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To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non-patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

Rationale: The disease burden of sickle cell disease (SCD) is highest among U.S. Black and Hispanic populations, which are often disproportionately represented in communities with poor air quality. There are limited data on the effects of air pollution exposure and social environmental factors on health outcomes in children with SCD. Objectives: The objectives of our study were to examine the associations between air pollution exposure and acute respiratory and vaso-occlusive pain crises (VOCs) and to further study the associations when stratifying by asthma status and neighborhood disadvantages. Methods: We conducted a retrospective study, collecting data on outpatient sick and emergency department visits, hospital admissions for respiratory events (i.e., respiratory tract infections, asthma exacerbation, acute chest syndrome), and hospitalizations for VOCs among children with SCD in a tertiary care center in New York City from 2015 to 2018. Modeled data from the New York City Community Air Survey data using home addresses' estimated street-level annual average exposure to air pollution (i.e., black carbon, particulate matter with an aerodynamic diameter ≤2.5 μm, and nitrogen dioxide). The area deprivation index (ADI) continuous national ranking percentile (1–100) was used, representing a composite index for neighborhood-level social disadvantage. We further dichotomized study participants at the upper tertile (high vs. low ADI). Multivariable Poisson regression in generalized estimating equation models were used to estimate relative risks (RRs) after adjusting for potential covariates. Results: A total of 114 children with SCD were included in this study and had between one and four annual repeated measures of annual average air pollutants over a total of 425 visits. Overall, there were no significant associations between air pollution levels and acute respiratory pain crises and VOCs among children with SCD and when stratified by asthma status. We found significant interactions between air pollution levels and the continuous ADI variable on respiratory outpatient and frequent respiratory outpatient/ED visits (P < 0.1). When stratified by high ADI, increased exposure to particulate matter with an aerodynamic diameter ≤2.5 μm was significantly associated with more frequent respiratory outpatient/emergency department visits among children residing in higher ADI neighborhoods (RR [95% confidence interval], 1.13 [1.01, 1.27]; P < 0.05), but not among those in lower ADI neighborhoods. Increased exposure to nitrogen dioxide was associated with more outpatient respiratory events for children in high ADI neighborhoods (RR [95% confidence interval], 2.74 [1.24, 6.08]; P < 0.05) compared with low ADI neighborhoods. Conclusions: Air pollution exposures increased respiratory complications among children with SCD living in deprived neighborhoods. [ABSTRACT FROM AUTHOR]

Background The Department of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children ('Advisory Committee') makes recommendations to the HHS Secretary regarding addition of new conditions to the national Recommended Uniform Screening Panel for newborns. The Advisory Committee's decision-making process includes assessing the net benefit of screening for nominated conditions, informed by systematic evidence reviews generated by an independent Condition Review Workgroup. The evidence base regarding harms associated with screening for specific conditions is often more limited than that for benefits. Procedures The process for defining potential harms from newborn screening reviewed the frameworks from other public health evidence-based review processes, adapted to newborn screening by experts in systematic review, newborn screening programs and bioethics, with input from and approval by the Advisory Committee. Main findings To support the Advisory Committee's review of nominated conditions, the Workgroup has developed a standardized approach to evaluation of harms and relevant gaps in the evidence. Types of harms include the physical burden to infants; psychosocial and logistic burdens to families from screening or diagnostic evaluation; increased risk of medical treatment for infants diagnosed earlier than children with clinical presentation; delayed diagnosis from false negative results; psychosocial harm from false positive results; uncertainty of clinical diagnosis, age of onset or clinical spectrum; and disparities in access to diagnosis or therapy. Conclusions Estimating the numbers of children at risk, the magnitude, timing and likelihood of harms will be integrated into Workgroup reports to the Advisory Committee., Author(s): Aaron J. Goldenberg[sup.1] , Anne Marie Comeau[sup.2] , Scott D. Grosse[sup.3] , Susan Tanksley[sup.4] , Lisa A. Prosser[sup.5] [sup.6] , Jelili Ojodu[sup.7] , Jeffrey R. Botkin[sup.8] , Alex R. [...]

The term "pilot study" has been used over the years to describe the evaluation of the many elements involved in deciding whether a proposed condition should be added to a newborn screening (NBS) panel, and until recently, was unilaterally used to describe the evaluation of the assay to be used before the condition was officially adopted by a state for its newborn screening panel. Since Guthrie's introduction of screening for PKU, each time a new condition was added to the panel, the screening assay itself was validated through a population-based trial, in which the test was performed with de-identified samples to avoid association between the test result and the infant. This is considered by the laboratory as the "pilot phase" of adding a new condition. To advance the science of NBS, especially to accommodate new technologies that may provide new types of information (genetic versus physiological) for each new condition, pilot programs are essential. Involvement of the clinical community serves to improve these evaluations and provides the needed clinical validation of decisions made as a result of it. This paper describes the historical context of pilot programs in population-based NBS that utilize laboratory-based markers as indicators of concern; specifically, three applications that demonstrate different approaches to the use of pilots in adding conditions to a NBS panel are described.

Expansion of newborn screening (NBS) has been driven primarily by a combination of advances in technology and medical treatment, and the sustained advocacy efforts of consumers and voluntary health organizations. The longstanding leadership of the March of Dimes has been credited by many as a critical factor in the expansion and improvement of state NBS programs. From the historic vantage point of four decades of March of Dimes involvement with newborn screening, this report reviews the unique origin of the first newborn screening test, and identifies from this point of origin several of the elements which still define the evolution of advocacy for NBS today. It also documents activities at the federal level and in seven states that have lead to expanded screening for newborns. Advances in NBS technology and medical treatment have informed policy development. Mobilization of volunteers and focused advocacy activities have brought about expansion of screening opportunities for newborns across the United States. But more work is needed. Continued application of the effective strategies identified in this report will help assure that all families have the best possible chance of assuring that their newborns do not have to suffer the complications of conditions that we know can be treated effectively. (Contains 2 figures.)