Expert Evaluation of Strategies to Modernize Newborn Screening in the United States | Genetics and Genomics | JAMA Network Open | JAMA Network
[Skip to Navigation]
Sign In
Table 1.  Solution Domains and Survey Items Associated With Each
Solution Domains and Survey Items Associated With Each
Table 2.  Participant Demographic Characteristics
Participant Demographic Characteristics
Table 3.  Expert Ratings of Agreement With 4 Dimensions for Each of 20 Potential Solutions
Expert Ratings of Agreement With 4 Dimensions for Each of 20 Potential Solutions
1.
Boyle  CA, Bocchini  JA  Jr, Kelly  J.  Reflections on 50 years of newborn screening.   Pediatrics. 2014;133(6):961-963. doi:10.1542/peds.2013-3658PubMedGoogle ScholarCrossref
2.
Kemper  AR, Green  NS, Calonge  N,  et al.  Decision-making process for conditions nominated to the recommended uniform screening panel: statement of the US Department of Health and Human Services Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children.   Genet Med. 2014;16(2):183-187. doi:10.1038/gim.2013.98PubMedGoogle ScholarCrossref
3.
Kellar-Guenther  Y, McKasson  S, Hale  K, Singh  S, Sontag  MK, Ojodu  J.  Implementing statewide newborn screening for new disorders: U.S. program experiences.   Int J Neonatal Screen. 2020;6(2):35. doi:10.3390/ijns6020035PubMedGoogle ScholarCrossref
4.
NewSTEPs. Newborn screening status for all disorders. Accessed June 2, 2021. https://www.newsteps.org/data-resources/reports/screened-conditions-report
5.
Bailey  DB  Jr, Gehtland  L.  Newborn screening: evolving challenges in an era of rapid discovery.   JAMA. 2015;313(15):1511-1512. doi:10.1001/jama.2014.17488PubMedGoogle ScholarCrossref
6.
McCandless  SE, Wright  EJ.  Mandatory newborn screening in the United States: history, current status, and existential challenges.   Birth Defects Res. 2020;112(4):350-366. doi:10.1002/bdr2.1653PubMedGoogle ScholarCrossref
7.
New Drug Development Paradigms Initiative. Updated projection of US durable cell and gene therapies product-indication approvals based on December 2019 development pipeline. Accessed June 2, 2021. https://newdigs.mit.edu/sites/default/files/NEWDIGS-Research-Brief-2020F207v51-PipelineAnalysis.pdf
8.
Bryan  WW. FDA/CBER Office of Tissues and Advanced Therapies (OTAT) selected topics. Presented at: American Society of Gene & Cell Therapy (ASGCT) Liaison Meeting. November 8, 2020; virtual.
9.
Lowes  LP, Alfano  LN, Arnold  WD,  et al.  Impact of age and motor function in a phase 1/2A study of infants with SMA type 1 receiving single-dose gene replacement therapy.   Pediatr Neurol. 2019;98:39-45. doi:10.1016/j.pediatrneurol.2019.05.005PubMedGoogle ScholarCrossref
10.
Grosse  SD, Lam  WKK, Wiggins  LD, Kemper  AR.  Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1.   Genet Med. 2017;19(9):975-982. doi:10.1038/gim.2016.223PubMedGoogle ScholarCrossref
11.
Valdez  R, Grosse  SD, Khoury  MJ.  The need for a next-generation public health response to rare diseases.   Genet Med. 2016;19(5):489-490. doi:10.1038/gim.2016.166PubMedGoogle ScholarCrossref
12.
Denny  JC, Collins  FS.  Precision medicine in 2030—seven ways to transform healthcare.   Cell. 2021;184(6):1415-1419. doi:10.1016/j.cell.2021.01.015PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Views 3,503
    Citations 0
    Original Investigation
    Pediatrics
    December 29, 2021

    Expert Evaluation of Strategies to Modernize Newborn Screening in the United States

    Author Affiliations
    • 1RTI International, Research Triangle Park, North Carolina
    JAMA Netw Open. 2021;4(12):e2140998. doi:10.1001/jamanetworkopen.2021.40998
    Key Points

    Question  What solutions do subject matter experts recommend to prepare newborn screening for a rapid increase in the number of transformative therapies that must be provided early in life?

