The Daily - Investigating the Prenatal Testing Market

Episode Date: January 4, 2022

About a decade ago, companies began offering pregnant women tests that promised to detect rare genetic disorders in their fetuses.The tests initially looked for Down syndrome and worked well, but later tests for rarer conditions did not. An investigation has found that the grave predictions made by those newer tests are usually incorrect.We look at why the tests are so wrong and what can be done about it.Guest: Sarah Kliff, an investigative reporter for The New York Times. Sign up here to get The Daily in your inbox each morning. And for an exclusive look at how the biggest stories on our show come together, subscribe to our newsletter. Background reading: In just over a decade, prenatal tests have gone from laboratory experiments to an industry that serves more than a third of the pregnant women in America. The grave predictions of rare genetic disorders made by newer tests, however, are usually wrong.For more information on today’s episode, visit nytimes.com/thedaily. Transcripts of each episode will be made available by the next workday.

From the New York Times, I'm Astead Herndon. This is The Daily. Today. Over the past decade, medical companies have begun offering pregnant women new screening tests that promise to detect rare genetic disorders in their fetuses. promised to detect rare genetic disorders in their fetuses. What those women weren't told was that if they tested positive, there would be a high likelihood that the result would be wrong. A Times investigation reveals how tests that promise peace of mind

have instead caused anguish and confusion. I spoke with my colleague, Sarah Cliff. It's Tuesday, January 4th. So Sarah, how did you come to this story? Yeah, I usually cover medical billing for The Times, and readers often send me odd, surprising bills they've received. And I'd received a handful for this certain type of prenatal test. And they were hundreds to thousands of dollars.

So I was looking into the bill, and my editor suggested just looking into what these and my editor suggested just looking into what these tests are in the first place. So I just started doing the basic research that I usually do, reading some academic studies, looking through people's experiences with them online. And I came across a Reddit community focused on this type of screening and just kept seeing the same kind of story repeated again and again, where someone who was pregnant went to the doctor, took this particular type of screening test, and was really surprised to get a positive result for a disorder they had never heard of. And they often talked about a really agonizing month between this first screening and a follow-up test that was either going to confirm or disprove the original results. and a follow-up test that was either going to confirm or disprove the original results.

And in the end, it turned out that the original test was wrong, and there's actually nothing wrong with the pregnancy. And they went on to have babies without the conditions that they had screened positive for. And so that kind of, you know, piqued my interest a little bit to think, you know, what is going on here? And why are so many women reporting this type of story. So what exactly is this test? So this test, it's known as a few things. It's known as cell-free DNA screening or non-invasive prenatal testing. And it's usually drawn at a doctor's office or a laboratory.

And this is a test that screens for chromosomal abnormalities in a fetus. And before this test existed, this was done with a number of ultrasounds, a number of blood draws over multiple prenatal visits to mostly screen for Down syndrome. And they produced a decent number of false positives. And then about 10 years ago, this test comes along. It can be done at 10 weeks. It just requires one blood draw.

And it turns out to be really quite accurate at screening for Down syndrome. And it's a pretty remarkable advancement. So are these tests well-received? It seems as if they are providing a real niche to streamline that screening process. Yeah, they really are. Obstetricians are happy with them because they feel like they are able to provide a service to their patients. They're not having to do as many invasive procedures like an amniocentesis. So they're pretty happy with the technology. Patients are happy with it because it can also screen for what your baby's sex is at 10 weeks.

That's something you before this couldn't know until about 20 weeks pregnancy. Oh, wow. So obstetricians found patients were coming into their offices, you know, asking, I want the test that screens for sex. So they were quite well received. And you saw companies realizing there was a market in this type of testing. About 4 million women give birth each year. And that was 4 million women who could, you know, potentially use this type of screening product.

So after the first test launches in 2011, And that was 4 million women who could, you know, potentially use this type of screening product. So after the first test launches in 2011, you really quickly see about a half dozen other companies trying to get into this space. Some of them are big laboratory companies like LabCorp, for example, which buys a test called Maternity 21 from a smaller biotech startup. A company called Nutera gets into this space and they quickly become the market leader. Quest Diagnostics, Myriad, these are all different companies getting into the space. And they are looking at ways to differentiate their products. And one of the things that starts to happen is they start screening for conditions that are rarer than Down syndrome.

