ArticleBMJ open2024
Direct oral anticoagulant approvals by four major regulatory agencies: a cross-sectional analysis of premarket and postmarket evidence.
Article in BMJ open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
objectivesTo compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies.
designCross-sectional.
settingEuropean Medicines Association (EMA), US Food and Drug Administration (FDA), Health Canada and Australian Therapeutic Goods Administration (TGA).
participantsApixaban, dabigatran, edoxaban and rivaroxaban marketing authorisations. OUTCOME MEASURES: Concordance among regulatory agencies with respect to (1) premarket evidence used to establish efficacy and safety and (2) postmarket safety boxed warnings and postmarketing study requirements.
resultsApixaban, dabigatran and rivaroxaban were approved by each of the four regulatory agencies; edoxaban was only not approved by TGA. For premarket efficacy evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for three (75%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for four (100%) drugs and number of phase 2 trials for three (75%) drugs. For the premarket safety evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for two (50%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for three (75%) drugs and number of phase 2 trials for zero (0%) drugs. For postmarket safety information, FDA was the only agency that issued boxed warnings (for three (75%) drugs). Additionally, EMA and TGA required postmarketing studies (for four (100%) and two (50%) drugs, respectively), while FDA and Health Canada did not have any postmarketing requirements.
conclusionsThere was a high degree of concordance in the phase 3 trial premarket evidence used to establish efficacy and safety of direct oral anticoagulant approvals across four major regulatory agencies, but discordance in the phase 2 trial premarket evidence used, as well as in postmarket safety boxed warnings and postmarketing study requirements. These discrepancies highlight opportunities for further harmonisation in the evaluation and regulation of medical products globally.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.