Category Archives: Guest Blogger

Guest Post: If Gay Means Happy, Then Why am I so Sad?

By Austin McKittrick

Austin is a genetic counselor for Genetic Support Foundation, a non-profit genetic counseling group, where he provides telehealth genetic counseling from his home base in Vancouver, WA. He a first time blogger, long time reader of the DNA Exchange.

 

A study recently published in Science sought to answer the age-old question: Where’s the ‘gay gene’? As a member of both the genetics and LGBTQ+ community, this headline naturally piqued my interest. I’ve always thought that this question is inherently a double-edged sword: by ‘proving’ that non-same sex attraction is in some way genetic, the whole ‘it’s a choice’ argument can finally be put to rest. But finding a scientifically detectable ‘cause’ for non-heteronormative behavior naturally brings up an equal (if not greater) level of concern.

The intentions of researchers are often not what is embodied by the products of that research. I honestly don’t think that the creators of genetic testing for ancestry thought that this testing would one day be used by the Canadian government to try to sort out where migrants to their country are ethnically from. But maybe they should have.

Even when we think we understand the genetics of a trait, the outcomes often aren’t as straightforward as we once believed. Particularly for a trait such as ‘nonheterosexual behavior’, where social, religious, family, and political influences also strongly affect one’s beliefs and how they may choose to reconcile those beliefs with their lifestyle. Genetics is leaping forward faster than the majority of us had probably anticipated, and we’re getting a real lesson about putting the cart before the horse.

There are some issues with how the study was conducted, as sexual identity is very complex and some of the questions have been viewed as being too binary and focused on behavior rather than sexual orientation. The researchers categorized people into two buckets: those who have EVER had ONE or more same-sex sexual experience are categorized as ‘nonheterosexual’ while those who have never had a same-sex sexual experience are categorized as ‘heterosexual’. They do make an attempt later in the study to outline that sexuality is a spectrum, but that assertion is buried amongst other extrapolations.

The data sets for this study were collected from the UK Biobank, as well as direct-to-consumer testing company 23andMe. Companies such as these encourage their customers to consent to having their DNA used for research, promising that their selfless contribution will further the field of genetics and healthcare. In all actuality, it appears that this data is being sold to entities that are using it for less medically noble endeavors. Aside from individuals not fully understanding that their data could be used for such ‘research’, they may actually unknowingly be participating in research that could potentially lead to discrimination and other harms against them in the future.

The authors of the ‘gay gene’ study determined that ‘like other behavioral traits, nonheterosexual behavior is polygenic’. There you have it folks: it’s not ONE gene. It’s LOTS of genes! Is that better? Worse? Depends on what you do with that information…

Enter GenePlaza, a company that boasts that it can take the DNA information that you’ve received from companies like 23andMe and Ancestry.com and use its internal apps to tell you things like how smart you are or how good you are at math (in case your grades in school didn’t tell you already). With data taken from this new study, GenePlaza proposed that for $5.50 they could tell you exactly how gay you are.

Backlash to the announcement of the app was swift, and a petition was quickly announced in an effort to get the app shut down. Although at the time of this publication it not yet reached its goal of 2,500 signatures, it appears to have been effective as there is no sign of the app now on GenePlaza’s app site.

It’s tempting to want to give GenePlaza the benefit of the doubt. ‘Oh they just thought it would be a harmless app’ or ‘They probably just thought it’d be a good party trick’. However, the revelations that the app’s developer, Joel Bellenson, is based full-time in Uganda paired with the news that this year Uganda is announcing plans that would make the death penalty punishment for homosexuality makes it seem that something more nefarious may be at play.

As the authors of the study said, we should resist ‘simplistic conclusions because the behavioral phenotypes are complex, because our genetic insights are rudimentary, and because there is a long history of misusing genetic results for social purposes.’

Some have raised concerns about the motivation of such research studies. But once something like this is out of the bag, it’s very difficult to put back in. No matter the motivation, this is another shining example that when it comes to genetic technology, we regularly need to be asking ourselves not only ‘Can we?’, but ‘Should we?’.

