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2.
J Manag Care Spec Pharm ; 26(5): 668-672, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32347183

RESUMO

BACKGROUND: Oxymorphone's metabolism does not involve the hepatic cytochrome P450 (CYP) system. The effect of this pharmacokinetic feature of oxymorphone on opioid prescribing is unknown. OBJECTIVE: To assess the relative frequency with which oxymorphone and oxycodone (a CYP3A-metabolized opioid analgesic) were each prescribed to patients concomitantly receiving CYP3A-modifying drugs (i.e., inducers and inhibitors) to characterize opioid-prescribing patterns in patients at risk for CYP3A-related drug interactions. METHODS: We analyzed the Sentinel Distributed Database from January 1, 2013, to December 31, 2016, to identify the proportion of patients with concomitant dispensing of selected CYP3A modifiers among initiators of oxymorphone. We then repeated the analysis using oxycodone instead of oxymorphone. We conducted sensitivity analyses that varied the washout periods for each opioid to account for potential opioid switching. RESULTS: In the primary analysis, the proportion of patients with concomitant incident dispensings of oxymorphone and selected CYP3A modifiers was 3.26% (95% CI = 3.09%-3.43%), and the proportion of patients with incident dispensings of oxycodone and selected CYP3A modifiers was 2.82% (95% CI = 2.79%-2.85%). The difference between proportions was 0.43% (95% CI = 0.26%-0.60%). Sensitivity analyses that varied the washout periods for each opioid with respect to the other opioid to account for switching yielded similar results. CONCLUSIONS: We observed similar proportions of patients using selected CYP3A modifiers concomitantly with both oxymorphone and oxycodone. While the CIs of the point estimates did not overlap, the absolute differences between the proportions were small. DISCLOSURES: This project was supported by Task Order HHSF22301001T under Master Agreement HHSF223201400030I from the U.S. Food and Drug Administration (FDA). The FDA approved the study protocol, including the statistical analysis plan, and reviewed and approved the manuscript. Coauthors from the FDA participated in the results interpretation and in the preparation and decision to submit the manuscript for publication. Coyle, Money, Staffa, Meyer, and Woods are employed by the FDA. The other authors have no financial conflicts of interest to report. The views expressed are those of the authors and not necessarily those of the U.S. Department of Health and Human Services, U.S. Food and Drug Administration.

3.
JAMA Surg ; : e200087, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129809

RESUMO

Importance: Bariatric surgery can lead to substantial improvements in type 2 diabetes (T2DM), but outcomes vary across procedures and populations. It is unclear which bariatric procedure has the most benefits for patients with T2DM. Objective: To evaluate associations of bariatric surgery with T2DM outcomes. Design, Setting, and Participants: This cohort study was conducted in 34 US health system sites in the National Patient-Centered Clinical Research Network Bariatric Study. Adult patients with T2DM who had bariatric surgery between January 1, 2005, and September 30, 2015, were included. Data analysis was conducted from April 2017 to August 2019. Interventions: Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Main Outcome and Measures: Type 2 diabetes remission, T2DM relapse, percentage of total weight lost, and change in glycosylated hemoglobin (hemoglobin A1c). Results: A total of 9710 patients were included (median [interquartile range] follow-up time, 2.7 [2.9] years; 7051 female patients [72.6%]; mean [SD] age, 49.8 [10.5] years; mean [SD] BMI, 49.0 [8.4]; 6040 white patients [72.2%]). Weight loss was significantly greater with RYGB than SG at 1 year (mean difference, 6.3 [95% CI, 5.8-6.7] percentage points) and 5 years (mean difference, 8.1 [95% CI, 6.6-9.6] percentage points). The T2DM remission rate was approximately 10% higher in patients who had RYGB (hazard ratio, 1.10 [95% CI, 1.04-1.16]) than those who had SG. Estimated adjusted cumulative T2DM remission rates for patients who had RYGB and SG were 59.2% (95% CI, 57.7%-60.7%) and 55.9% (95% CI, 53.9%-57.9%), respectively, at 1 year and 86.1% (95% CI, 84.7%-87.3%) and 83.5% (95% CI, 81.6%-85.1%) at 5 years postsurgery. Among 6141 patients who experienced T2DM remission, the subsequent T2DM relapse rate was lower for those who had RYGB than those who had SG (hazard ratio, 0.75 [95% CI, 0.67-0.84]). Estimated relapse rates for those who had RYGB and SG were 8.4% (95% CI, 7.4%-9.3%) and 11.0% (95% CI, 9.6%-12.4%) at 1 year and 33.1% (95% CI, 29.6%-36.5%) and 41.6% (95% CI, 36.8%-46.1%) at 5 years after surgery. At 5 years, compared with baseline, hemoglobin A1c was reduced 0.45 (95% CI, 0.27-0.63) percentage points more for patients who had RYGB vs patients who had SG. Conclusions and Relevance: In this large multicenter study, patients who had RYGB had greater weight loss, a slightly higher T2DM remission rate, less T2DM relapse, and better long-term glycemic control compared with those who had SG. These findings can help inform patient-centered surgical decision-making.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32003065

