Is Test Uptake A Good Measure of Genetic Counseling Effectiveness? I Don’t Think So

The last few years have seen a growing trend for patients to undergo genetic testing without first seeing a genetic counselor or other genetic specialist. As I have commented before, genetic counselors are no longer the gatekeepers of genetic testing. Anyone can obtain DNA analysis through non-genetics specialists or any health care provider, on Amazon.com and other internet sites, and at their workplaces (which, honestly, makes me very uneasy; it is going to be awfully difficult for some employers to keep their noses out of their employees’ genetic information and it may provide an opportunity to chisel away at the protections afforded by GINA). Many genetic counselors have accepted this as a fact of life, even if we are not altogether comfortable with it.

Historically, the genetic counseling profession has done a poor job of demonstrating its value to the health care system. Our importance seemed pretty obvious to us and because we didn’t have much in the way of competition we were never strongly motivated to undertake large scale studies to prove our worth.

Comparative studies are starting to address the value of pre-test counseling by a genetic counselor, particularly in the field of hereditary cancer genetic testing. This as a good thing.  Still, it bothers me if studies claim that genetic counseling is failing patients because fewer people undergo genetic testing if they need to see a genetic counselor first. Sure, genetic testing should be readily available to those who need it, and barriers need to be removed. If seeing a genetic counselor turns out to be one of those barriers, then we need to do something about that. But test uptake may not always be in the best interests of patients.

For example, the most common reason an unaffected patient declines genetic testing after seeing me for hereditary cancer counseling is that, for the moment, they are the “wrong” person to test to most accurately determine their hereditary cancer risks. Even though the patient may technically meet standard criteria for genetic testing, they may still not be the best person to test within the context of their specific family history. Not undergoing genetic testing is not due to a lack of timely access to me, the cost of my services, or me somehow talking them out of testing. Instead, after reviewing their family history, it turns out that testing their mother with breast cancer or their brother with colon cancer is the most appropriate person to test before deciding if the patient and other unaffected relatives should undergo testing. If that affected relative has a normal genetic test result, then testing my patient and other relatives is usually a waste of money.

It is also difficult to interpret a negative test result in a family where a mutation has not already been identified. Now, I am a grizzled veteran of the Family Dynamics Wars, and I realize that sometimes that affected relative is deceased or just not willing to undergo testing, and you have to make do with the realities of the situation at hand. And, of course, this argument does not apply to testing patients who have been diagnosed with cancer (although it may apply in situations where patients meet NCCN guidelines but not their insurer’s criteria for coverage, but an affected relative does meet their insurer’s criteria). Still, testing an affected relative should be utilized whenever feasible because it is clinically and economically the most effective strategy. Therefore, if a study finds that test uptake is increased when patients do not first see a genetic counselor, the researchers are obliged to demonstrate that this is not simply due to more cases of the “wrong” person being tested or the providers not willing to take the time to work with the extended family.

Along these same lines, in many situations, even genetic test results of an affected relative are often uninformative for risk assessment. Such families may still need to be followed as high risk, with screening and risk reducing protocols based on family history and clinician judgment. Effectiveness studies therefore need to investigate whether there are differences in clinical recommendations provided to patients who see a genetic counselor compared to those who do not.

Studies of genetic counseling vs. no genetic counseling also need to provide data on patient adherence to screening and other risk reduction guidelines. Increased test uptake is not particularly helpful if patients do not have the motivation or wherewithal to undergo breast MRI, salpingo-oophorectomy, join the Annual Colonoscopy For Life Club, or whatever else is recommended. Other outcomes that effectiveness studies should address include communication of test results to family members, interpretation of variants of uncertain significance, and patients’ psychological adaptation to their risk status. I imagine many of you reading this posting can suggest additional outcomes that need to be addressed.

My other concern about reduced genetic counselor involvement with pre-test counseling is that “counseling” will eventually be reduced to a pamphlet or a brief video, perhaps provided by the testing lab itself. This is already a major concern with how NIPT is presented to pregnant women, and I can see it becoming a problem in other areas of genetic testing. No matter how earnestly labs may claim that their educational material is not a subtle sales pitch, they are only human and can easily be blinded by their business needs. This is an area where GCs can develop better and less biased educational materials.

If research demonstrates that other genetic testing delivery models are more effective than, or at least non-inferior to (non-inferior sounds like a back-handed compliment,doesn’t it?), the traditional approach of First See A GC Before Your Test, then the genetic counseling profession should re-focus itself and use our many other skills to work towards improving patients’ lives and the medical care system. Besides, I have never liked conflating genetic counseling with genetic testing.

I do worry, though, that either the research will not be conducted, or that, even in the face of evidence to the contrary, market forces will dictate testing strategies. I am not concerned that it would portend the end of the genetic counseling profession. Genetic counselors are forever expanding their professional roles, and in fact have continually reinvented themselves since, well, we first invented ourselves in the 1970s. Like David Bowie, we never stood still and as soon as you had us pinned down as Ziggy Stardust, all of a sudden we were Aladdin Sane, and already sprouting within him are the seeds of The Thin White Duke (well, okay, it’s a stretch comparing genetic counselors to David Bowie, but you get my point). What matters is that all patients affected with or at risk for hereditary disorders receive the most competent and compassionate care delivered effectively, equitably, and timely.

Bobbin Sane
(Graphic by Emily Singh)

Leave a comment

Filed under Robert Resta

The Hidden Costs of “Free” Genetic Counseling

A Guest Post by Eleanor Griffith, MS, CGC

Eleanor is the founder of Grey Genetics, a telehealth genetic counseling and consulting company.  Find Eleanor on twitter @elo81.