They start with something called Trisomy 13 and trisomy 18, and then they move into a new category of testing for micro deletions, which are kind of small missing pieces of chromosomes. And those micro deletions are sometimes associated with certain syndromes. Some of the better known ones are DeGeorge syndrome, which becomes a screening, Kreda shots, Engelman and Prader-Willi, they tend to be pretty rare. So they are often not familiar to patients, but these are the things that are starting to be added on to this type of screening. They also get marketed directly to patients, directly to doctors as quite accurate products. You start seeing language like total confidence in every result or

information for your peace of mind. They say they're going to give you clear answers, clear positives and negatives, and kind of information you can trust. And you get to the point where in 2020, a third of pregnant women, that's over a million people, are getting the down screening with the sex test. Some share of those, we don't know exactly how many, are getting the expanded tests that are looking for the rarer conditions. But the problem that I found in my reporting is when it comes to those newer expanded tests, the problem is that the positive results on those tests, they are often wrong. So what exactly did you find?

Yeah, so before I get into the findings, I think it's just important to have some context. One is that the test is still quite reliable for Down syndrome when it's screening for that condition. And second, most people who take this test are going to screen negative on it. Most people will not get a positive result. But for the people who do get a positive result. But for the people who do get a positive result, there's about a half dozen tests where we found that those positive results are wrong about 85% of the time. Wow. I mean, we're talking about testing for rare conditions.

So as you're saying, most of these are going to come negative. Yes. But for the positive ones, you're saying as many as more than 80% of them, 80 out of 100 of those positive tests could be incorrect? Yeah, and the numbers can get even higher. we looked at for a condition that occurs in about 1 in 20,000 births, we found that 93% of the positive results for that test turn out to be wrong on further testing. So it's a pretty big share. And again, these are the tests that are being sold in that marketing that is talking about total confidence, peace of mind, clear results. These are some of the tests being sold with that type of language.

We'll be right back. Sarah, so you said a lot of these positive tests end up being wrong. Why are they so wrong? How is this happening? It mostly has to do with the fact that these are pretty rare conditions. These are conditions that occur in maybe 1 in 4,000 to, at the rarest, 1 in 100,000 births. And when you have a rare condition, this isn't just true in prenatal testing, it's true in a lot of testing. When you have a rare condition, you're likely going to

generate more false positives than true ones because you're just looking for something that doesn't exist a lot. Right. Needle in a haystack. Exactly. And so you find a lot of hay in the haystack when you are just looking for that one needle. Do the companies know about any of this? They have marketed themselves as the ones who can identify these rare genetic conditions. But what we're seeing from these test results are that the positive results are often not true. Did they know that before you did? Some of them did, and they certainly could have. Some of them did, and they certainly could have, because the way that we did our research was essentially looking for any study we could find in the academic world, outside the academic world, that had looked at how well these tests work. And we eventually found about a half dozen studies in this space.

Some were conducted by testing companies themselves, other by independent academic researchers. other by independent academic researchers. And working with a few experts in this space, we developed some methods to combine all those findings and kind of produce the most comprehensive look that we could at how well these positive results are doing. And so the data we have is all public. It's all out there. You know, we took the time to sift through it and combine it.

And that's how we got to our findings about how many of these positive results turn out to be wrong. I know that you've owned the medical billing. B, these companies, I'm sure, are frightened at the idea of a Sarah Cliff email. But what did they actually say when you took your findings to them? So they said, you know, many acknowledged our findings and said that they still believe there's value in this type of screening test because it is picking up the true positives, that it is finding some of these cases of disorders that parents would not have known about otherwise, and that they said they try their best to be very, very clear that it is a screening test. It is not a diagnostic test. The patient should be counseled on this test before. So essentially be told, here's what a positive result would mean for you.

So they are making the case that these tests are doing more good by identifying cases of disease. But that experience they talk about, how each patient should be counseled, how they should give consent for these tests. That was really different than the experience I heard about interviewing more than a dozen women who had received a positive result that turned out to be wrong. Yeah, that's what I was going to ask. What is the experience of these women who are getting the positive results? Because of course, when they receive that test result, they don't know it's a false positive, right? So how does what is seemingly very, very bad news being received by these women?

I had multiple women describe this as the worst time of their lives, the time between when they received this result and when they later learned that the result was wrong. received this result and when they later learned that the result was wrong. And, you know, I met a lot of these women through the Reddit forum I mentioned earlier. One that really stands out to me is a woman named Yael Geller, who, you know, spent a year of fertility treatments trying to get pregnant with her second child and was so, so excited when her pregnancy test was positive. You know, she had a normal ultrasound. She told her three-year-old about this brother or sister that was in her tummy. It seemed like everything was finally working. And she is driving her son home from school one day when she gets this call saying she had screened positive for a condition she didn't even know she was being screened for. It's called Prader-Willi

syndrome. And it's a pretty serious condition. She know, she starts doing a lot of research, a lot of Googling. She'd never heard of this before. Yeah. I've never heard of this either. What is it? Yeah. So it is not well known because it's quite rare. So the outcomes can be quite variable, but we know it's associated with mental illness. It's associated with significant developmental delays. And there really is very little chance of independent living as an adult for people who have this condition. And she, you know, went home.

