Clinical trial NCT05368038: ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program
Official title: ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Acid Sphingomyelinase Deficiency
Ceroid Lipofuscinosis, Neuronal, 2
Cerebrotendinous Xanthomatosis
Fabry Disease
GM1 Gangliosidosis
Gaucher Disease
Lysosomal Acid Lipase Deficiency
Metachromatic Leukodystrophy
Mucopolysaccharidosis II
Mucopolysaccharidosis III-B
Mucopolysaccharidosis IV A
Mucopolysaccharidosis VI
Mucopolysaccharidosis VII
Niemann-Pick Disease, Type C
Keywords: Newborn Screening
Rare Diseases
Families
Genetics
ELSI
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Alexion Pharmaceuticals, Inc.
name: Ara Parseghian Medical Research Foundation
name: BioMarin Pharmaceutical
name: Cure Sanfilippo Foundation
name: Danas Angels Research Trust (DART)
name: Mirum Pharmaceuticals, Inc.
name: Orchard Therapeutics
name: Passage Bio, Inc.
name: Genzyme, a Sanofi Company
name: Sio Gene Therapies
name: Takeda Pharmaceuticals North America, Inc.
name: The FireFly Fund
name: The Noah's Hope - Hope 4 Bridget Family Foundations
name: Travere Therapeutics, Inc.
name: Ultragenyx Pharmaceutical Inc
First posted: 2022-05-10
Enrollment: 100000
Sex: ALL
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newborns born at a ScreenPlus pilot hospital who are less than four weeks old.

Brief summary: ScreenPlus is a consented, multi-disorder pilot newborn screening program implemented in conjunction with the New York State Newborn Screening Program that provides families the option to have their newborn(s) screened for a panel of additional conditions. The study has three primary objectives: 1) define the analytic and clinical validity of multi-tiered screening assays for a flexible panel of disorders, 2) determine disease incidence in an ethnically diverse population, and 3) assess the impact of early diagnosis on health outcomes. Over a five-year period, ScreenPlus aims to screen 100,000 infants born in nine high birthrate, ethnically diverse pilot hospitals in New York for a flexible panel of 14 rare genetic disorders. This study will also involve an evaluation of the Ethical, Legal and Social issues pertaining to NBS for complex disorders, which will be done via online surveys that will be directed towards ScreenPlus parents who opt to participate and qualitative interviews with families of infants who are identified through ScreenPlus.

Detailed description: Soon after birth, all babies born in the United States have a newborn screening (NBS) test to check for certain medical conditions. All babies are screened, even if they appear healthy, because most of these conditions have no obvious physical findings in a newborn and might otherwise be diagnosed only after the development of serious problems, such as brain damage, organ damage, or death. In fact, NBS has been an integral part of preventable health care for over five decades, ever since the discovery that phenylketonuria is an easily diagnosed, preventable cause of intellectual disability.

Over the past two decades, there have been dramatic advances in screening technology, with a resulting increase in the number and complexity of disorders on NBS panels. This enhanced ability to screen brings questions about what types of disorders are appropriate for NBS. To that end, the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) was established in 2003 to make evidence-based recommendations at the national level regarding the suitability of various disorders for NBS. At present, the Recommended Uniform Screening Panel, or the RUSP, includes 35 core disorders. The RUSP nomination process uses information about disease incidence and severity, natural history, benefits of early detection, safety and efficacy of treatment, analytic and clinical validity of the screening tests, as well as consideration of potential harms associated with screening and public health impact to determine whether a particular disorder is appropriate for NBS. However, there are many disorders for which this data is insufficient or missing. There are other disorders that challenge traditional NBS criteria by having predominantly later-onset phenotypes, poorly defined natural history, or unclear treatment outcomes. As these potentially life-threatening disorders might benefit from early detection, gathering and analyzing this data is both critical and timely. Accordingly, there is a great deal of interest in pilot NBS studies as a means to gather objective evidence about whether a disorder is appropriate for widespread screening.

