Tag Archives: informed consent

Guest Post: NIPS And The Threat To Informed Decision Making

by Katie Stoll

Katie Stoll is a genetic counselor in Washington State. She graduated from the Brandeis University training program in 2003 and since that time has held positions in the areas of prenatal, pediatric and cancer genetic counseling.

A few months ago, I reached out to the DNA Exchange readership and called for more truth in advertising by the Noninvasive Prenatal Screening companies regarding the accuracy of test results. I recently returned from the National Society of Genetic Counselors meeting where I had the opportunity to survey the marketing and patient materials from labs offering NIPS and to learn about the experiences of my fellow genetic counselors with these new tests.

Not surprisingly, in this dynamic and rapidly evolving field, all of the companies have updated their materials. Some brochures proudly acknowledge how quickly this testing is being integrated into clinical use. It feels like we are being patted on the back for adopting this new test quickly and without question.

I remain very concerned about the misleading claims in the marketing materials aimed at providers and in the patient directed brochures. It is easy to see how the language of the brochures could lead healthcare providers and patients to conclude that these tests are diagnostic or near-diagnostic. These quotes from the materials illustrate my point:

“Definite, informative results.”

“Positive or negative results.  Never maybe.”

“No confusion.  Just simple, clear results.”

To my knowledge, there are no new large studies to dispel my concerns about the positive predictive value of NIPS. Depending on the prior probability, a significant portion of positive results may be false positives– especially with rarer conditions such as Trisomy 18 and Trisomy 13. And because these technologies have been rapidly integrated into clinical practice based on limited research, we do not have robust outcome data to see how false positive and false negative data are playing out in clinical practice.

Since most NIPS testing is done outside of a clinical research protocol, the labs that choose to put resources into follow-up are at the mercy of the providers to share that outcomes information.  Even in the best scenarios, voluntarily reported outcome data are not likely to tell the whole story. I spoke with a testing company representative regarding a poster presented at ACMG last year which based its false positive and false negative results on ad hoc feedback. When I inquired about the meaning of ad hoc feedback, it was explained to me that the company didn’t have the resources to track outcomes so were relying on providers to let them know if the testing results were incorrect. Of course, if a patient terminates her pregnancy based on a false positive test result, nobody will know that the NIPS result was incorrect.

Don’t think a patient would terminate based on NIPS alone? We all hope that women who receive adequate counseling about the limitations of the testing would confirm results with a diagnostic test, but this is not always the case. At a presentation during the recent NSGC Annual Education Conference, one lab referenced preliminary data showing some patients are terminating pregnancies without first getting diagnostic testing, and in the absence of ultrasound findings. While this tracking has some limitations, this lab should be applauded for investing resources in tracking outcomes data and for sharing these data with genetic counselors. Hopefully we will see it published soon and other labs will follow suit.

This situation of patients making reproductive decisions based only on NIPS results may be particularly problematic in communities that don’t have ready access to genetic counseling and/or maternal fetal medicine services.

Imagine this scenario:  a 35-year-old woman living in small town, USA who has limited access to abortion services beyond the first trimester, receives a positive result for Trisomy 13. Based on positive predictive values calculations, there is an 8% chance that her “positive” result is a true positive. But, the patient – and her doctor – may think the probability is much higher, maybe even close to 100%, based on the reporting practices of the labs, which may say “Aneuploidy detected” or “Positive” for Trisomy 13. This does not support informed reproductive decisions.

This patient has 3 options:

  1.  Wait for an appointment at a high risk referral center, at some distance from her home to undergo diagnostic testing. This may limit her reproductive options by delaying time to diagnosis (the later a pregnancy termination occurs, the more expensive it is, and pregnancy termination outside of the first trimester is often not available in many smaller communities).
  2. Seek out pregnancy termination options in her local community based on the NIPS results alone – knowing that she is up against a gestational age ticking clock.
  3. Decline further testing and continue the pregnancy.

If the patient feels that she would not want to continue a pregnancy given a Trisomy 13 diagnosis, and she understands the limitations of the testing, I would imagine that she likely would feel it was worth the wait and the travel for diagnostic testing. However, given the emphasis on the accuracy of NIPS based on the lab reports, and the misconception by OB providers that this testing is “nearly diagnostic”, it is easy to imagine a scenario where she may elect to have a termination based on NIPS alone.

Based on an aggregate of data from the NIPS companies from the first quarter of 2013, one health economist estimates that NIPS is utilized by 40% of the high-risk population in the US, and this number is growing rapidly. So while the patients you see in your genetic counseling practice may be very informed about the limitations of the testing given your expert counsel, this statistic suggests that most NIPS is probably taking place outside of our offices.

We must continue the conversation about how NIPS is marketed and used in prenatal care. While the advantages to a more sensitive screening test are obvious (e.g. fewer women needing to undergo diagnostic testing), we must recognize the largely undisclosed limitations and dangers. Without adequate counseling, patients are being harmed by the misleading claims about the accuracy

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23andMe Reveals a Snippet of it’s own DNA

You have got to feel sorry for 23andMe.

