Clinical utility of novel biomarkers for prediction of early pregnancy failure

Active Project Grant Awarded Last action

Award ID
R01HD110448
Recipient
Awarding agency
Obligated
$8,097,493

Award facts

Completion date 74% complete
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The diagnosis and management for women who are at risk for ectopic pregnancy (EP) and spontaneous abortion (SAB), has not changed substantially in decades. While ultrasound can diagnose a significant portion of women at presentation, because of its limited accuracy in abnormal and early gestation, a large number of women need serial tests and procedures to determine the final location and viability of an early pregnancy. Misdiagnosis and iatrogenic complications during this time are still too common. This conundrum results in great stress and uncertainty for women undergoing clinical care and their health care teams. To date, we have demonstrated (and validated) that multiplexed biomarkers from divergent biological pathways can be used to minimize both false positive and false negative discrimination (rather than balancing the two errors with lower accuracy). In parallel, we have discovered and screened more than 54 novel biomarkers to obtain 11 candidates that can predict early pregnancy outcome. Using machine learning we have demonstrated that as few as 3 of these markers can predict the location of an early gestation (IUP VS EP or SAB) with 95% accuracy. Additionally, an overlapping group of 3 markers can predict the viability of a gestation (IUP VS SAB or EP) with 94% accuracy. When both tests are used in combination the accuracy is 96.9%. We now plan to externally validate these companion diagnostic(s) in a separate population-based prospective study and to determine the optimal conditions of use. We will optimize performance in women presenting with a pregnancy of unknown location as well as assess predictive values for all women presenting at risk for early pregnancy loss using an independent population-based prospective study (SA1). We will determine if accuracy can be improved with the combination of presenting signs, symptoms, and ultrasound findings (SA2). Moreover, we will validate our biomarker tests in two distinct populations of interest: women with high and low risk for EP: a) asymptomatic women prior to presentation for care (eager trial) and b) women diagnosed with a persistent pregnancy of unknown location (actornot trial) (SA3). Developing novel biomarkers that distinguish normal physiology from the presence of gynecologic disorders is an nichd research priority area. Our productive and established team is proposing rigorous cross disciplinary, state of the art, and novel research with great scientific impact that has the potential to produce a paradigm shift in clinical care models for the diagnosis and management of women in early pregnancy. Our detailed plan for biomarker development is iterative and nimble and, importantly, includes validation. Our development plan is informed by methodology from successful biomarker development, is designed to minimize known pitfalls, and is developed with FDA guidance.

Transactions

Action Obligated Date
Amendment $66,407
Amendment $597,672
Amendment $597,672
Amendment $66,951
Amendment $66,951
Amendment $602,560
Amendment $602,560
Amendment $61,004
Amendment $61,004
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Amendment $610,044
Amendment $610,044
Amendment $610,044
Amendment $610,044
Amendment $718,383
Amendment $718,383
Amendment $718,383
Original award $718,383
Show all 18

Subawards

Subrecipient Amount Awarded
Northwestern University Dr. Jungheim and her clinical associates will enroll patients presenting to Northwestern Memorial who are presenting for evaluation of early pregnancy. HCG data… $58,203
Old Dominion University "We propose to conduct a series of two case control studies using well phenotyped bio-specimens, followed by a prospective cohort study to refine and validate a… $50,559
Northwestern University Dr. Jungheim and her clinical associates will enroll patients presenting to Northwestern Memorial who are presenting for evaluation of early pregnancy. HCG data… $58,205
Northwestern University $95,394
Old Dominion University We propose to conduct a series of two case control studies using well phenotyped bio-specimens, followed by a prospective cohort study to refine and validate… $91,200

Quick answers

Who received award R01HD110448?

R01HD110448 was awarded to The Trustees Of The University Of Pennsylvania by National Institute of Child Health and Human Development (National Institutes of Health) on February 1, 2023.

How much is award R01HD110448 worth?

$8,097,493 has been obligated on R01HD110448.

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