Grace periods and exposure misclassification in self-controlled case-series studies of drug-drug interactions.

Am J Epidemiol

Center for Real-World Safety and Effectiveness of Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Published: July 2024

AI Article Synopsis

  • The self-controlled case-series (SCCS) design is used in studies to evaluate drug-drug interactions (DDIs), focusing on the comparison of incidence rates when taking two drugs together versus one alone.
  • Inaccuracies can arise when inferring day-level drug exposure from dispensing claims, which may lead to biased incidence rate ratios (IRRs), particularly when using grace periods that assume treatment effects continue after medication runs out.
  • Research findings indicate that misclassifying the precipitant (the drug causing the interaction) consistently biases the IRR towards null, while misclassifying the object drug can bias it in various directions; to reduce bias, it is recommended to avoid grace periods for object drugs and include a washout period after

Article Abstract

The self-controlled case-series (SCCS) research design is increasingly used in pharmacoepidemiologic studies of drug-drug interactions (DDIs), with the target of inference being the incidence rate ratio (IRR) associated with concomitant exposure to the object plus precipitant drug versus the object drug alone. While day-level drug exposure can be inferred from dispensing claims, these inferences may be inaccurate, leading to biased IRRs. Grace periods (periods assuming continued treatment impact after days' supply exhaustion) are frequently used by researchers, but the impact of grace period decisions on bias from exposure misclassification remains unclear. Motivated by an SCCS study examining the potential DDI between clopidogrel (object) and warfarin (precipitant), we investigated bias due to precipitant or object exposure misclassification using simulations. We show that misclassified precipitant treatment always biases the estimated IRR toward the null, whereas misclassified object treatment may lead to bias in either direction or no bias, depending on the scenario. Further, including a grace period for each object dispensing may unintentionally increase the risk of misclassification bias. To minimize such bias, we recommend 1) avoiding the use of grace periods when specifying object drug exposure episodes; and 2) including a washout period following each precipitant exposed period.

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Source
http://dx.doi.org/10.1093/aje/kwae231DOI Listing

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