Author Archives: Robert Resta

A Diagnosis Is Not The End Of The Odyssey

by Robert Resta, Jennifer A. Sullivan, Allyn McConkie-Rosell

Allyn McConkie-Rosell, Ph.D., CGC, is a Professor in the Division of Medical Genetics at Duke University Medical Center. Jennifer A. Sullivan, MS, CGC is a
Senior Genetic Counselor in the Division of Medical Genetics at Duke University Medical Center. Robert Resta, MS, CGC, is a genetic counselor at Swedish Medical Center in Seattle and a frequent contributor to The DNA Exchange.

The Diagnostic Odyssey – that meandering, lengthy, and frustrating quest for a diagnosis. Genetic counselors, medical geneticists, and patients with rare disorders and their families are achingly familiar with it. The allusion to Homer’s Odyssey is apt. Odysseus’s decade of wanderings are replete with perils, disappointment, love, wonder, whimsical gods, adventure, and frustration. Surely some specialist somewhere in the world can tell me what condition my child has been born with, and I will brave the wine dark seas for as long as I must to find that expert! Genetic testing technologies like whole exome/genome sequencing have shortened the quest for many patients, though perhaps not as often as one would have hoped.

The label Diagnostic Odyssey suggests that the diagnosis is the end of the odyssey. And therein lies the problem. Many families and patients discover that a diagnosis does not necessarily allow them to settle down happily with Penelope in the kingdom of Ithaca. A successful diagnostic workup may be the end of the odyssey for clinicians, but for patients and families the diagnostic quest is just one phase in the life cycle of genetic disorders.

A diagnosis may answer some questions such as cause and recurrence risk, but it can also create a whole new set of issues. For patients diagnosed with ultra-rare conditions, families may be faced with frustration from a lack of available knowledge about treatment or prognosis. Even if medical interventions are possible, finding and accessing those resources, and getting health insurers to pay for them, can be a major undertaking. Or a condition’s rarity may make it impossible to form an effective patient/family community to provide advocacy and support. The diagnostic odyssey may result in some patients feeling like diagnostic oddities.

If a newly diagnosed syndrome turns out to be untreatable or life-shortening, parents may lose all hope and descend into existential despair. A non-diagnosis at least holds the glimmer of a chance for a treatment or cure out there somewhere. Patients who have a diagnosis changed from a previous incorrect diagnosis may lose the sense of identity and support supplied by the disease community that they had been involved with for years.

The label Diagnostic Odyssey focuses on one medical aspect of a condition. Clinicians can take much-deserved professional satisfaction in having finally solved a long-standing mystery. But for many families, living with a genetic condition is not a temporally demarcated event and, above all, not only a medical experience. Patients will also still need to implement strategies and solutions to the social, educational, lifestyle, and psychological ramifications of the disorder. It is an ongoing journey, one that continues to unfold as patients age and develop new symptoms, family structures evolve over time, medical treatment advances, and sociocultural changes re-shape attitudes toward inclusivity and the availability of resources. A genetic condition, named or not, will continually present new challenges throughout the entire life of a patient.

We do not mean to imply that a diagnosis is unimportant. We recognize the emotional and potential medical value of finally “putting a name on it.” But the name just points the ship in a new direction to unexplored regions with different threats, problems, and rewards.

Perhaps the Diagnostic Odyssey label needs to be retired or renamed to more accurately reflect its role in the process of living with, and adapting to, genetic conditions. So we turn to the Good Readers of The DNA Exchange to offer their suggestions – what do you think?


Genetic Counselor Talent Show Friday, November 16th

Are you attending the 2018 Annual Education Conference of the National Society of Genetic Counselors in Atlanta next week? Worried that days of  PowerPoint presentations and polite applause will make you forget what fun is? Want to have a blast one evening and see your genetic counseling colleagues in a very different light? Then attend the Genetic Support Foundation’s GC’s Got Talent  2018 genetic counselor talent show on Friday evening November 16th. Cancel all your other evening plans for Friday, November 16th. Trust me – there will be nothing even close for entertainment. With Yours Truly, Bob Resta, as Master of Ceremonies, how could anything beat it? Can you dance, sing, or play an instrument? Are you a Slam Poet? Then show off your talents to your colleagues! Or, if like me, you have Zero Talent, then join me as part of the Story Telling Crew. I have a goofy and weird story to tell. But we all also have poignant, tragic, comic – or all of the above – tales to tell. If I can do it, then you can do it. If you wish to impress your colleagues with your talent, send an email to info@geneticsupport.org to sign up. Show up et regarder les bon temps rouler.

