Tag Archives: LDT’s

TOP TEN STORIES IN GENETICS, 2016: An Adolescent Science Meets the Big World

Clinical genetics is a young science, not yet come of age – a new discipline. It’s early days, say the small group of clinicians and researchers who have watched over its formative years, dreaming like proud parents of a future where genetics and genomics are integral to clinical medicine. And as for many parents, it may sometimes have seemed that the all-consuming, semi-hermetic little laboratory of childhood would go on forever.

But guess what, people? I believe we have entered the teenage years.  I believe baby has borrowed the car keys and taken it out for a spin.  I see a field boasting a few real accomplishments, and on the cusp of so many changes, from therapies for genetic disease and cancer to a suddenly burgeoning DTC marketplace. And like all parents, geneticists are poised to discover the limits of our ability to control what we have nurtured. That’s exciting, more than a little bit scary, and the theme of this year’s top ten.

  1. FDA CANCELS PLANS TO REGULATE LDT’s

Over the past two decades, a single technological advancement has revolutionized the way we practice medicine.

I am talking, of course, about overnight delivery of packages.

Years ago, laboratory testing services were divided into large companies that sold test kits and devices nationwide, and the small labs in hospitals and other clinical settings providing services to their local providers. With limited resources, government regulators focused on the tests that affected more people, and agreed by convention that ‘laboratory-developed tests’ would not be subject to the same scrutiny. Today these distinctions are virtually meaningless, as giant companies like LabCorp and Quest perform tests ‘in-house’ on samples gathered worldwide, tossed in a box and sent overnight. Still laboratory-developed tests (or LDT’s) – a category that includes virtually all genetic tests – remain in regulatory limbo.

In 2010, the FDA announced its intention to address this loophole. In July 2014, they issued draft guidance detailing their plan for a regulatory structure that divided the LDT universe into high, low and medium risk tests. While some professional organizations disputed the FDA’s right to have a role in regulation of LDT’s and threatened legal action, others approved the framework in principle but disagreed on specifics, including how to handle the thorny new territory of exome and genome sequencing. A dialogue ensued with representatives of labs, clinicians and patients that has lasted two years and included multiple workshops and public meetings. That process, it was widely assumed, was nearing its end, with the resulting draft guidance expected to be sent to Congress for approval in the near term.

And then came November 8th and the election of Donald J. Trump, ushering in an executive opposed to regulation on principle, to join a similarly inclined House and Senate. Ten days later, the FDA ran up the white flag, announcing that the agency would not take steps to finalize its existing plan and would instead reopen the discussion with a new administration and a new Congress. What this means precisely is a matter of some interesting speculation, but in general it suggests that an industry that has been struggling for years to avoid too much regulation will have to consider the consequences of living with none at all.

 

  1. IS THIS THE FUTURE? CRISPR EXPERIMENT ADDS RARE PROTECTIVE VARIANTS TO HUMAN EMBRYOS

The second experimental use of CRISPR technology to alter human embryos was reported in May of 2016, again by a group out of China. Again, the embryos used were not viable, and no attempt was made to transfer them for reproductive purposes. While this experiment did not produce the same ethical firestorm as the first, it was in several ways a more significant indicator of both the potential and the peril of human germline engineering using CRISPR.

In the first experiment investigators attempted to alter a gene variant responsible for causing hemoglobinopathy, with limited success – proof in principle that it could be done, but nothing to assure worried observers that it could be done safely. In version 2.0 there were fewer off target effects, but researchers were not able to consistently control the content of changes introduced in place of the edited DNA. This is not inconsistent with what we know so far about CRISPR: if we envision it as a word processing search-and-replace function, it is good at the finding and erasing part, but hit or miss when it comes to  putting in a replacement.

What stands out about the second experiment is that the goal was not to eliminate a disease-causing gene, but to insert a rare and protective one – in this case, the CCR5Δ32 allele that offers the bearer reduced susceptibility to AIDS. Gene editing is often envisioned as a way that individuals whose children are at risk can avoid or change genes that cause disease, but in the vast majority of these cases there are simpler and better established tools such as PGD if the goal is to obtain embryos that do not carry a specific variant associated with some catastrophic risk. Why use technology to substitute out a pathogenic BRCA variant or a double dose of the sickle cell genes when the parents are perfectly capable of producing a healthy embryo themselves? What CRISPR and related technologies can do that is not available through other means is to introduce a gene that neither parent carries. That is a powerful new option, and it is both exciting and scary in the manner of all things powerful and new.

