Medical Research Study: Postmarket Drug Safety

Background

Safety issues are detected in about one-third of prescription drugs in the years following approval. Older adults with chronic kidney disease are particularly at risk of adverse reactions. This protocol outlines a new approach to identifying drug-safety signals through administrative health care data.

Study Design and Setting

The studies are population-based, new-user cohort studies conducted using Ontario's healthcare databases from 2008 to 2020. They cover 700+ cohorts comparing new prescription drug users to nonusers with similar baseline health characteristics, examining 74 acute outcomes over 30 days.

Outcomes and Analysis

Comparisons of new users and nonusers yield weighted risk ratios and risk differences, exploring drug-outcome associations, additive and multiplicative interactions, and other analyses.

Analysis Techniques

In each cohort, eGFR-stratum-specific risk ratios and risk differences are calculated using modified Poisson regression and binomial regression, respectively. This includes examining both additive and multiplicative interactions by eGFR category. Detected drug-outcome associations undergo further analysis, including survival, negative-control exposure, and E-value assessments.

Study Scale

The initial medication cohorts have a median of 6120 new users per cohort (IQR: 1469-38,839) and a median of 1,088,301 nonusers (IQR: 751,697-1,267,009). The medications with the most new users are amoxicillin trihydrate, cephalexin, prescription acetaminophen, and ciprofloxacin, ranging from 19% to 29% having an eGFR <60 ml/min per 1.73 m2.

Limitations

Despite the use of robust techniques to balance baseline indicators and control for confounding by indication, residual confounding remains a possibility. Only acute (30-day) outcomes are examined, and data sources do not include non-prescription drugs, prescriptions issued in hospitals, or children and adults under 65.