For more information, visit: https://geneticsupportfoundation.org/gc2018

 

 

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Black-ish, Jewish-ish, and Scientific-ish: Some Problems Created By Racial Admixture

Race. I don’t think there is a more controversial and polarizing issue today. Skin color-based racial categories are considered scientifically invalid, yet race is included in government-collected population data as well as in scientific research.  But racial categories – real or imagined –  always create social problems. Those problems can become magnified – and the absurdity of classifications highlighted – when the discussion turns to racial admixture. Population genetics  tell us that no one is purely of any one race. Since hominids first wandered out of Africa, lust and wanderlust have combined to produce a species that is basically a bunch of “polyhybrid heterogeneous bastards.” The recent discovery of a fossil from a half Neanderthal/half Denisovan female in a Siberian cave proves that this genetic messiness has been going on for a long time.

Thomas Jefferson, for one, fretted about racial admixture. And not in an abstract or philosophical way. He was very much concerned with the practical question of whether the children he fathered with Sally Hemmings, one of the more than 600 slaves he owned throughout his life, would be considered black, and thus slaves, or white, and therefore free people. Hemmings was 16 and Jefferson was 46 when they conceived the first of seven children she was to bear by him. According to Virginia law at the time, a person who was 7/8 white was considered, well, white.

Hemmings had white ancestry; she was the half-sister of Jefferson’s (white) wife. As recounted in These Truths, Jill Lepore’s recently published delightful history of the United States, Jefferson engaged in some mendelian-sounding calculations about his children’s racial status (comments in brackets added by me):

“Let the third crossing be of q [Hemmings] and C [Jefferson], their offspring will be q/2 + C/2 = A/8 [a “pure” white] + B/4 [ a second “pure” white] + C/2, call this e (eighth), who having less than 1/4 of a, or pure negro blood, to wit 1/8 only, is no longer a mulatto, so that a third cross clears the blood.”

In other words, Jefferson calculated that his 4 surviving children with the partially black Hemmings would be considered white under Virginia law and thus would not technically be slaves, even if they were de facto slaves. In practice, he freed one of the four during his lifetime, a second he “let” escape, and the other two were freed in his will. Incidentally, Jefferson was not alone among presidents in owning slaves –  18 US presidents owned slaves, some while they were in the White House. A seemingly insignificant bit of trivia underscores the inhumanity with which even the “good guys” viewed slaves – 9 of the teeth in George Washington’s dentures likely came from the mouths of his slaves (which, in a manner of speaking, would make Washington a racial hybrid – teeth of a black man, jaws of a white man). The slaves may have been paid for this but that hardly justifies the act. Ethically, it is no different than when desperately poor people sell their organs for money to feed their families.

George Washington’s dentures

 

Medical geneticists have had to struggle with problems stemming from racial admixture and trying to define race. For example, one of the most common reasons for referral to American genetics clinics in the 1940s and 1950s was to determine the future racial appearance of children put up for adoption, often the product of trans-racial matings. Adoption agencies usually had a policy of trying to match the race of the child with the race of the adoptive parents. Some Southern states even passed legislation that banned trans-racial adoptions. Geneticists were often tasked with predicting the future physical appearance of children, based on their skin color or the presence or absence of certain traits thought to be more or less common in different races. By assigning a child to a specific race, geneticists also assigned that child to a social and economic life dictated by that race. No doubt many of these geneticists – like today’s genetic counselors – would never describe themselves as racists. Nonetheless, the clinical services they provided helped reinforce the pervasive racism of American society.

