Improving the value of clinical research through the use of Common Data Elements.

The use of Common Data Elements can facilitate cross-study comparisons, data aggregation, and meta-analyses; simplify training and operations; improve overall efficiency; promote interoperability between different systems; and improve the quality of data collection. A Common Data Element is a combination of a precisely defined question (variable) paired with a specified set of responses to the question that is common to multiple datasets or used across different studies. Common Data Elements, especially when they conform to accepted standards, are identified by research communities from variable sets currently in use or are newly developed to address a designated data need. There are no formal international specifications governing the construction or use of Common Data Elements. Consequently, Common Data Elements tend to be made available by research communities on an empiric basis. Some limitations of Common Data Elements are that there may still be differences across studies in the interpretation and implementation of the Common Data Elements, variable validity in different populations, and inhibition by some existing research practices and the use of legacy data systems. Current National Institutes of Health efforts to support Common Data Element use are linked to the strengthening of National Institutes of Health Data Sharing policies and the investments in data repositories. Initiatives include cross-domain and domain-specific resources, construction of a Common Data Element Portal, and establishment of trans-National Institutes of Health working groups to address technical and implementation topics. The National Institutes of Health is seeking to lower the barriers to Common Data Element use through greater awareness and encourage the culture change necessary for their uptake and use. As National Institutes of Health, other agencies, professional societies, patient registries, and advocacy groups continue efforts to develop and promote the responsible use of Common Data Elements, particularly if linked to accepted data standards and terminologies, continued engagement with and feedback from the research community will remain important.

Mortality of New York children with sickle cell disease identified through newborn screening.

PURPOSE: Long-term follow-up of newborn screening for conditions such as sickle cell disease can be conducted using linkages to population-based data. We sought to estimate childhood sickle cell disease mortality and risk factors among a statewide birth cohort with sickle cell disease identified through newborn screening. METHODS: Children with sickle cell disease identified by newborn screening and born to New York residents in 2000-2008 were matched to birth and death certificates. Mortality rates were calculated (using numbers of deaths and observed person-years at risk) and compared with mortality rates for all New York children by maternal race/ethnicity. Stratified analyses were conducted to examine associations between selected factors and mortality. RESULTS: Among 1,911 infants with sickle cell disease matched to birth certificates, 21 deaths were identified. All-cause mortality following diagnosis was 3.8 per 1,000 person-years in the first 2 years of life and 1.0 per 1,000 person-years at ages 2-9 years. The mortality rate was significantly lower among children of foreign-born mothers and was significantly higher among preterm infants with low birth weight. The mortality rates were not significantly higher for infants after 28 days with sickle cell disease than for all New York births, but they were 2.7-8.4 times higher for children 1 through 9 years old with homozygous sickle cell disease than for those of all non-Hispanic black or Hispanic children born to New York residents. CONCLUSION: Estimated mortality risk in children with homozygous sickle cell disease remains elevated even after adjustment for maternal race/ethnicity. These results provide evidence regarding the current burden of child mortality among children with sickle cell disease despite newborn screening.Genet Med 17 6, 452-459.

State-based surveillance for selected hemoglobinopathies.

PURPOSE: The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies. METHODS: The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004-2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information. RESULTS: In total, 31,144 individuals who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina. CONCLUSION: This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems.

Patient reports of health outcome for adults living with sickle cell disease: development and testing of the ASCQ-Me item banks.

