal.

● Aliments Transgènics: El llibre analitza la controvèrsia al voltant dels organismes modificats genèticament (OMG) o aliments transgènics . Explora els arguments a favor i en contra dels OMG i com la percepció pública va influir en la seva regulació . Es menciona l'interès per cultius modificats genèticament per a regions d'Àfrica que busquen millorar la seguretat alimentària i combatre la desnutrició .

● Bioseguretat i Bioweapons: El llibre aprofundeix en els temes de bioseguretat i l'ús potencial de la tecnologia genètica per a la creació de bioweapons . Explora la història dels programes de bioweapons a la Unió Soviètica i en altres països . També examina els riscos de l'ús malintencionat de tecnologies com CRISPR .

● Aspectes Ètics i Socials: Es discuteixen àmpliament els dilemes ètics i socials que planteja l'edició genètica. El llibre posa èmfasi en la necessitat de considerar no només els beneficis potencials, sinó també els possibles riscos per a la salut humana, la societat i el medi ambient. Hi ha una menció de la importància del diàleg entre científics i el públic .

En resum, "The Genetic Age" és una anàlisi exhaustiva dels avenços i les complexitats de l'enginyeria genètica. El llibre posa de manifest la necessitat d'un debat continu sobre les implicacions d'aquesta tecnologia, així com la importància de la col·laboració entre científics, reguladors i el públic en general per tal de garantir que els avenços genètics s'utilitzin de manera responsable i per al bé comú.

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

Opening the door to recreational genetics testing

On February 19th, the US Food and Drug Administration (FDA) authorized 23andMe to market a direct-to-consumer (DTC) carrier test for Bloom syndrome. Such test was classified as a medical device, and exempting it from premarket review. This may pave the way for DTC genetic testing in the US market.
The decision to open door for one test may represent the biggest move towards a recreational genetic testing market. You know that from this blog I have backed a ban on developing such markets and the need for an effective regulatory review different from the flawed medical device system.
The european regulator is still on holiday, I said that some months ago and it is still "out".

PS. Variations in health care in GCS Blog.

An ongoing tug-of-war

Understanding Differences Between High- And Low-Price Hospitals: Implications For Efforts To Rein In Costs

Consolidation of private healthcare providers is an increasing trend nowadays. The exact implications for competition and choice are usually unknown. It is worth having a look at other markets. This article in HA explains the impact for the US context:

Prior research shows that private hospital prices vary considerably both within and across markets, even after differences in patient populations and services provided are accounted for. The wide variations in price and the high prices at some hospitals reflect an ongoing tug-of-war between increasingly consolidated buyers (health plans) and increasingly consolidated sellers (hospitals and hospital systems).

Given the intense and growing pressure to rein in the growth in private health insurance premiums, the continuation of current trends appears to be unsustainable. It remains to be seen whether or not health plans will somehow regain the upper hand. If they do not, more radical approaches—such as state-based rate setting or restrictions on contracting arrangements between hospitals and health plans—may gain traction.

PS. HA Blog, a comment.

PS. On limiting bisphenol in food.

PS. Health expenditures NEJM Graphic 

PS.Health Policy Basics: Health Insurance Marketplaces

PS. Are Human Genes Patentable? 

PS. Regulating 23andMe to Death Won’t Stop the New Age of Genetic Testing

The time to stop recreational testing has come

 Direct-to-Consumer Genetic Testing: Value and Risk

Piecing together information from a variety of sources, one reporter concluded that by early 2019, more than 26 million people worldwide had been tested by the four leading companies, 23andMe, Ancestry, Gene By Gene, and MyHeritage (1). That volume was fueled by aggressive marketing, including discounts in the lead-up to major holidays to promote gifting of test kits. As of May 2020, the  undiscounted price of the basic test offered by the leading companies was $59–$99.

This is an example of what should not had happened. Recreative genomics doesn't add value and increases uncertainty and anxiety. 

Although many consumers of DTCgenetic testing express an intention to modify their lifestyle to address risk factors, studies typically show no changes at follow-up (15, 30). In the PGen Study, 59% of participants said that test results would influence their management of their health (31). However, an analysis of the 762 participants who had complete cancer-related data found that those who received elevated risk estimates were not significantly more likely to change lifestyle or engage in cancer screening than those who received average or below-average risk estimates (44). It may be relevant that no participants tested positive for pathogenic variants in highly penetrant cancer susceptibility genes. As for population health, the Centers for Disease Control and Prevention identify three conditions—hereditary breast and ovarian cancer syndrome,Lynch syndrome, and familial hypercholesterolemia—that are poorly ascertained despite the potential for early detection and intervention to significantly reduce morbidity and mortality (45). The hope is that DTC genetic testing could improve the situation (15). However,DTC genetic testing as currently carried out is likely to fill gaps in haphazard fashion, given the characteristics of purchasers, the scope of available products, and integration issues.