Felix von Luschan’s skin color charts, a common way of assessing skin color up to the 1950s

Current day geneticists continue to struggle with the problem of the biological validity of race and racial admixture. Mis-assigned or mixed ancestry, either by researchers or participants themselves, can lead to false conclusions about the pathogenicity of gene variants or generate false positive or false negative associations in SNP studies. We have also begun to see genetic ancestry tests, what some see as a modern pseudo-scientific racism, enter into the clinic. Genetic counselors typically query clients about their ancestry when constructing a pedigree. In my experience – which I am pretty sure is not unique – many patients respond that they have taken a direct-to-consumer ancestry test and then recite a scientific sounding breakdown of the different percentages of their genetic ancestry, e.g. 23% Welsh, 21% Irish, 10% French. Where this can become a problem is when it is used to guide genetic testing decisions. How much Ashkenazi Jewish ancestry warrants a specific genetic test or set of tests considered appropriate to that population (expanded carrier screening avoids that particular problem in some settings, but it has its own set of other issues)?

A recent referral to our clinic highlighted this dilemma. We were asked to see a patient for BRCA testing because she was reportedly Ashkenazi Jewish. As it turned out, an ancestry test had indicated that she was “1% Ashkenazi Jewish.” We have had several other referrals where this has come up. To keep our referring providers happy, we have very arbitrarily set a policy of a 10% rule – for patients who have had an ancestry, results should indicate at least 10% Ashkenazi Jewish ancestry before we consider them “Jewish.” Sort of our equivalent of Virginia’s 7/8 rule. Meshugunnah, I know. Never mind who your mother is.

Given the history of extreme persecution of Jews and other groups like the Rohingya in Myanmar or the Japanese Americans who were put into internment camps in the US during WWII, along with the rise of anti-immigrant sentiments and political intolerance, genetic testing that allegedly “proves” ancestry should be not be publicly available information. Somewhere, in some part of the world, at some future time, being “10% Jewish” or whatever ancestry could be a very harmful data point. Admixture can determine your life’s trajectory. Or enslave. Or kill.

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Press Secretaries and Prenatal Diagnosis

The prevailing psychological paradigm views the human mind as two different interacting agencies – the unconscious and the conscious. The influence of the unconscious on the conscious mind began receiving scientific attention in the 19th century, reaching a critical juncture with Sigmund Freud’s deep dive into the murky and lurid waters of the unconscious. While many of Freud’s theories have not stood the test of time, his core concept that our unconscious mind is driven by darker instincts that our conscious mind tries to cover over is still widely accepted. And, in a sort of cosmic joke, it is extraordinarily difficult for us to know our own minds because our brains were shaped by evolution to deceive us into thinking we are good people who are conscientious members of society. We are really good at lying to, and believing, ourselves. I like the imagery employed in Kevin Simler’s and Robin Hanson’s recently published book The Elephant in The Brain that compares the conscious mind to a press secretary that tries to positively portray the less saintly aspects of the unconscious mind. Think of a governmental press secretary who has to explain a leader’s questionable statements and decisions without always being aware of what the leader is saying or doing.

So what does the deep mind and its personal Press Secretary have to do with genetic counseling? Well, a lot actually. In previous posts, I have discussed how the unconscious mind can influence genetic counselors’ perceptions of their conflicts of interest, how the pauses in a conversation between speakers can subliminally communicate meaning, and how I sometimes struggle to not let my darker thoughts insinuate themselves into my interactions with patients. In this posting, I look at the role of the unconscious mind in patients’ decisions to accept an offer of prenatal screening for Down syndrome and in deciding whether to continue a pregnancy in which a fetus has been diagnosed with this condition.

There is a common and deep negative attitude toward people with disabilities, even among their care providers, that sometimes borders on fear. Pick your reasons for this – ego threat, announcing to the world your reproductive unfitness, an assault on your concept of an ideal child and family, selfishness to prevent the loss of how you want your life to play out, rejection of those different from us. Readers more astute than I at probing the unconscious can probably think of others. This negative attitude is the driving engine of the prenatal screening train – given a choice, many people do not want to raise a child who will have significant cognitive or physical impairments. Some of this stems from misunderstanding and misinformation about disability. But decisions are typically based on the darker motives of the unconscious mind, not on information.

