Abraham G. Hartzema

Advancing the Science for Active Surveillance: Rationale and Design for the Observational Medical Outcomes Partnership

The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 mandated that the FDA develop a system for using automated health care data to identify risks of marketed drugs and other medical products. The Observational Medical Outcomes Partnership is a public-private partnership among the FDA, academia, data owners, and the pharmaceutical industry that is responding to the need to advance the science of active medical product safety surveillance by using existing observational databases. The Observational Medical Outcomes Partnerships transparent, open innovation approach is designed to systematically and empirically study critical governance, data resource, and methodological issues and their interrelationships in establishing a viable national program of active drug safety surveillance by using observational data. This article describes the governance structure, data-access model, methods-testing approach, and technology development of this effort, as well as the work that has been initiated.

Disability Measures in Stroke Relationship Among the Barthel Index, the Functional Independence Measure, and the Modified Rankin Scale

Background and Purpose— Residual disability after stroke presents a major economic and humanistic burden. To quantify disability in patients, activities of daily living (ADL; Barthel Index [BI], and motor component of Functional Independence Measure [M-FIM]) and categorical disability measures (Modified Rankin Scale [MRS]) are used. The purpose of this study is to examine the predicting ability of ADL measures to global disability scale. Methods— Kansas City Stroke Study data were used for the present study. Correlation coefficient, Kruskal-Wallis test, and polytomous logistic regression analysis were applied to examine the relationship between the ADL measure and global disability scale. Model fit statistics were examined to verify logistic regression appropriateness. A categorization scheme, which minimized the false-positive response rate, was selected as the optimal categorizing system. Results— The 3 measures were highly correlated. Both BI and M-FIM differentiated disability better in lower than higher disability. In logistic regression, BI differentiated 4 disability levels; M-FIM differentiated 3 levels in MRS. However, on the basis of results of the Kruskal-Wallis and multiple comparison tests, we suspect that M-FIM may have the potential to predict MRS categories better with a different model. Conclusions— The proposed categorization scheme can serve as a translation between measures. However, because of the ceiling effect of BI and M-FIM, the translation could not be completed for all 6 levels of MRS. No apparent variation over time in the categorization scheme was observed. Further research needs to be conducted to develop better prediction models explaining the relationship between M-FIM and MRS.

The cost of health care for children and adults with sickle cell disease.

Although sickle cell disease (SCD) is marked by high utilization of medical resources, the full cost of care for patients with SCD, including care not directly related to SCD, is unknown. The purpose of this study was to estimate the total cost of medical care for a population of children and adults with SCD. We used data from individuals diagnosed with SCD enrolled in the Florida Medicaid program during 2001–2005 to estimate total, SCD‐related, and non‐SCD‐related cost per patient‐month based on patient age at the time of health care use. Across the 4,294 patient samples, total health care costs generally rose with age, from

Empirical assessment of methods for risk identification in healthcare data: results from the experiments of the Observational Medical Outcomes Partnership.

892 to

Evaluating the Impact of Database Heterogeneity on Observational Study Results

2,562 per patient‐month in the 0–9‐ and 50–64‐year age groups, respectively. Average cost per patient‐month was

Effect of vaccination by community pharmacists among adult prescription recipients.

1,389. Overall, 51.8% of care was directly related to SCD, the majority of which (80.5%) was associated with inpatient hospitalizations. Notably, non‐SCD‐related costs were substantially higher than those reported for the general US population. These results suggest a discounted (3% discount rate) lifetime cost of care averaging

Defining a Reference Set to Support Methodological Research in Drug Safety

460,151 per patient with SCD. Interventions designed to prevent SCD complications and avoid hospitalizations may reduce the significant economic burden of the disease. Am. J. Hematol. 2009.

Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis

BACKGROUND Expanded availability of observational healthcare data (both administrative claims and electronic health records) has prompted the development of statistical methods for identifying adverse events associated with medical products, but the operating characteristics of these methods when applied to the real-world data are unknown. METHODS We studied the performance of eight analytic methods for estimating of the strength of association-relative risk (RR) and associated standard error of 53 drug-adverse event outcome pairs, both positive and negative controls. The methods were applied to a network of ten observational healthcare databases, comprising over 130 million lives. Performance measures included sensitivity, specificity, and positive predictive value of methods at RR thresholds achieving statistical significance of p < 0.05 or p < 0.001 and with absolute threshold RR > 1.5, as well as threshold-free measures such as area under receiver operating characteristic curve (AUC). RESULTS Although no specific method demonstrated superior performance, the aggregate results provide a benchmark and baseline expectation for risk identification method performance. At traditional levels of statistical significance (RR > 1, p < 0.05), all methods have a false positive rate >18%, with positive predictive value <38%. The best predictive model, high-dimensional propensity score, achieved an AUC  =  0.77. At 50% sensitivity, false positive rate ranged from 16% to 30%. At 10% false positive rate, sensitivity of the methods ranged from 9% to 33%. CONCLUSIONS Systematic processes for risk identification can provide useful information to supplement an overall safety assessment, but assessment of methods performance suggests a substantial chance of identifying false positive associations.

Demographics, health behaviors, and past drug use as predictors of recall accuracy for previous prescription medication use

Clinical studies that use observational databases to evaluate the effects of medical products have become commonplace. Such studies begin by selecting a particular database, a decision that published papers invariably report but do not discuss. Studies of the same issue in different databases, however, can and do generate different results, sometimes with strikingly different clinical implications. In this paper, we systematically study heterogeneity among databases, holding other study methods constant, by exploring relative risk estimates for 53 drug-outcome pairs and 2 widely used study designs (cohort studies and self-controlled case series) across 10 observational databases. When holding the study design constant, our analysis shows that estimated relative risks range from a statistically significant decreased risk to a statistically significant increased risk in 11 of 53 (21%) of drug-outcome pairs that use a cohort design and 19 of 53 (36%) of drug-outcome pairs that use a self-controlled case series design. This exceeds the proportion of pairs that were consistent across databases in both direction and statistical significance, which was 9 of 53 (17%) for cohort studies and 5 of 53 (9%) for self-controlled case series. Our findings show that clinical studies that use observational databases can be sensitive to the choice of database. More attention is needed to consider how the choice of data source may be affecting results.

COMMUNITY PHARMACISTS AS IMMUNIZATION ADVOCATES : COST-EFFECTIVENESS OF A CUE TO INFLUENZA VACCINATION

Background.Millions of doses of influenza vaccine are administered each year in the United States at nontraditional sites and by nontraditional vaccine providers. Pharmacists are increasingly becoming vaccine providers. Objectives.To measure association between availability of pharmacist-immunizers and immunization delivery to adult prescription recipients, and the relative contributions of various types of vaccine providers. Research Design. Mailed survey in spring 1999, contrasting adults in urban Washington State, where pharmacists administer vaccines, to adults in urban Oregon, where pharmacists did not. Subjects.Cluster sample based on October 1998 prescription records suggesting need for influenza vaccine, derived from 24 community pharmacies belonging to one pharmacy chain. Measures.Vaccination status and choice of vaccine provider. Results.Influenza vaccination rates among respondents 65 years or older increased 4.7% more in Washington than in Oregon between 1997 and 1998 (P = 0.20). The net increase in influenza vaccination rate among younger respondents taking indicator medications for chronic diseases for which influenza vaccination is recommended was 10.6% (P = 0.05). Among respondents unvaccinated against influenza in 1997, the 1998 influenza vaccination rate was 34.7% in Washington, compared with 23.9% in Oregon (P = 0.01). Conclusions.Vaccine delivery by pharmacists is associated with higher rates of vaccination among those younger than 65 taking indicator medications medications for chronic diseases, as well as prescription recipients unvaccinated against influenza in the previous year.