Background Post-market pharmacovigilance relies predominantly on single-database disproportionality analysis of spontaneous adverse event reports, which lacks corroboration across independent evidence streams and cannot integrate randomised trial evidence. No publicly accessible platform has previously combined European national pharmacovigilance registries, the US FDA Adverse Event Reporting System (FAERS), and clinical trial meta-analyses into a unified, continuously scored signal detection framework.

Methods We describe the Signal Consensus Index (SCI), a composite 0-100 pharmacovigilance signal score integrating disproportionality evidence from the Danish National Pharmacovigilance Database, the UK MHRA Yellow Card scheme, and FAERS, with DerSimonian-Laird meta-analytic risk ratios from ClinicalTrials.gov, across 6,905,874 drug-adverse event pairs. Each source contributes a continuous score derived from the lower bounds of three complementary disproportionality metrics (ROR, PRR, IC025) for spontaneous reporting sources, and from the pooled risk ratio lower confidence bound for clinical trials. The SCI is publicly accessible via the Adverse Event Atlas (aeatlas.com). We report reference set validation against the EU-ADR reference standard, a single-source comparison with discordance characterisation, temporal stability analysis across eight cumulative data windows (2015-2023), and a weight sensitivity analysis across seven pre-specified weighting schemes.

Results The SCI generated 129,176 Moderate-or-Strong signals (SCI ≥ 50, confidence ≥ 50) and 7,290 Strong signals (SCI ≥ 70, confidence ≥ 70). Reference set validation against 88 classifiable drug-event pairs (44 positive controls, 44 negative controls) yielded 18 true positives, 0 false positives, 44 true negatives, and 26 false negatives (sensitivity 40.9%, specificity 100.0%, PPV 100.0%, NPV 62.9%). Zero false positives were observed across all 44 classifiable negative controls, with five false negatives attributable to the confidence gate correctly suppressing single-source signals pending multi-source corroboration. Single-source comparison demonstrated that FAERS alone generated 1,438,246 disproportionality signals, of which 94.8% were not confirmed by the SCI, while 54,184 SCI-detected signals were absent from FAERS, of which 8.3% involved drugs absent from the US reporting system. Discordance analysis showed that 99.8% of Danish non-confirmation reflected data availability constraints. Temporal stability was high: 98.5% of pairs received identical classifications across all seven weight scenarios, and 57.0% of final Strong signals were already detectable as Moderate or Strong in the earliest data window (2015-2016). Strong classifications were stable across weight scenarios (94.0% of Strong observations remaining Strong).

Conclusions The SCI provides a transparent, openly accessible framework for cross-source pharmacovigilance signal prioritisation with 100% specificity and PPV against an established reference standard and stable classifications across weighting schemes. Progressive signal emergence through the Moderate tier supports its use as an early detection layer. The platform is available at aeatlas.com.

The authors have declared no competing interest.

This study did not receive any funding

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

https://www.vigiaccess.org/ https://laegemiddelstyrelsen.dk/da/bivirkninger/bivirkninger-ved-medicin/interaktive-bivirkningsoversigter/ https://yellowcard.mhra.gov.uk/ https://open.fda.gov/data/faers/ https://clinicaltrials.gov/

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