Selecting PedsQL items to derive the PedsUtil health state classification system to measure health utilities in children.

BACKGROUND: There is a lack of preference-based health-related quality of life (HRQoL) measures that consistently value health across a full range of child age groups. The PedsQL is a generic HRQoL instrument validated for children 2-18 years, but it is not preference-based. The objective of this study was to derive the PedsUtil health state classification system from the PedsQL as a basis for a preference-based HRQoL measure for children. METHODS: A two-step process was used to select PedsQL items to include in the health state classification system: 1) exclude poorly functioning items according to Rasch analysis in each of the previously established seven dimensions of the PedsUtil health state classification system and 2) select a single item to represent each dimension based on Rasch and psychometric analyses, as well as input from child health experts and parents. All secondary analyses were conducted using data from the Longitudinal Study of Australian Children (LSAC). Analyses were stratified by age group (i.e., 2-5 years, 6-13 years, and 14-17 years) to represent the different developmental stages of children and to reflect the study design of the LSAC. Rasch analyses were also performed on five random subsamples for each age group to enhance robustness of results. RESULTS: Twelve items were excluded from the PedsUtil health state classification system after the first step of the item selection process. An additional four items were excluded in the second step, resulting in seven items that were selected to represent the seven dimensions of the PedsUtil health state classification system: Physical Functioning ("participating in sports activity or exercise"), Pain ("having hurts or aches"), Fatigue ("low energy level"), Emotional Functioning ("worrying about what will happen to them"), Social Functioning ("other kids not wanting to be their friend"), School Functioning ("keeping up with schoolwork"), and School Absence ("missing school because of not feeling well"). CONCLUSIONS: The PedsUtil health state classification system was derived from the PedsQL based on several criteria and was constructed to be applicable to children two years and older. Research is ongoing to elicit preferences for the PedsUtil health state classification system to construct the PedsUtil scoring system.

Evidence and recommendation for mucopolysaccharidosis type II newborn screening in the United States.

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.

Eliciting Trade-Offs Between Equity and Efficiency: A Methodological Scoping Review.

OBJECTIVES: To identify differences in the approaches and results of studies that elicit equity-efficiency trade-offs that can inform equity-informative cost-effectiveness analysis for healthcare resource allocation. METHODS: We searched Ovid (Medline), EconLit, and Scopus prior to June 25, 2021. Inclusion criteria were: (1) peer-reviewed or (2) gray literature; (3) published in English; (4) survey-based; (5) parameterized a social welfare function to quantify inequality aversion or (6) elicited a trade-off in equity and efficiency characteristics of health interventions. Exclusion criteria were: (1) studies that did not conduct a trade-off or (2) theoretical studies. We abstracted details on study methods, results, and limitations. Studies were grouped by following approach: (1) social welfare function or (2) preference ranking and distributional weighting. We described findings separately for each approach category. RESULTS: Seventy-seven papers were included, 28 parameterized social welfare functions and 49 were classified as preference ranking and distributional weighting. Study methods were heterogeneous. Studies were conducted across 29 countries. Sample sizes and composition, survey methods and question framing varied. Preferences for equity were mixed. Across both approach categories: 39 studies were classified as clear evidence of inequality aversion; 33 found mixed evidence; and 4 had no evidence of aversion. Evidence of between and within-study heterogeneity was found. Preferences for equity may differ by gender, profession, political ideology, income, and education. CONCLUSIONS: Substantial variability in study methods limit the direct comparability of findings and their use in equity-informed cost-effectiveness analysis. Future researches using representative samples that explore within and between country heterogeneity is needed.

Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

Preferences for Sexually Transmitted Infection and Cancer Vaccines in the United States and in China.

