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SNIIRAM/SNDS, the French administrative health care database, covers around 99 % of the population. Its main limitation is the absence of clinical information and biological results. This report exposes the value of SNIIRAM/SNDS enrichment by external databases, and the linkage issues. It is illustrated by examples: the well-known population-based cohort CONSTANCES created to answer to epidemiological research questions with a specific interest on occupational and social factors, chronic diseases, and aging; the CANARI study, a regional-based study that collected Gleason score in all pathology laboratories in Brittany and then, linked pathology results to an ad hoc extraction from SNIIRAM database; the goal was to investigate the risk of high grade prostate cancer in patients treated by 5-alphareductase inhibitors for a symptomatic benign prostatic hyperplasia; the SACHA study, that identified and medically validated major bleeding event referred to emergency wards, then linked those clinical data to SNIIRAM; the goal was to minimize misclassification bias when estimating bleeding risk in patients who were prescribed antithrombotic drugs; the ISO-PSY study linked the SNIIRAM with the national cause of death registry (CépiDc) and the nationwide emergency department surveillance system (OSCOUR® Network) to investigate the potential link between isotretinoin and suicidal risk; the EFEMERIS cohort that assesses drugs prescriptions in French pregnant women who delivered in the Haute-Garonne region; the EPI-GETB-AM study that derived a SNIIRAM/SNDS-based algorithm to identify venous thromboembolism and linked SNIIRAM/SNDS to the EPI-GETBO-III survey for validation. Another perspective of SNDS enrichment is clinical trials' data for medico-economic assessment, and extended follow-up without attrition bias. Linkage is not straightforward. Apart from regulatory approbation and authorized data center issues, which could be solved by the Health Data Hub Initiative, a multidisciplinary team with medical, pharmacological and methodological knowledge, as well as with technical skills is essential to handle the whole process.

Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin‐releasing hormone (GnRH) agonists, whereas randomised‐controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real‐world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random‐effects meta‐analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96‐1.61; I2: 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11‐2.35; I2: 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11‐2.15, I2: 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists—though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage.

Abiraterone acetate (ABI) and enzalutamide (ENZ) are considered as clinically relevant comparators among chemotherapy-naïve castration-resistant prostate cancer patients. No clinical trials comparing overall survival (OS) of ABI to ENZ in a head-to-head approach have been published so far. A few observational studies with lack of power suggested a potential benefit of ENZ. Among chemotherapy-naïve castration-resistant prostate cancer patients, we used the French National Health Data System (‘SNDS’), to compare OS of new users of ABI and ENZ in 2014-2017, followed through 2018 (the SPEAR cohort, a 2014-2018 cohort study). With an “intent-to-treat” approach, a survival analysis was performed, estimating hazard ratios (HRs) for OS with the inverse probability weighted Cox model method. Among 10 308 new users, 64% were treated with ABI, 36% with ENZ. The crude mortality rate was 25.2 per 100 person-years, 95% CI: 24.4, 26.0 for ABI and 23.7 per 100 person-years, 95% CI: 22.6, 24.9 for ENZ. In the weigthed analysis, ENZ was associated with better OS compared to ABI (HR 0.90, 95% CI: 0.85,0.96; median OS, 31.7 months for ABI and 34.2 months for ENZ). When restricting to 2015-2017 new users, the effect estimate shifted up to HR 0.93, 95% CI: 0.86, 1.01.

The objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real-world data. Methods: A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism). Results: Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37-0.82 and 0.54, 0.26-1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29-0.58 and 0.41, 0.22-0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding. Conclusion: There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.

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Aim. Safety profiles of abiraterone and enzalutamide mainly rely on phase III clinical trials.Our objective was to estimate the incidence rate ratio (IRR) for certain adverse events leading in real life to hospitalization (atrial fibrillation, acute heart failure, ischemic heart disease, acute kidney injury (AKI), ischemic stroke, torsade de pointe / QT interval prolongation, hepatitis, and seizure), comparing abiraterone to enzalutamide. We also set out to discuss previously identified safety signals.Method. Using the French National Health Insurance System database, all patients newly exposed to abiraterone or enzalutamide between 2013 and 2017 and followed until December 31 st , 2018 were targeted. IRR for each event were estimated using a Poisson model in a sub-population of patients without contraindications or precautions for use for either treatment.Results. Among 11,534 new users of abiraterone and enzalutamide, AKI (IRR 1.42, 95% CI:1.01-2.00), liver monitoring suggestive of hepatic damage (IRR 3.06, 95% CI: 2.66 -3.53), and atrial fibrillation (IRR 1.12, 95% CI: 1.05 -1.19) were significantly more often observed with abiraterone than with enzalutamide. Conclusion.Our study provides knowledge on abiraterone and enzalutamide real-life safety profiles, especially for events leading to hospitalisation. Despite several limitations, including the lack of clinical data, the safety signal for AKI under abiraterone is in line with results of an analysis of the French pharmacovigilance database, which requires further specific investigations. Enlightening the clinicians' therapeutic choices for patients treated for prostate cancer, our study should lead to clinicians to be cautious in the use of abiraterone..