BACKGROUND: Providers and patients have called for improved understanding of the health care requirements of adults with sickle cell disease (SCD) and have identified the need for a systematic, reliable and valid method to document the patient-reported outcomes (PRO) of adult SCD care. To address this need, the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) was designed to complement the Patient Reported Outcome Measurement Information System (PROMIS®). Here we describe methods and results of the psychometric evaluation of ASCQ-Me item banks (IBs). METHODS: At seven geographically-disbursed clinics within the US, 556 patients responded to questions generated to assess cognitive, emotional, physical and social impacts of SCD. We evaluated the construct validity of the hypothesized domains using exploratory factor analysis (EFA), parallel analysis (PA), and bi-factor analysis (Item Response Theory Graded Response Model, IRT-GRM). We used IRT-GRM and the Wald method to identify bias in responses across gender and age. We used IRT and Cronbach's alpha coefficient to evaluate the reliability of the IBs and then tested the ability of summary scores based on IRT calibrations to discriminate among tertiles of respondents defined by SCD severity. RESULTS: Of the original 140 questions tested, we eliminated 48 that either did not form clean factors or provided biased measurement across subgroups defined by age and gender. Via EFA and PA, we identified three subfactors within physical impact: sleep, pain and stiffness impacts. Analysis of the resulting six item sets (sleep, pain, stiffness, cognitive, emotional and social impacts of SCD) supported their essential unidimensionality. With the exception of the cognitive impact IB, these item sets also were highly reliable across a broad range of values and highly significantly related to SCD disease severity. CONCLUSION: ASCQ-Me pain, sleep, stiffness, emotional and social SCD impact IBs demonstrated exceptional measurement properties using modern and classical psychometric methods of evaluation. Further development of the cognitive impact IB is required to improve its sensitivity to differences in SCD disease severity. Future research will evaluate the sensitivity of the ASCQ-Me IBs to change in SCD disease severity over time due to health interventions.

A vast icefish breeding colony discovered in the Antarctic.

A breeding colony of notothenioid icefish (Neopagetopsis ionah, Nybelin 1947) of globally unprecedented extent has been discovered in the southern Weddell Sea, Antarctica. The colony was estimated to cover at least ∼240 km2 of the eastern flank of the Filchner Trough, comprised of fish nests at a density of 0.26 nests per square meter, representing an estimated total of ∼60 million active nests and associated fish biomass of >60,000 tonnes. The majority of nests were each occupied by 1 adult fish guarding 1,735 eggs (±433 SD). Bottom water temperatures measured across the nesting colony were up to 2°C warmer than the surrounding bottom waters, indicating a spatial correlation between the modified Warm Deep Water (mWDW) upflow onto the Weddell Shelf and the active nesting area. Historical and concurrently collected seal movement data indicate that this concentrated fish biomass may be utilized by predators such as Weddell seals (Leptonychotes weddellii, Lesson 1826). Numerous degraded fish carcasses within and near the nesting colony suggest that, in death as well as life, these fish provide input for local food webs and influence local biogeochemical processing. To our knowledge, the area surveyed harbors the most spatially expansive continuous fish breeding colony discovered to date globally at any depth, as well as an exceptionally high Antarctic seafloor biomass. This discovery provides support for the establishment of a regional marine protected area in the Southern Ocean under the Convention on the Conservation of Antarctic Marine Living Resources (CCAMLR) umbrella. VIDEO ABSTRACT.

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain.

To address the global burden of sickle cell disease (SCD) 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 outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Standard measures for sickle cell disease research: the PhenX Toolkit sickle cell disease collections.

Standard measures and common data elements for sickle cell disease (SCD) will improve the data quality and comparability necessary for cross-study analyses and the development of guidelines that support effective treatments and interventions. In 2014, the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) funded an Administrative Supplement to the PhenX Toolkit (consensus measures for Phenotypes and eXposures; https://www.phenxtoolkit.org/) to identify common measures to promote data comparability across SCD research. An 11-member Sickle Cell Disease Research and Scientific Panel provided guidance to the project, establishing a core collection of SCD-related measures and defining the scope of 2 specialty collections: (1) cardiovascular, pulmonary, and renal complications, and (2) neurology, quality-of-life, and health services. For each specialty collection, a working group of SCD experts selected high-priority measures using a consensus process that included scientific community input. The SCD measures were released into the Toolkit in August 2015. The 25 measures included in the core collection are recommended for use by all NHLBI-funded investigators performing human-subject SCD research. The 10 neurology, quality-of-life, and health services measures and 14 cardiovascular, pulmonary, and renal measures are recommended for use within these specialized research areas. For SCD and other researchers, PhenX measures will promote collaborations with clinicians and patients, facilitate cross-study analysis, accelerate translational research, and lead to greater understanding of SCD phenotypes and epigenetics. For clinicians, using PhenX measures will help elucidate the etiology, progression, and treatment of SCD, leading to improved patient care and quality of life.