Her husband rushed home from work and they sit down on the couch and she's, you know, crying as she's saying, we might have to think about terminating this pregnancy that we really, really wanted. And so for Yael, her next steps move actually pretty quickly. She is able to get an appointment for a diagnostic test, something that's going to give her a more definitive result the next day.

And it's a test that involves basically sticking a very large needle into her placenta and pulling out a bit of tissue. She found it pretty painful. She had to take a few days to rest in bed. Her toddler was asking about the boo-boo on her stomach. And then they wait. They wait to get the results and see what's happening. And it's a pretty agonizing time to not know which way this is going to go.

And then they finally, about two weeks later, get the phone call that it turns out the original result looks to be wrong and that their future child does not have Prader-Willi syndrome. And, you know, they were quite relieved, but, you know, again, describe it as a really, really challenging experience to have gone through. And yeah, Elle's wait was actually pretty short. You know, most of the women I talked to had to wait, you know, a month or longer, in some cases, two months to get their follow-up testing done and learn if this original result was right or wrong. And that's a really long time to kind of sit with this kind of uncertainty. You know, they described

some taking time off of school or work because they just couldn't focus the lost income that came along with that. Some spent thousands of dollars on their follow-up testing for things that their insurance companies wouldn't cover. You know, they tried to hide their pregnancies wearing baggy clothes to, you know, not let people know. Because in some of these cases that they're testing for, the infant mortality rate is incredibly high. So the stakes are really quite high of the type of things they're testing for. And we do know some portion that's likely quite small but does exist don't get that follow-up testing that they are supposed to. In doing my reporting for this story, I talked to three geneticists who were involved with cases where someone screened positive on one of the tests I was writing about and terminated a pregnancy either before or with never getting a diagnostic test afterwards. Again, we do not think this is

the dominant experience, but we've seen it documented in some academic literature, in a previous investigation, and in my own reporting. So you're saying that in some rare instances, women actually terminated their pregnancy under what is essentially false pretenses, given bad information. Yes. Wow.

And, you know, it's possible some women face a really wrenching choice about whether they can wait. As abortion laws get more restrictive, this type of test is usually done about 10 weeks of pregnancy. An amniocentesis can't be performed. That's commonly the diagnostic test until 15 or 16 weeks of pregnancy. In that time, some women with more restrictive abortion laws, you know, things might change about whether they can obtain an abortion or not. And, you know, I spoke with another woman who lives in Indiana who talked about really struggling to schedule all the diagnostic follow-up testing before her state's abortion ban began. Wow. And even, you know, gaming out plans.

If I do have to terminate this pregnancy, what state am I going to drive to in order to be able to do that? And even the people who do get a diagnostic test, they find out it's a false positive, their baby doesn't have the condition it's screened positive for. Some of them really attributed it to kind of the stress of going through this experience of thinking that their baby had a pretty significant disorder. I talked to a new mom who was a 10-month-old who initially screened positive for a disorder, later learned that it was wrong. She said she sometimes finds herself Googling the symptoms for whatever month old he is of that disorder. She wonders in the back of her head if the initial screening was wrong. Well, maybe the diagnostic test was wrong.

And she says, you know, I know it sounds a little crazy. You know, I hope I stop doing this kind of Googling soon. But it just really stays in the back of my mind that it feels like some kind of possibility that was introduced into my child's future. I mean, these screenings introduce something that has such a potentially big impact on these women at such a fraught time, but do so with such little accuracy. Did the company speak to this kind of emotional question? Did they recognize that this isn't just a small thing, that they're introducing a really big variable into these folks' lives without, you know, accuracy? Yeah, I think the thing I heard a lot from the companies is that there should be this whole universe that's around those tests, that there should be genetic counseling before you

get the test, there should be informed consent by the doctor saying, I'm testing you for these things, and that afterwards, everyone should have access to some kind of genetic counseling if they do get a positive result that can walk them through what this actually means. In practice, though, that universe just doesn't seem to exist for a lot of women who are getting positive results. We're finding that they are done in quick prenatal appointments. Some doctors decide not to run these tests because they find them quite unreliable. I talked to a number who said, I would not use this on my patients. And some of those who do, we found in our reporting, talking to patients just didn't seem to understand what exactly a positive result on this test meant.