 

A lot of genetic testing companies are now offering genetic counseling along with genetic testing. That’s great, right? Great to see genetic testing companies hiring genetic counselors. Great for patients because it expands access to genetic counseling services to patients who wouldn’t otherwise receive genetic counseling.

Or actually, maybe not so great. Concerns related to conflicts of interest have been discussed on the DNA Exchange and elsewhere and are worth discussing further and at length. For starters, see here, here, and here.

But my gripe is that when a lab offers “free” genetic counselingit’s not really free. The cost is just hidden, bundled into the cost of the test. Hiding the true cost of genetic counseling in turn diminishes the perceived value of genetic counseling services.

Genetic counselors providing “free” genetic counseling get paid for their work. And they should. But the amount that it actually costs to provide genetic counseling vs. the amount that it costs to run a genetic test is not transparent—not to the patient, not to the physician, and not to the insurance company—which may or may not cover “genetic counseling.” Or may or may not realize that they do, in fact, cover the cost of some sort of genetic counseling(-ish) services by covering the cost of the test.

From a business perspective, for genetic testing labs, “free genetic counseling” is a no-brainer. It’s a big selling point and increases the odds that a healthcare provider will keep sending tests to the laboratory that is able to meet the very real counseling needs of their practice. As long as laws and regulations allow it, I don’t see this changing.

If the recognized product is the genetic test, and the main (or only) source of revenue for genetic testing labs is insurance reimbursement or out-of-pocket payments from patients, then the salaries of genetic counselors working for genetic testing laboratories are basically being paid by insurers + patients. If you follow my logic, this means that insurers will cover and patients do in fact pay for the (hidden) cost of lab-based genetic counseling, bundled into the cost of genetic testing. But insurers often don’t cover the cost of independent genetic counseling. Conflict of interest aside, this strikes me as ridiculous.

Away from the morass of insurance, patients and consumers of healthcare are being trained to see price tags attached to direct-to-consumer genetic testing products of dubious value, while genetic counseling is “free with purchase!” Even for clinical genetic tests ordered through physicians, self-pay prices are becoming more accessible. The logic, of course, is that labs will have a high enough volume of tests to scale and still make as much or more of a profit from testing…. Genetic counseling, however, cannot scale in the same way. This is why widgets get cheaper and cheaper while the cost of most professional services that require advanced degrees and involve working with clients one-on-one—lawyers, doctors, psychologists, financial consultants—remains relatively high.

While building up my private practice, I work part-time for an agency offering “free” genetic counseling to patients who respond to a quiz on facebook. I love it and I hate it.

I love it because I speak with high-risk patients who have never been referred to genetic counseling in a traditional way—many of whom have never heard of the BRCA genes. Patients who are interested in going forward with testing receive a copy of my consult note (yep, and a test kit) to take to their healthcare provider. Those who decline testing still receive a consult note with a copy of their family history and are encouraged to share it with their healthcare provider. Their healthcare provider has the option of including my name on the test requisition form so that I can receive and review results with their patient. Initially, I’m scheduled for an hour with each patient. If the patient needs more time to gather family history or to speak with someone in the family who would be a more appropriate candidate for testing—no problem, I just schedule her for a second call. I’m connecting with patients who would otherwise never have known of the option of genetic testing, would never have guessed that their insurance would cover the cost of testing for them, and had no idea of the impact it could have on their medical management and the value it could provide to their family members.

I hate it because the agency of course has a relationship with a specific laboratory. That laboratory happens to be the laboratory that I would recommend above others for hereditary cancer testing. This makes me feel good about the quality of testing that patients actually end up having—but also means that my professed recommendation should be looked upon with skepticism. Although the modest amount I’m paid is not affected by whether or not a patient goes ahead with genetic testing, and although I’m not privy to the details of the arrangement  between the agency I work for and the genetic testing laboratory—in reality, I’m obviously still being indirectly paid by the commercial testing laboratory. I’m just part of their operating costs.

I address patients’ questions about the costs of genetic testing, the likelihood that it will be covered by insurance. But there’s never a question as to how I’m getting paid, or why I’m getting paid. There’s no price tag assigned to the 30-90 minutes I spend talking with them. Sometimes patients are in a quiet place for our phone conversations. Sometimes they’re washing dishes, driving a car, picking kids up from school. After all, it’s a free call related to an impulse click on facebook. I have a Master’s Degree in Human Genetics, but my time costs them…. absolutely nothing. Or rather, the cost of my time is bundled into the cost of the agency’s services which is in turn paid by the laboratory which is in turn paid by insurers, which is in turn paid by my patients’ insurance premiums and/or taxes.

I feel less icky about this set-up than I had expected. (See the love paragraph.) Conflict of interest aside, however, this is a nasty bandage on a broken system in which the cost of genetic counseling is bundled along with the cost of testing rather than being recognized and billed for as a service provided by specialized medical professionals.

As uncomfortable as I feel getting indirectly paid by a laboratory, I feel equally but differently uncomfortable with charging patients for genetic counseling—which is exactly what I’m doing in private practice. The first patient who paid upfront and told me how valuable my time had been to her and how appreciative she was made it easier. But I still feel awkward asking patients to pay me. Most of us who have worked in hospitals have been similarly used to having the cost of our services swept up into other hospital costs and have not had to tell patients, “It will cost $X to see me.”

I think our time and services are worth $$$. Whether we work in industry, private practice, or for a hospital, I think we need to learn to be unapologetic about the fact that even if we love and find meaning in our jobs, we also work to make a living. The value of genetic counseling services should be accurately reflected in an associated cost. We’ve come a very short way from being a collection of mostly white, upper-middle class housewives who are happy to do volunteer work and don’t need to make an income. We need to take another step and get comfortable with transparently charging for the work we do.