OBJECTIVES: This study assessed preferences for hypothetical vaccines for children in 2 large vaccine markets according to how the vaccine-preventable disease is transmitted via a discrete choice experiment. METHODS: Surveys in China (N = 1350) and the United States (N = 1413) were conducted from April to May 2021. The discrete choice experiment included attributes of cost, age at vaccination, transmission mode of the vaccine-preventable disease, and whether the vaccine prevents cancer. Preference utilities were modeled in a Bayesian, multinomial logistic regression model, and respondents were grouped by vaccine preference classification through a latent class analysis. RESULTS: Individuals favored vaccines against diseases with transmission modes other than sexual transmission (vaccine for sexually transmitted infection [STI] vs airborne disease, in the United States, odds ratio 0.71; 95% credible interval 0.64-0.78; in China, odds ratio 0.76; 95% credible interval 0.69-0.84). The latent class analysis revealed 6 classes: vaccine rejecters (19% in the United States and 8% in China), careful deciders (18% and 17%), preferring cancer vaccination (20% and 19%), preferring vaccinating children at older ages (10% and 11%), preferring vaccinating older ages, but indifferent about cancer vaccines (23% and 25%), and preferring vaccinating children at younger ages (10% and 19%). Vaccine rejection was higher with age in the United States versus more vaccine rejection among those at the age of 18 to 24 and ≥ 64 years in China. CONCLUSION: The public had strong preferences against giving their child an STI vaccine, and the class preferring a cancer vaccine was less accepting of an STI vaccine. Overall, this study points to the need for more education about how some STI vaccines could also prevent cancers.

Developing Criteria for Health Economic Quality Evaluation Tool.

OBJECTIVES: Because existing publication guidelines and checklists have limitations when used to assess the quality of cost-effectiveness analysis, we developed a novel quality assessment tool for cost-effectiveness analyses, differentiating methods and reporting quality and incorporating the relative importance of different quality attributes. METHODS: We defined 15 quality domains from a scoping review and identified 72 methods and reporting quality attributes (36 each). After designing a best-worst scaling survey, we fielded an online survey to researchers and practitioners to estimate the relative importance of the attributes in February 2021. We analyzed the survey data using a sequential conditional logit model. The final tool included 48 quality attributes deemed most important for assessing methods and reporting quality (24 each), accompanied by a free and web-based scoring system. RESULTS: A total of 524 participants completed the methodology section, and 372 completed both methodology and reporting sections. Quality attributes pertaining to the "modeling" and "data inputs and evidence synthesis" domains were deemed most important for methods quality, including "structure of the model reflects the underlying condition and intervention's impact" and "model validation is conducted." Quality attributes pertaining to "modeling" and "Intervention/comparator(s)" domains were considered most important for reporting quality, including "model descriptions are detailed enough for replication." Despite its growing prominence, "equity considerations" were not deemed as important as other quality attributes. CONCLUSIONS: The Criteria for Health Economic Quality Evaluation tool allows users to differentiate methods and reporting as well as quantifies the relative importance of quality attributes. Alongside other considerations, it could help assess and improve the quality of cost-effectiveness evidence to inform value-based decisions.

Preferences and experiences of pediatricians on implementing national guidelines on universal routine screening of adolescents for major depressive disorder: A qualitative study.

BACKGROUND: To explore the preferences of pediatricians for key factors around the implementation of universal routine screening guidelines for major depressive disorder in adolescent patients in a primary care setting. METHOD: Semi-structured qualitative interviews were conducted with U.S. pediatricians. Participants were recruited by convenience sampling and snowball sampling. Qualitive data were summarized using thematic analysis to identify themes relevant to preferences around implementing screening strategies for adolescent patients. Recruitment ended upon reaching thematic saturation when no new themes were revealed. RESULTS: Of the 14 participants, 11 identified as female, 3 male, 10 white, and 4 Asian. Top themes among pediatrician participants were around the screening modality (14/14 participants), screening validity (14/14), time barriers (14/14), and confidentiality barriers (12/14). Less frequently mentioned themes by pediatricians were workplace coordination and logistics (7/14), alternative starting ages for screening (7/14), more frequent screenings than annual screenings (3/14), and additional clinical training regarding depression diagnosis and treatment (2/14). LIMITATIONS: Pool of interviewed participants was limited by diversity in terms of geography, race/ethnicity, or practice settings. CONCLUSIONS: To promote the uptake of universal routine screening of adolescent major depression, pediatricians expressed it was important to address key implementation factors regarding the screening modality, screening validity, time constraints, and confidential care concerns in a primary care delivery context. Findings could be used to inform the development of implementation strategies to facilitate depression screening in primary care. Future research is needed to quantitively assess decisions and tradeoffs that pediatricians make when implementing universal screening to support adolescent mental health.

Economic Evaluation Design within the HEAL Prevention Cooperative.

