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Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65-24 months; body weight range, 2.5-12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57-274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.

BackgroundDouble-checking the administration of medications has been standard practice in paediatric hospitals around the world for decades. While the practice is widespread, evidence of its effectiveness in reducing errors or harm is scarce.ObjectivesTo measure the association between double-checking, and the occurrence and potential severity of medication administration errors (MAEs); check duration; and factors associated with double-checking adherence.MethodsDirect observational study of 298 nurses, administering 5140 medication doses to 1523 patients, across nine wards, in a paediatric hospital. Independent observers recorded details of administrations and double-checking (independent; primed—one nurse shares information which may influence the checking nurse; incomplete; or none) in real time during weekdays and weekends between 07:00 and 22:00. Observational medication data were compared with patients’ medical records by a reviewer (blinded to checking-status), to identify MAEs. MAEs were rated for potential severity. Observations included administrations where double-checking was mandated, or optional. Multivariable regression examined the association between double-checking, MAEs and potential severity; and factors associated with policy adherence.ResultsFor 3563 administrations double-checking was mandated. Of these, 36 (1·0%) received independent double-checks, 3296 (92·5%) primed and 231 (6·5%) no/incomplete double-checks. For 1577 administrations double-checking was not mandatory, but in 26·3% (n=416) nurses chose to double-check. Where double-checking was mandated there was no significant association between double-checking and MAEs (OR 0·89 (0·65–1·21); p=0·44), or potential MAE severity (OR 0·86 (0·65–1·15); p=0·31). Where double-checking was not mandated, but performed, MAEs were less likely to occur (OR 0·71 (0·54–0·95); p=0·02) and had lower potential severity (OR 0·75 (0·57–0·99); p=0·04). Each double-check took an average of 6·4 min (107 hours/1000 administrations).ConclusionsCompliance with mandated double-checking was very high, but rarely independent. Primed double-checking was highly prevalent but compared with single-checking conferred no benefit in terms of reduced errors or severity. Our findings raise questions about if, when and how double-checking policies deliver safety benefits and warrant the considerable resource investments required in modern clinical settings.