RESUMO

Following the release of the framework for the Real-World Evidence (RWE) Program, the US Food and Drug Administration (FDA) is actively evaluating and exploring ways to optimize the utility of real-world data (RWD) and RWE to support regulatory decision making. For rare conditions, conducting traditional randomized clinical trials may not always be feasible, and RWD and RWE have played and will continue to play an important role. We use three case examples-cerliponase alfa, asfotase alfa, and uridine triacetate-to illustrate how RWD from disease registries, medical records with chart review, and literature, respectively, have been used to generate RWE to support regulatory decisions for selected rare diseases. These examples highlight the need for improving data reliability and quality in existing data to expand use of RWD and RWE beyond "hard endpoints" and standardizing data collection for outcome measures in patient registries to expand its utility. We also discuss a recent FDA guidance for using RWE in supporting rare disease drug development, including its recommendations about using natural history studies as external control groups for single-arm interventional trials. The external control group needs to be comparable with the treated group. Selection bias and confounding are major concerns because of lack of randomization and unrecognized baseline differences. Use of valid epidemiological approaches can reduce these biases. Lastly, we discuss future directions to expand the use of RWD and RWE to support orphan drug approvals, including the need for including patient experience data as an important source of RWD.

5.
Pharmacoepidemiol Drug Saf ; 29(4): 409-418, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32067286

RESUMO

PURPOSE: The CHA2 DS2 -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 CHA2 DS2 -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 CHA2 DS2 -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 CHA2 DS2 -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 CHA2 DS2 -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 CHA2 DS2 -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 CHA2 DS2 -VaSc; 0.719 [0.702-0.737] for HAS-BLED) or direct OACs (0.695 [0.654-0.735] for CHA2 DS2 -VaSc; 0.700 [0.673-0.728] for HAS-BLED) than those taking warfarin (0.655 [0.613-0.697] for CHA2 DS2 -VaSc; 0.663 [0.6320.695] for HAS-BLED). CONCLUSIONS: Existing mapping strategies generally preserved the distributions of CHA2 DS2 -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.

6.
JAMA Surg ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940024

RESUMO

Importance: Additional data comparing longer-term problems associated with various bariatric surgical procedures are needed for shared decision-making. Objective: To compare the risks of intervention, operation, endoscopy, hospitalization, and mortality up to 5 years after 2 bariatric surgical procedures. Design, Setting, and Participants: Adults who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 1, 2005, and September 30, 2015, within the National Patient-Centered Clinical Research Network. Data from 33 560 adults at 10 centers within 4 clinical data research networks were included in this cohort study. Information was extracted from electronic health records using a common data model and linked to insurance claims and mortality indices. Analyses were conducted from January 2018 through October 2019. Exposures: Bariatric surgical procedures. Main Outcomes and Measures: The primary outcome was time until operation or intervention. Secondary outcomes included endoscopy, hospitalization, and mortality rates. Results: Of 33 560 adults, 18 056 (54%) underwent RYGB, and 15 504 (46%) underwent SG. The median (interquartile range) follow-up for operation or intervention was 3.4 (1.6-5.0) years for RYGB and 2.2 (0.9-3.6) years for SG. The overall mean (SD) patient age was 45.0 (11.5) years, and the overall mean (SD) patient body mass index was 49.1 (7.9). The cohort was composed predominantly of women (80%) and white individuals (66%), with 26% of Hispanic ethnicity. Operation or intervention was less likely for SG than for RYGB (hazard ratio, 0.72; 95% CI, 0.65-0.79; P < .001). The estimated, adjusted cumulative incidence rates of operation or intervention at 5 years were 8.94% (95% CI, 8.23%-9.65%) for SG and 12.27% (95% CI, 11.49%-13.05%) for RYGB. Hospitalization was less likely for SG than for RYGB (hazard ratio, 0.82; 95% CI, 0.78-0.87; P < .001), and the 5-year adjusted cumulative incidence rates were 32.79% (95% CI, 31.62%-33.94%) for SG and 38.33% (95% CI, 37.17%-39.46%) for RYGB. Endoscopy was less likely for SG than for RYGB (hazard ratio, 0.47; 95% CI, 0.43-0.52; P < .001), and the adjusted cumulative incidence rates at 5 years were 7.80% (95% CI, 7.15%-8.43%) for SG and 15.83% (95% CI, 14.94%-16.71%) for RYGB. There were no differences in all-cause mortality between SG and RYGB. Conclusions and Relevance: Interventions, operations, and hospitalizations were relatively common after bariatric surgical procedures and were more often associated with RYGB than SG. Trial Registration: ClinicalTrials.gov identifier: NCT02741674.