 

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Guest Post: We Can Do Better – The Experience of a Minority Genetic Counselor, by Tala Berro

Tala Berro is a genetic counselor in the Boston area. She is a queer, Arab woman who is also a racial justice and LGBTQIA+ activist. You can follow Tala on twitter here: @tala_berro

Bob Resta recently wrote a blog on his experience of being a man, as well as the advantages and disadvantages of being a woman, in our woman-dominated field. He called upon us good readers to share experiences “where you are not quite like everyone else.” Being a queer person of color in genetic counseling, I immediately took up his call. In part due to my various identities, there have been countless instances during my genetic counseling training and career when I have felt “not quite like everyone else.”

Let’s start with intersectionality, a term coined by Black feminist scholar Kimberlé Crenshaw in 1989 to highlight the ways in which black women were excluded from the feminist movement. Crenshaw notes that “not only are women of color in fact overlooked, but their exclusion is reinforced when white women speak for and as women.” In this blog post, I want to take a deeper dive into how my own intersecting identities as a queer, Arab woman affect my experience as a genetic counselor.

The genetic counseling profession within the Unites States is overwhelmingly white. As reported by the National Society of Genetic Counselors (NSGC), 92% of the 2018 Professional Status Survey respondents identified as white, which is easily visualized when one walks through the exhibit hall at the NSGC Annual Education Conference. Although there are many reasons why we often see a higher percentage of white individuals in jobs that require a graduate degree, genetic counseling is an especially white field. In comparison, 54% of software engineers are white, 80% of public school teachers are white , and 68.2% of physicians/surgeons are white.

The foundation of empathy is what drew me to the genetic counseling profession. I knew that I would come in as an outsider, but I hoped that caring, open-minded genetic counselors would make for caring, open-minded classmates, supervisors, and coworkers. However, we have a long way to go. Genetic counseling training programs incorporate lessons on the importance of culturally appropriate counseling of patients, but this same openness and acceptance is not always extended to fellow genetic counselors.

I started to notice my “otherness” in the field of genetic counseling from the beginning of graduate school. Being an Arab genetic counseling student always had its pros and cons. My favorite instances as a student were when an Arabic speaking patient would come into a genetic counseling session and I could utilize my knowledge of Arabic. This shared language and its ability to add comfort to my patient always felt really special. More often than not, though, sessions with Arab patients would end in a debriefing session with a supervisor who would ignorantly state microaggressions, judging family sizes, and gender dynamics. After one of these sessions, my supervisor and I were discussing the patient and mentioned the specific Arab country they were from. A medical professional in the workroom overheard and noted that, to her, this specific country is associated with danger and violence. There was no response to this comment. I was left shocked, dismayed, and anxious, without an outlet to seek support from other genetic counselors of color or Arab background.

What is currently seared into my mind as a genetic counselor of Arab descent whose community often attends mosque, is the massacre in New Zealand. I came to work devastated and shaken. While not all individuals of Arab descent are Muslim, I (and many others) consider those who are Muslim to be members of my community. Perhaps a genetic counselor saw a Muslim patient that Friday and provided comforting words. I wondered, though, how many genetic counselors reached out to their peers or students who may have been impacted by this. From my own experience of not receiving messages of support, I would guess not many.

In addition to racial barriers, being a queer genetic counselor comes with its own barriers to navigate. Based on my training experience, genetic counselors are growing in their awareness of pronouns and gender identity, often using the word “partner” when counseling. However, on an interpersonal level, it takes more than just awareness for true inclusion. I recall a conversation from back when I first started as a genetic counseling student in which I proudly identified myself as queer. This statement was met with discomfort and confusion. I know that genetic counselors are educated on the importance of mindfulness and inclusivity of the LGBTQIA+ community and are taught to be verbally-inclusive with patients who identify this way during a session. However, there seems to be a discrepancy in how these lessons of acceptance are actively applied by genetic counselors in and out of clinic. The ability to sustain a relationship with a patient over a 60-minute genetic counseling session does not translate to intentionally cultivating an authentic relationship with someone of a different identity from you.

One universally challenging aspect of genetic counseling training is providing and receiving feedback. To be evaluated on your words, demeanor, and body language while you are learning to interact with patients and cope with emotional situations is difficult. However, feeling like you are also being evaluated for your values, beliefs, and cultural upbringing is much harder. At times, I have been critiqued for my character and values, as opposed to my specific counseling skills. I have been encouraged to “play devil’s advocate” to my own beliefs. For example, during my training, I was given feedback that highlighted my potential to advocate for underserved patient populations, and also challenged me to find ways of connecting with patients who are different from me. This feedback came before I even had the opportunity to interact with a single patient. I felt critiqued not on behaviors I exhibited but on behaviors that were assumed of me. It also felt like this feedback was unnecessary reiteration that I am different, as the minority, and that I will be expected to live and fit in a world of the majority. Through these experiences I wondered: were my professors and supervisors feeling defensive because I was different from them and teaching me felt different than teaching others in our field? Who could I turn to within the field to talk about my thoughts and concerns?