    Findings  In this survey study, 40 experts in newborn screening evaluated 20 potential solutions. The highest rated solutions addressed cross-state variability, national harmonization, data needed for clinical and policy decisions, and support to expedite state implementation.

    Meaning  These findings suggest that a coordinated national vision that incorporates effective solutions will be needed for newborn screening to accommodate an increasing number of transformative therapies.

    Abstract

    Importance  Novel therapies, including cell and gene therapies, can radically improve outcomes among patients with rare disorders, especially if provided early. Newborn screening (NBS) could support early access to novel therapies, but the speed of new therapy development is a disruptive event for which the public health NBS system and state newborn screening programs are unprepared.

    Objective  To identify and evaluate possible solutions for modernizing NBS.

    Design, Setting, and Participants  In this survey study, NBS experts representing clinical research, federal or state advisory boards, patient advocacy groups, industry, or state laboratories completed an online survey in which they considered 20 potential solutions for modernizing NBS and rated each.

    Exposures  Participants considered 20 potential solutions in the 5 following domains: (1) timeliness of disorder review, (2) alternative mechanisms to offer screening for new disorders not currently part of NBS, (3) expanded data collection, (4) support for states, and (5) emerging methods of screening and their consequences.

    Main Outcomes and Measures  Mean ratings for each solution on efficacy, acceptability, feasibility, and sustainability.

    Results  The survey was completed by 40 NBS experts (median [range] age, 54 [37-73] years; 22 [55.0%] women). Participants acknowledged that substantial change is needed to prepare the NBS system for rapid expansion of novel therapies; on a scale of 0 (no change) to 10 (extensive change), the median (range) score was 8 (2-10), with 18 respondents (45.0%) believing that the NBS would need many new components or an entirely new system to accommodate the changes. All solutions for modernization were considered potentially efficacious by at least 23 respondents (57.5%). The 2 most strongly endorsed were to establish mechanisms for cross-state data coordination for provisional disorders (38 respondents [95.0%]) and create a network of regional screening laboratories (36 [90.0%]). These were closely followed by aligning programs across federal agencies (35 [87.5%]), expanding funding for research (34 [85.0%]), expanding funding to states (34 [85.0%]), building capacity to identify genetic variants and an associated clinical database (34 [85.0%]), and conducting surveillance to study long-term outcomes (34 [85.0%]).

    Conclusions and Relevance  In this study, there was consensus among experts that NBS needs to change if the system is to be prepared for a rapid increase in transformative therapies. To our knowledge, this is the first systematic inventory of potential solutions for modernizing NBS and expert perceptions of each. The findings suggest that the modernization of NBS will require the integration of highly rated solutions, strategic planning, and coordination among multiple stakeholders.

    Introduction

    Newborn screening (NBS) is a highly successful public health program.1 All US states, with guidance from the US Department of Health and Human Services (DHHS), screen for disorders for which there are clear benefits from early detection and treatment. DHHS recommends 35 core disorders as part of the Recommended Uniform Screening Panel (RUSP), informed by an evidence review by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC).2 Because NBS programs operate under state auspice, each state decides whether to add an RUSP disorder to its screening panel. Most states screen for at least 30 recommended disorders and are gradually implementing the remainder.3,4

    Unfortunately, NBS does not have the capacity to keep pace with a new generation of transformative therapies.5,6 The ACHDNC has only recommended 6 new disorders to be added to the RUSP since it was established in 2006. At best, it would take nearly 2 years for a condition to be nominated, fully reviewed, and recommended by the secretary. After that, state implementation varies widely, sometimes taking 3 to 5 years or longer. For example, spinal muscular atrophy was first nominated in 2008, but it was not until 2018, after the benefits of nusinersen had been demonstrated, that it was approved for the RUSP. The number of transformative treatments is growing dramatically, with projections of at least 60 cell and gene therapy approvals by 20307 and hundreds more under investigation.8 Disorders previously lacking treatments could soon have interventions that are curative or significantly disease modifying. Their efficacy almost certainly will be maximized if provided early, underscoring the necessity of early screening and diagnosis.9

    As new treatments are being developed, patient advocacy groups are becoming more active at both the state and national level, arguing that as soon as a treatment becomes available for a particular condition, it should be added to the RUSP. However, a critical feature of NBS policy is that an effective treatment is necessary but insufficient to justify screening for virtually any disorder. Information is needed about natural history, screening methods, follow-up protocols, and long-term outcomes. Although novel therapies could be transformative, their clinical utility will be complicated because of variable penetrance and phenotypic heterogeneity, the lack of predictive biomarkers, and uncertainties about long-term benefits and risks.