7.
Epidemiology ; 31(1): 82-89, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31569120

RESUMO

Estimating hazard ratios (HR) presents challenges for propensity score (PS)-based analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to become unbalanced on baseline characteristics over time as "susceptible" individuals drop out of the population at risk differentially across treatment groups due to having outcome events. This imbalance in baseline covariates causes marginal (population-averaged) HRs to diverge from conditional (covariate-adjusted) HRs over time and systematically move toward the null. Methods that condition on a baseline PS yield HR estimates that fall between the marginal and conditional HRs when these diverge. Unconditional methods that match on the PS or weight by a function of the PS can estimate the marginal HR consistently but are prone to misinterpretation when the marginal HR diverges toward the null. Here, we present results from a series of simulations to help analysts gain insight on these issues. We propose a novel approach that uses time-dependent PSs to consistently estimate conditional HRs, regardless of whether susceptibles have been depleted differentially. Simulations show that adjustment for time-dependent PSs can adjust for covariate imbalances over time that are caused by depletion of susceptibles. Updating the PS is unnecessary when outcome incidence is so low that depletion of susceptibles is negligible. But if incidence is high, and covariates and treatment affect risk, then covariate imbalances arise as susceptibles are depleted, and PS-based methods can consistently estimate the conditional HR only if the PS is periodically updated.

8.
Clin Pharmacol Ther ; 107(4): 834-842, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31869442

RESUMO

A wide range of analytic and data sharing options are available in nonexperimental multidatabase studies designed to assess the real-world benefits and risks of medical products. Researchers often consider six scientific domains when choosing among these options-study design, exposure type, outcome type, covariate summarization technique, covariate adjustment method, and data sharing approach. This article reviews available analytic and data sharing options and discusses key scientific and practical considerations when choosing among these options in multidatabase studies of comparative effectiveness and safety of medical products. The scientific considerations must be balanced against what the data-contributing sites are able or willing to share. While pooling of person-level data sets remains the most familiar and analytically flexible approach, newer analytic and data sharing approaches that share less granular summary-level information may be equally valid and preferred in some multidatabase studies, especially when sharing of person-level data is challenging or infeasible.

9.
BMC Med Res Methodol ; 19(1): 228, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805872

RESUMO

BACKGROUND: Multi-center studies can generate robust and generalizable evidence, but privacy considerations and legal restrictions often make it challenging or impossible to pool individual-level data across data-contributing sites. With binary outcomes, privacy-protecting distributed algorithms to conduct logistic regression analyses have been developed. However, the risk ratio often provides a more transparent interpretation of the exposure-outcome association than the odds ratio. Modified Poisson regression has been proposed to directly estimate adjusted risk ratios and produce confidence intervals with the correct nominal coverage when individual-level data are available. There are currently no distributed regression algorithms to estimate adjusted risk ratios while avoiding pooling of individual-level data in multi-center studies. METHODS: By leveraging the Newton-Raphson procedure, we adapted the modified Poisson regression method to estimate multivariable-adjusted risk ratios using only summary-level information in multi-center studies. We developed and tested the proposed method using both simulated and real-world data examples. We compared its results with the results from the corresponding pooled individual-level data analysis. RESULTS: Our proposed method produced the same adjusted risk ratio estimates and standard errors as the corresponding pooled individual-level data analysis without pooling individual-level data across data-contributing sites. CONCLUSIONS: We developed and validated a distributed modified Poisson regression algorithm for valid and privacy-protecting estimation of adjusted risk ratios and confidence intervals in multi-center studies. This method allows computation of a more interpretable measure of association for binary outcomes, along with valid construction of confidence intervals, without sharing of individual-level data.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31828887