Whenever I hear the term devil’s advocate, I think back on a blog post by Juliana Britto Schwartz. She writes, “dearest devil’s advocates: speak for yourself, not for the ‘devil’. Teach yourself. Consider that people have been advocating for your cause for centuries, so take a seat. It’s our time to be heard.” It is often forgotten that those with underrepresented identities have lived their entire lives being forced to understand the majority. These same privileged experiences to which I was encouraged to have an open mind are mirrored by what I read about in fiction, watch on television, and learn about in the history books. As a queer genetic counselor of color, I understand how to navigate these spaces because I have been forced to my whole life and will continue to do so in my professional life. Instead of ensuring that I understand and empathize with the majority experience, why don’t we make sure that the majority understands and empathizes with the minority experience?

As genetic counselors, we consistently discuss and learn about empathy for our patients. My hope is that we can take these lessons and apply them to our colleagues and peers outside of a counseling session. To my fellow genetic counselors, I propose the following version of the golden rule: treat your peers as you treat your patients.

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Anonymous Guest Post: Being A Genetic Counselor As Someone Affected by Mental Illness

This anonymous guest post was written in response to a request in a recent blogpost by Bob Resta asking for genetic counselors who feel that they are different in some way to write about their professional experiences. In a departure from the usual policy of The DNA Exchange, we have agreed to respect the author’s wish to maintain anonymity. For another view of life as a genetic counselor with a perceived disability, see Kelly Rogel’s post from about 10 years ago.

Around six years into my career as a genetic counselor I was given the diagnosis of bipolar type I. Previously I had a diagnosis of severe depressive mood disorder since I was 18 and had managed to make my way through college and into the work force (although it was a very rocky path) before I received the proper diagnosis and medication.

How did this diagnosis affect me as a genetic counselor?

The stigma surrounding mental illness is huge. While I believe it is getting better, I have been at clinical meetings where patients with mental illness have been discussed by different specialists and it seems that the patient is reduced to just their diagnosis. Bipolar, schizophrenia, obsessive compulsive disorder…this make me fearful of disclosing my disorder to colleagues. At the present time my direct supervisor and the head of the department know my diagnosis and are highly supportive. I struck it lucky, however. Unfortunately, in a lot of situations once you have that label of being bipolar it seems everyone looks at you through that lens all the time. Having a bad day? Oh, it’s the bipolar and you’re depressed. Feeling great? You must be manic. It’s frustrating and also means you are constantly second guessing yourself. It also means people aren’t recognizing that you have the normal range of emotions as everyone else – you are not your diagnosis.

It is both a blessing and a curse that bipolar is an ‘invisible’ disorder. You can’t look at me and tell that I have a mental illness, so I don’t have to disclose it to anyone if I don’t want to. However, there are days where getting yourself dressed to go to work feels like walking through quick sand, or you have foggy thinking due to the medication you have to take, and it’s hard to explain this to people when on the outside there’s nothing “wrong” with you. Obviously if these side effects are extreme then it might not be appropriate to be in the workplace, but there are many days that you do have side effects from medication, for example, but it’s not severe enough that you need to take a sick day. It’s a bit like having a mild cold and going to work anyway.

With bipolar, if you want to function then you have to learn how to develop insight into your condition and know your “‘red flags” for both depression and mania. This means that if I feel myself heading in one direction or another, I can nip it in the bud using medication and other treatments before I become a danger to myself or to patients. Unfortunately, I have experienced psychosis several times and have needed hospitalization once in my time as a genetic counselor. While my mental state was deteriorating my supervisor and I made the decision to take me off seeing patients until I recovered. An independent clinician provided by the hospital saw me to assess when it was safe for me to begin seeing patients again.

