Early Check: Expanded Screening in Newborns
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Other Indications, Neurology, Neurology, Orthopedic |
| Therapuetic Areas: | Neurology, Orthopedics / Podiatry, Other |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 12/15/2018 |
| Start Date: | October 15, 2018 |
| End Date: | December 2022 |
Early Check: A Collaborative Innovation to Facilitate Pre-Symptomatic Clinical Trials in Newborns
Early Check provides voluntary screening of newborns for a selected panel of conditions. The
study has three main objectives: 1) develop and implement an approach to identify affected
infants, 2) address the impact on infants and families who screen positive, and 3) evaluate
the Early Check program. The Early Check screening will lead to earlier identification of
newborns with rare health conditions in addition to providing important data on the
implementation of this model program. Early diagnosis may result in health and development
benefits for the newborns. Infants who have newborn screening in North Carolina will be
eligible to participate, equating to over 120,000 eligible infants a year. Over 95% of
participants are expected to screen negative. Newborns who screen positive and their parents
are invited to additional research activities and services. Parents can enroll eligible
newborns on the Early Check electronic Research Portal. Screening tests are conducted on
residual blood from existing newborn screening dried blood spots. Confirmatory testing is
provided free-of-charge for infants who screen positive, and carrier testing is provided to
mothers of infants with fragile X. Affected newborns have a physical and developmental
evaluation. Their parents have genetic counseling and are invited to participate in surveys
and interviews. Ongoing evaluation of the program includes additional parent interviews.
study has three main objectives: 1) develop and implement an approach to identify affected
infants, 2) address the impact on infants and families who screen positive, and 3) evaluate
the Early Check program. The Early Check screening will lead to earlier identification of
newborns with rare health conditions in addition to providing important data on the
implementation of this model program. Early diagnosis may result in health and development
benefits for the newborns. Infants who have newborn screening in North Carolina will be
eligible to participate, equating to over 120,000 eligible infants a year. Over 95% of
participants are expected to screen negative. Newborns who screen positive and their parents
are invited to additional research activities and services. Parents can enroll eligible
newborns on the Early Check electronic Research Portal. Screening tests are conducted on
residual blood from existing newborn screening dried blood spots. Confirmatory testing is
provided free-of-charge for infants who screen positive, and carrier testing is provided to
mothers of infants with fragile X. Affected newborns have a physical and developmental
evaluation. Their parents have genetic counseling and are invited to participate in surveys
and interviews. Ongoing evaluation of the program includes additional parent interviews.
Newborn screening (NBS) is a state-based public health program that screens babies for a
panel of over 30 conditions. It is estimated that about 12,500 newborns each year in the
United States are identified with one of the conditions screened in NBS, with each child
receiving the benefit of early treatment [Centers for Disease Control and Prevention (CDC)
Morbidity and Mortality Weekly Report (MMWR) 2012]. For inclusion in newborn screening there
must be evidence that pre-symptomatic treatment is more effective than treatment after
clinical presentation. Most conditions proposed for newborn screening are rare, however, and
researchers have difficulty identifying sufficient numbers of babies to test the benefits of
pre-symptomatic identification and treatment. This lack of data is central to challenges that
the U.S. Department of Health and Human Services (HHS) Advisory Committee on Heritable
Disorders in Newborns and Children (ACHDNC) faces when making federal recommendations to
states on which conditions should be included in newborn screening programs. ACHDNC is often
asked to consider conditions for inclusion in newborn screening for which there is limited
evidence of the natural history, prevalence, and especially about the benefit of early
treatment. That evidence gap, especially in the rare disease context, makes it important to
develop and test a system to efficiently generate high-quality data about conditions that
have the potential to be candidates for state newborn screening. The Early Check program will
address this gap through screening newborns for a carefully selected panel of conditions,
offered under a research protocol with maternal permission. Early Check will identify
pre-symptomatic infants with rare disorders, accelerate the acquisition of data on the early
natural history of rare disorders, and demonstrate the feasibility of a statewide program to
offer voluntary opt-in newborn screening for a panel of conditions not currently included in
state' standard newborn screening. Further, Early Check will facilitate the public health
'on-boarding' of conditions that are ultimately recommended for state newborn screening
programs. The initial panel of conditions screened in the Early Check program include spinal
muscular atrophy (SMA) and fragile X syndrome (FXS). SMA causes progressive weakness and FXS
causes intellectual disability and behavioral outcomes. These conditions are rare; SMA has an
estimated incidence of 1 in ~10,000 and FXS has an estimated incidence of 1 in ~4,000 males
and 1 in ~4,000-6,000 females. We also propose a sub-study with a secondary permission
process that offers mothers the choice to obtain additional data about the gene that causes
FXS: specifically, whether the infant has a premutation in the gene, which has an uncertain
impact on the infant's learning and development. This uncertainty is the reason why
premutation results are offered separately under a sub-study. For a wide range of rare
disorders there is evidence that a delayed diagnosis (i.e., the frequently-described
diagnostic odyssey as parents search for a diagnosis) can have negative health outcomes on
children who miss out on treatments or interventions and on families who experience negative
psychosocial impact. Thus, the identification of affected newborns through Early Check may
improve health outcomes for the children and the wellbeing of their parents and families. The
evidence supporting the benefit of newborn identification of SMA is strong enough that on
July 2, 2018, SMA was added to the Recommended Uniform Screening Panel (RUSP) by the
Secretary of HHS. There will likely be a considerable time lag (historically multiple years)
before SMA newborn screening can be implemented by individual states. The inclusion of SMA on
the Early Check panel will provide important data to the North Carolina State Laboratory of
Public Health as they prepare for implementation, without delaying the access of infants with
SMA to the potential benefits of early diagnosis. In the future, Early Check will integrate
new conditions to the screening platform as science advances and funding is secured, and
conditions may be removed from the screening platform as associated research questions are
answered and/or conditions achieve inclusion in state newborn screening programs (as may be
the case with SMA). The overall research question is whether Early Check is an effective
onboarding program to inform newborn screening policy decision-making.
