Impact of time-varying exposure on estimated effects in observational studies using routinely collected data: protocol for a cross-sectional study

Abstract

IntroductionTime-varying exposure is an important issue that should be addressed in longitudinal observational studies using routinely collected data (RCD) for drug treatment effects. How well investigators designed, analysed and reported time-varying exposure, and to what extent the divergence that can be observed between different methods used for handling time-varying exposure in these studies remains uncertain. We will conduct a cross-sectional study to comprehensively address this question.Methods and analysisWe have developed a comprehensive search strategy to identify all studies exploring drug treatment effects including both effectiveness and safety that used RCD and were published in core journals between 2018 and 2020. We will collect information regarding general study characteristics, data source profile, methods for handling time-varying exposure, results and the interpretation of findings from each eligibility. Paired reviewers will screen and extract data, resolving disagreements through discussion. We will describe the characteristics of included studies, and summarise the method used for handling time-varying exposure in primary analysis and sensitivity analysis. We will also compare the divergence between different approaches for handling time-varying exposure using ratio of risk ratios.Ethics and disseminationNo ethical approval is required because the data we will use do not include individual patient data. Findings will be disseminated through peer-reviewed publications.

Reporting, handling, and interpretation of time‐varying drug treatments in observational studies using routinely collected healthcare data

“…We have previously published the study protocol, detailing the eligibility criteria, literature search, selection process, data extraction, and statistical analysis 17 . Time‐varying drug treatments refer to the changes in drug treatment strategy throughout the course of treatment, including treatment discontinuation, switching and add‐on 17 . Treatment discontinuation occurred when individuals ceased taking a target treatment; treatment switching occurred if individuals in the exposure group switched to the control, or vice versa; and treatment add‐on was defined as individuals receiving treatments from both the exposure and control groups.…”

“…This study is part of a major research project examining the reporting and methodologic characteristics of time‐varying drug treatments in observational studies using RCD. We have previously published the study protocol, detailing the eligibility criteria, literature search, selection process, data extraction, and statistical analysis 17 . Time‐varying drug treatments refer to the changes in drug treatment strategy throughout the course of treatment, including treatment discontinuation, switching and add‐on 17 .…”

“…The absence of such information has obscured the efforts to improve observational studies of drug effects. Although a few previous studies investigated issues about statistical analyses and compared specific methods, 10,17 systematic efforts are strongly warranted to bridge the current gaps. Thus, we conducted a cross-sectional study to comprehensively investigate how time-varying treatments were managed and reported in observational studies using routinely collected data as well as how potential bias resulting from treatment change was interpreted.…”