RESUMO

PURPOSE: To describe utilization of filgrastim and infliximab, the first two products with biosimilars approved in the United States. METHODS: We identified use of filgrastim (reference, tbo-filgrastim, and filgrastim-sndz) and infliximab (reference, infliximab-dyyb, and infliximab-abda) in the Sentinel Distributed Database using Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes (NDCs) from January 2015 to August 2018. We calculated the proportion of use by code type and assessed uptake over time. We compared baseline patient characteristics and treatment indications. Among patients with >1 exposure episode, we characterized gaps between episodes. RESULTS: Use was identified primarily via HCPCS codes (filgrastim: 86.4%-97.7%; infliximab: 87.8%-100%) although some was identified via NDCs (filgrastim: 2.2%-13.5%; infliximab: <0.1%-6.5%). Filgrastim reference product use declined from 89.4% in January 2015 to 30.3% in June 2018, with corresponding increases in filgrastim-sndz (0% to 49.3%) and tbo-filgrastim (10.6% to 20.4%). Infliximab biosimilar uptake was low (9.7% in June 2018). We identified 94 846 filgrastim reference product, 27 143 tbo-filgrastim, and 38 264 filgrastim-sndz users. For infliximab, we identified 125 412 reference product, 1034 infliximab-dyyb, 49 infliximab-abda, and 4855 undetermined biosimilar users. Patients receiving filgrastim products were largely similar, but differences in age, sex, and indication were observed across infliximab product users. The median exposure episode gap ranged from 1 to 3 days for filgrastim and 48 to 50 days for infliximab. CONCLUSION: Use of biosimilar filgrastim has increased in the United States, but infliximab biosimilar use remains low. Data on identification of biosimilars in claims data and observed gaps between exposure episodes can be used to support drug safety studies of biosimilars.

11.
BMC Pregnancy Childbirth ; 19(1): 441, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775682

RESUMO

BACKGROUND: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant. METHODS: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013. ADD use was estimated using outpatient pharmacy dispensing claims and days-supplied among three cohorts: all livebirth pregnancies, pregnancies among women with pre-existing diabetes, and pregnancies among women without prior ADD use. RESULTS: Among the 1.9 million pregnancies in the MSDD that resulted in a livebirth from 2001 to 2013, 4.4% were exposed to an ADD. Of the 15,606 pregnancies (0.8%) with pre-existing diabetes, 92.8% were also exposed during the pregnancy period. The most commonly used product in these pregnancies was insulin (75.6% of pregnancies). In contrast, in pregnancies of women without prior ADD use, the most commonly used products were glyburide and insulin, and most of these users were diagnosed with gestational diabetes. CONCLUSIONS: Patterns of ADD use during pregnancy described here, along with changes in disease incidence and management, highlight the importance of continuing surveillance of ADD utilization patterns and examining the safety and effectiveness of these products in pregnancy.

12.
Pediatr Res ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578038

RESUMO

BACKGROUND: Privacy-protecting analytic approaches without centralized pooling of individual-level data, such as distributed regression, are particularly important for vulnerable populations, such as children, but these methods have not yet been tested in multi-center pediatric studies. METHODS: Using the electronic health data from 34 healthcare institutions in the National Patient-Centered Clinical Research Network (PCORnet), we fit 12 multivariable-adjusted linear regression models to assess the associations of antibiotic use <24 months of age with body mass index z-score at 48 to <72 months of age. We ran these models using pooled individual-level data and conventional multivariable-adjusted regression (reference method), as well as using the more privacy-protecting pooled summary-level intermediate statistics and distributed regression technique. We compared the results from these two methods. RESULTS: Pooled individual-level and distributed linear regression analyses produced virtually identical parameter estimates and standard errors. Across all 12 models, the maximum difference in any of the parameter estimates or standard errors was 4.4833 × 10-10. CONCLUSIONS: We demonstrated empirically the feasibility and validity of distributed linear regression analysis using only summary-level information within a large multi-center study of children. This approach could enable expanded opportunities for multi-center pediatric research, especially when sharing of granular individual-level data is challenging.

