Objectives: To evaluate the clinical effectiveness\ud and incremental cost-effectiveness of amantadine,\ud oseltamivir and zanamivir for seasonal and postexposure\ud prophylaxis of influenza.\ud Data sources: A MEDLINE search strategy was used\ud and searches were carried out in July 2007.\ud Review methods: An independent health economic\ud model was developed based on a review of existing\ud cost-effectiveness models and clinical advice. The model\ud draws together a broad spectrum of evidence relating\ud to the costs and consequences associated with influenza\ud and its prevention. Where direct evidence concerning\ud the effectiveness of prophylaxis within specific model\ud subgroups was lacking, the model uses estimates from\ud mixed subgroups or extrapolates from other mutually\ud exclusive subgroups.\ud Results: Twenty-six published references relating to 22\ud randomised controlled trials (RCTs) were included in the\ud clinical effectiveness review, along with one unpublished\ud report. Eight, six and nine RCTs were included for\ud amantadine, oseltamivir and zanamivir respectively.\ud The study quality was variable and gaps in the evidence\ud base limited the assessment of the clinical effectiveness\ud of the interventions. For seasonal prophylaxis, there\ud was limited evidence for the efficacy of amantadine in\ud preventing symptomatic, laboratory-confirmed influenza\ud (SLCI) in healthy adults [relative risk (RR) 0.40, 95%\ud confidence interval (CI) 0.08–2.03]. Oseltamivir was\ud effective in preventing SLCI, particularly when used in\ud at-risk elderly subjects (RR 0.08, 95% CI 0.01–0.63).\ud The preventative efficacy of zanamivir was most notable\ud in at-risk adults and adolescents (RR 0.17, 95% CI 0.07–\ud 0.44), and healthy and at-risk elderly subjects (RR 0.20,\ud 95% CI 0.02–1.72). For post-exposure prophylaxis,\ud data on the use of amantadine were again limited: in\ud adolescents an RR of 0.10 (95% CI 0.03–0.34) was\ud reported for the prevention of SLCI. Oseltamivir was\ud effective in households of mixed composition (RR\ud 0.19, 95% CI 0.08–0.45). The efficacy of zanamivir in\ud post-exposure prophylaxis within households was also\ud reported (RR 0.21, 95% CI 0.13–0.33). Interventions\ud appeared to be well tolerated. Limited evidence was\ud available for the effectiveness of the interventions in\ud preventing complications and hospitalisation and in\ud minimising length of illness and time to return to normal\ud activities. No clinical effectiveness data were identified\ud for health-related quality of life or mortality outcomes.\ud With the exception of at-risk children, the incremental\ud cost–utility of seasonal influenza prophylaxis is expected\ud to be in the range £38,000–£428,000 per QALY gained\ud (depending on subgroup). The cost-effectiveness\ud ratios for oseltamivir and zanamivir as post-exposure\ud prophylaxis are expected to be below £30,000 per\ud QALY gained in healthy children, at-risk children, healthy\ud elderly and at-risk elderly individuals. Despite favourable\ud clinical efficacy estimates, the incorporation of recent\ud evidence of viral resistance to amantadine led to it being\ud dominated in every economic comparison.\ud Conclusions: All three interventions showed some\ud efficacy for seasonal and post-exposure prophylaxis.\ud However, weaknesses and gaps in the clinical evidence\ud base are directly relevant to the interpretation of\ud the health economic model and rendered the use of\ud advanced statistical analyses inappropriate. These data\ud limitations should be borne in mind in interpreting the findings of the review.Produced under the auspices of the NHS R & D Health Technology Assessment Programme. Monographs in this series are also available from the National Coordinating Centre for Health Technology Assessment (NCCHTA) website at www.ncchta.org.Peer reviewedPublisher versio
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