6 Comments

Filed under Guest Blogger

Medical Strategy or Marketing Strategy?

A well-known direct-to-consumer (DTC) genetic testing company now has FDA approval to include a very limited form of BRCA testing with its DNA genotyping product. I refrain from mentioning the company’s name because they already got enough free press from the announcement. You probably know what company I am referring to, and if you don’t, well, follow the above link. Sorry Unnamed Company, but I am not going to make the free advertising that easy for you, no matter how insignificant the source. Besides, I see it as a bigger issue than just one company’s policy.

For now, the analysis is limited to the three BRCA1&2 mutations that are more common among Ashkenazi Jews. Actually, the company offered the same 3 mutation test until they were slapped with a cease and desist letter from FDA in 2013 to stop all medically related testing. So this new announcement amounts to a resurrection of a nearly decade-old policy, not a groundbreaking innovation. Funny, though, that there was not this much to-do when the test was first offered.

The genetic counseling community is in a bit of a dither about this, including me, though admittedly part of the reason I am writing this blogpost is to help me figure out just what I am dithering about.

Some of the concerns are obvious. People may be under the misconception that a negative result = no increased risk of hereditary breast/ovarian cancer and thus some high risk women may forego potentially lifesaving surgery and appropriate screening strategies. Then there is the worry that patients will not follow through with genetic counseling if the testing is positive, or that high risk patients will not seek genetic counseling and more testing if the result is negative. If you are not Ashkenazi Jewish, the test does not seem to offer much benefit. And even for Ashkenazi Jews, the testing does not include the ~10 other genes linked to hereditary breast cancer and the ~10 other genes linked to hereditary ovarian cancer.

The company recommends verifying positive results with an experienced clinical lab.  For that matter, then, why not verify a negative result, if there is that much uncertainty? Why bother having a test if you can’t fully trust the result? I suspect though that there is probably little reason to doubt the test result and that the company makes this recommendation to keep FDA happy and to minimize their legal exposure rather than concerns about assay validity.

Incidentally, the cost of the company’s product is really not much different than the more comprehensive multigene hereditary cancer panels offered by some of the clinical testing labs, and in some cases more expensive.

Eight years ago I shared my first experience with a patient whose BRCA carrier status was detected through DTC testing. My patient’s experience and a few more cases I encountered since then have not been that different than my patients who went through the usual counseling and testing process. A 2013 study by the company  showed that the 11 women and 14 men who discovered their BRCA status through DTC testing had experiences similar to my patients. That last statement is brimming with caveats – small sample size, at least for my patients they were savvy enough to want to see a genetic counselor, personality traits of the earliest users of new products, no long-term follow-up, etc. But I am not aware of any independent, large-scale studies of patients who learned their BRCA status through DTC testing to more definitively address the pros and cons, other than studies offering BRCA testing that targeted all Ashkenazi Jewish women.

I readily admit that I may be proven wrong, but I am guessing that most of the consumers of this DTC product – note they are not patients because the test is not intended for clinical use – will opt to learn their BRCA status. After all, people have this testing to learn about their genetic makeup. I am also guessing that this may be the company’s proverbial toe-in-the-water; I would not be at all surprised if additional clinically useful testing is part of the company’s future product and marketing plans.

At heart, I don’t like the idea of DTC BRCA testing. I think about all the ways it can go wrong, and inevitably some of those ways will come to pass. But will it go right often enough, and go wrong infrequently enough, that there will be adequate benefit to justify offering DTC testing? Undoubtedly, some of my uneasiness stems from a professional conflict of interest; DTC eliminates my role as an interface between patients and testing. Personally, I think being a middleman is a good thing because it can help patients take a thoughtful deep breath before leaping into the gene pool. But that could be because I have been trained to think that way and because it supports the value of my professional career. What I really should want is for patients to have access to genetic information in a manner that is affordable, accurate, psychologically and emotionally appropriate, and medically useful. If DTC and other forms of offering BRCA testing works for many men and women, then I should swallow my professional pride and acknowledge it.

So having stewed on this for a while, I have come to the realization that my argument isn’t with this company per se. Other companies aggressively market hereditary cancer and other genetic testing to average risk people. For example, one company approached my institution with the idea of offering their product to all women coming in for breast imaging, with saliva kits kept in the mammography center along with a prescription pad with a genetic counselor’s name on it acting as an ordering provider for the test (legal in my state). Although many labs employ genetic counselors who work directly with patients to review test results, this is still not the same experience as meeting with a genetic counselor before undergoing testing to explore the complex medical and psychological issues surrounding genetic testing. And the highly respected Dr. Mary-Claire King has advocated for population based genetic screening for establishing hereditary breast cancer risk. Are DTC clinical testing and other consumer-friendly strategies disruptive ideas that will bring about much-needed change or are they just bad but well-intentioned ideas that will also fill company’s coffers and keep investors happy?

Having sifted through and weighed my thoughts and feelings about DTC testing or other genetic test delivery models, I have concluded that my problem is not with DTC or other models per se. My argument is with how these new testing approaches are introduced into clinical practice, typically under some version of the banner of liberating testing and bringing it to the people. I do not doubt the labs’ sincerity when they say they are trying to improve access to medical care and reduce the suffering from cancer and other illnesses. But these are as much marketing strategies as they are medical strategies. Labs should not be calling the shots on the introduction of new tests and practice models because, in the absence of well designed studies, we really have no idea if these new approaches are effective in reducing cancer risks and increasing high risk screening when indicated, or if they are in the patients’ best emotional and psychological interests. Just throwing a mess of tests out there and encouraging everyone to take one is, in my view, irresponsible.