Quality of care in sickle cell disease: Cross-sectional study and development of a measure for adults reporting on ambulatory and emergency department care.

Documented deficiencies in adult sickle cell disease (SCD) care include poor access to knowledgeable providers and inadequate treatment in emergency departments (EDs).The aim of this study was to create patient-reported outcome measures of the quality of ambulatory and ED care for adults with SCD.We developed and pilot tested SCD quality of care questions consistent with Consumer Assessments of Healthcare Providers and Systems surveys. We applied psychometric methods to develop scores and evaluate reliability and validity.The participants of this study were adults with SCD (n = 556)-63% aged 18 to 34 years; 64% female; 64% SCD-SS-at 7 US sites.The measure used was Adult Sickle Cell Quality of Life Measurement information system Quality of Care survey.Most participants (90%) reported at least 1 severe pain episode (pain intensity 7.8 ±â€Š2.3, 0-10 scale) in the past year. Most (81%) chose to manage pain at home rather than the ED, citing negative ED experiences (83%). Using factor analysis, we identified Access, Provider Interaction, and ED Care composites with reliable scores (Cronbach α 0.70-0.83) and construct validity (r = 0.32-0.83 correlations with global care ratings). Compared to general adult Consumer Assessments of Healthcare Providers and Systems scores, adults with SCD had worse care, adjusted for age, education, and general health.Results were consistent with other research reflecting deficiencies in ED care for adults with SCD. The Adult Sickle Cell Quality of Life Measurement Quality of Care measure is a useful self-report measure for documenting and tracking disparities in quality of SCD care.

Differences in Hemoglobin A1c Between Hispanics/Latinos and Non-Hispanic Whites: An Analysis of the Hispanic Community Health Study/Study of Latinos and the 2007-2012 National Health and Nutrition Examination Survey.

OBJECTIVE: To determine whether, after adjustment for glycemia and other selected covariates, hemoglobin A1c (HbA1c) differed among adults from six Hispanic/Latino heritage groups (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) and between Hispanic/Latino and non-Hispanic white adults without self-reported diabetes. RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of data from 13,083 individuals without self-reported diabetes from six Hispanic/Latino heritage groups, enrolled from 2008 to 2011 in the Hispanic Community Health Study/Study of Latinos, and 2,242 non-Hispanic white adults enrolled during the 2007-2012 cycles of the National Health and Nutrition Examination Survey. We compared HbA1c levels among Hispanics/Latinos and between Hispanics/Latinos and non-Hispanic whites before and after adjustment for age, sex, fasting (FPG) and 2-h post-oral glucose tolerance test (2hPG) glucose, anthropometric measurements, and selected biochemical and hematologic variables and after stratification by diabetes status: unrecognized diabetes (FPG ≥7.1 mmol/L or 2hPG ≥11.2 mmol/L), prediabetes (FPG 5.6-7.0 mmol/L or 2hPG 7.8-11.1 mmol/L), and normal glucose tolerance (FPG <5.6 mmol/L and 2hPG <7.8 mmol/L). RESULTS: Adjusted mean HbA1c differed significantly across all seven groups (P < 0.001). Non-Hispanic whites had significantly lower HbA1c (P < 0.05) than each individual Hispanic/Latino heritage group. Upon stratification by diabetes status, statistically significant differences (P < 0.001) in adjusted mean HbA1c persisted across all seven groups. CONCLUSIONS: HbA1c differs among Hispanics/Latinos of diverse heritage groups and between non-Hispanic whites and Hispanics/Latinos after adjustment for glycemia and other covariates. The clinical significance of these differences is unknown.

