Development and evaluation of a common data model enabling active drug safety surveillance using disparate healthcare databases.

OBJECTIVE: Active drug safety surveillance may be enhanced by analysis of multiple observational healthcare databases, including administrative claims and electronic health records. The objective of this study was to develop and evaluate a common data model (CDM) enabling rapid, comparable, systematic analyses across disparate observational data sources to identify and evaluate the effects of medicines. DESIGN: The CDM uses a person-centric design, with attributes for demographics, drug exposures, and condition occurrence. Drug eras, constructed to represent periods of persistent drug use, are derived from available elements from pharmacy dispensings, prescriptions written, and other medication history. Condition eras aggregate diagnoses that occur within a single episode of care. Drugs and conditions from source data are mapped to biomedical ontologies to standardize terminologies and enable analyses of higher-order effects. MEASUREMENTS: The CDM was applied to two source types: an administrative claims and an electronic medical record database. Descriptive statistics were used to evaluate transformation rules. Two case studies demonstrate the ability of the CDM to enable standard analyses across disparate sources: analyses of persons exposed to rofecoxib and persons with an acute myocardial infarction. RESULTS: Over 43 million persons, with nearly 1 billion drug exposures and 3.7 billion condition occurrences from both databases were successfully transformed into the CDM. An analysis routine applied to transformed data from each database produced consistent, comparable results. CONCLUSION: A CDM can normalize the structure and content of disparate observational data, enabling standardized analyses that are meaningfully comparable when assessing the effects of medicines.

Semi-automated risk estimation using large databases: quinolones and Clostridium difficile associated diarrhea.

PURPOSE: The availability of large databases with person time information and appropriate statistical methods allow for relatively rapid pharmacovigilance analyses. A semi-automated method was used to investigate the effect of fluoroquinolones on the incidence of C. difficile associated diarrhea (CDAD). METHODS: Two US databases, an electronic medical record (EMR) and a large medical claims database for the period 2006-2007 were evaluated using a semi-automated methodology. The raw EMR and claims datasets were subject to a normalization procedure that aligns the drug exposures and conditions using ontologies; Snowmed for medications and MedDRA for conditions. A retrospective cohort design was used together with matching by means of the propensity score. The association between exposure and outcome was evaluated using a Poisson regression model after taking into account potential confounders. RESULTS: A comparison between quinolones as the target cohort and macrolides as the comparison cohort produced a total of 564,797 subjects exposed to a quinolone in the claims data and 233,090 subjects in the EMR. They were matched with replacement within six strata of the propensity score. Among the matched cohorts there were a total of 488 and 158 outcomes in the claims and the EMR respectively. Quinolones were found to be twice more likely to be significantly associated with CDAD than macrolides adjusting for risk factors (IRR 2.75, 95%CI 2.18-3.48). CONCLUSIONS: Use of a semi-automated method was successfully applied to two observational databases and was able to rapidly identify a potential for increased risk of developing CDAD with quinolones.

Surfactant replacement for ventilator-associated pneumonia: a preliminary report.

BACKGROUND: Surfactant abnormalities have been described in bacterial pneumonia. OBJECTIVE: To determine the safety and effect of exogenous surfactant replacement in patients with ventilator-associated pneumonia (VAP). METHODS: Patients with VAP were randomized in a double-blind study to receive either an artificial surfactant (Exosurf) consisting mostly of disaturated phospholipids (DSPL) or saline via a continuous nebulizer system for 5 days. Patients underwent bronchoscopy and bronchoalveolar lavage (BAL) prior to and after 4 days of therapy. RESULTS: Twenty-two patients were randomized, with 8 receiving Exosurf. There was no detected difference in outcome between the saline- and Exosurf-treated patients in terms of days on ventilator, 30-day or hospital mortality. At the follow-up lavage, the patients treated with Exosurf had a significant rise in the level of DSPL (p < 0.05), while the saline group did not, suggesting delivery of drug. Also at the follow-up lavage, the percentage of neutrophils in the BAL fell in the Exosurf patients (p < 0.01), but not in the saline group. CONCLUSION: Exogenous surfactant replacement given to patients with VAP increased the amount of DSPL retrieved by BAL. This treatment was associated with a fall in the neutrophil response to pneumonia.