A better approach is to first conduct controlled and ideally randomized studies that evaluate both new and novel testing strategies to determine the most beneficial one(s) for patients, or if different types of patients benefit differently from different strategies. For example, age, family history, medical history, psychological functioning, and socio-economic status could all conceivably affect outcomes, not too mention the all too real possibility that many Americans may lose health insurance in the near future. While labs should play a critical role in that evaluative process, to keep it as clean as possible the studies need to be conducted and overseen by researchers who have no financial benefit from the outcomes of such studies.

We are in this together, so let’s work together.

2 Comments

Filed under Robert Resta

Is A Lab A Health Care Professional? An Update On “Everyone’s Worst Nightmare”

Two years ago I authored a blogpost, Everyone’s Worst Nightmare , about a family’s experience with genetic variant interpretation, communication (or lack of) by healthcare providers with families, and an outcome that couldn’t be more tragic – the death of a child. Here I am providing an update on the legal status of the lawsuit brought on behalf of the child by his mother. In my original posting, I did not identify the child’s syndrome or the specific court case. However, since then, the story has been picked up by a variety of media outlets (Turna Ray at GenomeWeb has done the best reporting on the details) and it now being a matter of public record, I have included some particulars here .

Briefly, the story began about 12 years ago when the child was experiencing multiple, intractable seizures and had a clinical picture consistent with Dravet syndrome. Unbeknownst to the parents, genetic testing was ordered and the child was found to carry a mutation in SCN1A, the gene linked to Dravet syndrome. The mutation was interpreted as a variant of uncertain significance, though at the time there was reason to believe that it could be pathogenic. Based on the genetic test result, it was felt that the child did not have Dravet syndrome and was kept on a sodium channel blocker, which unfortunately is contra-indicated for patients with this syndrome. Not long afterwards the child died of seizures at the age of two.

The patient did not find out that genetic testing had been performed until about 7 years after the test was ordered. Shortly after the mother learned of the test result and inquired into its meaning, the lab reclassified the variant as pathogenic.

In February 2016 the mother initiated a lawsuit on behalf of her deceased child in the fifth judicial circuit court in Richland County, South Carolina. The defendant’s lawyers requested that the case be dismissed on the grounds of restrictions imposed by the state’s statute of repose, i.e., a law that states legal action must be initiated within a certain period from the time the alleged offense occurred (it is similar to but slightly different from a statute of limitations). The defendants presented the argument that a genetic testing laboratory is a licensed health care provider and South Carolina has a 3 year statute of repose for lawsuits brought against licensed health care providers. Since the events took place a decade ago, the defendants asserted that the case should be dismissed. The plaintiff countered that, under South Carolina state law, a genetic testing lab that is separate from a hospital or a clinic cannot be considered a licensed health care provider and therefore the statute of repose did not apply. The plaintiff contended that this is a case of ordinary negligence, not medical malpractice, since the lab should not be considered a licensed health care provider and therefore the suit should be allowed to proceed.

The case was then sent to the US District Court in 2017 to rule on whether dismissal was warranted based on the defendant’s argument that the lab is a licensed health care provider and therefore the statue of repose applies. The federal judge then referred the case to the South Carolina Supreme Court to, as the legal lingo goes, certify the question of whether a lab can be considered a licensed health care provider under the specific provisions of South Carolina Code of Laws Section 38-79-410. Although we may have our individual opinions on this question, it is strictly a matter of law that varies by state. South Carolina law defines a licensed health care provider as “physicians and surgeons; directors, officers, and trustees of hospitals; nurses; oral surgeons; dentists; pharmacists; chiropractors; optometrists; podiatrists; hospitals; nursing homes; or any similar category of licensed health care providers.” (italics added)

The South Carolina Supreme Court heard the case on February 14th, 2018. For those of you who have never witnessed a state Supreme Court hearing, I recommend that you watch the ~40 minute video of the session. The court’s decision, which will be about whether the suit can proceed rather than determining liability, will depend on how it interprets whether a laboratory is a “similar category” to the health professionals listed in the state code. I thought that the five justices were insightful and asked thoughtful questions. As a side note, at about the 29-30 minute mark of the hearing, Justice Few gives a shout out to our genetics colleagues at the Greenwood Genetics Center.

The court does not have a set date on when they will issue an opinion; as the Supremes, they call that shot (the South Carolina Supreme Court’s motto is Nil ultra, which roughly translates as “Nothing is above us”). Typically, though, the time frame on a ruling is in weeks or months. If the court decides that the lab is not a healthcare provider, then the plaintiff’s suit will be allowed to continue, though I got the sense that the court felt that even if the ruling were in favor of the defendants that the plaintiff may still have alternate legal pathways to pursue a case. I will keep the good readers of The DNA Exchange posted on important developments in this case, which I suspect will continue to drag on for some time after the Supreme Court’s ruling.

With the rapid expansion of genetic testing in the clinical and consumer spaces, and the growing involvement of non-genetics professionals in ordering genetic testing, bad clinical outcome scenarios are likely to become more common. Critical questions about variant interpretation and legal liability aside, from a genetic counseling standpoint, this case highlights the importance of clear and ongoing communication with patients and their families about the limits and clinical interpretation of genetic testing. This can be extraordinarily difficult when a family is trying to cope with caring for a child with a life-threatening disease, but genetic counselors are trained to work precisely in those situations. Genetic testing may be simple to order and widely available but it benefits no one without good clinical care and counseling.