    Even when a disorder is added to the RUSP, wide variability exists in state implementation, which can take years.10 Families, patient advocacy groups, and clinicians are frustrated by what they consider an unnecessarily long process of decision-making and implementation, resulting in preventable death, disability, or a lifetime of needed care. Policy makers, on the other hand, are concerned about adding new disorders without adequate evidence. Additionally, most state NBS laboratories cannot add new disorders without legislative approval, funding, and time to ensure adequate implementation.

    Despite these challenges, transformative therapy development will continue, and pressure to add treatable disorders to NBS panels will be substantial. An onslaught of new and more effective therapies will constitute a disruptive event for which NBS is unprepared, and modernization of the entire NBS system seems unavoidable. But how should this modernization be accomplished? Anticipating this scenario, we enlisted expert stakeholders to identify solutions to challenges facing NBS and rate their efficacy, feasibility, acceptability, and sustainability.

    Methods

    Research activities were framed around the following scenario: “It is 2030—ten years from today. Thirty or more new transformative gene or cell therapies have been approved by the FDA to treat monogenic, non-oncology rare disorders. Please consider the following assumptions. These assumptions may not reflect future reality but will be useful to frame our upcoming group discussion.

    • Each treats a different genetic disorder.

    • Each has a valid screening assay that is not prohibitively costly.

    • The therapies are curative or significantly disease modifying if given early in life, but much less or not effective if given later.

    • The longer-term risks and duration of efficacy are unknown.

    • Assume that the cost of the therapies will be completely covered by payers (eg, insurance, Medicaid).”

    Participants

    We recruited prominent individuals from 5 groups: (1) NBS researchers and clinicians, (2) state NBS program leaders, (3) patient advocacy organizations, (4) federal or state advisory committees, and (5) pharmaceutical or diagnostic companies. Participants were nominated by the research team, augmented by suggestions from project funders. A total of 55 invitations were sent, with the goal of at least 8 representatives from each group. Participants were offered a $100 gift card. The study was determined exempt by the RTI institutional review board. All participants provided written informed consent. This study followed American Association for Public Opinion Research (AAPOR) reporting guideline.

    Overall, 42 experts participated in the first 2 phases of the study, and 40 completed all 3 phases. All but 1 participant were from the United States, and all had considerable NBS expertise. Although we selected by group—9 researchers/clinicians, 8 from state laboratories, 10 from patient advocacy groups, 8 from advisory committees, and 7 from industry—many represented multiple perspectives (eg, a clinician also on an advisory group). Participants were not asked to represent 1 group but to draw on the totality of their experiences and perspectives.

    Study Design

    The study had 3 phases. First, there was a prepanel survey. After reviewing informed consent information and submitting an online acknowledgment of consent to participate in the study at large, 42 participants completed an online survey, rating their expertise in NBS and the likelihood of NBS expansion. On a scale from 0 (not at all) to 10 (extremely), participants rated knowledge of cell and gene therapies, NBS, and RUSP review. On a scale from 0 (not at all) to 10 (highly), participants rated the likelihood of (1) FDA approval of 30 therapies in 10 years; (2) the addition of those disorders to the RUSP by 2030; and (3) state implementation within 3 years of RUSP approval.

    Second, we conducted 5 multistakeholder expert panels with 7 to 10 participants per panel (December 2020 to January 2021). Each was led by an author (H.L.P) experienced in moderation, with at least 1 representative from each group. A semi-structured guide was used to examine challenges facing NBS and explore solutions, their feasibility, and steps to implementation. We conducted a rapid qualitative analysis of discussions to identify and categorize solutions proposed by participants. A detailed qualitative analysis of data from the expert panels is forthcoming (S.M.A., unpublished paper, 2021).