 

8. GENETIC DISCRIMINATION MAKES A CAMEO

Many wise observers have noted that for all our deeply felt concerns about genetic discrimination, to date the examples are few, far between, and usually more clumsy than systemic (looking at you, Burlington Northern Santa Fe Railroad). These arguments, redux, were on display in 2016 as Canada debated and ultimately passed its own national genetic discrimination law. Yes, Globe and Mail Guy, there is little evidence of a big problem, and a look at law suits filed between 2010 and 2015 under GINA, America’s genetic discrimination law, proves the point. But one real unanswered question remains: is the absence of institutionalized discrimination a sign that it is destined to be a bit player in the big picture of genomics, or is it only too soon to tell? Big companies, whether they are offering insurance or providing employment, may not have had an incentive to weather a PR shitstorm in order to use genetic information to limit their exposure to risk when not that many people have been tested, and the reliability of the data is debatable – which it has been in these early days. Genetic discrimination, in other words, may be making an appearance in Act II.

Two stories got some attention in 2016; whether they are one off events or signs of the future – well, that’s crystal ball territory. Are they important? They are something to which we should be paying attention. Attention should be paid.

In January, Stephanie Lee at Buzzfeed published an account of a boy named Colman Chadam who was asked to leave his Palo Alto, CA school because he carried two mutations commonly associated with cystic fibrosis, although he did not have any signs or symptoms of the disease. The results of genetic testing, inappropriately revealed by a teacher at the school, were taken, also inappropriately, as diagnostic. The reason this got him thrown out of school was to avoid contact with another student who did have CF. The emphasis on keeping children with CF apart, which sounds weird if you don’t know much about the disease, was about the only appropriate thing that happened, because individuals with CF are at risk of passing one another dangerous and life-limiting infections.

Although Colman did not have to leave the school, and the Chadam’s lawsuit against the school district has settled, the case continues to raise issues about how genotype as distinct from phenotype can be used under the law. In addition, it may signal the need for measures to protect personal privacy (no such thing, I know, I know) in an age when genetic testing is commonplace.

Three weeks later, Christina Farr wrote an article for Fast Company about a woman who was turned down for life insurance because she had a risk-conferring BRCA1 variant. Unlike the Chadam case, this is not a result of genetic illiteracy, and it is not a violation of any law: GINA does not cover insurance for life or long-term care. It is, in fact, exactly the kind of genetic discrimination that ethicists and patients thinking about genetic testing have worried about over the years, and if systemic, would certainly be an important point for genetic counselors to raise in pretest counseling (if pretest counseling is still something we do, which is an issue unto itself…but related). According to the article, genetic testing for cancer susceptibility is not required by any insurance company, although nothing stops them from doing that, but companies are starting to request to see test results when they exist. Failure to answer questions honestly can invalidate policies if you are caught.

If this becomes the status quo, it may affect uptake of genetic testing. If it is curbed through regulation, genetic testing may change the way the insurance industry operates. Act II is going to be interesting! I am having a couple of stiff drinks and heading back to my seat.

 

7. TYPE II DIABETES: RESISTANT TO INSULIN AND EASY ANSWERS

Genome wide association studies (GWAS), a way of looking at common variants in the gene pool to identify genetic susceptibility to common diseases, have been unable to explain the degree to which liability to these common diseases is inherited, although it clearly is. If you are in genetics and this is news to you, you have not been paying attention.

Many reasons for this have been proposed, and many are likely a part of the answer. One thought was that individually rare variants might be collectively common enough to play a big role in generating risk, which would not be picked up by GWAS, as it traditionally looked only at variants carried by at least 5% of the population (“the population,” as though there was only one!). Looking at rare variants takes a village, but that is what a googleplex of Type II Diabetes researchers did to produce an epic July 2016 paper in Nature.

Okay 300 authors on the paper so close enough.

The report by first author Christian Fuchsberger showed that MEGA*GWAS produced the most GWAS-y result possible: intellectually interesting, informative and ultimately inadequate. Using exome and whole genome data to capture a broader range of variation, the study found significant association to a handful of previously unknown common variants, and then failed to replicate a good chunk of what we thought we knew. Uncommon variation? The researchers found 23 loci that appeared significant, which was meaningful, but nowhere near enough to validate the rare variant hypothesis as the smoking gun in the Mystery of the Missing Heritability. “A comprehensive and extremely well written paper,” said Dan Koboldt at MassGenomics, and you can almost hear him sigh.