4 Comments

Filed under Robert Resta

Growing Pains

With the rapid growth of the genetic testing industry, professional opportunities for genetic counselors have expanded rapidly.  Not only are genetic counselors now working in nearly every area of healthcare, many are embracing new roles as laboratory specialists, clinical science liaisons, and in sales and marketing roles for genetic testing companies. Some are entrepreneurs founding their own companies and pioneering new models for access to genetic information. It’s not surprising to see genetic counselors embracing these new roles. Like the founders of our field, seeing opportunities in change and forging new trails in uncharted territory seems to be characteristic of genetic counselors.

But navigating new terrain isn’t often easy.  As written by Alexandra Minna Stern in her historical account of the profession, ”the emergence of the genetic counselor as a bona fide professional was neither inevitable nor smooth.”  

Do other genetic counselors feel that we are currently in the midst of a most turbulent and rocky stretch of our profession’s journey through time?

Although we have had graduates from Master’s level genetic counseling training programs for more than 40 years, as well as a growing body of evidence regarding the value we bring to patient care, we are still reaching for recognition as healthcare professionals. While we seem to be making progress towards this goal, we have yet to be recognized by Medicare and many commercial payers as healthcare providers. Additionally, in many states the quest for licensure remains an incredible challenge.  

One of the biggest obstacles genetic counselors currently face is public perception of genetics and genetic testing. It seems that genetic discoveries that are part of evidenced based strategies to improve human health are increasingly being overshadowed by consumer genetic testing for entertainment. For example, screening for and treating familial hypercholesterolemia is considered to be a Tier 1 genomics application by the CDC given the level of evidence and potential to benefit public health. However it is estimated that less than 1% of the affected population in the US have been diagnosed.

On the other hand, consumer genetic tests are being increasingly utilized. Home DNA test kits through companies such as 23andMe and Ancestry.com were among the top selling holiday gifts this year. Consumer genomic testing claims to provide information about everything from personalized skin care recommendations, to what one’s ideal fitness regimen will work best, to what one’s hypothetical future children may look like. Some companies combine a mix of evidenced based health information with unproven claims related to entertainment and wellness information which leaves many in the field of genetics uncomfortable.

As genetic counselors, we are regarded as experts when it comes to genetic testing. So how should we respond to the flood of options in the direct to consumer space?  How should we be talking about these tests with our patients?  How should we be talking about these tests with other healthcare providers?  These are crucial questions for our profession, but ones that genetic counselors don’t seem to seem to agree on.

Through the media, through our professional discussion forums, and in conversations at genetics conferences over the past couple of years, I have heard two predominant and conflicting messages regarding genetic counselors’ opinion on consumer genomic testing. Some are enthusiastic, and believe the use of such tests should be encouraged as an opportunity for to engage people in the area of genetics, and hopeful that such engagement in any genetic testing will lead to better adoption of genetics into healthcare. Some are concerned about the proliferation of these tests and believe that they may cause more harm than good by blurring the lines between medicine and entertainment, leading to misinformed health decisions, compromising privacy, and creating new and unanticipated conflict for psychosocial family dynamics.

Our field is small with only about 4,000 genetic counselors nationwide. We are all only separated by only a degree or two of separation. A tight-knit community. So it is not surprising that with our profession expanding in so many directions, that we are experiencing some tension and growing pains with these emerging issues.

Whether we believe that consumer genomics is something to be feared or embraced, these tests are out there, people are using them, and it is crucial that we adapt to be able to help the public, our patients, and each other navigate this new terrain.

Do you see consumer genomics as an area that we should encourage, participate in, and guide?  Or should genetic counselors discourage the use of these tests, both on an individual patient level and in policy?  How do you see us adapting to the brave new world of consumer genomics?  

3 Comments

Filed under Katie Stoll

Top Ten Stories in Genetics in 2017

Mark it in your calendar: 2017 was the year when gene therapy (broadly defined) became something more than hypothetical.  Hard to talk about 2017 as a great year, but that’s the storyline in genetics.  Here’s the countdown:

  1. Ohio Bans Abortions for a Fetus Affected with Down Syndrome

In December 2017, Ohio became the 3rd state to criminalize abortion to avoid the birth of a child with a genetic condition. The first law was passed in North Dakota in 2013 and remains on the books, and a similar measure in Indiana that focuses specifically on Down syndrome was enjoined by court order after an ACLU challenge.

Ohio’s law makes it a felony to perform an abortion if the patient’s motivation is to avoid the birth of a child with Down syndrome. These laws appear unlikely to be enforced: unconstitutional under Roe v Wade, they should not survive a court challenge, and if they did, they would be incredibly difficult to enforce. Still, there are several reasons why it is worth paying attention to what must now officially be called a trend.

First, these laws didn’t pop up organically, and they indicate that therapeutic abortion is on the radar of anti-abortion groups. Expect more of the same, and battles on related fronts, including insurance coverage for prenatal testing.

Second, even if the law is never enforced, it could affect practice. A woman’s motivation is hard to prove, but the motivation of a genetic counselor or a physician discussing termination after a diagnosis of Down syndrome is crystal clear, and could put them at risk. Even a distant and unlikely threat of a felony prosecution is a great disincentive to any clinician. Discouraging counseling may pr may not prevent abortion but it absolutely deprives couples of the good, unbiased information that Down syndrome advocates have been working on for years. And as usual, it increases disparities in care for individuals with fewer resources or less education.

Third, polling suggests that a slim majority of the country believes abortion should be available for pregnant women when the fetus faces cognitive impairment, but it’s emotionally tricky territory and norms may shift to make therapeutic abortion more stigmatized. There’s a reason why the second and third iterations of the law specified Down syndrome: this is a public relations campaign and Down syndrome kids present a sweet and photogenic face. “Every Ohioan deserves a right to life, no matter how many chromosomes they have,” said the head of the Ohio Right to Life, neatly eliminating the difference between a fetus and a child.

Fourth, expect a whole lot more of this if we lose Roe v Wade.