One message. Right now and until we don't know the implications of recreational genetic testing, direct to consumers testing should stop.

Banksy

 

Brandant com un saltamartí

Epigenetic protein families: a new frontier for drug discovery

Si ja sabem que al costat de la genòmica hi tenim la proteòmica i la metabolòmica, i que per sobre encara hi tenim l'epigenètica (que literalment vol dir més enllà de la genètica), ara a Nature ens expliquen les diferent famílies i el que representen per al futur de la recerca en nous medicaments.
L'article de revisió és d'aquells que em guardaré perquè si fins ara s'explicava la importància de l'epigènetica i com el paradigma genòmic de la predestinació brandava com un saltamartí, calia posar ordre a les idees. Però també perquè explica amb tot detall com:

Epigenetic regulation of gene expression is a dynamic and reversible process that establishes normal cellular phenotypes but also contributes to human diseases. At the molecular level, epigenetic regulation involves hierarchical covalent modification of DNA and the proteins that package DNA, such as histones. Here, we review the key protein families that mediate epigenetic signalling through the acetylation and methylation of histones, including histone deacetylases, protein methyltransferases, lysine demethylases, bromodomain-containing proteins and proteins that bind to methylated histones. These protein families are emerging as druggable classes of enzymes and druggable classes of protein–protein interaction domains.

L'explicació inicial m'ha semblat un resum útil:

 Although all cells in an organism inherit the same genetic material, the ability of cells to maintain the unique physical characteristics and biological functions of specific tissues and organs is due to heritable differences in the packaging of DNA and chromatin. These differences dictate distinct cellular gene expression programmes but do not involve changes in the underlying DNA sequence of the organism. Thus, epigenetics (which literally means ‘above genetics’) underpins the fundamental basis of human physiology. Importantly, the epigenetic state of a cell is malleable; it evolves in an ordered manner during the cellular differentiation and development of an organism, and epigenetic changes are responsible for cellular plasticity that enables cellular reprogramming and response to the environment. Because epigenetic mechanisms are responsible for the integration of environmental cues at the cellular level, they have an important role in diseases related to diet, lifestyle, early life experience and environmental exposure to toxins1. Thus, epigenetics is of therapeutic relevance in multiple diseases such as cancer, inflammation, metabolic disease and neuropsychiatric disorders, as well as in  regenerative medicine

Així doncs, ens trobem davant un horitzó de noves descobertes que es va configurant i que explica en bona part perquè s'ha tardat més d'una dècada en traslladar el projecte genoma humà  cap a aplicacions terapèutiques àmplies. Però també s'obre un nou interrogant sobre a seguretat dels modificadors epigenètics dels medicaments. La forma com caldrà avaluar-ho suposarà més exigència al regulador i una necessitat de transparència de la caixa negra encara més gran. Seguirem atents,  perquè per ara ja se li ha girat feina amb els inhibidors HDAC, per al limfoma cutani de cèl.lules T, el primer d'aquests medicaments.

PS. I si voleu una perspectiva diferent, consulteu aquest article.

PS. Millor no saber-ho. Ja ho vaig explicar fa temps i ara ho trobareu al WSJ. Cal conèixer la teva predisposició a l'Alzheimer mitjançant un test genètic? de què et servirà. Podeu llegir aquí una història real que em confirma el que deia.

PS. I si l'altre dia teníem una galleda d'aigua freda, ara en tenim una altra de calenta. 23andMe acaba d'obtenir una patent genòmica als USA. I precisament ho fa utilitzant arsenal de dades epigenètiques. Després de cinc anys sense beneficis i sense haver apostat per les patents, han trobat un forat i el podrien fer més gran. Cal estar atents.

In “Round Hill” (1977), the light is a harsh glare, enveloping five languid bathers in the Caribbean in a self-contained, enclosed moment of time and place. The figure in the foreground turns away from us, so we see only the back of his head; the others are self-absorbed, expressions hidden behind sunglasses.

Alex Katz: Give Me Tomorrow’, Tate St Ives to September 23, www.tate.org.uk