    Third, we created a postpanel survey. Approximately 1 month after the panels (February 2021), we sent a second online survey, completed by 40 panelists (95.0%). They rated the magnitude of change required to permit the timely inclusion of 30 new conditions in NBS, on a scale from 0 (no change) to 10 (extensive change throughout the NBS system). Respondents also chose a preferred approach from the 4 following options: (1) retain the current NBS system and make all changes within it; (2) retain most aspects of the current NBS system and make changes within it, while also developing a small number of new system components; (3) develop many new system components while retaining only a modest portion of the current NBS system; or (4) develop an entirely new system. We presented 20 potential solutions derived from the panel discussions. Solutions were organized into 5 domains, as follows: (1) revise and improve timeliness of RUSP review, (2) create mechanisms to offer screening for conditions in addition to those on the RUSP, (3) accelerate and expand data collection to inform policy decisions and implementation, (4) help states expedite comprehensive implementation of screening for new disorders, and (5) evaluate emerging methods of screening and their consequences. Using a 5-point scale from strongly disagree to strongly agree, respondents rated each solution on 4 dimensions: the extent to which each solution is efficacious, acceptable, feasible, and sustainable. Respondents could provide open-ended comments after each solution.

    Data Analysis

    In this article, we report descriptive analysis of the postpanel survey data and an overview of the open-ended comments associated with each solution domain. Full descriptions of solutions are displayed in Table 1. Survey responses were aggregated and summarized quantitatively (range and percentage of respondents). To simplify response summaries, we combined ratings of agree and strongly agree to create a single agreement score per solution. Given the sample size and the exploratory nature of this work, statistical tests were not used to compare solutions or model factors related to solutions.

    Results

    Experts representing the 5 key stakeholder groups (clinical researchers, state or federal advisory committees, patient advocacy organizations, state laboratories, and industry) completed presurvey ratings of their knowledge of NBS and reaction to the study scenario and a follow-up survey rating each of 20 potential solutions for modernizing NBS in anticipation of new transformative therapies. The 40 participants had a median (range) age of 54 (37-73) years, and 22 (55.0%) were women (Table 2).

    Self-rated Knowledge of NBS and Reaction to the Scenario

    Participants were moderately knowledgeable about novel therapies (median [range] score, 7 [0-10]) and highly knowledgeable about NBS (median [range] score, 9 [5-10]) and RUSP review (median [range] score, 9 [5-10]). They were moderately optimistic about FDA approval of 30 transformative therapies within 10 years (median [range] score, 6 [0-10]). Fewer believed that all 30 could be added to the RUSP by 2030 (median [range] score, 3 [0-8]), and even fewer believed that states could add 30 within 3 years of RUSP approval (median [range] score, 2 [0-9]).

    Overall Perceptions of Magnitude and Focus of Change

    Respondents to the postpanel survey agreed that substantial changes would be needed to add 30 disorders within a decade (median [range] score, 8 [2-10]), with nearly half (18 [45.0%]) responding with a 9 or 10. They were divided in their preferred approach for improving NBS. Slightly more than half (22 [55.0%]) preferred to retain the current system and make all changes within it, while developing a small number of new components. Others (18 [45.0%]) felt that more substantial changes were needed, developing many new components or an entirely new system.

    Overall Ratings of Solutions

    Ratings for each solution are displayed in Table 3. Across all solutions, a mean of 78.0% of respondents agreed they were potentially efficacious, with a range from 57.5% to 95.0%. A mean of 74.0% (range, 35.0%-92.5%) agreed that the solutions would be acceptable. However, they were less optimistic about feasibility (median [range], 54.0% [42.5%-80.0%]) and sustainability (median [range], 47.6% [30.0%-62.5%]).

    Domain 1: Revise and Improve Timeliness of RUSP Review

    Four solutions addressed the slow pace of ACHDNC review: (1.1) greatly expand funding for the ACHDNC, (1.2) support advocates to prepare nominations, (1.3) review bundles of disorders, and (1.4) expand criteria for what constitutes net benefit. The solution considered most efficacious was to expand funding to allow simultaneous review of multiple disorders (33 participants [82.5%]), followed by a related solution—review bundles of disorders at the same time (30 [75.0%]). Expanded funding was rated more acceptable (32 [80.0%]) than reviewing bundles (23 [57.5%]), but fewer than half rated either as feasible or sustainable.