The rapid rise in opioid misuse, disorder, and opioid-involved deaths among older adolescents and young adults is an urgent public health problem. Prevention is a vital part of the nation's response to the opioid crisis, yet preventive interventions for those at risk for opioid misuse and opioid use disorder are scarce. In 2019, the National Institutes of Health (NIH) launched the Preventing Opioid Use Disorder in Older Adolescents and Young Adults cooperative as part of its broader Helping to End Addiction Long-term (HEAL) Initiative ( https://heal.nih.gov/ ). The HEAL Prevention Cooperative (HPC) includes ten research projects funded with the goal of developing effective prevention interventions across various settings (e.g., community, health care, juvenile justice, school) for older adolescent and young adults at risk for opioid misuse and opioid use disorder (OUD). An important component of the HPC is the inclusion of an economic evaluation by nine of these research projects that will provide information on the costs, cost-effectiveness, and sustainability of these interventions. The HPC economic evaluation is integrated into each research project's overall design with start-up costs and ongoing delivery costs collected prospectively using an activity-based costing approach. The primary objectives of the economic evaluation are to estimate the intervention implementation costs to providers, estimate the cost-effectiveness of each intervention for reducing opioid misuse initiation and escalation among youth, and use simulation modeling to estimate the budget impact of broader implementation of the interventions within the various settings over multiple years. The HPC offers an extraordinary opportunity to generate economic evidence for substance use prevention programming, providing policy makers and providers with critical information on the investments needed to start-up prevention interventions, as well as the cost-effectiveness of these interventions relative to alternatives. These data will help demonstrate the valuable role that prevention can play in combating the opioid crisis.

Health and economic outcomes of newborn screening for infantile-onset Pompe disease.

PURPOSE: To estimate health and economic outcomes associated with newborn screening (NBS) for infantile-onset Pompe disease in the United States. METHODS: A decision analytic microsimulation model simulated health and economic outcomes of a birth cohort of 4 million children in the United States. Universal NBS and treatment was compared with clinical identification and treatment of infantile-onset Pompe disease. Main outcomes were projected cases identified, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) over the life course. RESULTS: Universal NBS for Pompe disease and confirmatory testing was estimated to cost an additional $26 million annually. Additional medication costs associated with earlier treatment initiation were $181 million; however, $8 million in medical care costs for other services were averted due to delayed disease progression. Infants with screened and treated infantile-onset Pompe disease experienced an average lifetime increase of 11.66 QALYs compared with clinical detection. The ICER was $379,000/QALY from a societal perspective and $408,000/QALY from the health-care perspective. Results were sensitive to the cost of enzyme replacement therapy. CONCLUSION: Newborn screening for Pompe disease results in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.

Examining Equity Effects of Health Interventions in Cost-Effectiveness Analysis: A Systematic Review.

OBJECTIVE: This systematic review aims to catalogue and describe published applications of equity-informative cost-effectiveness analysis (CEAs). METHODS: Following PRISMA guidelines, we searched Medline for English-language, peer-reviewed CEAs published on or before August 2019. We included CEAs that evaluated 2 or more alternatives; explicitly mentioned equity as a consideration or decision-making principle; and applied an equity-informative CEA method to analyze or examine at least 1 equity criterion in an applied CEA. We extracted data on selected characteristics and analyzed reporting quality using the CHEERS checklist. RESULTS: Fifty-four articles identified through a search and bibliography reviews met the inclusion criteria. All articles were published on or after 2010, with 80% published after 2015. Most studies evaluated primary prevention interventions in disease areas such as cancer, infectious diseases, and cardiovascular disease. Equity impact analysis alone was the most common equity-informative CEA (56%), followed by equity impact analysis with financial protection effects (30%). At least 11 different equity criteria have been used in equity-informative CEAs; socioeconomic status and race/ethnicity were used most frequently. Seventy-eight percent of studies reported finding "greater value" in an intervention after examining its distributional effects. CONCLUSION: The number of equity-informative CEAs is increasing, and the wide range of equity criteria, diseases, interventions, settings, and populations represented suggests that broad application of these methods is feasible but will require further refinement. Inclusion of equity into CEAs may shift the value of evaluated interventions and can provide crucial additional information for decision makers.

A Cost-Effectiveness Analysis of Vaccination for Prevention of Herpes Zoster and Related Complications: Input for National Recommendations.