13.
Clin Pharmacol Ther ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31630391

RESUMO

The US Sentinel System and the Canadian Network for Observational Drug Effect Studies (CNODES) are two medical product safety surveillance networks. Using Sentinel's preprogrammed, parameterizable analytic tools, we reproduced two protocol-based studies conducted by CNODES to assess the risks of acute pancreatitis and heart failure (HF) associated with the use of incretin-based drugs, compared with use of ≥ 2 oral hypoglycemic agents. Results from the replication new-user cohort analyses aligned with those from the CNODES nested case-control studies. The adjusted hazard ratios were 0.95 (0.81-1.12; vs. 1.03 (0.87-1.22) in CNODES) for acute pancreatitis and 0.91 (0.84-1.00; vs. 0.82 (0.67-1.00) in CNODES) for HF among patients without HF history. The CNODES's common protocol approach allows studies tailored to specific safety questions, whereas the Sentinel's common data model plus pretested program approach enables more rapid analysis. Despite these differences, it is possible to obtain comparable results using both approaches.

14.
Clin Ther ; 41(12): 2467-2476, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563392

RESUMO

Medication use in pregnancy is common, but information about the safety of most medications in pregnant women or their infants is limited. In the absence of data from randomized clinical trials to guide decisions made by regulators, clinicians, and patients, we often have to rely on well-designed observational studies to generate valid evidence about the benefits and risks of medications in pregnancy. Spontaneous reporting, primary case-control and cohort studies, pregnancy exposure registries, and electronic health data have been used extensively for studying medication safety in pregnancy. This article discusses these data sources, their strengths and limitations, and possible strategies and approaches to mitigating limitations when planning studies or interpreting findings from the literature. Strategies discussed include combining data sources across institutional or national borders, developing and using more sophisticated study designs, and taking advantage of existing analytic methods for more complex data structures, such as time-varying exposure or unmeasured confounding. Finally, we make recommendations for study designs that aid in better risk-related communication.

15.
Pharmacoepidemiol Drug Saf ; 28(10): 1405-1410, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31483085

RESUMO

PURPOSE: In July 2015, the US Food and Drug Administration (FDA) published a drug safety communication regarding errors in prescribing and dispensing of the antidepressant Brintellix (vortioxetine) and the antiplatelet Brilinta (ticagrelor) that arose due to proprietary drug name confusion. Brintellix is indicated for major depressive disorder; Brilinta is indicated to reduce cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or history of myocardial infarction. Brintellix was renamed to Trintellix in May 2016. Using Brilinta and Brintellix as a proof-of-concept feasibility use case, we assessed whether drug name confusion errors between the pair could be identified in electronic health care data via the combination of a claims-based algorithm and limited manual claims data review. METHODS: Using data from the Sentinel System, we defined potential errors as Brintellix users without an on- or off-label indication for Brintellix, without a dispensing for a drug with the same indications as Brintellix, and with an on- or off-label indication for Brilinta between -365 and +30 days after index Brintellix dispensing; the reverse was done for Brilinta. We manually reviewed claims profiles of potential cases. RESULTS: We identified 27 (0.1%) potential errors among 21 208 Brintellix users; 16 appeared to be likely errors based on claims profile review. Fifty-one (0.3%) of the 16 779 Brilinta users were identified as potential errors, and four appeared to be likely errors. CONCLUSIONS: A claims-based algorithm combined with manual review of claims profiles could identify potential drug name confusion errors, and narrow down likely errors that warrant further investigation.

16.
Clin Infect Dis ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412356

RESUMO

Concerns have been raised about progestin-containing contraceptives and risk of HIV acquisition. Based on health insurance data from 622,565 women in the U.S. with intrauterine device (IUD) insertions during 2011-2018, there was no increased risk of incident HIV diagnosis among women using levonorgestrel-releasing IUDs compared with those using copper IUDs.

17.
Stat Methods Med Res ; : 962280219869742, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31448681

RESUMO

The inverse probability weighted Cox proportional hazards model can be used to estimate the marginal hazard ratio. In multi-site studies, it may be infeasible to pool individual-level datasets due to privacy and other considerations. We propose three methods for making inference on hazard ratios without the need for pooling individual-level datasets across sites. The first method requires a summary-level eight-column risk-set table to produce the same hazard ratio estimate and robust sandwich variance estimate as those from the corresponding pooled individual-level data analysis (reference analysis). The second and third methods, which are based on two bootstrap re-sampling strategies, require a summary-level four-column risk-set table and bootstrap-based risk-set tables from each site to produce the same hazard ratio and bootstrap variance estimates as those from their reference analyses. All three methods require only one file transfer between the data-contributing sites and the analysis center. We justify these methods theoretically, illustrate their use, and demonstrate their statistical performance using both simulated and real-world data.