With patients it’s given me empathy and an understanding of those who have their own mental illness. I am often able to suggest resources available through the public health system that I am aware of that others may not be. For several reasons, though, I do not in any circumstances disclose my condition to patients. I feel that it would be unprofessional to do so as it takes the spotlight off the patient and moves it on to me, I feel the stigma around mental illness may be detrimental to the counseling relationship, and I also feel that you don’t have to have a mental illness to feel empathy towards someone with the condition. I also do not want my patients or colleagues feeling that my clinical care is impacted by my diagnosis.

It’s a difficult life to lead, but I know I’m very lucky to have highly supportive supervisors who have truly made an effort to understand the condition and how it is managed. I imagine my experience would have been very different if the resources available were not in place or I didn’t have access to them.

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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.

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The GC Crucible: the pressures on modern genetic counselors open the doors to opportunity

A Guest Post By Brianne Kirkpatrick

In a chemistry lab, a ceramic crucible held over an open flame melds disparate materials into a single, new, cohesive thing. Indestructible, it stands up to the heat and pressure. When used in metaphor, it’s a severe test or tribulation that leads to transformation. What comes out of a metaphorical crucible is the true character brought about by the need to adapt and change in a new environment.

 

If there is one thing I can get behind, it’s a belief that our job as genetic counselors is getting

harder. We work in a cauldron of new pressures and new challenges, ones that are causing us to adapt and discover what is at the core of our profession and what make us strong and unique, as individuals and as a cohesive group. We’re in a crucible right now, and that Bunsen burner is cranked up high.

 

Our clinical challenge is that the more we learn about genetics, the more complexity we discover (see item two in Laura Hercher’s top ten stories list for 2015 ). More information makes our job harder, even as it provides new hope for our patients. Similarly, the challenges of discovery and complexity that complicate our lives also provide new opportunities for genetic counselors.

 

How do we capitalize on those opportunities? Here are three suggestions:

 

  1. Rally around the development of the Genetic Counseling Assistant vocation. The NSGC funded a grant to study this, and there have been discussions about this at recent meetings and on various listservs. GCAs job are available, and individuals are employed as GCAs around the country already, in laboratory and clinical settings. Like a para-legal to a lawyer, GCAs master administrative tasks and carry the burden of extra work that often sidelines the genetic counselor or reduces his or her efficiency – phone calls, paper work, records requests, insurance pre-certifications, initial intakes, and the like. The only way we are going to keep up with the demand for GC services is to increase efficiency for ourselves and free up genetic counselors from work that impedes their ability to serve all who need and are seeking their services.

 

  1. Evolve or die. We as a profession must figure out how the future of genomics will include us. To do this we must immerse ourselves in current issues – in the clinic, in the research world, in the spheres of business and government – and then speak up when the genetic counselor voice must be heard. Get involved in your state’s genetic counselors’ group (consider founding one if it doesn’t exist). Volunteer in groups and for projects of the National Society of Genetic Counselors. Develop a professional social media presence. I chose to involve myself in the NSGC Public Policy Committee, believing strongly that taking a stand on issues of policy that affect us as genetic counselors allows us to determine our profession’s destiny, not others. Every committee and special interest group and task force of the NSGC contributes important work to the genetic counseling profession, but none of that work happens unless individuals decide to take that step and get involved.

 

  1. Embrace the expansion of our professional opportunities, despite the shortage of genetic counselors to fill existing clinical and laboratory roles. GC’s are finding opportunities to do something new and different, which is fitting for a group who collectively are thinkers outside of boxes. For as long as the profession has existed, GCs have used creativity, ingenuity and chutzpah, trailblazing new roles out of necessity. In every city and in every specialty area, there was a “first” GC there. If you have been contemplating blazing your own trail, now might be a good time to test out the waters, to find your niche and try something you’ve been dreaming of.

 

There are role models for those looking for them, as GCs excel at identifying needs and making connections. We’re problem-solvers and sleuths, and we’re a resourceful bunch. From this, we have seen Bonnie Liebers develop Genetic Counseling Services, which creates specialized teams of genetic counselors for growing businesses who need them, utilizing a world-wide network of CGCs. A group of GCs recently published an article in the Journal of Genetic Counseling sharing their experiences working for startup companies. I recently launched my own solo venture, WatershedDNA, to provide consultations on ancestry and other home DNA tests, both privately and as a part of larger projects or for companies. The niche I found was filling a need for genetic genealogists, adult adoptees, the donor-conceived community and others, all of them looking for someone who understood the psycho-social dimensions and the science behind genetic testing for ancestry and ethnicity. A perfect role for a genetic counselor, and a match for my own natural interests and passion.

