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Purpose: Develop and test a flexible, scalable tool using interrupted time series (ITS) analysis to assess the impact of Food and Drug Administration (FDA) regulatory actions on drug use. Methods: We applied the tool in the Sentinel Distributed Database to assess the impact of FDA's 2010 drug safety communications (DSC) concerning the safety of long‐acting beta2‐agonists (LABA) in adult asthma patients. We evaluated changes in LABA use by measuring the initiation of LABA alone and concomitant use of LABA and asthma controller medications (ACM) after the DSCs. The tool generated ITS graphs and used segmented regression to estimate baseline slope, level change, slope change, and absolute and relative changes at up to two user‐specified time point (s) after the intervention. We tested the tool and compared our results against prior analyses that used similar measures. Results: Initiation of LABA alone declined among asthma patients aged 18–45 years before FDA DSCs (−0.10% per quarter; 95%CI: −0.11% to −0.09%) and the downward trend continued after. Concomitant use of LABA and ACM was stable before FDA DSCs. After FDA DSCs, there was a small trend decrease of 0.006% per quarter (95% CI, −0.008% to −0.003%). We found similar results among those aged 46–64 years and patients with poorly‐controlled asthma. Our results were consistent with previous studies, confirming the performance of the new tool. Conclusions: We developed and tested a reusable ITS tool in real‐world databases formatted to the Sentinel Common Data Model that can assess the impact of regulatory actions on drug use. [ABSTRACT FROM AUTHOR]

Purpose The CHA2DS2‐VaSc and HAS‐BLED risk scores are commonly used in the studies of oral anticoagulants (OACs). The best ways to map these scores to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD‐10‐CM) codes is unclear, as is how they perform in various types of OAC users. We aimed to assess the distributions of CHA2DS2‐VaSc and HAS‐BLED scores and C‐statistics for outcome prediction in the ICD‐10‐CM era using different mapping strategies. Methods: We compared the distributions of CHA2DS2‐VaSc and HAS‐BLED scores from various mapping strategies in atrial fibrillation patients before, during, and after ICD‐10‐CM transition. We estimated the C‐statistics predicting the 90‐day risk of hospitalized stroke (for CHA2DS2‐VaSc) or hospitalized bleeding (for HAS‐BLED) in patients identified at least 6 months after the ICD‐10‐CM transition, overall and by anticoagulant type. Results: Forward‐backward mapping produced higher CHA2DS2‐VaSc and HAS‐BLED scores in the ICD‐10‐CM era compared to the ICD‐9‐CM era: the mean difference was 0.074 (95% confidence interval 0.064‐0.085) for CHA2DS2‐VaSc and 0.055 (0.048‐0.062) for HAS‐BLED. Both scores had higher C‐statistics in patients taking no OACs (0.697 [0.677‐0.717] for CHA2DS2‐VaSc; 0.719 [0.702‐0.737] for HAS‐BLED) or direct OACs (0.695 [0.654‐0.735] for CHA2DS2‐VaSc; 0.700 [0.673‐0.728] for HAS‐BLED) than those taking warfarin (0.655 [0.613‐0.697] for CHA2DS2‐VaSc; 0.663 [0.6320.695] for HAS‐BLED). Conclusions: Existing mapping strategies generally preserved the distributions of CHA2DS2‐VaSc and HAS‐BLED scores after ICD‐10‐CM transition. Both scores performed better in patients on no OACs or direct OACs than patients on warfarin. [ABSTRACT FROM AUTHOR]

Background: Epidemiological study reporting is improving but is not transparent enough for easy evaluation or replication. One barrier is insufficient details about design elements in published studies. Methods: Using a previously conducted drug safety evaluation in claims as a test case, we investigated the impact of small changes in five key design elements on risk estimation. These elements are index day of incident exposure's determination of look‐back or follow‐up periods, exposure duration algorithms, heparin exposure exclusion, propensity score model variables, and Cox proportional hazard model stratification. We covaried these elements using a fractional factorial design, resulting in 24 risk estimates for one outcome. We repeated eight of these combinations for two additional outcomes. We measured design effects on cohort sizes, follow‐up time, and risk estimates. Results: Small changes in specifications of index day and exposure algorithm affected the risk estimation process the most. They affected cohort size on average by 8 to 10%, follow‐up time by up to 31%, and magnitude of log hazard ratios by up to 0.22. Other elements affected cohort before matching or risk estimate's precision but not its magnitude. Any change in design substantially altered the matched control‐group subjects in 1:1 matching. Conclusions: Exposure‐related design elements require attention from investigators initiating, evaluating, or wishing to replicate a study or from analysts standardizing definitions. The methods we developed, using factorial design and mapping design effect on causal estimation process, are applicable to planning of sensitivity analyses in similar studies. [ABSTRACT FROM AUTHOR]