Background: The U.S. Advisory Committee on Immunization Practices recently developed recommendations for use of a new recombinant zoster vaccine (RZV). Objective: To evaluate the cost-effectiveness of vaccination with RZV compared with zoster vaccine live (ZVL) and no vaccination, the cost-effectiveness of vaccination with RZV for persons who have previously received ZVL, and the cost-effectiveness of preferential vaccination with RZV over ZVL. Design: Simulation (state-transition) model using U.S. epidemiologic, clinical, and cost data. Data Sources: Published data. Target Population: Hypothetical cohort of immunocompetent U.S. adults aged 50 years or older. Time Horizon: Lifetime. Perspective: Societal and health care sector. Intervention: Vaccination with RZV (recommended 2-dose regimen), vaccination with ZVL, and no vaccination. Outcome Measures: The primary outcome measure was the incremental cost-effectiveness ratio (ICER). Results of Base-Case Analysis: For vaccination with RZV compared with no vaccination, ICERs ranged by age from $10 000 to $47 000 per quality-adjusted life-year (QALY), using a societal perspective and assuming 100% completion of the 2-dose RZV regimen. For persons aged 60 years or older, ICERs were less than $60 000 per QALY. Vaccination with ZVL was dominated by vaccination with RZV for all age groups 60 years or older. Results of Sensitivity Analysis: Results were most sensitive to changes in vaccine effectiveness, duration of protection, herpes zoster incidence, and probability of postherpetic neuralgia. Vaccination with RZV after previous administration of ZVL yielded an ICER of less than $60 000 per QALY for persons aged 60 years or older. In probabilistic sensitivity analyses, RZV remained the preferred strategy in at least 95% of simulations, including those with 50% completion of the second dose. Limitation: Few data were available on risk for serious adverse events, adherence to the recommended 2-dose regimen, and probability of recurrent zoster. Conclusion: Vaccination with RZV yields cost-effectiveness ratios lower than those for many recommended adult vaccines, including ZVL. Results are robust over a wide range of plausible values. Primary Funding Source: Centers for Disease Control and Prevention.

Outcomes and Patterns of Healthcare Utilization After Hospitalization for Pediatric Critical Illness Due to Respiratory Failure.

OBJECTIVES: To quantify home care needs, healthcare utilization, and 2-year mortality after pediatric critical illness due to respiratory failure, and evaluate the impact of new morbidity and abnormal function at hospital discharge on resource use and outcomes. DESIGN: Retrospective cohort study. SETTING: Quaternary care PICU. PATIENTS: Patients less than or equal to 18 years with respiratory failure from January 1, 2013, to December 31, 2014. MEASUREMENTS AND MAIN RESULTS: Patient demographics, hospitalization characteristics, and healthcare utilization were quantified and compared according to morbidity development and discharge functional status. Multivariable regression methods evaluated 2-year readmission rates and mortality by morbidity development and discharge functional status. Of 163 patients, the median age was 2.1 years (interquartile range, 0.6-10.9 yr), 61 (37.4%) had a comorbidity, and 73 (44.8%) had abnormal function at admission. Median ventilation duration was 6.0 days (interquartile range, 3.0-11.7 d), and median PICU and hospital length of stay were 8 (interquartile range, 4-15) and 14 days (interquartile range, 8-23 d), respectively. At hospital discharge, eight of 163 (4.9%) had died, and 14 of 163 (8.6%) had a new morbidity. Of the surviving 155 patients at hospital discharge, 87 (56.1%) had abnormal function, 120 (77.4%) had new medications, 24 (15.5%) had new medical devices, and 43 (27.7%) had new home care equipment. Cumulative 2-year mortality was 14 of 163 (8.6%) with six of 163 (3.7%) occurring after discharge. Within 2 years, 81 of 155 of patients (52.2%) were readmitted, often (58/81, 71.6%) to the PICU. Abnormal function at discharge was associated with elevated odds of readmission to the hospital (odds ratio, 1.49; 1.28-1.74; p < 0.0001) and PICU (odds ratio, 1.47; 1.27-1.71; p < 0.0001) within 2 years. CONCLUSIONS: After critical illness, children have significant new healthcare burdens heretofore unrecognized. Abnormal functional status at hospital discharge was associated with increased healthcare utilization up to 2 years thereafter.

Priorities for Investing in Community Health Improvement: A Comparison of Decision Makers in Public Health, Nonprofit Hospitals, and Community Nonprofits.