Early Check will also provide the infrastructure to facilitate translational research studies
and clinical trials. A dilemma in research in rare diseases is a lack of sufficient numbers
of presymptomatic patients. New treatments are being developed for rare diseases at a rapid
pace. Presymptomatic treatment often has the best potential for effective treatment.
Currently, early identification and intervention is based on the prenatal or early diagnosis
of a sibling of a patient with known disease, which greatly limits the numbers of
presymptomatic patients available for trials. Newborn screening has the greatest potential to
identify presymptomatic infants. Ultimately the research program should more rapidly advance
understanding of diseases and treatments, reducing the length of time for appropriate
conditions to be added to the recommended panel for inclusion in state newborn screening
programs, and provide early identification of affected newborns.
panel of over 30 conditions. It is estimated that about 12,500 newborns each year in the
United States are identified with one of the conditions screened in NBS, with each child
receiving the benefit of early treatment [Centers for Disease Control and Prevention (CDC)
Morbidity and Mortality Weekly Report (MMWR) 2012]. For inclusion in newborn screening there
must be evidence that pre-symptomatic treatment is more effective than treatment after
clinical presentation. Most conditions proposed for newborn screening are rare, however, and
researchers have difficulty identifying sufficient numbers of babies to test the benefits of
pre-symptomatic identification and treatment. This lack of data is central to challenges that
the U.S. Department of Health and Human Services (HHS) Advisory Committee on Heritable
Disorders in Newborns and Children (ACHDNC) faces when making federal recommendations to
states on which conditions should be included in newborn screening programs. ACHDNC is often
asked to consider conditions for inclusion in newborn screening for which there is limited
evidence of the natural history, prevalence, and especially about the benefit of early
treatment. That evidence gap, especially in the rare disease context, makes it important to
develop and test a system to efficiently generate high-quality data about conditions that
have the potential to be candidates for state newborn screening. The Early Check program will
address this gap through screening newborns for a carefully selected panel of conditions,
offered under a research protocol with maternal permission. Early Check will identify
pre-symptomatic infants with rare disorders, accelerate the acquisition of data on the early
natural history of rare disorders, and demonstrate the feasibility of a statewide program to
offer voluntary opt-in newborn screening for a panel of conditions not currently included in
state' standard newborn screening. Further, Early Check will facilitate the public health
'on-boarding' of conditions that are ultimately recommended for state newborn screening
programs. The initial panel of conditions screened in the Early Check program include spinal
muscular atrophy (SMA) and fragile X syndrome (FXS). SMA causes progressive weakness and FXS
causes intellectual disability and behavioral outcomes. These conditions are rare; SMA has an
estimated incidence of 1 in ~10,000 and FXS has an estimated incidence of 1 in ~4,000 males
and 1 in ~4,000-6,000 females. We also propose a sub-study with a secondary permission
process that offers mothers the choice to obtain additional data about the gene that causes
FXS: specifically, whether the infant has a premutation in the gene, which has an uncertain
impact on the infant's learning and development. This uncertainty is the reason why
premutation results are offered separately under a sub-study. For a wide range of rare
disorders there is evidence that a delayed diagnosis (i.e., the frequently-described
diagnostic odyssey as parents search for a diagnosis) can have negative health outcomes on
children who miss out on treatments or interventions and on families who experience negative
psychosocial impact. Thus, the identification of affected newborns through Early Check may
improve health outcomes for the children and the wellbeing of their parents and families. The
evidence supporting the benefit of newborn identification of SMA is strong enough that on
July 2, 2018, SMA was added to the Recommended Uniform Screening Panel (RUSP) by the
Secretary of HHS. There will likely be a considerable time lag (historically multiple years)
before SMA newborn screening can be implemented by individual states. The inclusion of SMA on
the Early Check panel will provide important data to the North Carolina State Laboratory of
Public Health as they prepare for implementation, without delaying the access of infants with
SMA to the potential benefits of early diagnosis. In the future, Early Check will integrate
new conditions to the screening platform as science advances and funding is secured, and
conditions may be removed from the screening platform as associated research questions are
answered and/or conditions achieve inclusion in state newborn screening programs (as may be
the case with SMA). The overall research question is whether Early Check is an effective
onboarding program to inform newborn screening policy decision-making.
Early Check will also provide the infrastructure to facilitate translational research studies
and clinical trials. A dilemma in research in rare diseases is a lack of sufficient numbers
of presymptomatic patients. New treatments are being developed for rare diseases at a rapid
pace. Presymptomatic treatment often has the best potential for effective treatment.
Currently, early identification and intervention is based on the prenatal or early diagnosis
of a sibling of a patient with known disease, which greatly limits the numbers of
presymptomatic patients available for trials. Newborn screening has the greatest potential to
identify presymptomatic infants. Ultimately the research program should more rapidly advance
understanding of diseases and treatments, reducing the length of time for appropriate
conditions to be added to the recommended panel for inclusion in state newborn screening
programs, and provide early identification of affected newborns.
Inclusion Criteria:
- Newborn has newborn screening in North Carolina
- Newborn lives in North Carolina or South Carolina
- Newborn is less than 4 weeks old
- Mother must have legal custody of newborn to give permission for participation
- Mother must be able to interact with the online permission portal (available in
English and Spanish) and give permission online
Exclusion Criteria:
- A newborn screening (NBS) sample is unavailable for the newborn
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