 

6. DATABASES: IT’S NOT JUST FOR WHITE PEOPLE ANYMORE

We don’t have enough diversity in our databases. It’s not exactly news, and yet publication of an article called “Genetic Misdiagnoses and the Potential for Health Disparities” in the August issue of the New England Journal of Medicine felt like a slap in the face.

The methodology was not complex. For hypertrophic cardiomyopathy patients, doctors use genotyping to identify individuals and family members at risk for sudden and catastrophic cardiac events. Identification as ‘at risk’ is a traumatic and often life changing event, requiring ongoing medical screening and behavioral modifications. For these families, a lot rides on whether or not a variant is considered pathogenic. One bioinformatics tool is to look at databases, because there are limits on how bad a variant can be if it shows up regularly in healthy individuals. The study checked variants labeled pathogenic against an increasing wealth of exome data available in public databases and found that a number were common in the African-American population. Result: reclassification from pathogenic to benign of multiple variants affecting primarily African-American families.

“Simulations,” said the authors, “showed that the inclusion of even small numbers of black Americans in control cohorts probably would have prevented these misclassifications.

 

5. IMMUNOTHERAPY: A NEW STAR BURNS BRIGHT AND HOT

Earlier this week, my sister-in-law was telling me about a friend with a cancer deemed treatable but not curable. “But if they get it in remission,” she said, “and he has more time, maybe there will be something new.” There it was – the cancer prayer. May There Be Something New. And I thought, has there ever been a moment when those words felt more hopeful than right now?

Hopes have been raised before, by promises that money would bring answers, and we wandered down blind alleys and into mazes waving cash as though the scent of it would draw the answers to us, but this time, progress is lighting the way like street lamps, and money follows hope instead of the other way round. Immunotherapy – engineered cells meant to light the bodies own defenses into a controlled burn that destroys cancer cells and leaves the rest untouched – has burst onto the scene since 2015. Cancer researchers report on progress in Hemingway stories, terse narratives of a few more days, an extra month or two, and that’s a win, but suddenly we are getting Gabriel Garcia-Marquez fables of magic beans and people rising from their deathbed.

So which story is more 2016: Sean Parker’s 250 million dollar cancer institute, connecting Silicon Valley money with Car-T cells that he describes as “little computers,” and presenting to the NIH in comic sans? Or the unexpected lethal immune response that shut down a Car-T trial by Juno Therapeutics in November, after four people died of cerebral edema?

It’s the two in conjunction that tell the tale. Immunotherapy is truly a candle in the wilderness, but it’s a candle that burns rocket fuel. Or perhaps I should say, in the spirit of the season: catch a falling star and put it in your pocket – bet it burns a hole in your ass.

 

4. A NEW DTC GENETICS EMERGES WITH HELIX

In October, Helix announced the first fruit of its partnership with DNA-lifestyle start-up Exploragen and it’s grapes: Vinome, a company that promises to sell you wine tailored to your genetic profile for something like fifty bucks a bottle. I’m not a wine drinker and that sounds like a lot of money but, hey, you do you.

For Helix, the Illumina spinoff that debuted in 2015, this was one of a series of 2016 announcements giving us a more concrete vision of their plans for a sequence-once-access-often platform for DTC genomics. The structure of it is like Apple, if your IPhone didn’t even pretend to be a phone, and existed entirely as a vehicle for apps. With your first purchase, Helix will underwrite the cost of sequencing and storing your entire exome, and then sell it back to you bit by bit in the guise of applications created by partners.

Effectively, the Helix model lowers the barrier of entry for any product based on DNA testing, by spreading out the cost over a myriad of marketing opportunities. Some current players in the DTC universe have signaled their interest in playing in Helix’s playground; Geno 2.0, National Geographic’s version of ancestry testing, is already available on the Helix website. Others may take their toys and stay at home. Daniel MacArthur of the Broad Institute once penned an April Fool’s Day account of a company named Helix Health’s plans for a hostile takeover of 23andMe using Somali pirates, but for real the entry of an Illumina-backed company into the DTC space must have some Mountain View observers concerned that the current industry thought leader might end up the Blockbuster Video of the genomics world.

The uncorking of Vinome raises a few questions that existing partnerships with, say, the Mayo Clinic or the Icahn School of Medicine at Mt Sinai do not. One role that Helix could potentially play is to provide the vetting service much needed in the consumer genomics world, with its mishmash of pharmacogenetics and Warrior Gene testing and supplements designed just for your DNA.

