Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension. OBJECTIVE: The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis. METHODS: Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum's de-identified Clinformatics® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework. RESULTS: In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence. CONCLUSIONS: This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.

Reproducible variability: assessing investigator discordance across 9 research teams attempting to reproduce the same observational study.

OBJECTIVE: Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations' variability on patient characteristics. MATERIALS AND METHODS: Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams' cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics. RESULTS: On average, the teams' interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts' size varied from one-third of the master cohort size to 10 times the cohort size (2159-63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3-16.2%). The teams' cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5. CONCLUSIONS: Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices.

Leveraging Machine Learning to Facilitate Individual Case Causality Assessment of Adverse Drug Reactions.

INTRODUCTION: Causality assessment of individual case safety reports (ICSRs) is an important step in pharmacovigilance case-level review and aims to establish a position on whether a patient's exposure to a drug is causally related to the patient experiencing an untoward adverse event. There are many different approaches for case causality adjudication, including the use of expert opinions and algorithmic frameworks; however, a great deal of variability exists between assessment methods, products, therapeutic classes, individual physicians, change of process and conventions over time, and other factors. OBJECTIVE: The objective of this study was to develop a machine learning-based model that can predict the likelihood of a causal association of an observed drug-reaction combination in an ICSR. METHODS: In this study, we used a set of annotated solicited ICSRs (50K cases) from a company post-marketing database. These data were enriched with novel supplementary features from external and internal data sources that aim to capture facets such as temporal plausibility, scientific validity, and confoundedness that have been shown to contribute to causality adjudication. Using these features, we constructed a Bayesian network (BN) model to predict drug-event pair causality assessment. BN topology was driven by an internally developed ICSR causality decision support tool. Performance of the model was evaluated through examination of sensitivity, positive predictive value (PPV), and the area under the receiver operating characteristic curve (AUC) on an independent set of data from a temporally adjacent interval (20K cases). No external validation was performed because of a lack of publicly available ICSRs with causality assessments for drug-event pairs. RESULTS: The model demonstrated high performance in predicting the causality assessment of drug-event pairs compared with clinical judgment using global introspection (AUC 0.924; 95% confidence interval [CI] 0.922-0.927). The sensitivity of the model was 0.900 (95% CI 0.896-0.904), and the PPV of the model was 0.778 (95% CI 0.773-0.783). CONCLUSION: These results show that robust probabilistic modeling of ICSR causality is feasible, and the approach used in the development of the model can serve as a framework for such causality assessments, leading to improvements in safety decision making.