 

Currently, I work one-on-one with clients referred to me by the genetic genealogy community, mostly individuals who have already pursued a home DNA test or are considering it. Just as in a clinical setting, we begin with family history when available and identify a client’s goals and areas of concern. We review any results they already have and discuss additional testing options, and how they might affect them and family members, now and in the future. Working fee for service and owning my own business come with financial uncertainty and lots of unknowns, but it gives me other freedoms, including flexibility and the sense of adventure that comes with pursuing an entrepreneurial path (like my father and grandfather – genetics?). It isn’t easy; I’m a worrier by nature, and some days that Bunsen feels like it’s a-burnin’ hotter than usual. But like the genetic counseling profession as a whole, I’ve found myself in the midst of a crucible that isn’t trying to destroy me; it is providing me an opportunity. A chance to change and create, to extend the reach of genetic counselors. It will engender a future of great things, if I allow it.

 

Let’s be willing to face the uncertainty that the wild west of genetics brings, be daring, and embrace the shades of gray as we blaze new trails. None of us chose the profession of genetic counseling because we thought it would be easy.

 

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Guest Post: Sometimes It’s Okay To Fail

by Lisa Demers and Stephanie Snow

Stephanie Snow, MS, CGC has 11 years of prenatal genetic counseling experience. She worked as a clinical site coordinator and genetic counselor for the FASTER study and as a clinical research coordinator for the NEXT study. Lisa Demers, MS, LGC has 12 years of prenatal genetic counseling experience and currently works with Ariosa Diagnostics as a Medical Science Liaison.

The landscape of prenatal screening is changing. The use of non-invasive prenatal testing (NIPT) in clinical practice is already common and is being adopted quickly by generalist obstetricians and maternal fetal medicine specialists. While the cell-free DNA technology is innovative and the impact on patient care is significant, there is a rising chatter about NIPT failures – the 1-8% (depending on the company) of reports that return without a test result. This is a dual issue – there’s the underlying “annoyance” that NIPT occasionally fails to produce a result, and then there are publications suggesting an association between fetal aneuploidy and test failure. The latter is a conversation for another day.

Although these “no call” results frustrate patients and their doctors, the negativity surrounding these failures is surprising. The concept of a test failing is not new in medicine, and certainly not within prenatal medicine. Increasing rates of maternal obesity are just one reason for limited prenatal surveillance, with one study demonstrating that 41% or less of fetal survey ultrasounds on patients with a BMI of 30 or higher were able to be completed on the first try. When it comes to first trimester measurement of nuchal translucency (NT), the FASTER trial noted an overall 7.5% failure rate, either because of an inability to measure or due to inaccurate measurement. In a review of patients within one clinic, where nearly 50% of patients had a BMI over 25 and 25% had a BMI of 30 or more, 4% of patients had an NT failure on the first attempt and of those who opted for a second attempt, 18% failed. Overall in this population, 2.7% of patients did not achieve a NT measurement.

This is not to say that test failures are necessarily bad. When an NIPT test fails, it is often because quality metrics are in place to ensure proper test performance – just as there are standards for NT measurement which are established by the Fetal Medicine Foundation (FMF) and the Nuchal Translucency Quality Review (NTQR) program. An NT may “fail” because a patient presents for screening outside of the appropriate gestational age requirements or because of suboptimal fetal positioning. The nuchal translucency measurement is critical in obtaining aneuploidy risk assessment when combined with serum biochemistry, and even the slightest over or under estimation dramatically impacts clinical care. Such is the case with NIPT quality metrics. These metrics are in place to ensure appropriate risk assessment for the pregnancy, with the most important of these being fetal fraction. Fetal fraction is greatly affected by maternal weight, with obese women less likely having the required minimum concentration of fetal DNA in circulation. Here again, maternal obesity reduces our ability to accurately assess the well-being of a fetus.

In reality, any test failure rate can be a nuisance to a busy clinic. Having patients return for an additional visit is inconvenient to patient and provider alike. However, there are biological and technical reasons for at least some NIPT tests to fail. The thoughtful provider will consider the various metrics involved with the NIPT options and select one that balances high quality metrics (including fetal fraction) and low rate of technical failures.