    Open-ended comments generally reflected the opinion that something must be done to expedite condition reviews, but there was less agreement on how that might be accomplished. Reviewing bundles of disorders elicited the most open-ended comments, generally reflecting concern that each disorder would have unique features that must be considered.

    Participants moderately agreed that supporting advocates to prepare nominations would be efficacious (25 [62.5%]) and considered this solution acceptable (32 [80.0%]) and feasible (32 [80.0%]). Expanding criteria for net benefit also received moderate endorsement for efficacious (37 [67.5%]) and acceptable (24 [60.0%]), but less agreement that it would be feasible (19 [47.5%]) or sustainable (17 [42.5%]). One said, “Solution 1.4 is what we should strive for—that’s what would help the patients the most,” yet another said, “I do not think that expanding the definition of net benefit will speed up… the process.… [R]ather it would likely have just the opposite effect.” A third participant was concerned that expanding the definition of benefit might “risk states no longer regarding the RUSP so highly.”

    Domain 2: Create Mechanisms to Offer Screening for Conditions in Addition to the RUSP

    Three solutions suggested alternative screening options prior to RUSP approval: (2.1) establish a provisional RUSP, (2.2) establish a voluntary RUSP, and (2.3) create public-private partnerships. The solution considered most efficacious was public-private partnerships to support expanded NBS (32 [80.0%]), which was also generally considered acceptable (30 [75.0%]) and feasible (30 [75.0%]), although with less certainty about sustainability (24 [60.0%]). Some were concerned about potential conflicts of interest if partners included diagnostic or pharmaceutical companies. Establishing a provisional RUSP (23 [57.5%] ) or a voluntary RUSP (26 [65.0%]) were considered less efficacious, with considerable uncertainty about feasibility and sustainability. Transformative therapies themselves are not likely to evoke radically different ethical issues or push NBS to change to a consented model, but a voluntary, 2-tier system would. Open-ended comments reflected concerns about how expensive and complicated it would be to set up these systems and the risks imposed to current NBS if research and consent processes were introduced.

    Domain 3: Accelerate and Expand Data Collection to Inform Policy and Implementation

    Five solutions addressed the fact that even with an approved therapy, absence of critical data will impede rapid expansion: (3.1) align programs across federal agencies, (3.2) expand funding for research, (3.3) establish mechanisms for cross-state coordination for provisional disorders, (3.4) establish a network of research centers, and (3.5) establish a national center for longitudinal follow-up. All were considered potentially efficacious by most respondents. Solution 3.3 (cross-state coordination) was the highest rated in any domain, endorsed by 38 respondents (95.0%). All were generally considered acceptable, with 35 respondents (87.5%) supporting aligning programs across federal agencies and 34 [85.0%]) supporting expanding funding for research, but feasibility and sustainability reflected less certainty.

    Open-ended comments generally reflected support for expanded data collection. As 1 participant said, “A coordinated national effort to harmonize data collection and facilitate pilot studies would be the single most effective way to enhance NBS in the future.” Several comments emphasized the need for a stronger federal role, but competing agency priorities was a barrier, as were states’ willingness or ability to collect and share data.

    Domain 4: Help States Expedite Comprehensive Implementation of Screening for New Disorders

    Five solutions addressed state implementation: (4.1) expand state technical assistance, (4.2) expand federal funding to states, (4.3) create a network of regional screening laboratories, (4.4) create state or regional models for specialized treatment access, and (4.5) launch a national public awareness campaign about the benefits of NBS. Four were endorsed as likely efficacious by 80% or more respondents: expand state technical assistance (32 [80.0%]), expand federal funding to states (34 [85.0%]), create a network of regional screening laboratories (36 [90.0%]), and build models for specialized treatment access (32 [80.0%]). Although 85.0% supported expanding federal funding to states, only 15 (37.5%) believed such a program would be sustainable. A public awareness campaign was the lowest rated for efficacious across all domains but still was endorsed by 23 respondents (57.5%).

