Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03420274 |
| Other study ID # |
17-987 |
| Secondary ID |
R01HG010092 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 19, 2018 |
| Est. completion date |
June 15, 2023 |
Study information
| Verified date |
June 2023 |
| Source |
The Cleveland Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Noninvasive prenatal genetic testing (NIPT) is an important new screening test option
provided to pregnant women in the first trimester of pregnancy. The advantage of this screen
is that is provides information about the risk of trisomy 13, trisomy 18, and trisomy 21 with
greater accuracy than conventional screens. At the same time, NIPT can produce information
about the risk of a cohort of other fetal genetic variants, including sex chromosome
aneuploidies and microdeletion syndromes. While not yet clinically available for whole exome
sequencing, the potential for this next clinical application already exists. The challenge is
that, while this is an important new test, there are little data about how to best structure
patient-centered decisions about its use, including decisions if to use this screen and how
the information may directly inform subsequent prenatal care decisions. The purpose of this
study is to gain formative data about current practice patterns with respect to how NIPT is
discussed in the clinical visit and to use these data to help inform best practices for its
continued use in the clinical setting.
Description:
Noninvasive prenatal genetic testing (NIPT), also known as cell-free fetal DNA screening, has
dramatically altered the delivery of prenatal care. Prior to NIPT, fetal aneuploidy risk was
assessed using conventional screens, most commonly maternal serum screens (MSS, e.g. the
Quadruple screen). While MSS provided information about the risk of trisomy (T) 21, T13, and
T18, its use led to many false positive results which required amniocentesis or chorionic
villus sampling to clarify. The risk of iatrogenic miscarriage from these diagnostic
procedures is low, but the possibility of this consequence is a major driver in how
healthcare providers and patients think about prenatal genetic risk and assessment. NIPT has
significantly changed this long-standing paradigm. While not diagnostic, NIPT offers
increased accuracy with lower false positive and false negative rates than MSS when screening
for common autosomal aneuploidies. Unlike conventional screens, NIPT provides information
never before a part of routine screening, such as the presence of sex chromosome aneuploidies
(SCAs), microdeletions, and fetal sex. Already the capability exists to utilize NIPT in
conjunction with whole exome sequencing to detect an unlimited number of fetal genomic
variants, many with undetermined significance. The list of conditions that NIPT can screen
for is expanding rapidly and has outpaced the rate at which evidence-based strategies for its
integration can be developed and implemented.
Expectant parents must be prepared to make informed decisions about NIPT, including whether
to use it and how to address the prenatal care decisions that result from that choice. For
some, information from NIPT may inform the decision to undergo additional tests and either
prepare for the birth of a child with a serious, potentially life-threatening condition, or
end the pregnancy if a condition is confirmed by diagnostic testing. While this has been the
case for all forms of prenatal testing, NIPT presents unique challenges to this
decision-making process because it provides information about a series of conditions with
variable phenotypic severity of which patients have little familiarity (e.g., Turner
syndrome, Klinefelter syndrome), as well as providing information about markers of
undetermined significance. As with conventional screening, there is the potential for a false
positive or false negative result for each of these findings. Furthermore, information gained
from NIPT may have unintended consequences by identifying maternal or paternal factors that
may be unwanted or unexpected. Previous studies have demonstrated that expectant parents
already face a number of challenges in obtaining accurate, unbiased in-formation and
decisional support when navigating conventional prenatal genetic screens and diagnostic tests
(abbreviated as "prenatal testing" in the rest of this document) and the consequences of
being un-prepared for a positive test result. This situation has been exacerbated with the
introduction of NIPT and will worsen with its expansion. Initially, NIPT was indicated for a
subset of the obstetric population, namely women considered high-risk for aneuploidy due to
advanced maternal age or reproductive history. Now, NIPT is becoming available for use by the
general obstetric population as a primary screen. Clinicians will have to provide
individualized counseling to pregnant patients about the advantages and dis-advantages of
NIPT compared to other prenatal testing options. As part of this process, they will need to
assist patients in placing this information in the context of their goals, values, and
beliefs about parenthood, disability, and termination. The magnitude of the resulting
challenge becomes evident when considering that over four million women receive prenatal care
in the U.S. annually10 and there are not enough prenatal genetic counselors (GC) or
maternal-fetal medicine specialists (MFM) to meet this demand, particularly in rural and
urban settings that already face poorer obstetric outcomes due to barriers in access to
prenatal care. It is unclear how the medical profession will respond to this unprecedented
challenge.
