Use of real-world evidence in translational pharmacology research.

Real-world evidence (RWE) refers to observational data gathered outside the formalism of randomized controlled trials, in real life situations, on marketed drugs. While clinical trials are the gold standards to demonstrate the efficacy and tolerability of a medicinal product, the generalizability of their results to actual use in real-life is limited by the biases induced by the very nature of clinical trials; indeed, the patients included in the trials may differ from actual users because of their concomitant diseases or treatments, or other factors excluding them from the trials. Clinical researchers and pharmaceutical industries have hence become increasingly interested in expanding and integrating RWE into clinical research, by capitalizing on the exponential growth in access to data from electronic health records, claims databases, electronic devices, software or mobile applications, registries embedded in clinical practice and social media. Meanwhile, applications of RWE may also be used for drug discovery and repurposing, for clinical developments and post-marketing studies. The aim of this review is to provide our opinion regarding the use of RWE in translational research, including non-clinical and clinical pharmacology research, at the different step of drugs development use.

Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results.

AIM: The MITOCARE study evaluated the efficacy and safety of TRO40303 for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). METHODS: Patients presenting with STEMI within 6 h of the onset of pain randomly received TRO40303 (n = 83) or placebo (n = 80) via i.v. bolus injection prior to balloon inflation during primary percutaneous coronary intervention in a double-blind manner. The primary endpoint was infarct size expressed as area under the curve (AUC) for creatine kinase (CK) and for troponin I (TnI) over 3 days. Secondary endpoints included measures of infarct size using cardiac magnetic resonance (CMR) and safety outcomes. RESULTS: The median pain-to-balloon time was 180 min for both groups, and the median (mean) door-to-balloon time was 60 (38) min for all sites. Infarct size, as measured by CK and TnI AUCs at 3 days, was not significantly different between treatment groups. There were no significant differences in the CMR-assessed myocardial salvage index (1-infarct size/myocardium at risk) (mean 52 vs. 58% with placebo, P = 0.1000), mean CMR-assessed infarct size (21.9 g vs. 20.0 g, or 17 vs. 15% of LV-mass) or left ventricular ejection fraction (LVEF) (46 vs. 48%), or in the mean 30-day echocardiographic LVEF (51.5 vs. 52.2%) between TRO40303 and placebo. A greater number of adjudicated safety events occurred in the TRO40303 group for unexplained reasons. CONCLUSION: This study in STEMI patients treated with contemporary mechanical revascularization principles did not show any effect of TRO40303 in limiting reperfusion injury of the ischaemic myocardium.