    Some open-ended comments reflected concerns about state vs federal authority. One respondent said, “More mandates from the feds, even if funded, are not going to be swallowed very easily by many states”; in contrast another said, “In our current climate, a federal mandate to screen would be well-accepted by many states.” One participant suggested that commercializing NBS might be the answer, whereas another said, “It really seems that a regionalization approach is the best and most innovative solution.”

    Domain 5: Evaluate Emerging Methods of Screening and Their Consequences

    Many conditions that could be treated by transformative therapies will need to be identified through genetic testing, and ultimately, next-generation sequencing could be used to multiplex many conditions at the same time. But sequencing can evoke a wide range of concerns, from the technical to the clinical, and most states have limited capacity for multiplexed genetic screening. Three solutions addressed concerns about disorder heterogeneity, uncertainty about who would need treatment, the need for long-term surveillance, and genomic screening: (5.1) build national capacity to identify genetic variants and an associated clinical database, (5.2) launch coordinated research to evaluate genetic and genomic screening approaches, and (5.3) conduct surveillance to study long-term outcomes for children and families. All 3 solutions were endorsed as efficacious by more than 80% of respondents, and all were similarly considered acceptable. Both building national capacity to identify genetic variants and an associated clinical database and conducting a series of studies on the long-term consequences of false-positive results and surveillance of screen-positive cases were supported by 34 respondents (85.0%), and only a few respondents expressed strong disagreement with these solutions.

    Discussion

    Transformative therapies threaten to overwhelm state and national NBS capacity. Although the problems are well known,11,12 the solutions are less obvious. To address this limitation, we engaged expert NBS stakeholders to suggest and rate solutions. The findings provide policy-relevant information about the viability of solutions needed to prepare NBS for new therapies. Several observations are noteworthy.

    First, substantial change is needed to prepare NBS for treatment advances. There was little optimism among participants that 30 new disorders could be added to the RUSP by 2030 or that states could add 30 within 3 years of RUSP approval. There was strong agreement that some form of modernization is essential. Participants varied in the extent to which they thought changes should be made within the existing NBS system or whether many new components are needed.

    Second, all solutions for modernization were considered potentially efficacious by most respondents (>57.0%). The 2 most strongly endorsed were to establish mechanisms for cross-state data coordination for provisional disorders (95%) and create a network of regional screening labs (90.0%). These were closely followed by aligning programs across federal agencies (87.5%), expanding funding for research (85.0%), expanding funding to states (85.0%), building capacity to identify genetic variants and an associated clinical database (85.0%), and conducting surveillance to study long-term outcomes (85.0%).

    Third, variability in perceived efficacy was evident across solutions and participants. This could be partly attributed to the fact that many solutions had multiple components. We did not compare variability across stakeholder groups because many participants had multiple affiliations. Variability in stakeholder perspectives will need to be addressed if any modernization initiative is to be successful.

    NBS as we know it needs substantial reform. Ideally, this would lead to a well-coordinated and nimble national system. In reality, NBS is a complex and loosely interconnected set of independent state programs with many components, under the auspices of state health departments, guided by national recommendations, slowly evolving in response to forces outside of its control. The inevitability of new and more effective therapies is one such force for which the current system is unprepared, creating an urgency to quickly identify and implement workable solutions.

    But modernizing NBS will require a clearly articulated strategy. Changing a well-established system after 60 years will not be easy, especially given the varying perspectives of state and federal governments, researchers, clinicians, industry representatives, and patient advocates. These stakeholders share the same goal: identify infants with serious health conditions and provide treatments as early as possible. But they vary considerably in auspice, history, resources, priorities, and responsibilities, and so it is not surprising that they do not speak with a common voice.

    The highest rated solutions suggest critical steps. First, there is an urgent need for better data. A near-term goal should be coordinated efforts to integrate disparate data systems and conduct analyses to answer critical questions required for decision-making. In the meantime, work should begin to establish a more formal national data system driven by key overarching questions and nimble enough to respond quickly to needs for data. Second, there is an urgent need to help states expedite implementation. This will likely require a combination of national leadership, an infusion of federal funds, and perhaps regionalization of laboratory services.