Here is where the Press Secretary comes in to play. People prefer not to admit to these less socially acceptable thoughts. Instead, they manufacture very plausible explanations to justify their decisions. Mind you, I am not implying that people are liars, hypocrites, or morally derelict. Rather, the unconscious mind usually rules the roost and leaves it to the Press Secretary to put a positive spin on it. This is how the human mind works, and it is crucial to understanding how patients make difficult and morally ambiguous decisions. It is like a role reversal in the Wizard of Oz.* Professor Marvel, Acclaimed by the Crown Heads of Europe, isn’t behind the curtain. Instead, the flaming, smoking, blustering, self-important gigantic head of The Great and Terrible Oz is back there. Oz doesn’t have the heart or courage to fight the Wicked Witch of the West and manipulates Professor Marvel to impart the task to Dorothy the Small and Meek (and, yes, Toto too). Professor Marvel is a bad wizard trying to pass himself off as a good man.

 

For example, what I often heard from patients as an underlying reason for a decision to proceed with testing or terminations shifted the focus from darker to more personally and socially acceptable reasons:

  • “We wouldn’t want our other children to bear the burden of caring for a disabled sibling after we are gone.”
  • “It would be unfair to our other children if we had to devote so much attention to a disabled sibling.”
  • “My doctor thinks it is the right thing to do and really wants me to have the test.”
  • “The world can be cruel to people who are different. I remember how a boy with Down syndrome was mercilessly teased in my neighborhood when I was growing up. I would not want to put my child through that.”
  • “It would put too much of a strain on our marriage. I know I could deal with it, but it would be devastating to my spouse.”
  • “I want to take advantage of advances in medical testing and information to make sure my baby is healthy.”

As a counselor, there is nothing to be gained from criticizing any of these as being invalid justifications. Indeed there is a measure of truth to them that provides plausibility. Patients are not concocting nonsense reasons or blatant falsehoods. But they also transform the less desirable urges of the unconscious mind into a message that allows the conscious mind to maintain its self-image of a Good Person and to avoid the negative judgment of family, friends, and social networks. On top of this, a well-oiled medical and economic machinery capitalizes on negative attitudes toward disability and reinforces the idea that prenatal screening is a wise choice for responsible parents.

This also has implications for critics of prenatal testing who claim that if pregnant women better understood the quality of the lives of people with disabilities, then more people would reject prenatal screening. This is true only to an extent. The unconscious mind is not usually persuaded by mere facts and will ignore them, reframe “truth” to make it more compatible with the motives of the unconscious, or filter out the parts that it doesn’t want to hear. Bias against physically and cognitively different people is found in all cultures and over time, though there is variation as to which conditions are the focus of a society’s prejudices and fears. People with albinism have been traditionally well-integrated into Hopi society and often play special roles in ceremonial dances; in parts of Africa they fear for their lives. Education alone is unlikely to alter attitudes. Change will require large-scale cultural shifts in views towards specific disabilities and conditions.

Unless we appreciate how the unconscious mind drives behavior and choices, we will never understand our patients – or ourselves.


  • – The day after I drafted an early version of this posting, I came across the same allusion to the Wizard of Oz in Leonard Mlodinow’s Subliminal – How Your Unconscious Mind Rules Your BehaviorIncidentally, in L. Frank Baum’s Oz books, Professor Marvel explains that his full name is Oscar Zoroaster Phadrig Isaac Norman Henkle Emmannuel Ambroise Diggs, the acronym of which is OZPINHEAD. In yet one more example of bias towards people with disabilities, he chose his name by using the first two letters of that acronym – Oz – and dropping the “pinhead” part.

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When Perfection Causes Imperfection: A Potential Non-Genomic Complication Of Germline Editing

There is wide consensus that we should not only treat but also try to cure genetic conditions that cause profound suffering. CRISPR and related technologies have descended on us like a deus ex machina from the heavens and made it possible to “cure” genetic diseases through germline editing. Precision molecular microsurgery has stimulated provocative discussions about which diseases are serious, where we draw the line, the acceptance of people who are different in appearance and abilities, increasing the disparities between wealthy and poor, religious concerns, etc. I don’t have any helpful insights into these issues but I hope that vigorous debate continues and that if germline editing becomes a reality, we proceed veeerrrrrryyyyy slowly, cautiously, and incrementally.