As for Vinome, the eminently quotable Jim Evans called it “silly” in an article by Rebecca Robbins in STAT. “Their motto of ‘A little science and a lot of fun’ would be more accurately put as ‘No science and a lot of fun,’” said Evans — which I guess is true, if paying fifty dollars for a bottle of wine is your idea of fun. But like Apple, Helix is going to have to make some hard decisions about how much it takes responsibility for the quality of the partners it allows to come play in its sandbox.

 

3. GENOMES OF MASS DESTRUCTION

In February, for the first time but probably not the last, the U.S. Director of National Intelligence’s assessment of worldwide threats included genome editing as a weapon of mass destruction. Congratulations, genetics: we’ve made the big time.

The report pointed to the widespread use of new genetic technologies like CRISPR in countries with different regulatory and ethical standards, its low cost and the rapid pace of change as pre-conditions that might lead to intentional or unintentional misuse, though it was vague as to what form they thought the threat might take. More specific concerns were articulated later in the year by the Pentagon’s Defense Advanced Research Projects Agency (called DARPA of course, because…government) in announcing a program called Safe Genes intended to establish a military response to of dangerous uses engineered genes. DARPA, which Scientific American reports has been a major funder of synthetic biology, will support projects that look at ways to remove engineered genes from a variety of habitats and in a variety of circumstances, including those spread through gene drive.

 

2. A BREAKTHROUGH DEFIES CONVENTION AND GEOGRAPHY

On April 6, 2016, a baby was born after the transfer of his mother’s nuclear DNA into an enucleated donor egg in an effort to avoid the mitochondrial disease that killed the couple’s two previous children. The success of mitochondrial transfer therapy itself was not a shock, since earlier experiments had demonstrated good outcomes in animal models and in in vitro human embryos. The circumstances, however, were startling: the procedure was done in Mexico, for Jordanian parents, with the help of a New York-based fertility doctor with no known expertise in mitochondrial disease.

Some have argued that mitochondrial transfer therapy represents a violation of international norms forbidding any germline genetic change, which were meant to provide a clear dividing line between somatic changes associated with gene therapy and genetic engineering with the potential to impact future generations. Pretty clear in theory, but all of these divisions are less clear in reality – there are no guarantees that gene therapy doesn’t affect eggs or sperm, and mitochondrial DNA itself challenges any simple equivalence between the molecular structure of DNA and the intellectual concept of our ‘germline’.

Mitochondrial transfer is illegal in the United States but permitted in Great Britain under a 2015 law, and applications for clinical use have been approved for 2017. Its apparent success – independent sources confirm that the baby appears to have traces of maternal mt DNA associated with Leigh syndrome but no sign of disease – is a cause for celebration for the families whose children are at risk. The step forward is a milestone, but so is the way in which it occurred, which demonstrates the extent to which geography and national laws are no match for money and access in determining what is possible.

Personal note: on my wish list for 2017, can we PLEASE stop cheapening the concept of parenthood by using the term ‘3-parent babies’? If I donated a kidney, that person would have some of my DNA, but it wouldn’t make me their momma.

 

1. WHITE SUPREMACISTS LOVE GENETICS, BUT GENETICS DOES NOT LOVE THEM BACK

Nothing about the year 2016 was more disturbing than the empowerment of the alt right, an all-purpose term for the angry souls that crept out from under rocks to preach hate and division. Here at home and all around the world, narratives of race and ancestry emerged as powerful drivers in political and social movements based on appeals to base and tribal instincts – fear mongering about immigrants, Islamaphobia, white supremacy. In October, Elspeth Reeve at Vice ran a story about white supremacists posting their 23andMe results to prove their whiteness.

This embrace of a science that does not love them back is evident even without a deep dive into the world of Stormfront and 4chan.  Twitter trolls talk about ‘founder effects’ and ‘genetic drift’. A Breitbart tech editor, now barred from twitter, writes gleefully about associations between race, behavior and intelligence, mocking disbelievers as prisoners of an “all-consuming cult of equality.”  The L.A. Times describes the alt-right as “young, web-savvy racists who are trying to intellectualize and mainstream bigotry.”   These viewpoints aren’t mainstream, but their proponents can no longer be dismissed as fringe, with Breitbart’s founder about to be ensconced in the White House as chief strategist, and reports suggesting that the presumptive next National Security Advisor Michael Flynn taking meetings with the head of an Austrian political party founded by former Nazis.