    Increased funding will be essential to enable critical decision-making, conduct evidence reviews, support pilot studies and research, harmonize and integrate data, support state implementation, and build regional screening labs. But a massive increase in funds without a coordinated strategic plan will be ineffective and potentially counterproductive. The vision for such a plan must be to bring the benefits of safe and effective treatments to infants more quickly. Building a next-generation NBS system to accomplish this vision will require extensive stakeholder engagement to create community consensus, a willingness of federal agencies to cooperate in implementing solutions, an intensive effort to harmonize state policies and resources, and ultimately national legislation.

    Limitations

    Several limitations should be noted. We invited a nationally prominent group of participants, but the sample was nominated based on expertise and not selected to be representative. Although other suggestions came up during the panel, we focused on cross-cutting solutions, most of which included multiple components, to create a manageable survey. Third, although participants rated discrete solutions, we did not ask them to propose a combined package. Clearly, efficacy would be enhanced if multiple solutions were implemented in a complementary fashion.

    Conclusions

    This survey study found that NBS experts recommended substantial changes to the current system to prepare for rapid increases in transformative therapies. These solutions included establishing mechanisms for cross-state data coordination for provisional disorders and creating a network of regional screening laboratories. The recommended changes will require national leadership and funding as well as further study of optimal ways to harmonize state policies and resources.

    Back to top
    Article Information

    Accepted for Publication: November 2, 2021.

    Published: December 29, 2021. doi:10.1001/jamanetworkopen.2021.40998

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Bailey DB Jr et al. JAMA Network Open.

    Corresponding Author: Donald B. Bailey, Jr, PhD, RTI International, 3040 E Cornwallis Rd, Research Triangle Park, NC 27709 (dbailey@rti.org).

    Author Contributions: Drs Bailey and Peay had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Bailey, Porter, Andrews, Raspa, Peay.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Bailey, Porter, Peay.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Gwaltney.

    Obtained funding: Bailey.

    Administrative, technical, or material support: Bailey, Porter, Andrews, Raspa.

    Supervision: Bailey, Peay.

    Conflict of Interest Disclosures: All authors are employees of RTI International. Dr Bailey reported receiving grants from Orchard Therapeutics, Sarepta Pharmaceuticals, BioMarin, Travere, and EveryLife Foundation during the conduct of the study and grants from Janssen Pharmaceuticals and the John Merck fund as well as donated reagents and loaned equipment from Asuragen outside the submitted work. Dr Porter reported receiving grants from Orchard Therapeutics, Sarepta Pharmaceuticals, BioMarin, Travere, and EveryLife Foundation during the conduct of the study and grants from Janssen Pharmaceuticals, the John Merck Fund, and Health Resources and Services Administration (HRSA) as well as donated reagents and loaned equipment from Asuragen outside the submitted work. Dr Andrews reported receiving grants from Sarepta Therapeutics, Orchard Therapeutics, BioMarin Pharmaceutical, Travere Therapeutics, and EveryLife Foundation for Rare Diseases during the conduct of the study and grants from the John Merck Fund, CureSMA, the Muscular Dystrophy Association, and Sarepta Therapeutics as well as donated reagents and equipment from Asuragen outside the submitted work. Dr Raspa reported receiving grants from Sarepta Therapeutics, Orchard Therapeutics, BioMarin Therapeutics, Travere Therapeutics, and EveryLife Foundation during the conduct of the study and grants from HRSA Evaluation of Heritable Disorders Program, HRSA Severe Combined Immunodeficiency (SCID) Screening and Education: SCID Compass, HRSA New York Mid-Atlantic Caribbean Regional Genetics Network, and the Centers for Disease Control and Prevention Enhancing Disease Detection in Newborns: Building Capacity in Public Health Laboratories outside the submitted work. Dr Gwaltney reported receiving grants from Orchard Therapeutics, Serepta Pharmaceuticals, BioMarin, Traverse, and EveryLife Foundation during the conduct of the study and receiving grants from Early Check, HRSA SCID Screening and Education, and the John Merck Fund as well as donated reagents and equipment from Asurgen outside the submitted work. Dr Peay reported receiving grants from Orchard Therapeutics, Sarepta Therapeutics, Biomarin, Travere, and EveryLife Foundation during the conduct of the study and grants from Janssen Pharmaceuticals, the John Merck Fund, and Muscular Dystrophy Association as well as donated reagents and equipment from Asuragen outside the submitted work. No other disclosures were reported.