Purpose: To replicate the well-established association between angiotensinconverting enzyme inhibitors versus beta blockers and angioedema in the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) era. Methods: We conducted a retrospective, inception cohort study in a large insurance database formatted to the Sentinel Common Data Model. We defined study periods spanning the ICD-9-CM era only, ICD-10-CM era only, and ICD-9-CM and ICD-10-CM era and conducted simple-forward mapping (SFM), simple-backward mapping (SBM), and forward-backward mapping (FBM) referencing the General Equivalence Mappings to translate the outcome (angioedema) and covariates from ICD-9-CM to ICD-10-CM. We performed propensity score (PS)-matched and PSstratified Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In the ICD-9-CM and ICD-10-CM eras spanning April 1 to September 30 of 2015 and 2016, there were 152 017 and 145 232 angiotensin-converting enzyme inhibitor initiators and 115 073 and 116 652 beta-blocker initiators, respectively. The PS-matched HR was 4.19 (95% CI, 2.82-6.23) in the ICD-9-CM era, 4.37 (2.92-6.52) in the ICD-10-CM era using SFM, and 4.64 (3.05-7.07) in the ICD-10-CM era using SBM and FBM. The PS-matched HRs from the mixed ICD-9-CM and ICD-10-CM eras ranged from 3.91 (2.69-5.68) to 4.35 (3.33-5.70). Conclusion: The adjusted HRs across different diagnostic coding eras and the use of SFM versus SBM and FBM produced numerically different but clinically similar results. Additional investigations as ICD-10-CM data accumulate are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To describe the consistency in the frequency of 5 health outcomes across the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification (ICD-10-CM) eras in the US. Methods: We examined the incidence of 3 acute conditions (acute myocardial infarction [AMI], angioedema, ischemic stroke) and the prevalence of 2 chronic conditions (diabetes, hypertension) during the final 5 years of the ICD-9-CM era (January 2010-September 2015) and the first 15 months of the ICD-10-CM era (October 2015-December 2016) in 13 electronic health care databases in the Sentinel System. For each health outcome reviewed during the ICD-10-CM era, we evaluated 4 definitions, including published algorithms derived from other countries, as well as simple-forward, simple-backward, and forward-backward mapping using the General Equivalence Mappings. For acute conditions, we also compared the incidence between April to December 2014 and April to December 2016. Results: The analyses included data from approximately 172 million health plan members. While the incidence or prevalence of AMI and hypertension performed similarly across the 2 eras, the other 3 outcomes did not demonstrate consistent trends for some or all the ICD-10-CM definitions assessed. Conclusions: When using data from both the ICD-9-CM and ICD-10-CM eras, or when using results from ICD-10-CM data to compare to results from ICD-9-CM data, researchers should test multiple ICD-10-CM outcome definitions as part of sensitivity analysis. Ongoing assessment of the impact of ICD-10-CM transition on identification of health outcomes in US electronic health care databases should occur as more data accrue. [ABSTRACT FROM AUTHOR]

Background Existing studies suggested that concomitant use of calcium channel blockers (CCBs) may interfere with the antiplatelet effect of clopidogrel. The objective of this study was to examine the effect of concomitant use of CCBs and clopidogrel on risks of acute coronary syndrome (ACS) re-hospitalization in patients receiving percutaneous coronary intervention. Methods Using the Taiwan National Health Insurance Research Database, we identified 51 925 patients who were admitted for newly diagnosed ACS, received percutaneous coronary intervention, and used clopidogrel within 1 year after discharge. We further stratified them into three groups based on their uses of guideline-recommended secondary prevention medications for ACS (fully, partially, and non-compliant groups) to assess the potential modification effect of guideline compliance. For each group, we conducted a 1:1 propensity score matching to minimize selection bias. Cox proportional hazard models were used to investigate the effect of concomitant use of CCBs (overall, subclasses, and individual CCBs) and clopidogrel on risks of ACS re-hospitalization. Results Concomitant use of CCBs in patients discharged with clopidogrel was significantly associated with a lower risk of ACS re-hospitalization in the fully compliant group (HRfully compliant = 0.82 [95% confidence interval 0.75-0.89], p < 0.001) but was associated with increased risk of ACS re-hospitalization in the non-compliant group (HRnon-compliant = 1.22 [1.03-1.45], p = 0.0252). Conclusions Different guideline compliance of secondary prevention medications could modify the potential drug-drug interaction between clopidogrel and CCBs. Concomitant use of CCBs and clopidogrel was significantly associated with increased risk of ACS re-hospitalization in ACS patients not compliant to guideline-recommended secondary prevention drugs. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]