The more ardent “germline utopians” envision a world where all fertilized embryos undergo germline editing to prevent the resulting offspring from developing genetic disorders. Of course, this will never happen universally. Even in a fantasy world of full acceptance of, and unrestricted access to, germline editing, pregnancies have a habit of, well, happening on their own. But for argument’s sake, let’s make the unlikely assumption that many parents will utilize germline editing to prevent their children from developing genetic conditions. Given that Western societies place great value on individual autonomy and considering the conditions that are currently screened for through prenatal diagnosis and carrier screening, it is likely that prospective parents would choose to “correct” traits ranging in severity from hearing loss to profound physical and developmental disorders, and all points in between. And to twist the complexity we might see the reverse scenario where deaf parents choose to “correct” a hearing-abled embryo. Should genetic enhancement – adding a few IQ points, tacking on centimeters of height, a slimmer habitus, Faye Dunaway zygomatics – become a reality then a goodly number of parents will take advantage of that as well (please I hope never because it will bring out the worst in us).

Of course, this model of genetic disease prevention depends on whether the technique actually works and that it is safe. There is reason to believe that germline editing and “correction” of genetic conditions are technically achievable. Safety, however, is more open to question. Off-target genetic effects, among other safety issues, could relegate germline editing to the What If category of debate.

But let’s posit a world where efficacy is proven and off-target effects are negligible. There would still be another safety issue, unrelated to genomics. Germline microsurgery requires in vitro fertilization/intracyoplasmic sperm injection (IVF/ICSI) in order to gain access to the gamete or the fertilized egg and to achieve a pregnancy. And therein lies the rub – IVF/ICSI is associated with a higher risk of complications in singleton and multiple gestations, such as prematurity, low birthweight, small for gestational age, perinatal mortality, and congenital anomalies. It reminds me of the introduction of a phenylalanine-restricted diet to reduce the impact of PKU that eventually created the phenomenon of maternal PKU, in which maternal hyperphenylalaninemia produced babies with microcephaly, heart defects, and intellectual disabilities. The attempt to cure one problem can create a whole new set of problems.

Now maybe the complications of IVF/ICSI are in part due to the underlying causes of the parental infertility, and thus fertile couples may have lower complication rates. Maybe. Perhaps IVF/ICSI will become safer. Perhaps. Still, it is likely that some parents will be willing to accept the risks of pregnancy complications in return for not having a child with Tay-Sachs disease or severe ichthyosis. But are the pregnancy risks worth it to prevent genetic hearing loss, increase a child’s IQ, or create a child with movie star beauty?

You might understandably say “My God, we finally have the chance to prevent serious genetic problems and improve people’s lives. How can we not take advantage of it? We are just trying to do good in a world full of suffering.” Indeed, the goal of reducing suffering is as old as the field of Medical Genetics. But when we march beneath the banners of Cure, Good Intentions, and Highly Ethical Motivations, and throw in an unhealthy dose of hubris, our enthusiasm may blind us to the harm that we might do. Perfection comes with a price.

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Work Shift: A (Wrong?) Prediction

Genetic counselors are engaging in a bit of preening now that CareerCast has listed our profession as the top-rated career for 2018. Actually, it’s a bit of history repeating itself. Back in 1980, the genetics equivalent of The Neolithic, I learned about the profession when I came across an article in Working Woman magazine (now defunct, and not to be confused with Working Women magazine, which is still in circulation) touting the top 10 careers for the modern woman of the 1980s. My other time-killing choices that day were People, Reader’s Digest, and Ranger Rick. If I had picked up a different magazine, well, just imagine Ranger Robert. Funny how our lives play out.  Incidentally, even today, National Society of Genetic Counselor (NSGC) membership is 95% female, so that article in Working Woman really had its finger on the socioeconomic pulse.

Ranger Robert. Graphics by Emily Singh

 

The CareerCast story appeared just a few weeks after the publication of the latest Professional Status Survey (PSS) by the NSGC. The two pieces got me to thinking about historical changes in the employment picture of the profession and eventually, perhaps after a beer or two, a prediction popped into my head about a trending shift in who employs genetic counselors. I am not the first to notice the trend, so my contribution is to suggest the extreme to which the trend will run as well as its implications.

