Performance of the Self-Controlled Case Series With Active Comparators for Drug Safety Signal Detection Using the Clinical Practice Research Datalink (CPRD)
Abstract
Background: There is little evidence about signal detection using UK primary care electronic health records (EHRs). The self controlled case series (SCCS) is one of the most promising methods for drug safety signal detection using real world data, and incorporating active comparators could potentially improve its performance by addressing confounding by indication.
Objectives: This study aims to evaluate the performance of the SCCS with and without active comparators for signal detection using the UK Clinical Practice Research Datalink (CPRD) Aurum.
Methods: We applied the SCCS to macrolide and fluoroquinolone antibiotics, using amoxicillin and cefalexin as active comparators. In total seven drugs, and 30 outcomes from all organ classes were selected. We developed a reference set of 104 positive controls and 58 negative controls, using a taxonomy framework to ensure the selected drug outcome pairs are theoretically well suited to the SCCS design. Two-year observation periods with a 30-day risk window after each dispensing were used. Diagnostic performance was measured using sensitivity and specificity with respect to the product labels.
Results: The sensitivity and specificity of the SCCS without active comparator in the 2017/2018 observation period were 0.57 and 0.77 when limited to pairs with satisfactory power. Specificity increased up to 0.89 with active comparators, however sensitivity decreased to 0.18. Five drug-outcome pairs were signals of disproportionality before…
How strong is the evidence?
Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
- Levofloxacin-Induced Tendon Rupture: A Case Report and Review of the Literature
- Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)
- Neuroprotective Effects of Epicatechin against Oxidative Stress-Induced Cognitive Impairment: A Systematic Review and Meta-Analysis
- Quality evaluation and in vitro interaction studies between levofloxacin 250mg and diclofenac sodium 50mg tablets
- Molecular Epidemiology of mcr-1 -Positive Polymyxin B-Resistant Escherichia coli Producing Extended-Spectrum β-Lactamase (ESBL) in a Tertiary Hospital in Shandong, China
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.