ScreenPlus is a comprehensive, fluid, pilot NBS program that will screen 100,000 consented infants for specific disorders that are under consideration for universal NBS. This study will generate critical data about the validity of testing for these candidate disorders and provide estimates of disease incidence in a large, ethnically diverse population. The investigators will evaluate different consent and engagement models, including direct, in-person interaction and the use of a novel E-Consent framework to educate parents about pilot NBS. The investigators will also collect nuanced information about the ethical implications of NBS, by conducting qualitative interviews with parents of children who have received a positive or uncertain NBS result. Parents who are eligible to participate in ScreenPlus will also have the opportunity to complete a flexible set of surveys of parent opinions about expanded NBS, research using dried blood spots, and other relevant topics. Furthermore, newborns who screen positive will be followed by a ScreenPlus physician. Through thoughtful collaboration with disease experts, the investigators will help systematically collect disease specific measures through detailed long-term follow-up which will enable us to critically evaluate how affected children identified through ScreenPlus are faring, allowing objective assessment of the impact early diagnosis has on outcome.

The investigators will share this important data with the NBS community, including the ACHDNC, to help inform objective decision-making about widespread screening recommendations. The ScreenPlus panel is fluid and disorders may be added/removed as disorders satisfy the study inclusion criteria or are added to the RUSP and/or the New York State routine NBS panel. Additionally, recognizing that the NIH, advocacy groups, academics, and private industry all share a desire for clean, consented pilot NBS data, the investigators created a unique financial infrastructure. This investigator-driven arrangement permits all stakeholders to obtain aggregate data of interest in a mutually beneficial and cost-effective manner. ScreenPlus is guided by Scientific and Community Advisory Boards, who are comprised of rare disease experts, biochemistry specialists, physicians, bioethicists, and patient advocates. Overall, the investigators anticipate that ScreenPlus will become the premier consented pilot NBS program in the United States.

In sum, ScreenPlus will provide critical data about the appropriateness of NBS for candidate disorders, the feasibility and effectiveness of consented screening models, and parent informational needs and preferences as they relate to NBS for complex disorders.

Eligibility criteria: Inclusion Criteria:

* All newborn infants born at a ScreenPlus pilot hospital
* Infants who are less than four weeks old, regardless of sex, gestational age, or health status.

Exclusion Criteria:

* A newborn screening sample is unavailable
* Infants who are more than four weeks old

Primary outcomes:
measure: Evaluate the accuracy of the screening assays.
timeFrame: Through study completion up to 9 years.
measure: Define disease incidence in an ethnically diverse population.
timeFrame: Through study completion up to 9 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Jack D. Weiler Hospital
state: New York
city: Bronx
country: United States
facility: ScreenPlus Coordinating Core, Children's Hospital at Montefiore
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Brooklyn
country: United States
facility: NYU Langone Hospital - Brooklyn
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health - Tisch Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Queens
country: United States
facility: Long Island Jewish Medical Center
state: New York
Study officials:
affiliation: Albert Einstein College of Medicine
name: Melissa Wasserstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kelly NR, Orsini JJ, Goldenberg AJ, Mulrooney NS, Boychuk NA, Clarke MJ, Paleologos K, Martin MM, McNeight H, Caggana M, Bailey SM, Eiland LR, Ganesh J, Kupchik G, Lumba R, Nafday S, Stroustrup A, Gelb MH, Wasserstein MP. ScreenPlus: A comprehensive, multi-disorder newborn screening program. Mol Genet Metab Rep. 2023 Dec 14;38:101037. doi: 10.1016/j.ymgmr.2023.101037. eCollection 2024 Mar.
citation: Calonge N, Green NS, Rinaldo P, Lloyd-Puryear M, Dougherty D, Boyle C, Watson M, Trotter T, Terry SF, Howell RR; Advisory Committee on Heritable Disorders in Newborns and Children. Committee report: Method for evaluating conditions nominated for population-based screening of newborns and children. Genet Med. 2010 Mar;12(3):153-9. doi: 10.1097/GIM.0b013e3181d2af04.
citation: Wasserstein MP, Caggana M, Bailey SM, Desnick RJ, Edelmann L, Estrella L, Holzman I, Kelly NR, Kornreich R, Kupchik SG, Martin M, Nafday SM, Wasserman R, Yang A, Yu C, Orsini JJ. The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants. Genet Med. 2019 Mar;21(3):631-640. doi: 10.1038/s41436-018-0129-y. Epub 2018 Aug 10.