  1. STAT names the Swiss Army Knife the top CRISPR metaphorScreen Shot 2017-12-29 at 7.26.31 PM.png

Bacteria have been using CRISPR for aeons, but humans have only had it in their gene editing toolkit for five years. In that short span, technical advancements have occurred so quickly that 2012 CRISPR is starting to feel a bit old school. Some of these innovations improve the original CRISPR search-and-delete functionality – reducing off target effects, for example, or improving the odds of replacing deleted DNA segments with a scripted sequence delivered via a template. Other advancements add new types of functionality. In 2017, researchers introduced a modified CRISPR system uses the same search function but doesn’t cut; instead, it alters gene expression by changing the elaborate system of packaging that turns gene on or off. In another iteration of CRISPR search-and-don’t-cut functionality, scientists from Harvard and the Broad Institute have pioneered a technique called base editing, which locates a specific spot in the DNA sequence and replaces a single base through a series of chemical reactions without the riskier business of inducing a double-stranded break. In October, researchers from China announced that they had tested base editing in human embryos, and were able to correct a mutation that causes the blood disease beta thalassemia 23% of the time.

The proliferation of CRISPR varietals led writers at STAT to give top honors to “the Swiss army knife” in a ranking of CRISPR metaphors (runner up: “organic photoshop”).

 

  1. Harvard’s George Church opens up the George Church Institute in ChinaScreen Shot 2017-12-10 at 4.37.03 PM.png

Synthetic DNA made significant steps forward this year, starting with an announcement in January that researchers at the Scripps Institute in La Jolla have produced a modified a strain of E coli whose DNA has six rather than the usual four base pairs. The following October, in a story that my be the epitome of 2017, Harvard professor George Church traveled to China to announce the opening of the eponymous George Church Institute of Regenesis. This collaboration with Chinese giant BGI has plans to develop clinical applications of synthetic biology. The investment of substantial resources in artificial life forms and bio-manufacturing is one indication of where we are headed; sadly, the decision by one of America’s great science talents to launch an ambitious project halfway across the world may also prove to be a sign of things to come.

 

  1. Popular Culture Discovers CRISPR

This was the year I read my first sci-fi novel about a world where children (and pets) are routinely gene-edited. Although it was a dystopian vision, I have to admit I was intrigued by the tiger-ized house cat…

CRISPR has definitely captured the imagination of a good part of the universe, and my sense is that the jury is out on whether our new powers of gene editing are going to be viewed as cool or creepy. Meanwhile, here’s some unexpected places where CRISPR popped up in 2017.

On Jeopardy!

Screen Shot 2017-11-25 at 5.24.41 PM.png

In Ashton Kutcher’s twitter feed:

Screen Shot 2017-12-07 at 9.42.57 AM.png

Graffitied on the mean streets of San Francisco:

Screen Shot 2017-11-25 at 5.24.13 PM.png

This is a sleeper pick at number 7, but I believe it’s important to understand that people are paying attention, because (like the rest of us) they don’t yet know what to think. The early uses of CRISPR will have a great impact on public opinion, and very likely on support for research, development and commercialization of gene editing down the road. It’s something to think about.

 

  1. The FDA Changes Direction on DTC Genetic Testing

The FDA executed a remarkable about-face on direct-to-consumer genetic testing in 2017, beginning in April when the agency approved a new iteration of their SNP scan for liability to disease, 3 ½ years after they shut down sales of the alpha version, claiming it posed a risk to the health of those who bought it. In addition to signing off on testing for 10 complex conditions where the genetic contribution is important but not definitive, the FDA announcement established some ground rules that could be applied to other tests and other companies. First, the decision identified 23andMe as what they called a ‘trusted provider’ and indicated that having been so designated, they would not have to jump through regulatory hoops for every new test, and would be exempt from premarket review. Second, the agency created a category called “genetic health risk (GHR)” tests, as distinct from genetic tests that were diagnostic, which were explicitly excluded from exemption.

Presumably, the agency’s goal was twofold: to remove impediments to the growth of DTC, while carving out some rules for what belonged in that realm, as distinct from what belonged in a clinical setting. In November, the FDA made this explicit, announcing its intention to establish a new regulatory structure for GHR tests which would formalize the ‘trusted provider’ approach through a one-day FDA review, allowing them to introduce non-diagnostic tests and carrier screens without further premarket scrutiny.

This change in governance is likely a response to what is happening in Washington, where anti-regulatory sentiment is rife, and may also be due to changes in the marketplace, with major players like Illumina and Google making sizeable bets on DTC genetic testing ventures. There is little question that the FDA moves have had a big impact, and the fledgling DTC industry appears to have spread its wings and taken off. Strong Christmas sales for both Ancestry.com and 23andMe indicate that consumers are willing to give genetic testing a try; sustained success may be contingent on how that experience goes for the recipients.

 

  1. First RNAi Drugs Show Promise in Human Trials

Many of the early targets of gene therapy are diseases caused by a single missing or defective protein, and the goal in these cases is to introduce a gene that will produce what the body is lacking. Despite the fact that we have not been very successful to date, it is a simple model; often replacing a small fraction of normal production is enough to treat or effectively cure the disease. In some diseases, however, the problem is not the absence of a normal protein but the presence of an abnormal one which disrupts function or damages healthy tissue. In these cases, you can’t simply (‘simply’) replace what you don’t have but must find a way to silence the gene product that is causing all the trouble.