The connection between white nationalism and population genetics is proof once again that genetics as a field is uniquely susceptible to misuse by agenda-driven movements intent on the subjugation of others. Donald Trump ran against political correctness, but his rise has proven the importance of language. As Michelle Obama says, “words matter.” Push back against the misuse of genetics to fuel ‘racialist’ theory. Ancestry sites should think very hard about the manner in which they present their findings, which stress differences without acknowledging the greater than 99% of DNA that we all share. Scientists need to address and refute the ways in which their work can be misconstrued to reinforce prejudice and unsubstantiated visions of racial differences. We all have to be careful not to promote explanations of genetic effects that oversell the determinative power of genes.

Genetics is a science of the future. Let’s not let it be used to drag us back into a tribal past. Peace out, Genetics, and here’s to a better year in 2017.

 

 

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NEW PROPOSED REGULATIONS ON TESTING FROM THE FDA ARE LONG ON INTENTION AND SHORT ON DETAIL

On July 31st, the FDA announced its intention to regulate both laboratory developed tests (LDT”s) and in vitro diagnostic (IVD) companion devices, and it will soon be asking for public comment on the proposed regulations. Should genetic counselors be among the people commenting? Well yes, as the new rules are likely to affect genetics practice, since many of the tests that look at genetic susceptibility are LDT’s and could be subject to a premarket review by the FDA that will delay or deny the clinical availability of new tests, and a mandatory process of adverse result reporting. The impact will be felt most immediately in cancer settings, where genetic tests that look at tumor DNA for purposes of choosing targeted therapies or predicting prognosis are likely first candidates to draw FDA scrutiny, but eventually the new rules should affect a range of clinical specialties. At stake is finding the balance between too much regulation, wherein it becomes prohibitively difficult and expensive to introduce new tests that can help diagnose patients and personalize recommendations for screening and treatment, and too little regulation, wherein we suspect that our information on the accuracy and reliability of new tests is not adequately accurate or reliable (an ongoing issue, by the way, with non-invasive prenatal testing. See Katie Stoll’s post here and a study, new this week, suggesting that the dreaded false positive result may be more common than test makers have led us to believe).

 

A little background on the two closely related entities that are the focus of new regulations. LDT’s are what used to be called “home-brews”: tests that are used by a single lab and not marketed as a kit or a device. Somewhat by historical accident, LDT’s have come to exist in a regulatory grey area, effectively exempt from FDA oversight. The assumption behind this was that what went on in an individual lab affected only that lab’s patients and that no agency could track every one-off solution engineered by a mom-and-pop lab. As with everything else in 2014, the status quo has been disrupted by new technology – but in this instance the new technology isn’t the magic of Google or whole genome sequencing but overnight shipping. Yes, the world of genetic testing has been turned on its ear by the likes of UPS and Fed Ex.

 

In brief, now that the Pony Express has picked up its game, laboratories can test samples from all over the world in centralized locations with sophisticated and expensive testing capability that isn’t available back on the farm. At the same time, lab tests, including genetic tests and biomarkers like measures of gene expression, play an increasingly important role in making diagnoses and determining treatment. For this reason, the FDA has moved in its determined yet glacial manner to regulate a subset of tests that are considered high or medium risk – those tests which have the potential to alter medical care, and therefore have significant implications if the information they provide is incorrect. This risk-based approach is a measured step – it allows the FDA to continue to use discretion when tests are low risk or experimental or involve a rare disease for which there is no other test.

 

IVD companion diagnostics are tests developed to be used in conjunction with a drug or other therapy – tests that can be used to refine dosages or identify good candidates for a given therapy. Obviously pharmacogenetics is a subset of this broader category of companion testing. Again, the proposed regulatory framework would stratify the tests as high risk, moderate risk, low risk – requiring pre-market approval for higher risk tests, and allowing the agency to exercise “discretion” in low risk situations (discretion is FDA-speak for a wink and a nod). With regard to IVD diagnostics, the FDA intends not just that the tests on offer be confirmed as reliable, but is instituting the requirement that companion testing be included in the development of new therapies as a matter of course. In effect the government is mandating that all new therapies be individualized to the greatest extent possible: When an appropriate scientific rationale supports such an approach, FDA encourages the joint development of therapeutic products and diagnostic devices that are essential for the safe and effective use of those therapeutic products.” The age of personalized medicine is upon us, and the FDA is ON IT.

