NEW YORK (GenomeWeb) – A commentary this week, appearing as a preprint in the journal Prenatal Diagnosis, has resurrected what is now a partially resolved debate over the use of noninvasive prenatal testing in the screening of not just high-risk, but all pregnant women.
Adam Wolfberg — formerly an employee of NIPT firm Ariosa and now an obstetrician and chief medical officer at women's health media firm Ovia Health — argues in the piece that while the conflict of interest of companies that market NIPT tests is frequently bandied about, relatively scant attention has been paid to potential conflicts of interest that exist for clinicians and advisory bodies who serve as gatekeepers to the adoption of new technologies and procedures.
Doctors who practice maternal-fetal medicine derive a significant portion of their income from fetal ultrasound examinations, including measurement of the nuchal translucency that is part of most aneuploidy screening tests that are performed in the first trimester, Wolfberg wrote. And they continue to benefit from the follow-up testing generated from positive screens.
Wide use of NIPT therefore presents a financial challenge, not only because it reduces the use of ultrasound in traditional screening, but also because its lower false-positive rates imply lower rates of follow-up analyses.
However, "not a single article nor a single policy statement contains the disclaimer that expanded utilization of NIPT threatens the clinical income of any clinician who bills for ultrasound and makes their living performing these services," Wolfberg argues in the commentary.
The adoption of NIPT, first for high-risk cases, and now increasingly for average-risk pregnancies, is either racing ahead, or limping along, depending on who you ask.
Companies that market these tests hope for greater uptake, endorsement by professional societies, and payment by insurance companies. In that light, the fact that guidelines bodies like the American Congress of Obstetricians and Gynecologists do not yet recommend the use of NIPT outright for the screening of all pregnant women can be seen as an affliction or a hindrance.
On the other hand, obstetricians, maternal-fetal medicine doctors, and bodies like ACOG are watching NIPT fundamentally change certain aspects of their practice, and might be expected to be wary of possible downsides or harm in such sea change.
Wolfberg said that the purpose of his commentary this week was not to advance any particular goal other than to point out the plain fact of the existence of this source of conflict.
"This has been clear to me for a very long time [but it] seemed inappropriate to voice when I had a vested interest in NIPT," he said this week.
"Conflict of interest, we all have it in one way or another, and you can't eliminate it. It's more a matter of understanding everyone's perspective and what influences that," Wolfberg added. "We don’t ban people who work in industry from voicing their opinion, we just want to be able to look at their thoughts through that lens. I think that standard is not applied to clinicians and it ought to be."
In particular, Wolfberg cited the fact that members of the committees that have published recent guidelines on the use of NIPT in average-risk populations have failed to note the conflict of interest in question.
"Fifteen of 23 members of the ACOG committees and each of the 17 members of the [Society for Maternal-Fetal Medicine] publications committee … practice maternal-fetal medicine, a field that derives a significant portion of its income from fetal ultrasound examinations," he wrote.
Wolfberg does not argue that this means that that these organizations have been biased by this innate conflict, although NIPT companies frustrated by the content of the ACOG guidelines might feel so: recent updates are more sympathetic to broad use of NIPT, though still fail to outright recommend it.
Prompted by the publication of pivotal clinical studies of NIPT among high-risk and average-risk pregnancies, the American Congress of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine revised its committee opinion on cell-free DNA screening in September of 2015 to say that doctors can discuss it with their patients and allow for its use in the average-risk women who want it, replacing an opinion that stated that NIPT should only be offered to high-risk women..
Wolfberg also cites specific studies and authors in his commentary on conflict of interest, but he reiterated that his intent was only to discuss that this conflict question exists for clinicians who derive revenue from invasive maternal-fetal tests, not necessarily that this conflict has led to an actual bias in the way this community has received NIPT.
The latter is sometimes suggested, though. For example, he discusses his view that authors critical of NIPT have shifted their arguments against the technology as evidence has emerged that deflated their earlier objections.