One way to do this is to intercept the RNA messages before they are made into protein via RNA interference – designer RNA’s that find and bind to specific transcripts to prevent translation. Like many other forms of what might broadly be called gene therapy (I’m not into fights about semantics so don’t @ me), RNAi has not fulfilled it’s conceptual promise to date, but that seems to be on the verge of changing. In October Ionis Pharmaceuticals launched the first human trials of a RNAi drug for Huntington’s disease, and in November a Cambridge-based company called Alnylam announced that its RNAi drug for hereditary ATTR amyloidosis was showing success in phase 3 trials and might be up for FDA review in 2018.

 

  1. In Vivo Gene Editing Mitigates Deafness (in Mice)

Screen Shot 2017-12-29 at 7.00.23 PM.png

In another late entry into the Top Stories of 2017, researchers from the lab of David Liu published a December article in nature describing the use of in vivo gene editing to facilitate hearing in mice bred to exhibit a form of genetic deafness found in humans. Mice injected with CRISPR-Cas9 complexes showed more hair cells and improved response to auditory testing. While it is always good practice to remind ourselves that not everything that works in rodents works in people but… in vivo gene editing is a remarkable technical achievement with incredible potential. Brought to you, by the way, by a co-founder of Editas Medicine, so this maybe this blog post can double as a stock tip. 2017, ladies and gentlemen.

 

  1. A Gene Therapy Ready for Prime Time at Last!

We’ve been talking about gene therapy for so long it seems like old hat, except that this particular old hat has never been thrown into the ring… until now. On December 19th, the FDA approved Luxturna, a gene therapy for blindness. First of its kind, Luxturna introduces a gene into retinal cells by a viral vector and, in cells where uptake of the wildtype variant increases the production of normal protein.

Eyeballs are a uniquely accessible body part, making them low-hanging fruit for gene therapy, but low-hanging fruit is the place to start, and the take-home point here is that the new and improved gene editing technology and gene delivery systems are for real, as is (finally) gene therapy. Coming soon: gene therapies for blood-based diseases such as hemophilia and sickle cell. Still to be determined: how much all of this will cost.

 

  1. Immunotherapy Delivers a One-two Punch

The cancer field has been buzzing about Car-T therapy for years, hopeful that this new class of therapies designed to harness the body’s own immune system would not only expand the range of cancers we could fight, but do so in a targeted fashion that would reduce the toxicity associated with current chemotherapies. Immunotherapy has been through several rounds of hype-and-hate before getting out of the clinical trial phase, as stories about patients rescued from the deathbed have sent up smiley face trial balloons and deaths from unanticipated side effects have popped them.

After all the anticipation, approval of the first two Car-T drugs came only weeks apart, with Kymriah, a drug for pediatric leukemia, approved in August and Yescarta, for some forms of B-call lymphoma, following close behind. All the usual caveats apply – real-world safety and efficacy still to be worked out over time, and price price price price price plus access, but without setting that aside, I want to take a moment to congratulate everyone who worked to create and validate this new and important class of cancer therapies.

 

  1. The Boy who Got New Skin Is Everything You Ever Hoped For in a Stem Cell Success Story

Screen Shot 2017-12-29 at 7.38.53 PM.png

I was six paragraphs into Ed Yong’s story about a boy with epidermolysis bullosa when I realized it was going to be my top story in genetics for 2017. How many things are there to love about this story? First of all, it’s about a cure for EB, a disease that disrupts the normal structure of the skin, making it fragile, so that it is prone to rupture and blister. In bad cases, people are plagued with open sores that will not heal. It’s a biblical plague of a disease, and this kid was in terrible shape – shape – seven years old, and headed to hospice care.

And they fixed him.  This is also a stem cell success story, joining the list of finally-finally-at last therapeutic success stories in 2017. Doctors removed a small patch of precious intact skin from seven-year-old Hassan and sent it to researchers in Italy, who isolated and corrected skin stem cells, and then used them to grown sheets of skin in which to sheath the dying child. They replaced an astounding 80% of his old skin and – here’s the part from paragraph six – less than a year later he is back in school, playing sports and living the life of a normal child.

I promised myself never to talk about these high tech miracles without discussing cost and access, so here I raise relevant questions: what’s this going to cost, and who will be able to get it?   Honestly, I have no idea.   And for the record, this technique won’t work for all variants of the disease.  But there is a lot to celebrate.

It seems strange to talk about 2017 as a series of victories for humanity, but the year in genetics was full of hope and promise, and nowhere was that contrast more on display than here, in the a story of a global community coming together to save a life. A Syrian child, treated by German doctors together with Italian researchers who were mentored by an American pioneer…  It was the epitome of 2017 in genetics, though sadly not the epitome of 2017 in any other sphere.

 

Follow me on Twitter!

Leave a comment

Filed under Laura Hercher

The Rhythms of Silence

“It was a silence filled with many things going on in it.”

– Dorothy Parker

Shut my mouth.  That is one of the hardest things for me to do during a genetic counseling session, though paradoxically it is among the simplest. Despite decades of experience as a genetic counselor, I still have a tendency to dominate my interactions with patients. Maybe all of us are guilty of this to varying degrees. To some extent, it is a natural by-product of a clinical service with a significant educational component. Dialogue easily morphs into monologue.

But genetic counseling does not end at education. Instead the counseling component simultaneously flows from and shapes the educational aspects. I sometimes need a virtual dopeslap upside my head from Jon Weil’s or Seymour Kessler’s spiritual avatar to get things back on track.

How We Talk, a book about conversational analysis by the linguist N.J. Enfield, has helped heighten my awareness of my tendency to dominate counseling sessions. And it is a lot less psychologically painful than Jon’s or Seymour’s dopeslaps.

