On some contributions of STRATOS Topic Group 5 on Study Design: Guidance for the Design of Observational Studies to Estimate the Effects of Long-term Drug Exposures on Safety Outcomes

Despite advances in observational research methods used to estimate the effects of long-term drug exposures on safety outcomes, deficiencies in study design persist, potentially compromising the validity of reported evidence. STRATOS Topic Group 5 (TG5) focuses on developing guidance for designing observational studies, and is currently developing much-needed guidance in this area.

Informed by results of a scoping review on methods used in observational studies examining antidiabetic medications and fracture risk, this talk will review key study design aspects to consider when assessing the effects of long-term drug exposures on safety outcomes. Focus will be on establishing purposeful connections between etiologic and clinical pharmacology foundations and principles of pharmacoepidemiology. A case example will be presented to demonstrate how to appropriately consider key study design aspects when designing an observational study to estimate the effects of antidiabetic medications on hip fracture risk.
More specifically, three key study design aspects will be emphasized: (1) pathophysiology of the condition that indicated the drug exposure and how it may be implicated in the pathogenesis of the drug exposure-outcome relationship under study; (2) clinical pharmacology of the drug exposure; and (3) time trends in the drug exposure as well as in the outcome and other study variables at the population and individual levels.
In the context of the case example, aspects (1) and (2) are considered particularly important when defining a biologically plausible exposure risk window, exposure measurement, and a set of potential confounders. Aspect (3) is important to understand the time trends in the use of antidiabetic medications that may be due to changes in drug markets and policies at the population level, and in healthcare needs at the individual level, which may result in significantly biased effect estimates.
Careful consideration and transparent reporting of the three key study design aspects emphasized, and of study design and analytic approaches in general, will improve the validity of reported evidence from observational studies.

Study Design