18.
EGEMS (Wash DC) ; 7(1): 27, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31346542

RESUMO

Purpose: Little is known about how disease risk score (DRS) development should proceed under different pharmacoepidemiologic follow-up strategies. In an analysis of dabigatran vs. warfarin and risk of major bleeding, we compared the results of DRS adjustment when models were developed under "intention-to-treat" (ITT) and "as-treated" (AT) approaches. Methods: We assessed DRS model discrimination, calibration, and ability to induce prognostic balance via the "dry run analysis". AT treatment effects stratified on each DRS were compared with each other and with a propensity score (PS) stratified reference estimate. Bootstrap resampling of the historical cohort at 10 percent-90 percent sample size was performed to assess the impact of sample size on DRS estimation. Results: Historically-derived DRS models fit under AT showed greater decrements in discrimination and calibration than those fit under ITT when applied to the concurrent study population. Prognostic balance was approximately equal across DRS models (-6 percent to -7 percent "pseudo-bias" on the hazard ratio scale). Hazard ratios were between 0.76 and 0.78 with all methods of DRS adjustment, while the PS stratified hazard ratio was 0.83. In resampling, AT DRS models showed more overfitting and worse prognostic balance, and led to hazard ratios further from the reference estimate than did ITT DRSs, across sample sizes. Conclusions: In a study of anticoagulant safety, DRSs developed under an AT principle showed signs of overfitting and reduced confounding control. More research is needed to determine if development of DRSs under ITT is a viable solution to overfitting in other settings.

19.
J Clin Psychiatry ; 80(4)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31163104

RESUMO

OBJECTIVE: To evaluate stroke risk among users of typical antipsychotics compared to users of atypical antipsychotics in a non-elderly and non-demented US population. METHODS: New users of antipsychotics aged 18-64 years without dementia were identified via electronic health care data from 13 health plans participating in the Sentinel System from January 2001 to September 2015. The risk of hospitalized stroke events, identified via ICD-9-CM diagnostic criteria, was compared between typical and atypical antipsychotic users using 1:1 matching on propensity score. Adjusted hazard ratios (HRs) and 95% CIs during the entire follow-up period and during 1- to 15-day and 16- to 90-day risk windows were estimated. The risk associated with haloperidol use was estimated separately. RESULTS: A total of 45,495 typical antipsychotic users were matched 1:1 to atypical antipsychotic users. While unmatched HRs suggest an increased stroke risk among typical antipsychotic users compared to atypical antipsychotic users, no increased risk was observed after matching during the entire follow-up period (HR = 0.87; 95% CI, 0.54-1.41), the 1- to 15-day risk window (HR = 1.16; 95% CI, 0.41-3.32), or the 16- to 90-day risk window (HR = 0.52; 95% CI, 0.20-1.36). The adjusted HR for haloperidol was 1.31 (95% CI, 0.54-3.21). CONCLUSION: These findings were not suggestive of an increased stroke risk in typical antipsychotic users compared to atypical antipsychotic users in a non-elderly and non-demented population.

20.
EGEMS (Wash DC) ; 7(1): 11, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30993145

RESUMO

Researchers often use prescribing data from electronic health records (EHR) or dispensing data from medication or medical claims to determine medication utilization. However, neither source has complete information on medication use. We compared antibiotic prescribing and dispensing records for 200,395 patients in the National Patient-Centered Clinical Research Network (PCORnet) Antibiotics and Childhood Growth Study. We stratified analyses by delivery system type [closed integrated (cIDS) and non-cIDS]; 90.5 percent and 39.4 percent of prescribing records had matching dispensing records, and 92.7 percent and 64.0 percent of dispensing records had matching prescribing records at cIDS and non-cIDS, respectively. Most of the dispensings without a matching prescription did not have same-day encounters in the EHR, suggesting they were medications given outside the institution providing data, such as those from urgent care or retail clinics. The sensitivity of prescriptions in the EHR, using dispensings as a gold standard, was 99.1 percent and 89.9 percent for cIDS and non-cIDS, respectively. Only 0.7 percent and 6.1 percent of patients at cIDS and non-cIDS, respectively, were classified as false-negative, i.e. entirely unexposed to antibiotics when they in fact had dispensings. These patients were more likely to have a complex chronic condition or asthma. Overall, prescription records worked well to identify exposure to antibiotics. EHR data, such as the data available in PCORnet, is a unique and vital resource for clinical research. Closing data gaps by understanding why prescriptions may not be captured can improve this type of data, making it more robust for observational research.

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