A typical conversation flows with a rhythm guided by timing cues. Speaker A says something and then Speaker B seamlessly follows with a response to what Speaker A just said, and so the conversational turn-taking flows through to the conclusion of the conversation. In normal everyday conversation the average length of the transition between when Speaker A stops speaking and Speaker B responds is ~200 milliseconds. Literallly in the blink of an eye Speaker B recognizes that it is the appropriate time to speak and has a response ready. The brevity of the silence interval is mute testimony to the stunning complexity of the human brain. Conversation is like a John Cage musical composition based on a pattern of silences. Silence is to conversation as zero is to numbers.

Of course, there are within- and between- individual variations in any conversation. There are also differences between languages, but the differences are slight. For example, in the Mayan language Tzeltal, the average transition time is 67 milliseconds, in Italian it is 310 milliseconds, in Lao it is 420 milliseconds, and in Danish it is 470 milliseconds. English is just above average at 236 milliseconds. No doubt a Dane would drive a Tzeltal speaker crazy with the extended transition time, but the difference between the languages is under half a second, within the range of an eye blink.

The dialogue from the screwball comedies of the 1930s and 1940s move along at dizzying speed because we perceive the transition times as almost non-existent. The great screenwriters intuitively understood this and Cary Grant, Katharine Hepburn, et al., effortlessly deliver witty repartee that leaves your brain gasping for breath.

When the transition time exceeds a half second, and especially as it approaches one second, Speaker A perceives the response as taking too long and tends to jump back into the conversation, “out of turn.” This One Second Rule is called a standard maximum silence. It is often more than a matter of Speaker B needing more time to formulate a response to a complex statement or question. The longer than expected delay can communicate that Speaker B thinks the response is “non-preferred,” that is, something that Speaker B feels may not be the reply that Speaker A wants to hear. And when Speaker A jumps in out of turn, Speaker A will re-phrase in a way that makes it easier for Speaker B to give a non-preferred response. Subtle non-verbal emotional interplay takes place in the space of a silent second. The silence of the iambs. The following fictional counseling scenario demonstrates this:

Scenario A

Counselor: So, do you think you want to undergo this genetic test?

(1 second pause)

Counselor: You don’t have to make up your mind right now.

(800 millisecond pause)

Client: Well, the test could be helpful. I am not sure about my insurance coverage, though.

Here, the 1 second pause suggests that the patient may not want the test, and the “long” pause pushes the counselor to jump in and say something that makes it easier for the patient to decline testing. The patient replies in a way that that the patient feels the counselor prefers to hear – the test is important – but bringing up insurance coverage gives the patient a “legitimate” reason to decline testing. Even though the counselor may feel that she or he was non-directive, the patient may have picked up on a message that perhaps the counselor thinks the patient should undergo testing, even if the counselor is not saying it in so many words.

Generally, Yes/No responses that occur within the first half second of a transition are perceived as more definitive whereas responses that are closer to one second or longer are usually interpreted as ambiguous. The following fictional exchanges between a counselor and a client illustrate this:

Scenario B

Counselor: So, do you think you want to undergo this genetic test?

(200 millisecond pause)

Client: Yes.

 

Scenario C

Counselor: So, do you think you want to undergo this genetic test?

(1 second pause)

Client: Um (3oo millisecond pause) it might be a good idea.

In Scenario B, the short transition time of the client’s response suggests a strong desire to have testing. However, in Scenario C, it takes the client 1.3 seconds to arrive at a form of Yes, the hesitancy in the response possibly reflecting a hesitancy to undergo testing. The interjection “Um” before saying “Yes” reinforces the perception of ambiguity. This 1+ second difference in transition time is a clue to skilled counselors to more deeply investigate the patients’ desires and reasoning, even though the counselors and the clients may not be consciously aware that clients are communicating clues to their ambiguity.

Of course, in the context of a counseling session, a delayed response could be due to the cognitive processing required to comprehend technical medical information or it could be due to psychological processing of an emotionally laden discussion. Which, to some extent, is the point here. A genetic counseling session is not usually an ordinary conversation (though a skilled counselor can make it appear that way), so the turn-taking of the speakers can be expected to have a different rhythm and follow different timing cues. But because we are so subconsciously attuned to the rhythm of normal conversation, the tendency for genetic counselors to sometimes dominate a session may stem in part from relying on the wrong timing cues and to speak out of turn before patients are ready to articulate their thoughts.

An interesting research project would be to record counseling sessions with the purpose of timing transitions between counselor and client. This could then be correlated with outcomes such as patient satisfaction and uptake of recommendations to see if they were influenced by conversational transitions. Transition times could also be used to guide the development of better counseling skills by helping the counselor to understand ways that transition times were used appropriately or inappropriately during the course of a counseling session.

To be sure, transition times are not the only non-verbal influence on the rhythm of a conversation. Posture, gestures, facial expressions, and eye gaze can influence the flow of conversations and serve to articulate the psyche. Reading the body of clients is as important a skill as being attuned to their verbal language. People are generally less aware of their body language and thus it can more “honestly” and directly reveal underlying psychological and emotional processes than verbal language.

It is extraordinarily difficult to be keyed into what Enfield calls “the inner workings of conversation,” especially in the moment of the conversation. It involves unlearning, or more precisely becoming aware of and being able to manipulate, a language protocol that has been subconsciously engrained into us since we burst out of our amniotic sacs. Becoming a good counselor is not simple nor is the path always straight. The graph of professional growth follows a jagged and at times recursive line. There is no breakthrough moment when you permanently become the genetic counseling equivalent of a Jedi Master, able to manipulate the Counseling Force to your will and you are infused with Yoda-like wisdom. Easy it is not.

 

 

 


Thanks yet again to Emily Singh for help with graphics.

 

 

 

 


SaveSave

SaveSave

SaveSave

SaveSave

SaveSave

SaveSave

SaveSave

3 Comments

Filed under Robert Resta