"Initial editorials focused on the test performance of NIPT assays, and challenged the applicability of test results from 'high risk' populations to a 'low-risk' population [but] when the performance of NIPT in all populations became incontrovertible, articles and editorials largely shifted focus to the ability of traditional screening technologies to detect additional rare conditions," Wolfberg wrote.
"I can't get inside the head of academic clinician investigators that have been vocal on this topic," he added in an interview this week. "But it does seem convenient that when the first line of argument against NIPT was eliminated [after studies showed] that this is accurate in low-risk patients … the argument then shifted to why traditional screening is better due to the potential of detecting other anomalies that are not the three main trisomies."
Asked if disclosing a conflict of interest as described in his piece would change the reception of such studies, Wolfberg said he thinks so.
Ronald Wapner, vice chair of research in obstetrics and gynecology at Columbia University, said what Wolfberg says about conflict "is not untrue. The facts of the matter are correct."
But he disputed the concept that the types of procedures sidelined by increased use of NIPT are as much the bread and butter for maternal-fetal medicine doctors as Wolfberg's commentary might imply.
He also said that some aspects of Wolfberg's editorial seem tone deaf to what clinical investigators and advisory groups were actually concerned with as they have evolved their positions on NIPT over the last few years.
For example, he said, the fact that there was an evolution from analyses focused on the accuracy of the technology in average-risk women, to more recent discussions — about how replacing current screening methods with NIPT might affect the detection of other conditions or about public health implications of various kinds — are less evidence of a financially driven resistance to new technology, and more of a demonstration of how the field has progressively accepted evidence as it has been produced.
Prior to studies clearly proving the performance of NIPT in average-risk women, ACOG and other bodies did not endorse it. After those studies were done, they did.
"They have to see proof, and it has to be well-validated proof, and that's what they waited for," he said.
But according to Wapner, the question of whether this means that NIPT should be recommended to all women across the board is more complicated than that, hence the fact that ACOG has kept its guidance more oblique.
"I think now the concern is that patients be educated about these things. [NIPT] is a test for these main trisomies. Whereas, when you do nuchal translucency, you pick up other things. It's not comparing apples to apples," he said.
"So that's what the major orgs are trying to ensure now, is that you find out what your patient wants, fairly compare the two modalities, and make sure people know exactly what they are being tested for. It's way, way more than just a question of conflict of interest by practitioners."
Why NIPT companies would continue to be dissatisfied with the ACOG recommendations as they stand — despite the fact that they did change after studies proved the technology's accuracy in average-risk women — is likely a matter of reimbursement.
After the pivotal studies that led the congress to revise its position recommending against NIPT in average-risk women, reimbursement seemed to be growing steadily.
As of January 2016, analysts were estimating that about 20 payors currently covered NIPT for average-risk pregnancies, totaling almost 70 million covered lives.
Natera, which has led the charge in pushing its business into the average-risk population, said in late 2016 that it believed there had been continuous momentum, with about 60 percent growth in the number of covered lives that include NIPT for average risk since mid-2015.
But as recently as last year, there have also been moves in the opposite direction. Aetna, for example, updated its medical policy for NIPT last July, choosing not to cover screening for average-risk pregnancies. The payor, which covers around 17.9 million lives, wrote in its revised policy that it now considers cell-free DNA testing "medically necessary" only for the testing of women who are at an elevated risk.
Analysts at the time said that they believe that Aetna and other payors who are holding out on covering average-risk NIPT are waiting for ACOG to "formally endorse" the technology in women under 35. If that is so, the fact that the congress has not yet done so is a material hindrance for NIPT companies.
For his part, Wolfberg does not deny that things like this can operate as a source of bias for corporations promoting broader use of NIPT. But, he argues, the potential for conflict of interest among the physician community, which stands, in his eyes, to lose money, should also be more transparent as the discussion moves forward.