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BackgroundNon-interventional large-scale research on real-world patients who had a stroke requires the use of multiple data sources ensuring access to longitudinal data from large populations with clinically-detailed information. We sought to establish a framework for longitudinal research on patients hospitalised with stroke by linking information-rich, deidentified inpatient data from the Paul Coverdell National Acute Stroke Program (PCNASP) to commercial and Medicare Advantage longitudinal claims data.MethodsAll stroke admissions in PCNASP between 2008 and 2015 were evaluated for linkage to longitudinal claims from a commercial insurer using an algorithm based on six available common data fields (patient age, gender, admission date, discharge date, discharge diagnosis and state) and a hospital match. We evaluated the linkage quality (via the percentage of unique records in the linked dataset) and the representativeness of the linked population. We also described medical history, stroke severity and patterns of medication use among the PCNASP-claims linked cohort.ResultsThe linkage produced uniqueness equal to 99.1%. We identified 5644 linked and 98 896 unlinked patients who had an ischaemic stroke hospitalisation in claims data. Linked patients were younger than unlinked (69.7 vs 72.5 years), but otherwise similar by medical history, prestroke medication use or lab values. Stroke severity was mild and most patients were discharged home. Prestroke and discharge use of antihypertensive and statins in the PCNASP were greater than their use as measured by filled prescriptions in claims.ConclusionsHigh-quality linkage between the PCNASP and commercial claims data is feasible. This linkage identified differences between reported or recommended versus actual out-of-hospital medication utilisation, highlighting the importance of longitudinal data availability for research aimed to improve the care of patients who had a stroke.

Objective To evaluate safety alerts and recalls, publication of key trial outcomes, and subsequent US approval of high profile medical devices introduced in the European Union. Design Cohort study. Setting Novel cardiovascular, orthopedic, and neurologic devices approved in the EU through Conformite Europeenne marking between 2005 and 2010. Data sources Public and commercial databases searched up to January 2016 for press releases and announcements of approvals; public Food and Drug Administration and European regulatory authority databases for US approvals and safety alerts and recalls; and Medline, Embase, and Web of Science for peer reviewed publications. Main outcome measures We categorized the novelty of the devices in the study sample as a “major innovation” or an “other change,” and extracted descriptive data about the devices and information on any safety alerts and withdrawals. Linear regression models examined factors associated with differential EU and US approvals. Cox proportional hazards regression models were used to evaluate factors associated with safety alerts and recalls and the publication of trial outcomes for devices categorized as major innovations. Models controlled for time, therapeutic category, regulatory pathway, size of sponsoring company, and indicator variables for devices approved first in the EU and devices approved only in the EU. Results 67% (206/309) of devices identified were approved in both the US and the EU, of which 63% (129/206) were approved first in the EU. The unadjusted rate of safety alerts and recalls for devices approved first in the EU was 27% (62/232) compared with 14% (11/77) for devices approved first in the US. The adjusted hazard ratio for safety alerts and recalls was 2.9 (95% confidence interval 1.4 to 6.2) for devices approved first in the EU. The results of pivotal trials were published for 49% (37/75) of devices categorized as major innovations, with an overall publication rate of 37% five years after approval. Conclusions Devices approved first in the EU are associated with an increased risk of post-marketing safety alerts and recalls. Poor trial publication rates mean that patients and clinicians need greater regulatory transparency to make informed decisions about treatment.

