Performance of a computable phenotype for identification of patients with diabetes within PCORnet: The Patient-Centered Clinical Research Network.

PURPOSE: PCORnet, the National Patient-Centered Clinical Research Network, represents an innovative system for the conduct of observational and pragmatic studies. We describe the identification and validation of a retrospective cohort of patients with type 2 diabetes (T2DM) from four PCORnet sites. METHODS: We adapted existing computable phenotypes (CP) for the identification of patients with T2DM and evaluated their performance across four PCORnet sites (2012-2016). Patients entered the cohort on the earliest date they met one of three CP categories: (CP1) coded T2DM diagnosis (ICD-9/ICD-10) and an antidiabetic prescription, (CP2) diagnosis and glycosylated hemoglobin (HbA1c) ≥6.5%, or (CP3) an antidiabetic prescription and HbA1c ≥6.5%. We required evidence of health care utilization in each of the 2 prior years for each patient, as we also developed an incident T2DM CP to identify the subset of patients without documentation of T2DM in the 365 days before t0 . Among a systematic sample of patients, we calculated the positive predictive value (PPV) for the T2DM CP and incident-T2DM CP using electronic health record (EHR) review as reference. RESULTS: The CP identified 50 657 patients with T2DM. The PPV of patients randomly selected for validation was 96.2% (n = 1572; CI:95.1-97.0) and was consistently high across sites. The PPV for the incident-T2DM CP was 5.8% (CI:4.5-7.5). CONCLUSIONS: The T2DM CP accurately and efficiently identified patients with T2DM across multiple sites that participate in PCORnet, although the incident T2DM CP requires further study. PCORnet is a valuable data source for future epidemiological and comparative effectiveness research among patients with T2DM.

Uncovering Outcome Disparities of ß2 Adrenergic Agonists in Blacks: A Systematic Review.

PURPOSE: Outcome differences driven by variation in Blacks' biologic response to treatment may contribute to persistent racial disparities in asthma morbidity and mortality. This review assessed systematic variation in ß2 agonist treatment outcomes among Blacks compared to other groups. METHODS: We conducted a systematic review of studies reporting differential response to ß2 agonists among Blacks, including studies identifying pharmacogenetic variants. RESULTS: Of 3158 papers, 20 compared safety or efficacy of ß2 agonists among Blacks as compared with other subgroups. Six papers evaluating efficacy of short-acting ß2 agonists (SABA) found similar or improved results among Blacks compared with other groups, while one small study found reduced response to SABA therapy among Blacks. Reports of safety and efficacy of long-acting ß2 agonists (LABA) indicated similar results among Blacks in four papers, while four reports found reduced safety among Blacks, as compared with other groups. Four papers assessed genomic variation and relative treatment response in Blacks, with two finding significant effects of the p.Arg16Gly variant in ADRB2 on ß2 agonist response and one finding significant gene-gene IL6/IL6R interaction effects on albuterol response. CONCLUSIONS: Evidence suggests the potential for differences in ß2 agonist outcomes among Blacks compared with other groups. This literature, however, remains small and significantly underpowered for substantive conclusions. There are notable opportunities for adequately-powered investigations exploring safety and efficacy of ß2 agonists among Blacks, including pharmacogenomic modifiers of response.

Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

Purpose: Management of schizophrenia among Blacks in the United States is affected by persistent disparities. This review explored response to atypical antipsychotics among Blacks compared with other groups to assess systematic variation that may contribute to disparities. Methods: We conducted a quasi-systematic review of studies reporting response to atypical antipsychotics among Blacks compared with other groups, including effects of genetic variation. Results: Of 48 identified research articles, 29 assessed differences in outcomes without inclusion of genetic variation and 20 explored effects of genetic variation; of note: one article included both types of data. Analysis of the 29 papers with clinical outcomes only suggests that while data on efficacy and risk of movement disorders were heterogeneous, findings indicate increased risk of metabolic effects and neutropenia among Blacks. Of the 20 articles exploring effects of genetic variation, allelic or genotypic variations involving several genes were associated with altered efficacy or safety among Blacks but not Whites, including risk of decreased response involving variation in DRD4 and DRD1, and improved efficacy associated with variants in DRD2, COMT, and RGS4. Others showed significant improvement in treatment response only among Whites, including variation in DTNBP1, DRD4, and GNB3. Conclusions: The current analysis can help tailor management among Blacks using an atypical antipsychotic. Heterogeneity in genetic variation effects and response allele frequency suggests that pharmacogenetics approaches for atypical antipsychotics will need to explicitly incorporate race and ethnicity.