Relearning Bradford Hill through our final patient in the Tenecteplase in Central Retinal Artery Occlusion Study

Le résumé fourni par la source

Editor, an experience during our work on the Tenecteplase in Central Retinal Artery Occlusion Study (TenCRAOS), recently published in the New England Journal of Medicine, brought us back to the enduring insights of Sir Austin Bradford Hill and his seminal role in shaping the modern randomised clinical trial (1948; Ryan et al., 2026). By coincidence, one of the final patients was enrolled at our own hospital in Oslo, from which the study was coordinated. Recruiting 78 patients within the narrow thrombolysis window had been challenging, but we were nearing completion of the study, and a quiet sense of relief accompanied the moment when consent was obtained and the blinded intravenous bolus was administered. What followed was unforgettable: 10 minutes later, a veil seemed to lift from the patient's blind eye, and the vision returned. The following day, the grateful patient was discharged entirely symptom-free, and at the 4-week study visit, best-corrected visual acuity was 20/20 with a normal visual field. Had this occurred in routine clinical practice, it would most likely have prompted a case report, since full visual recovery after intravenous thrombolysis for central retinal artery occlusion would have offered a glimmer of therapeutic hope for this patient population. Yet in the controlled trial setting, we instead eagerly set about completing the dataset, locking the database, and finalising the statistical analysis plan so that we could unblind the results. As the paper shows, the primary outcome ultimately dashed our hopes for an effective treatment; the likelihood of visual recovery did not favour thrombolysis, contradicting the promising observational data that had motivated the study (Schrag et al., 2015). It was our final patient who reminded us of Bradford Hill's principles and the importance of considering the totality of evidence rather than only the most memorable or seemingly positive findings—for this patient, as it turned out, had regained vision 10 minutes after receiving a placebo infusion. TenCRAOS received support from Oslo University Hospital, the Norwegian Program for Clinical Therapy Research in the specialist health service, the South-Eastern Norway Regional Health Authority, the International Order of Odd Fellows and by an unconditional grant from Boehringer Ingelheim Norway for the purchase of tenecteplase.

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