    Funding/Support: The study was funded by a consortium of funders: Orchard Therapeutics, Sarepta Therapeutics, Travere, BioMarin, and the EveryLife Foundation.

    Role of the Funder/Sponsor: The funders provided feedback on the design and conduct of the study. They were not involved in the collection, management, analysis, or interpretation of the data, or in preparation of the manuscript. They reviewed the manuscript and provided feedback to the authors prior to submission for publication. Submission of at least 1 manuscript was a requirement for funding. The authors, all researchers at RTI International, conducted all data collection and analyses. Although consortium input was obtained at each stage of the research process, the RTI team was fully responsible for final decisions about study methodology and the content of this manuscript.

    Additional Contributions: We are grateful to the study participants whose expertise informed the study findings.

    Additional Information: A deidentified data set is available from the first author under a data use agreement.

    References
    1.
    Boyle  CA, Bocchini  JA  Jr, Kelly  J.  Reflections on 50 years of newborn screening.   Pediatrics. 2014;133(6):961-963. doi:10.1542/peds.2013-3658PubMedGoogle ScholarCrossref
    2.
    Kemper  AR, Green  NS, Calonge  N,  et al.  Decision-making process for conditions nominated to the recommended uniform screening panel: statement of the US Department of Health and Human Services Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children.   Genet Med. 2014;16(2):183-187. doi:10.1038/gim.2013.98PubMedGoogle ScholarCrossref
    3.
    Kellar-Guenther  Y, McKasson  S, Hale  K, Singh  S, Sontag  MK, Ojodu  J.  Implementing statewide newborn screening for new disorders: U.S. program experiences.   Int J Neonatal Screen. 2020;6(2):35. doi:10.3390/ijns6020035PubMedGoogle ScholarCrossref
    4.
    NewSTEPs. Newborn screening status for all disorders. Accessed June 2, 2021. https://www.newsteps.org/data-resources/reports/screened-conditions-report
    5.
    Bailey  DB  Jr, Gehtland  L.  Newborn screening: evolving challenges in an era of rapid discovery.   JAMA. 2015;313(15):1511-1512. doi:10.1001/jama.2014.17488PubMedGoogle ScholarCrossref
    6.
    McCandless  SE, Wright  EJ.  Mandatory newborn screening in the United States: history, current status, and existential challenges.   Birth Defects Res. 2020;112(4):350-366. doi:10.1002/bdr2.1653PubMedGoogle ScholarCrossref
    7.
    New Drug Development Paradigms Initiative. Updated projection of US durable cell and gene therapies product-indication approvals based on December 2019 development pipeline. Accessed June 2, 2021. https://newdigs.mit.edu/sites/default/files/NEWDIGS-Research-Brief-2020F207v51-PipelineAnalysis.pdf
    8.
    Bryan  WW. FDA/CBER Office of Tissues and Advanced Therapies (OTAT) selected topics. Presented at: American Society of Gene & Cell Therapy (ASGCT) Liaison Meeting. November 8, 2020; virtual.
    9.
    Lowes  LP, Alfano  LN, Arnold  WD,  et al.  Impact of age and motor function in a phase 1/2A study of infants with SMA type 1 receiving single-dose gene replacement therapy.   Pediatr Neurol. 2019;98:39-45. doi:10.1016/j.pediatrneurol.2019.05.005PubMedGoogle ScholarCrossref
    10.
    Grosse  SD, Lam  WKK, Wiggins  LD, Kemper  AR.  Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1.   Genet Med. 2017;19(9):975-982. doi:10.1038/gim.2016.223PubMedGoogle ScholarCrossref
    11.
    Valdez  R, Grosse  SD, Khoury  MJ.  The need for a next-generation public health response to rare diseases.   Genet Med. 2016;19(5):489-490. doi:10.1038/gim.2016.166PubMedGoogle ScholarCrossref
    12.
    Denny  JC, Collins  FS.  Precision medicine in 2030—seven ways to transform healthcare.   Cell. 2021;184(6):1415-1419. doi:10.1016/j.cell.2021.01.015PubMedGoogle ScholarCrossref
    ×