 

If all this sounds familiar, it only means that you have been paying attention. Since 2010, the FDA has been asserting publically that it has both the intention and the authority to regulate LDT’s and IVD’s. Going back even further, the Genomics and Personalized Medicine Act of 2006, introduced by then Senator Barack Obama, emphasized the development of companion diagnostics, calling on the National Academy of Sciences to recommend incentives and requiring the Institute of Medicine to improve “oversight and regulation of genetic tests.” While the bill was never passed, it is not surprising to see a similar emphasis under the current administration.

 

So, genetic counselors, are we for or against the proposed regulations? Probably the answer to that question is — yes. Like the FDA, most people seem to be in favor of some middle option – regulating everything is virtually impossible and regulating nothing is an appealing libertarian fantasy, but in fact it would put counselors in the uncomfortable position of having to rely on figures supplied by the companies who manufacture the tests. Careful observers like the Genetics and Public Policy Center have been calling for increased oversight for genetic testing for years. Their 2006 summary of a genetic testing quality initiative sums it up this way:

 

assessment of public attitudes shows that the public widely believes that the government regulates genetic tests to ensure their quality and, moreover, that the government should play this role. In fact, however, genetic tests are subject to very little governmental oversight when compared to other health care products. There is no formal approval procedure a laboratory has to go through before offering a new genetic test, and government requirements to ensure that genetic testing laboratories are getting the right answers to patients are minimal. Moreover, there is no government requirement that a test must be clinically valid – i.e., actually relate to a particular disease or risk of disease – in order to be sold.”

 

However, both the American Clinical Laboratory Association and the American Medical Association have reacted negatively to the proposed FDA regulatory strategy. The ACLA pushback comes as no surprise – few entities welcome idea of FDA regulation – and the organization has submitted a petition claiming that only CLIA and not the FDA had authority over LDT’s (the FDA rejects this). The more measured response of the AMA reflects the concerns of clinical care-givers, and may align with the attitude of many genetic counselors:

 

The draft FDA Framework for Oversight of Laboratory Developed Tests (LDTs) announced today, outlines a risk-based approach that raises a number of questions and concerns. 

The FDA proposal adds an additional layer of regulatory requirements which may result in patients losing access to timely life-saving diagnostic services and hinder advancements in the practice of medicine. 

The AMA is committed to ensuring that the proposal that is ultimately adopted by the FDA preserves rapid access to care and medical advancements. 

What makes it difficult to respond to the FDA is that there is a lot of wiggle room left in the regulations as written. High and moderate risk tests will be required to report adverse results and apply for pre-market review according to separate timetables – but the FDA will not define those terms for up to 2 years after the regulations are finalized (Policy and Medicine has a useful chart if you are looking for specifics on timelines). In other words, the FDA has designed a system that gives them room to maneuver – and is asking for respondents to give feedback on the plan without knowing where the agency plans to draw the line. For example, breast cancer susceptibility panels probably aren’t low risk; they are medically actionable and complicated to interpret. Are they high risk or moderate risk? The somewhat hyperbolic letter from the FDA to 23andMe last fall* suggested that the agency believes the fallout from breast cancer risk prediction done badly might be unnecessary mastectomies. That sounds pretty high risk – but is that the perceived reality of counselors who work with these tests?

 

The rare disease exemption in the FDA plan means that whole exome or whole genome sequencing would not be affected, in those cases where the patient presents with an apparently genetic condition that has eluded diagnosis. WES for those with no apparent disease, who wish to use the information prophylactically? I have literally no idea what risk the FDA would assign to clinical versions of genome scanning. What about the genetic testing done for children with autism? These supplement rather than point to a diagnosis and would rarely change treatment but may have a big impact on the parents reproductive choices – is that consequence enough to bump a test from low risk to high risk?

 

I might sound like I am criticizing the FDA, but in fact I am sympathetic to the difficulties inherent in a modulated approach and appreciate that they are attempting to tread that knife’s edge. I do think it makes it difficult to provide feedback, and I would suggest that their policy be reopened for public comment at critical junctures, such as the point at which high, low and moderate risk categories are more carefully defined. Useful commentary now, I would suggest, will need to be far more granular than the FDA regulatory language itself. What tests do you feel work well for you and your patients? Are there tests in use or in the pipeline that concern you? Which ones? Why? Share your concerns here, and I will write up a response incorporating reader response when the draft regulations are posted for public comment.

 

*Note: don’t bother telling the FDA that you are concerned about direct-to-consumer testing, because the agency has already noted that this applies only to testing in a clinical context. No DTC testing will be exempt from review – a footnote to the FDA’s announcement that had DTC advocates screaming foul – for details see Jennifer Wagner’s irritated response at the Genomics Law Report.

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