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Guest Post: PPV Puffery? Sizing Up NIPT Statistics

by Katie Stoll and Heidi Lindh

Heidi and Katie are genetic counselors and both work with the newly established charitable nonprofit, the Genetic Support Foundation (twitter @GeneticSupport), geneticsupportfoundation.org.

The importance of the Positive Predictive value (PPV) in interpreting Noninvasive Prenatal Testing (NIPT) results is increasingly on the minds of providers as evidenced by frequent discussions, presentations, and publications on the topic. But what if, in an effort to make their lab look like the best lab, the NIPT PPV was overstated in marketing materials or even on test reports? And what if providers and patients believed this information without question or further investigation?

Until 2014, four labs (Sequenom, Verinata Health/Illumina, Ariosa and Natera) were the only companies in the United States that offered NIPT. Over the past year, we have seen a burgeoning of new labs offering their own branded NIPT tests. In some cases, the 4 original companies act as “pass-through” labs in which the testing is branded and advertised through a secondary lab however the sample is ultimately sent to the primary lab for analysis and interpretation. In other cases, referral labs have brought NIPT testing in-house, developing their own algorithms and reporting, such as the case for the InformaSeqTM test offered by LabCorp and Integrated Genetics. In a recently published marketing document, Illumina lists 16 laboratory “partners” that all offer a version of the Illumina NIPT. The other primary NIPT labs are also distributing their tests through other labs as well; Quest Diagnostics and the Mayo Clinic have been secondary labs for the Sequenom NIPT (Quest also has their own brand, the “Q-Natal Advanced”and Natera’s NIPT is available through GenPath and ARUP).

The growing number of laboratories that offer some version of NIPT presents a significant challenge for healthcare providers who are struggling to navigate the various testing options to determine what is in the best interest of their patients. The competitive commercial landscape and aggressive marketing of NIPT to both patients and providers can further confound clinical decision-making given the paucity of information available to providers that is not delivered with an angle aimed at selling the test.

NIPT Statistics in Marketing Materials

We have noted that multiple labs offering testing have promoted extraordinarily high positive predictive values (PPVs) in their marketing materials distributed over the past year and on their websites ^ and on laboratory test reports. These tables include information regarding PPV frequently reference data from the Illumina platform and VerifiTM methodology and a study by Futch et al. as the source.

 

Performance Data Presented in Marketing Brochures for NIPT
Condition PPV NPV Sensitivity Specificity
T21 0.994 0.999 >99.9% 99.8%
T18 0.910 0.999 97.4% 99.6%
T13 0.843 0.999 87.5% >99.9%

These figures (or slight variations thereof) have been observed in the marketing materials for multiple laboratories offering NIPT. These specific statistics were reproduced from an InformaSeq brochure and sample test reports available online

 

The PPVs reported in this table – being widely distributed on test reports and as educational information for providers – have NOT been demonstrated by the referenced study by Futch et al. or any published NIPT studies of which we are aware.

Of course, the PPV of a screening test depends on the prevalence of the condition in the population being screened. Using the sensitivity and specificity of testing accompanying these predictive value data in the same brochure, one could only derive PPV of >99% if the prevalence of Down syndrome in the screened population was 25% or 1 in 4 pregnancies, far higher than the a priori risk for the vast majority of women undergoing prenatal screening.

PPV = (sensitivity x prevalence) / ((sensitivity x prevalence) + (1 – specificity)(1 – prevalence))

.994 = (.999x.25)/((.999x.25) + (1-.998)(1-.25)

In contrast, if we utilize performance statistics provided by the laboratories, we calculate a PPV of 33% in a population with a prevalence of 1 in 1,000 (which is similar to the prevalence for women in their 20’s) and a PPV of 83% in a population with a prevalence of 1 in 100 (which is similar to the prevalence in women age 40).

The Futch Factor

The study by Futch and colleagues that is frequently cited in marketing materials for NIPT does not demonstrate the high PPVs that are referenced, although we suspect that these statistics were arrived at through a series of assumptions about the Futch data that we will attempt to outline.

This study reported that in a cohort of 5,974 pregnant women tested, there were 155 positive calls for T21, 66 positive calls for trisomy 18, and 19 positive calls for trisomy 13. In this published report, only a fraction of the positive NIPT results had confirmation of the fetal karyotype, 52/155 cases of Down syndrome (33.5%); 13/66 cases of trisomy 18 (19.7%); and 7/19 cases of trisomy 13 (53.8%). There was 1 case of Trisomy 21 that had a normal NIPT result (false negative result), however negative test results were not methodically followed-up, so the true false negative rate for the screened conditions is unknown.

