A national data infrastructure for patient-centered outcomes research.

Concerted efforts are underway to improve healthcare decision-making through patient-centered outcomes research. These efforts are supported by the Patient-Centered Outcomes Research Trust Fund, which was established within the Patient Protection and Affordable Care Act. This article focuses on describing national data infrastructure efforts that support patient-centered outcomes research. A national data infrastructure has the potential to decrease research costs and improve research throughput. We describe early and current efforts that demonstrated this potential, how the national effort is utilizing the lessons learned from these predecessor efforts and remaining challenges.

The ARRA investment in CER: a description of the midstream evaluation and how the funds were allocated and CER priorities addressed.

AIM: To describe the evaluation design of the American Recovery and Reinvestment Act of 2009 comparative effectiveness research (CER) investment, how funds were allocated and how CER priorities were addressed. MATERIALS & METHODS: Primary and secondary data included information from redacted project proposals, an investigator survey and federal project officers, investigators and expert panel discussions. RESULTS: More than 420 projects (US$1.1 billion) were awarded. Those generating new or synthesizing existing CER made up the plurality (194, or US$524 million). Data infrastructure projects were the second-largest area (28%, US$302 million). More than three-fourths addressed at least one priority population, condition category or intervention category. CONCLUSION: These investments expanded the nation's CER activities and its future capacity to conduct CER.

Assessing the long-term impact of public investments in comparative effectiveness research: conceptual framework and lessons learned.

The American Recovery and Reinvestment Act (ARRA) of 2009 directed US$1.1 billion to the US Department of Health and Human Services for support of comparative effectiveness research (CER). As part of this investment, US Department of Health and Human Services commissioned a midstream evaluation of the ARRA CER portfolio. One goal of the evaluation was to identify issues to consider for a future evaluation of the long-term impact of this portfolio and other CER investments. In planning the ARRA CER evaluation, we developed and revised a conceptual framework and related policy research questions that may be useful to future efforts to assess the impact of CER or patient-centered outcomes research investments. In addition, we explored methodological challenges related to designing an evaluation to assess investments in CER that may be informative to any future plans to evaluate the long-term impact of ARRA CER as well subsequent investments made from the Patient-Centered Outcomes Research Trust Fund.

Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.

Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology.

There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.

Messages about black-box warnings: a comparative analysis of reports from the FDA and lay media in the US.

BACKGROUND: The US FDA and lay media are important sources of information for the public about the risks of adverse events associated with drugs, yet the quality of FDA and US lay media reports about medication 'black-box' warnings, which highlight potentially severe adverse events from medications, is unknown. OBJECTIVE: To determine and compare the content of FDA and US lay media reports about medication black-box warnings. METHODS: We assessed FDA and US lay media reports about medication black-box warnings published or aired between 1 January 2003 and 31 December 2007 for the presence of six core message components, including (i) the affected drug's brand name; (ii) generic name; (iii) treatment indication; (iv) reason for the black-box warning; (v) clinical recommendations for patients, such as warning signs and symptoms of the adverse effect addressed by the black-box warning; and (vi) encouragement to discuss the issue with a healthcare provider, and additional characteristics. RESULTS: FDA reports presented more core information than lay media reports (median 5 vs 3 message components; p < 0.001). FDA reports were more likely to mention generic names (84.6% vs 18.1%; p < 0.001) of affected drugs, while lay media reports less frequently detailed clinical recommendations for patients (43.9% vs 96.2%; p < 0.001). Only 10.6% of lay media reports encouraged patients to seek additional information from their healthcare provider, compared with 48.1% of FDA reports (p < 0.001). CONCLUSIONS: FDA and US lay media reports about medication black-box warnings presented different information. This may reflect a difference in underlying motivation for reporting of news about risks of adverse drug events. It may also indicate a lack of agreement and understanding about the best methods to communicate risk information to the public, thus indicating areas for future research.

Process quality measures and asthma exacerbations in the medicaid population.

BACKGROUND: Asthma quality assessment often focuses on controller medication use, yet claims-based studies find conflicting associations between this care process and clinical outcomes. OBJECTIVE: We sought to compare the association between 3 controller-based quality measures and asthma exacerbations to gain better understanding of how processes of care are related to clinical outcomes. METHODS: Identifying a cohort of Medicaid beneficiaries with persistent asthma by using Healthcare Effectiveness Data and Information Set (HEDIS) criteria for asthma in 2001-2002 in California and New York, we assessed 3 asthma quality metrics in 2002: (1) the current HEDIS measure of at least 1 controller medication filling; (2) at least 4 controller medication prescription fillings; and (3) a controller-to-total asthma medication ratio of at least 0.5. We calculated the odds of having an asthma exacerbation in 2003 as a function of performance on each quality metric, adjusting for race, sex, age, and prior outpatient and acute care use for asthma. RESULTS: Of 90,909 subjects with persistent asthma in California (48.1%) and New York (51.9%), those who obtained at least 1 or at least 4 controller medications had increased likelihood of poor outcomes (adjusted odds ratios, 1.80 [95% CI, 1.73-1.87] and 1.44 [95% CI 1.40-1.48], respectively). Beneficiaries meeting the controller-to-total asthma medication ratio measure were 23.0% less likely to have exacerbations (adjusted odds ratio, 0.77 [95% CI, 0.75-0.80]). CONCLUSIONS: A higher controller medication ratio indicated a lower likelihood of asthma exacerbations, whereas assessing the number of controller medication-dispensing events was associated with a higher odds of exacerbation.

Use of sirolimus in IPEX and IPEX-like children.

INTRODUCTION: IPEX (immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome), a rare inflammatory disease caused by mutations of Foxp3, destroys the immunoregulatory environment of affected male infants. Data on optimal therapy are limited. METHODS: We reviewed the effect of sirolimus use in our cohort of IPEX and IPEX-like patients (n = 7). RESULTS AND DISCUSSION: Our patients exhibited features of enteropathy and recurrent infections with bacterial and viral pathogens. Before initiating sirolimus, six patients were treated with corticosteroids. Several also received other immunosuppressive agents. After starting sirolimus, six patients had improvement in diarrhea, and two were able to decrease corticosteroid dosages. Several also had significantly decreased number of infections after treatment. Of the three patients with post-treatment duodenal biopsies, two showed improvement in villous architecture. No significant adverse events occurred. Our experience suggests that sirolimus is a clinically effective and safe therapeutic option in IPEX and IPEX-like patients.