Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data

Background: Observational studies claimed reducing effects of neuraminidase inhibitors (NI) on hospital mortality in patients with H1N1 influenza A. It has been criticized that such findings are prone to common and serious survival biases. Methods: With observational data from the FLU-CIN study group, multi-state and dynamic prediction models have been used to avoid such biases. The data included 1391 patients with confirmed pandemic influenza A/H1N1 infection collected during 2009-2010 in the UK. Due to their close relationship, the main outcome measures were hospital death and length of hospital stay. Findings: There is no direct effect of NI on the hospital death rate; the hazard ratio (HR) of NI was 1.03 (95%-CI: 0.64–1.66). The discharge rate is increased for NI patients (HR = 1.89 (95%-CI: 1.65–2.16)) indicating that NI-treated patients stay shorter in hospital than NI-untreated patients, on average 3.10 days (95%-CI: 2.07–4.14). We also showed that the initiation timing of NI treatment (≤ 2 days versus > 2 days after onset) made no difference on the effects on the hospital death and discharge hazards. The hazard ratios remain stable after adjusting for potential confounders measured at admission (such as comorbidities and influenza-related clinical symptoms). Conclusions: The potential beneficial effect of NI on hospitalized patients in the UK is rather a reduction of the length of hospital stay than a reduction of the mortality rate. There seems to be no confounding by indication and no differences if NI is given early or late. Different effects could be present in other populations (such as non-hospitalized individuals) or countries. Careful interpretation of the effect on length of hospital stay is needed due to potentially different discharge policies of NI-treated and NI-untreated patients.