CONTEXT: As a result of additional requirements for tax exemption, many nonprofit hospitals have become more actively involved in community health improvement. There is an open question, however, as to how decision makers in hospitals decide which kind of improvement projects should receive priority and how hospital managers' priorities compare with those of decision makers in public health agencies and community-based nonprofits. OBJECTIVE: To understand the priorities that guide decision makers in public health, nonprofit hospitals, and community nonprofits when allocating resources to community health projects. DESIGN: We conducted an online survey with a discrete choice experiment, asking respondents to choose between different types of community health projects, which varied along several project characteristics. Respondents included managers of community health and community benefit at nonprofit hospitals (n = 225), managers at local public health departments (n = 200), and leaders of community nonprofits (n = 136). Respondents were located in 47 of 50 US states. A conditional logit model was used to estimate how various project characteristics led to greater or lesser support of a given health project. Open-ended questions aided in interpretation of results. RESULTS: Respondents from all 3 groups showed strong agreement on community health priorities. Projects were more likely to be selected when they addressed a health issue identified on community health needs assessment, involved cross-sector collaboration, or were supported by evidence. Project characteristics that mattered less included the time needed to measure the project's impact and the project's target population. CONCLUSION: Elements often considered central to community health, such as long-term investment and prioritizing vulnerable populations, may not be considered by decision makers as important as other aspects of resource allocation. If we want greater priority for ideas such as health equity and social determinants of health, it will take a concerted effort from practitioners and policy makers to reshape expectations.

An Assessment of Public Preferences for Newborn Screening Using Best-Worst Scaling.

OBJECTIVE: To identify and quantify public preferences for attributes of newborn screening conditions. STUDY DESIGN: We conducted an online national survey of the public (n = 502) to evaluate preferences for attributes of candidate newborn screening conditions. Respondents were presented with hypothetical condition profiles that were defined using 10 attributes with 2-6 levels per attribute. Participants indicated whether they would recommend screening for a condition and which condition attributes were most and least important when making this decision (best-worst scaling). Difference scores were calculated and stratified by condition recommendation (recommend or not recommend for screening). Regression analyses were used to evaluate the effect of attributes on choice to screen or not screen. RESULTS: The number of babies diagnosed was important to those who would recommend newborn screening for a profile, and age at which the treatment would start was important to those who would not recommend newborn screening. Cost was considered to be a key attribute, and treatment effectiveness and impact of making the diagnosis through newborn screening were of low importance for both groups. CONCLUSION: Public preferences identified through survey methods that provide an adequate baseline understanding of newborn screening can be used to inform newborn screening decisions.

Application of a Discrete Choice Experiment to Assess Adherence-Related Motivation Among Adolescents and Young Adults With Cancer.

Objective: To develop and pilot test a discrete choice experiment (DCE) to assess the specific factors likely to motivate a given adolescent or young adult with cancer to adhere to medications included in treatment protocols. Methods: A multimethod and iterative approach was used. Twenty adolescents and young adults with cancer participated in DCE pilot testing and refinement. Hierarchical Bayes was used to estimate attribute and attribute-level preference scores for each participant. Results: The final DCE included nine choice sets composed of four attributes. The resulting DCE was modified with feedback from 20 adolescents and young adults (M[SD] age = 18.66 [2.95]) with cancer. The DCE was understandable and relevant. The factors likely to motivate adolescents and young adults with cancer to be adherent differed across individuals. Conclusions: DCEs including the measure developed in this manuscript offer a novel approach to understanding individual-level differences critical for informing adherence-promotion efforts.

The role of severity perceptions and beliefs in natural infections in Shanghai parents' vaccine decision-making: a qualitative study.

BACKGROUND: China has reduced incidence of vaccine-preventable diseases through its Expanded Program on Immunization (EPI). Vaccines outside of the EPI are not provided for free by the government, however. This study explored how the stated importance of different disease and vaccine-related attributes interacted with beliefs about the immune system of a child to affect Chinese parents' decision to obtain a non-EPI vaccine. METHODS: Mothers and fathers of young children at immunization clinics in Shanghai, China, were interviewed about vaccine decision-making and what attributes of a disease were important when making this decision. An inductive thematic analysis explored their beliefs about disease attributes and how these related to vaccination decisions. RESULTS: Among the 34 interviews, severity of the disease-particularly in causing long-term disability-was the most commonly cited factor influencing a parent's decision to get a vaccine for their child. Many parents believed that natural infection was preferable to vaccination, as long as disease was not severe, and many were concerned that imported vaccines were inadequate for Chinese children's physical constitutions. All these beliefs could influence the decision to vaccinate. CONCLUSIONS: Many parents do not appear to understand how and why vaccines can support development of a healthy immune system. Because severity emerged as parents' overriding concern when making decisions about vaccines, marketing for a childhood vaccine could focus on the severe condition that a vaccine can protect against.

Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation.

The secretary of the US Department of Health and Human Services in February 2016 recommended that X-linked adrenoleukodystrophy (X-ALD) be added to the recommended uniform screening panel for state newborn screening programs. This decision was informed by data presented on the accuracy of screening from New York, the only state that currently offers X-ALD newborn screening, and published and unpublished data showing health benefits of earlier treatment (hematopoietic stem cell transplantation and adrenal hormone replacement therapy) for the childhood cerebral form of X-ALD. X-ALD newborn screening also identifies individuals with later-onset disease, but poor genotype-phenotype correlation makes predicting health outcomes difficult and might increase the risk of unnecessary treatment. Few data are available regarding the harms of screening and presymptomatic identification. Significant challenges exist for implementing comprehensive X-ALD newborn screening, including incorporation of the test, coordinating follow-up diagnostic and treatment care, and coordination of extended family testing after case identification.Genet Med 19 1, 121-126.

Hospital-level variation in inpatient cost among children receiving extracorporeal membrane oxygenation.

OBJECTIVE: Pediatric extracorporeal membrane oxygenation (ECMO) varies in the way care is provided from hospital to hospital. This variability in hospital ECMO care can be represented by the variation in ECMO costs. We hypothesized that hospitals will demonstrate large variations in case-mix-adjusted ECMO inpatient costs for children requiring ECMO and higher volume hospitals will have lower associated costs. METHODS: We retrospectively analyzed the inpatient cost of children receiving ECMO in 2006, 2009 and 2012, using the Healthcare Cost and Utilization Project Kids' Inpatient Database. We used a hierarchical linear regression model and the intraclass correlation coefficient to quantify how much of the difference in ECMO inpatient costs was associated with the hospital where a child received care. To do this, we adjusted for patient factors, hospital factors and potentially modifiable factors such as complications, procedures and length of stay. RESULTS: The median inflation-adjusted inpatient costs for children requiring ECMO were $183,000, $240,000 and $241,000 in years 2006, 2009 and 2012, respectively. The largest median cost for ECMO cases in a given hospital in a given year ($690,000) was more than 11 times that of the smallest median cost ($60,000). After case-mix adjustment, 27% of the variation in inpatient costs was associated with the hospital where ECMO care was provided. Average hospital costs were not associated with hospital ECMO volume. CONCLUSIONS: The large variation in ECMO inpatient costs between hospitals suggests great variation in care between hospitals, which is important because hospitals have a co-existing variation in ECMO survival rates.

Evaluating Harms in the Assessment of Net Benefit: A Framework for Newborn Screening Condition Review.

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.

Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine.

IMPORTANCE: Since publication of the report by the Panel on Cost-Effectiveness in Health and Medicine in 1996, researchers have advanced the methods of cost-effectiveness analysis, and policy makers have experimented with its application. The need to deliver health care efficiently and the importance of using analytic techniques to understand the clinical and economic consequences of strategies to improve health have increased in recent years. OBJECTIVE: To review the state of the field and provide recommendations to improve the quality of cost-effectiveness analyses. The intended audiences include researchers, government policy makers, public health officials, health care administrators, payers, businesses, clinicians, patients, and consumers. DESIGN: In 2012, the Second Panel on Cost-Effectiveness in Health and Medicine was formed and included 2 co-chairs, 13 members, and 3 additional members of a leadership group. These members were selected on the basis of their experience in the field to provide broad expertise in the design, conduct, and use of cost-effectiveness analyses. Over the next 3.5 years, the panel developed recommendations by consensus. These recommendations were then reviewed by invited external reviewers and through a public posting process. FINDINGS: The concept of a "reference case" and a set of standard methodological practices that all cost-effectiveness analyses should follow to improve quality and comparability are recommended. All cost-effectiveness analyses should report 2 reference case analyses: one based on a health care sector perspective and another based on a societal perspective. The use of an "impact inventory," which is a structured table that contains consequences (both inside and outside the formal health care sector), intended to clarify the scope and boundaries of the 2 reference case analyses is also recommended. This special communication reviews these recommendations and others concerning the estimation of the consequences of interventions, the valuation of health outcomes, and the reporting of cost-effectiveness analyses. CONCLUSIONS AND RELEVANCE: The Second Panel reviewed the current status of the field of cost-effectiveness analysis and developed a new set of recommendations. Major changes include the recommendation to perform analyses from 2 reference case perspectives and to provide an impact inventory to clarify included consequences.