The current situation places a heavy burden on primary obstetric (OB) providers to play a
greater role in introducing patients to the option of NIPT and to facilitate decision-making
about its use. Already, there are growing numbers of OB providers ordering NIPT, either with
or without the involvement of a GC or a MFM, a trend that is expected to continue with the
ongoing expansion of NIPT.39 Thus, an urgent clinical problem has emerged: there is a lack of
evidence-based tools to guide OB providers in effective and individualized education and
decision support for NIPT. To date, the focus of interventions has been on the development of
decision aids and other educational resources to independently educate patients and OB
providers about prenatal genetic assessment. These tools may impart information and provide a
degree of decision support; however, they do not address the dynamic interaction that leads
to the exchange of such information during the clinical visit. Data accrued from our recent
work indicate that these strategies do not provide sufficient support or guidance about how
to structure effective shared decision-making (SDM) discussions between the patient and OB
provider. Studies, including work from our cur-rent R21, demonstrate that important barriers
exist for patients seeking the information and support needed to navigate their prenatal
testing options and make informed, value-reflective decisions about NIPT. While many women
are familiar with common autosomal aneuploidies such as T21, they have little knowledge of
SCAs and significantly less knowledge of microdeletion syndromes. Patients are over-whelmed
by the prospect of learning enough about each of the different conditions that NIPT can
detect. As a result, women increasingly rely upon guidance from OB providers with whom they
have an established relationship to help determine which, if any, prenatal testing option to
utilize. These are important discussions that take place in the clinical encounter and which
educational modules and decision aids alone cannot sufficiently replace. Barriers also exist
for OB providers, who report uncertainty about how to provide personalized, effective, and
patient-centered counseling about NIPT, particularly under conditions of limited time,
reimbursement for counseling, and resources to meet the needs of a diverse population of
patients with varying degrees of health literacy and knowledge of genetic conditions, as well
as different beliefs about parenthood, disability, and pregnancy termination. Current
educational and counseling efforts used by OB providers may not be meeting the self-reported
educational needs and decision-making preferences of patients considering NIPT, particularly
those pertaining to personal values. Moreover, both patients and providers are concerned
about being negatively judged or stereo-typed in discussing topics related to pregnancy
termination and infant/child disability, particularly as NIPT increasingly identifies
conditions with a range of phenotypes.
The delivery of high-quality, evidence-based prenatal care and access to NIPT will only occur
if patients have information and support to make informed, values-based choices about their
prenatal testing options. Given the relationship of informed decision-making with healthcare
quality, access, and outcomes, it is critical to have effective, evidence-based mechanisms
that are responsive to the needs and priorities of patients, the day-to-day challenges faced
by providers, and the current scientific evidence and clinical practice guidelines about
NIPT. While it is recognized that providers should involve patients in healthcare by means of
a SDM process, how to achieve that level of communication within the constraints and
challenges of the practice of obstetrics remains unknown. Thus, the goal of this study is to
conduct a cluster, randomized trial to test an evidence-based tool termed NEST (for NIPT
Education Sup-port Tool) to support patients' decision-making, focusing on the communication
that takes place in the clinical encounter. The investigators will also identify aspects of
the patient-provider interaction that are key to implementing effective strategies responsive
to the challenges posed by the continued development of NIPT. Our hypothesis is that, by
focusing on the dynamic interaction between the patient and provider, NEST will result in a
SDM process that, in turn, will both increase patients' ability to make an informed choice
about NIPT and decrease the decisional conflict associated with that choice. The expected
outcome of this study is a clinically relevant, point-of-care tool that can be utilized among
a diverse group of patients and providers to facilitate decisions that are informed,
consistent with the patient's values, and with which patients do not experience decisional
conflict.
The investigators will recruit three groups: 1) pregnant women, 2) partners of pregnant
women, and 3) prenatal healthcare providers. Randomization will occur at the level of the
healthcare provider. Pregnant women will be randomized per their prenatal healthcare provider
to NEST (intervention) or usual care (control).
The investigators anticipate that this study's findings will ultimately contribute to
improving the quality of prenatal care by empowering pregnant women to make informed choices
that reflect their needs and preferences as individuals and parents. The investigators also
anticipate that OB providers will feel more prepared and confident when approaching
conversations about NIPT.