My prediction is that within the next 5-10 years, a significant majority of US genetic counselors will be employed  by laboratories and other biotech firms, in both patient contact and non-contact roles, and, to a lesser extent, by private practice groups that offer their services over the Internet or whatever communication technology is predominant in 2025. Until about a decade or so ago, the vast majority of genetic counselors were employed by private and academic medical centers. This is still true; if I am interpreting the 2018 PSS correctly, about 2/3 of genetic counselors are employed by medical centers, public hospitals, HMOs, private hospitals, and physician private practices. However, there were also changes in the percentage employed by laboratories and biotechs. In 2010, 10.5% of genetic counselors were employed by labs and biotechs. By 2018, that percentage more than doubled to 22.5%, and another 2% of genetic counselor were employed by telegenetics companies in 2018 (the 2010 PSS did not have an equivalent category). In other words, about a quarter of the current genetic counseling workforce is employed by labs, biotechs, and telegenetics companies.

There are several factors driving this trend. First off, more laboratories are offering direct genetic counseling services to patients and thus need to hire more counselors  – Counsyl and its new owner Myriad Genetics, Color Genomics, LabCorp, and Invitae, to name a few. Second, salaries of laboratory genetic counselors are typically a good 20% higher (plus more to be made in bonuses and stock options) than those offered by medical centers, making labs more enticing to prospective employees. Third, more medical centers and large medical practices are looking to include genetic counseling among the services they provide to their patients. Since genetic counselors don’t typically generate enough income to pay their costs, medical centers may be relieved to have a laboratory provide genetic counseling to their patients, either on site or via telegenetics. Clinics would bear minimal costs and labs would get a pipeline for specimens. This in turn will create a competitive environment among labs to offer their genetic counseling services to more clinics to ensure they maintain reasonable share of the testing market. A lesser trend will be the growth of telegenetic services offered by dedicated telegenetic counseling companies and individual private practitioners (together, currently 2.2% of genetic counselors). I suspect this latter group will be limited in its employment share, in part because they will have a hard time competing with the deeper pockets of large corporations. The net effect will be that the percentage of genetic counselors employed by medical centers will decrease significantly.

A natural extension of this trend is that bigger labs will continue to swallow smaller labs, and mega-corporations will swallow the bigger labs. Its hard to fight economy of scale. Konica Minolta owns Ambry Genetics. Eventually BGI may get in on the act (then watch out!). Heck, it’s not out of the question that many genetic counselors could one day work for Amazon (see my posting Sour Grapes, a dystopian satire about this possibility).

Both good and bad will emerge from these trends. More patients will have access to genetic counseling through telegenetics, whether from labs or dedicated genetic counseling companies. With genetic counselors on staff, labs and medical centers can be confident that testing is ordered and interpreted appropriately, improving patient care and reducing economic waste. More career opportunities will open up for genetic counselors as corporations recognize their skills and smarts. Salaries and other benefits will likely become more generous.

There is plenty to worry about too, at least for professional fretters like me. With more mergers and acquisitions, there will be fewer employers of genetic counselors and so the field will lose some of its practice diversity. Employers will expect their employees to adhere to certain business practices and philosophies unique to each employer. Practice diversity has been a rich source and testing ground for new and different ways to conduct genetic counseling. More concerning to me is the potential loss of  carefully considered patient decisions about whether to undergo a genetic test. Acquisitions and mergers are driven by the desire to increase market share and market penetration, not by an altruistic urge to ensure that patients carefully consider the benefits, downsides, and psychological impact of genetic testing (although undoubtedly labs support the right of each patient to make independent decisions). This will become even more concerning  as labs are subsumed by larger corporate entities that are further removed from the practice of medicine and the ethos of genetic counselors, generating real concerns about conflicts of interest. Another possibility is that large labs will either set up or help finance genetic counseling training programs. Why not have a steady source of prospective employees who can be trained to develop skills and a counseling approach that are shaped to a particular corporate milieu?

I acknowledge that this is a very America-centric view of the genetic counseling profession. This trend may not play out to the same degree, or at all, in other countries. On the other hand, telegenetics knows no borders. Conseil Gènètique Sans Frontières. Governments are looking for ways to cut health care spending in the UK, Canada, and Australia, among others. International mega-corporations – Big Genoma – can offer enticing cost-savings to legislators looking to reduce expenses without increasing taxes.

Of course, like most prophets and self-appointed pundits, my predictions will be off, and perhaps even laughably so. The thing about the future is that nobody knows what it’s going to be like. So if you disagree with me, or are outraged by my thoughts, take solace in knowing that I will likely be wrong yet again. But I think there is enough meat on this bone that it’s worth chewing over.

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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)

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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.

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Filed under Robert Resta