New-user and prevalent-user designs and the definition of study time origin in pharmacoepidemiology: A review of reporting practices

Background Guidance reports for observational comparative effectiveness and drug safety research recommend implementing a new-user design whenever possible, since it reduces the risk of selection bias in exposure effect estimation compared to a prevalent-user design. The uptake of this guidance has not been studied extensively. Methods We reviewed 89 observational effectiveness and safety cohort studies published in six pharmacoepidemiological journals in 2018 and 2019. We developed an extraction tool to assess how frequently new-user and prevalent-user designs were reported to be implemented. For studies that implemented a new-user design in both treatment arms, we extracted information about the extent to which the moment of meeting eligibility criteria, treatment initiation, and start of follow-up were reported to be aligned. Results Of the 89 studies included, 40% reported implementing a new-user design for both the study exposure arm and the comparator arm, while 13% reported implementing a prevalent-user design in both arms. The moment of meeting eligibility criteria, treatment initiation, and start of follow-up were reported to be aligned in both treatment arms in 53% of studies that reported implementing a new-user design. We provided examples of studies that minimized the risk of introducing bias due to unclear definition of time origin in unexposed participants, immortal time, or a time lag. Conclusions Almost half of the included studies reported implementing a new-user design. Implications of misalignment of study design origin were difficult to assess because it would require explicit reporting of the target estimand in original studies. We recommend that the choice for a particular study time origin is explicitly motivated to enable assessment of validity of the study.

Automated summary

The study found that 40% of studies reported implementing a new-user design, while only 13% of studies used a prevalent-user design. Among studies reporting implementation of a new-user design, 53% reported alignment in eligibility criteria, treatment initiation, and start of follow-up in both treatment arms, reducing the risk of bias introduction.