Ha!  What a funny thing for me to say.  Genetic counselors don’t feel sorry for 23andMe.  After all, they offer a service of which many of us are deeply distrustful, suspecting that for all the data they provide, all the fact-filled blurbs and fancy graphics, their outpouring of information often serves to obscure rather than to illuminate the more significant truth: that most of the time, these reports are not a valid or reliable source on which to base decisions about your health and well-being.  That their message promotes a kind of mantra of genetic determinism that complicates our job, since it creates expectations that cannot be fulfilled.  That their credibility and media presence have less to do with scientific bona fides than an intimate relationship between their founder Anne Wojcicki and Google’s Sergei Brin, which gives 23andMe access to both some very deep pockets and the reflected glory of an association with the epitome of technological wizardry.

And now they are doing research, and they don’t even have to bother with an IRB.  It’s so unfair.

But really, you should feel sorry for 23andMe.  I’m serious.

It’s not easy being them.  Think about it this way: the entire premise of the 23andMe sales pitch is that they can offer you valuable information.  Valuable how?  Well, presumably because it will SAVE YOUR LIFE, or something to that effect.  “Personalize your healthcare,” they say on the website.  “Prepare for serious diseases.”  However, at the same time, 23andMe can not say that any of this valuable information is diagnostic.  They have to be careful not even to imply that it is diagnostic, because offering diagnostic information constitutes a medical test, and medical tests are subject to a much more rigorous degree of government regulation.  If you were a company, would you care to invite a greater degree of scrutiny from the FDA?  No, you would not.

It’s a fine line they walk.  You’d have to be clear-headed and on your game to walk a line like that.  I bet those guys in corporate communications at 23andMe have to stay stone cold sober all the time.  You know that show Mad Men?  The opposite of that.

Now, a tough job gets even tougher.  Last month, 23andMe announced their first-ever patent, awarded for a method of determining an individual’s risk for Parkinson’s disease, a finding drawn from a study of 5,000+ PD patients who were offered the 23andMe genome screen virtually for free – what the company refers to as “the largest Parkinson’s community for genetic research in the world.”  This was a big day for the company, since the patent represents not only a new potential line of revenue but proof in principle for their strategy of crowd-sourced genetic research.  Given their outsider status, 23andMe was probably prepared for a certain level of pushback from the standard-bearers of academic research.  What they may not have expected was that their big day would be marred by an insurrection in the ranks – but to their apparent surprise, the announcement drew outraged responses from many 23andMe research participants. 

It turns out that many in the “Parkinson’s community” felt betrayed by the patent application, perceiving it as an unexpected move to monetize on the part of the company they believed was only interested in a cure – after all, Sergei Brin himself has revealed that he has a genetic risk for PD.  While the press releases from 23andMe emphasize the importance of the patent as not a money-maker but an inducement for other companies to use this information to develop treatments – “the patent will be important for a biotech or pharmaceutical company to pursue drug development” – the majority of the voices making themselves heard seem to find this a dubious distinction.  Admittedly, it defies logic to assume that a commercial entity would file for a patent merely so someone else could (eventually) make a profit, and in fact if we are looking for evidence of capitalistic intent, we can find it conveniently staring out at us from the informed consent that all 23andMe customers are required to sign: If 23andMe develops intellectual property and/or commercializes products or services, directly or indirectly, based on the results of this study, you will not receive any compensation.”

So why did so many research participants feel deceived by a naked expression of commercial intent?  Well, it turns out that, once again, hard cold facts spelled out in black and white, however clearly stated, were less convincing than a fundamentally different message that was never articulated but merely implied, insinuated, forcefully and emotionally conveyed by the fundamental nature of the language used.  “Join us” they said.  “Everyone can help.”  23andMe research is billed as a community effort, “powering research breakthroughs.”  It’s like a research Wiki.   “I had assumed that 23andMe was against patenting genes and felt in total cahoots all along with you guys,” said one research participant. “If I’d known you might go that route with my data, I’m not sure I would have answered any surveys.”

Okay, so as insurrections go, this one is a bit of a tempest in a test tube.  Should we care?  Is it a problem if a small number of people who didn’t read the fine print feel misused?  C’MON PEOPLE.  You haven’t been abused.  You haven’t been robbed.  You did not sacrifice flesh or blood — just a little spit.  But the objections of the 23andMe crowd should be noted by all companies (or researchers) who want to make use of the DNA and altruism of willing donors.  It’s a very fine line you draw for yourself when you unpack those chromosomes: hard to walk, easy to trip over.  If you tell people that the genomic revolution is all about their health, and it turns out to be more about your profits, once-willing participants may be more inclined to spit at you than spit for you.  If 23andMe plans to make data mining an integral part of their revenue stream – and this patent is one pretty clear indication of their intent – then they will have to find a way to convince their target audience that this is a chimera of a company, a capitalist beast with the loving heart of a non-profit enterprise.

 

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