11 month-old twins with food avoidance.

CASE: Maggie and Lily are 11 month-old twins who are brought by their parents to the Developmental-Behavioral Pediatric Clinic for a life-long history of feeding difficulties. The twins are this couple's first children. Their mother is tearful as she recounts a stressful pregnancy complicated by pre-term labor beginning at 24 weeks gestation with strict bed rest for the remainder of the pregnancy. The twins were delivered at 35 weeks gestation by Caesarian Section. Lily weighed 5 lbs 11 oz; Maggie was small-for-gestational age with a birth weight of 3 lbs 13 oz. Maggie required oxygen with nasal prongs for only a few hours after birth. She remained in the Neonatal Intensive Care Unit (NICU) with initial nasogastric tube feeding; she was advanced to bottle feeding prior to discharge. Both Maggie and Lily were slow to initiate and sustain formula feeding. They required over 1 hour to consume 2 ounces of formula and "tire easily". At 1 month of age, Maggie resisted feedings by crying and arching her back. By 5 months of age, both children cried at the sight of the bottle and tried to push it away. However, they never lost weight. Maggie was treated with intermittent naso-gastric tube feeding at 5-6 months of age in order to gain adequate weight. At 11 months of age, both girls continued to resist feeding, but their mother was able to "get in" 24 ounces each day of a 31-calorie/ounce formula "with a lot of work". Dad observed that his wife's entire day revolved around getting the twins to eat and that became a significant stress for her as well as on their relationship. The children had a gastroenterology evaluation including an upper gastrointestinal series, pH probe and gastro-duodenal endoscopy with biopsies. All studies were normal. Trials of omeprazole, metoclopramide and thickened feeds did not improve their feeding problem. They are currently not on any medications. They have not had a history of vomiting, diarrhea, or diaphoresis with feeds, and they have experienced only 1 mild upper respiratory infection. One or two soft bowel movements occur each day. Developmentally, they are on track for their age. The parents report that they can pull up to a stand and cruise, use a pincer grasps, and speak "mama" discriminately. A review of their growth charts reveal that their weight is consistently between the 10-25% percentiles; weight is currently at the 25% percentile. Head circumference and height are between the 25-50% percentiles.

Enhancing measurement in health outcomes research supported by Agencies within the US Department of Health and Human Services.

Many of the Institutes, Agencies and Centers that make up the US Department of Health and Human Services (DHHS) have recognized the need for better instrumentation in health outcomes research, and provide support, both internally and externally, for research utilizing advances in measurement theory and computer technology (informatics). In this paper, representatives from several DHHS agencies and institutes will discuss their need for better instruments within their discipline and describe current or future initiatives for exploring the benefits of these technologies. Together, the perspectives underscore the importance of developing valid, precise, and efficient measures to capture the full burden of disease and treatment on patients. Initiatives, like the Patient-Reported Outcomes Measurement Information System (PROMIS) to create health-related quality of life item banks, represent a trans-DHHS effort to develop a standard set of measures for informing decision making in clinical research, practice, and health policy.

Hematology grants workshop.

Uppermost among the many concerns of young researchers is acquiring funding for beginning a career as a clinician-scientist. This chapter is targeted specifically at those individuals considering an academic physician-scientist career and those on the verge of becoming independent researchers. In Section I, Drs. Poncz and Iannone discuss the Mentored Career Development Award (K08). They summarize the application process, highlighting the critical components of a successful application and what the review process entails. In Section II, Dr. Werner discusses what applicants need to know about the NIH Institutes' program, review, and grants management function; the different NIH staff whom applicants should contact during the various stages of the grants process; and the important sections and key phrases in NIH Program Announcements for career development awards.