In analyzing the data presented by Futch et al, for marketing materials to derive PPVs of >99% for Down syndrome, 91% for trisomy 18 and 84% for trisomy 13 would require that all of the positive calls WITHOUT follow-up by karyotype confirmation were true positives.

 

Outcomes data from Futch et al, 2013 and projected PPVs based on category inclusion or exclusion as true positive.
T21 T18 T13
NIPT Positive 155 66 19
Confirmed (karyotype or birth outcome) 52 13 7
Discordant (Unexplained NIPT results that do not match karyotype from a source or birth outcome) 1 6 3
No information (laboratory did not obtain any information on outcomes) 22 12 0
Pregnancy loss (miscarriage , demise or termination without karyotype) 7 5 2
Unconfirmed (no karyotype or birth outcome known but history of clinical findings suspicious of aneuploidy such as ultrasound findings or high-risk biochemical screening results ) 73 30 7
Total Positive NIPTs where follow-up karyotype not confirmed 102 47 9
High End PPV* 99.4 90.1 84.2
Low end PPV** 33.5 19.7 36.8

*High end PPV- It appears that marketing material PPVs are considering all categories, including confirmed, no information, pregnancy loss, and unconfirmed to be TRUE positives in determination of PPVs.

**Low end PPV- calculated considering all cases, which were not discordant to be false positive results. A minority of positive NIPT results were confirmed with birth outcome or fetal karyotype information.

 

Given that Futch et al. did not have confirmed fetal karyotype or birth outcome follow-up for the majority of positive calls, it seems at best unlikely, and at worst impossible, that all of these positive NIPT results were correctly called, rendering claims of such high PPVs in the marketing materials based on this assumption to be unfounded. On the other end of the spectrum, if the PPV was calculated to include the not-karyotyped/no-birth outcome information pregnancies as false positive, the assumed PPVs would be 33.5% for Down syndrome, 19.7% for trisomy 18 and 36.8% for trisomy 13. Since the study does not report follow-up karyotype for the majority of positive test results, the true PPV for these NIPTs test likely lies somewhere in-between the high end PPV and low end PPV, perhaps closer to the 40-45% (for T18 and T21) previously reported in another Illumina sponsored study.

While the PPV of NIPT for Down syndrome, trisomy 18 and trisomy 13 exceeds that of traditional biochemical screening, no studies have demonstrated test performance as high as those presented in many of the PPV/NPV tables that are being provided to healthcare providers in marketing materials and, in some cases, on test reports.

A Call For Truth In Advertising And In Test Reporting

Honest communication about test performance metrics must be available to providers so that they can provide accurate counseling to patients making critical decisions about their pregnancies. While most labs do state that NIPTs are screening tests and that confirmatory testing of positive results is recommended, it is not surprising that providers and patients are having difficulty appreciating the possibility of false positive results when the laboratories are incorrectly reporting positive predictive values that exceed 99%. The consequences of relying on lab-developed materials rather than a careful analysis of the available literature are significant. There are reports of patients terminating pregnancies based on NIPT results alone. It is not surprising that some women choose not to pursue diagnostic testing to confirm abnormal NIPT results given the very high stated predictive value.

It is imperative that we recognize not only the potential benefits of these new technologies but also their risks and limitations. Testing companies are primarily responsible to their shareholders and investors, so information provided by companies about their products is largely aimed at increasing test uptake. Professional societies need to call for independent data and federal funds need to be made available to support independent research related to NIPT. Policies and best practices cannot arise from the industry-influenced studies that are currently available. While some regulatory oversight of marketing materials will likely be necessary, we urge the laboratories to consider their marketing approach and how it is affecting patients and providers. If laboratories want to truly partner with patients and providers, they need to provide accurate and straight-forward information to limit provider liability and likewise, help patients avoid making life-changing decisions based on inaccurate and/or confusing information related to test performance. As a medical profession can we come together and make this change without regulatory oversight? Now that would be a medical breakthrough.

^ – Notably, Counsyl has also recently produced a table that provides more accurate estimates of their NIPT predictive values

 

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