Objectives To compare stratified event rates from randomized controlled trials with predicted event rates from models developed in observational data, and assess their ability to accurately capture observed rates of thromboembolism and major bleeding for patients treated with dabigatran or warfarin as part of routine care. Design New initiator cohort study. Setting Data from United Health (October 2009 to June 2013), a commercial healthcare claims database in the United States. Participants 21 934 adults with atrial fibrillation initiating dabigatran (150 mg dose only) or warfarin treatment as part of routine care. Main outcome measures Predicted annual rates of thromboembolism or major bleeding, based on estimates from randomized controlled trials, models developed in routine care patients, and baseline risk scores (CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED). Thromboembolism was a composite outcome, including primary inpatient diagnosis codes for ischemic or ill defined stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, and systemic embolism. Major bleeding was a composite outcome including codes occurring in an inpatient setting for hemorrhagic stroke; major upper, lower, or unspecified gastrointestinal bleed; and major urogenital or other bleed. Results 6516 (30%) and 15 418 (70%) of patients initiated dabigatran and warfarin, respectively. Annual event rates per 100 patients were 1.7 for thromboembolism and 4.6 for major bleeding. For thromboembolism, calibration of estimates from randomized controlled trials was similar to calibration for model based predictions; however, trial estimates for major bleeding consistently underestimated the rate of bleeding among patients in routine care. Underestimation of bleeding rates was particularly pronounced in warfarin initiators with high HAS-BLED scores, where event rates were underestimated by up to 4.0 per 100 patient years. Harrell’s c indices for discrimination for thromboembolism or major bleeding in dabigatran and warfarin initiators ranged between 0.59 and 0.66 for randomized controlled trial predictions, and between 0.52 and 0.70 for cross validated model based predictions. Conclusion Estimated rates of thromboembolism under dabigatran or warfarin treatment in randomized controlled trials were close to observed rates in routine care patients. However, rates of major bleeding were underestimated. Models developed in routine care patients can provide accurate, tailored estimates of risk and benefit under alternative treatment to enhance patient centered care.

Background Generalisability has been reported as a barrier to using evidence in policy making. Little data are available on whether US and Canadian based evidence on cost-sharing and medication adherence is generalizable to international populations. To explore external validity, we compared the impact of two similar cost sharing policies, one in the US and one in Ireland, on medication adherence. Methods A repeated measures longitudinal study design was employed to measure individual drug adherence before and after the introduction of drug cost-sharing policies. The Irish policy introduced a 50 cent copayment/prescription item in a publicly insured population in 2010. A similar policy occurred in the Massachusetts Medicaid population in 2003. Prescription data were obtained from centrally held pharmacy claims databases; HSE-PCRS, in Ireland and Medicaid Analytical Extract in the US New users of anti-hypertensive, anti-hyperlipidaemic and anti-diabetes drugs entered the cohort 6 months prior to initiation of cost-sharing polices and were followed for 12 months post-policy change. Segmented regression with generalised estimating equations and an autoregressive correlation structure was used. Results The Irish policy change resulted in a 3.9% (95% CI, 2.91%-5.02%) immediate drop in adherence to anti-hypertensive drugs in Ireland, whereas the US policy did not affect anti-hypertensive adherence. Relative to the US, the Irish population had a 5.3% (95% CI, 3.68% - 6.92%) additional decrease in adherence to anti-hypertensive drugs immediately after the policy change. Adherence to anti-hyperlipidaemic drugs was insignificantly reduced (-0.6235%, 95% CI, - 2.41%-1.16%) immediately post-policy change in the U. S. However, adherence to anti-hyperlipidaemics was reduced in Ireland by 3.4% (95% CI, 2.25%-4.62%). Compared to the US, Irish patients decreased their adherence to anti-hyperlipidaemics by 2.8% (95% CI, 0.673%-4.945%). Adherence to anti-diabetic drugs did not differ internationally post-policy change. There was no evidence for international differences in the long-term impact (12 months) of policy changes. Conclusion Irish and US populations had different changes in adherence to anti-hypertensive and anti-hyperlipidaemic drugs directly after implementation of cost-sharing policies, with greater reductions in adherence in the Irish population. However, changes in adherence to anti-diabetic drugs were similar between the populations. This study suggests that North American and Canadian evidence may not be automatically internationally generalizable. Rather, the specific attributes of a setting should always be considered before applying evidence to policy. This novel study will be of interest to global policymakers as they seek to develop evidence based cost-sharing policies.