You also see doctors operating in an ecosystem where they are dealing with advertising that former FDA officials tell us is misleading, raises red flags. In one case, an ad for doctors with numbers that were described as meaningless by a former FDA official. So they're in a universe where the advertising isn't regulated. They're ordering a lot of tests for their patients and might not fully understand what it means when one of them comes positive for the test that we're writing about. How is it possible that such an inaccurate test is allowed to be marketed to doctors in the first place or is allowed to be marketed to doctors in the first place or is allowed to be marketed to patients as something that should give them peace of mind. I feel like we have a

highly regulated medical industry. How can this happen? Yeah, so these tests exist in a world where they do not get Food and Drug Administration oversight. They are pretty much exempt from that regulatory agency, which usually looks after blood tests and MRIs and all the sorts of other things we get in doctor offices. They're what's known as a laboratory-developed test, a test that was made in a laboratory, is run in that same laboratory. And for kind of wonky historical reasons, these tests are exempt from FDA oversight, which means there's no

one really reviewing the claims. There's no one looking over the data behind these tests to say, are the claims about what they're saying accurate? It's basically test makers designing their studies, creating data, and deciding how they want to describe that data to patients and doctors. You know, it's giving Theranos vibes. I mean, how is this not what you're describing, just a big loophole? Yeah. So I want to be clear again, this is not Theranos. The down screening is a good product that a lot of obstetricians really think is a great development. But when you get into these newer tests, there are a lot of obstetricians and geneticists that are questioning their value. And at the end of the day, it leads

to some important diagnoses for cases where they find true positives, but a lot of anguish and a lot of stress for the women who are getting the false positives that are more common than the true ones. So what should folks take away from that? If you are a pregnant woman listening to this podcast, should you get the test? Yeah, you know, as a pregnant woman taping this podcast, it's a question I care a lot about. And, you know, I think they should take away is one that the down screening is a reliable product. The body that governs obstetricians, they recommend that screening. They also recommend the screenings for trisomy 18 and 13. They feel like those are really accurate enough and have the data to be recommended to all pregnant women in the United States. But that if they want to pursue these other tests,

or if their doctor suggests they pursue these other tests, they should really go into that with their eyes open about what a positive result really means. Most expectant parents, including myself, get a negative result on these tests and they don't really think twice about it and go on with their pregnancy. But I would think about going into this

kind of prepared with your eyes open of what am I being screened for? How often are the positive results right? And if I get a positive result, you know, what happens next? And thinking of it, I guess, less as, you know, all upside, you're just going to learn something about your pregnancy, but that there are really risks that come along with taking a test like this. It seems like you're describing a situation kind of that the company said was the ideal one, that there would be that risk communication, that there would be that level of counseling and understanding of kind of what you're getting into, but that without that, it produces some of the experiences of the women that you talk to. that without that, it produces some of the experiences of the women that you talk to.

Yeah. And unfortunately, just the infrastructure for that is not there right now. You know, one genetic counselor I interviewed for this story said there just aren't enough of them to counsel all 4 million women who are pregnant. There just aren't enough genetic counselors. There are not enough time in these short prenatal care visits to really go through an informed consent process right now. So I think that ideal world is one that can be envisioned, but in terms of turning it into reality, we are pretty far from that right now. One thing that could stand in for the infrastructure is some kind of government regulation where instead of me as a patient asking my doctor all these questions, the government could be regulating the information that these test makers put out. They could say, you can't make that claim about having total confidence in every result, or you have to publish better data on how many of

your positive results are right or wrong. But without that kind of oversight, this seems like an area of prenatal testing that is going to keep growing. And the onus will really be on patients and their doctors to sort through some pretty complex information that took me and another reporter about four months to sort through to get to a really good understanding. And that feels like quite a burden to put on the expectant parents of America to do that exact kind of sorting. Just forcing every expectant parent to just become an investigative journalist. We could use a few more,

but I don't think this is the right way to do the recruiting. Thank you for your time. Thank you for your time. Thank you for reporting. And we'll be thinking of you in the coming weeks. Yeah, thanks, Ested. We'll be right back. Here's what else you should know today. After four months of court proceedings, Elizabeth Holmes, the founder of the failed blood testing startup Theranos,

was found guilty Monday on four wire fraud charges for lying to investors. Each count carries a maximum sentence of 20 years in prison. The jury found Holmes not guilty on three other charges of defrauding patients and were unable to reach a verdict on several other charges. patients and were unable to reach a verdict on several other charges. And as coronavirus infections continue to surge due to the Omicron variant, several major school districts from Detroit to Newark switch from in-person to remote learning. But in New York, the city's new mayor, Eric Adams, vowed to keep schools open, even as staff shortages threatened to become more severe. We're going to do everything that we have to do to keep our schools open.

And I know there's questions about schools. Today's episode was produced by Michael Simon Johnson and Sydney Harper. It was edited by Paige Cowan and Larissa Anderson. It contains original music by Marion Lozano, and it was engineered by Corey Schreffel. Our theme music is by Jim Brumberg and Ben Landsberg of Wonderly. That's it for The Daily. I'm Ested Herndon.

See you soon.