Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation

Objectives: To evaluate the clinical effectiveness\udand incremental cost-effectiveness of amantadine,\udoseltamivir and zanamivir for seasonal and postexposure\udprophylaxis of influenza.\udData sources: A MEDLINE search strategy was used\udand searches were carried out in July 2007.\udReview methods: An independent health economic\udmodel was developed based on a review of existing\udcost-effectiveness models and clinical advice. The model\uddraws together a broad spectrum of evidence relating\udto the costs and consequences associated with influenza\udand its prevention. Where direct evidence concerning\udthe effectiveness of prophylaxis within specific model\udsubgroups was lacking, the model uses estimates from\udmixed subgroups or extrapolates from other mutually\udexclusive subgroups.\udResults: Twenty-six published references relating to 22\udrandomised controlled trials (RCTs) were included in the\udclinical effectiveness review, along with one unpublished\udreport. Eight, six and nine RCTs were included for\udamantadine, oseltamivir and zanamivir respectively.\udThe study quality was variable and gaps in the evidence\udbase limited the assessment of the clinical effectiveness\udof the interventions. For seasonal prophylaxis, there\udwas limited evidence for the efficacy of amantadine in\udpreventing symptomatic, laboratory-confirmed influenza\ud(SLCI) in healthy adults [relative risk (RR) 0.40, 95%\udconfidence interval (CI) 0.08–2.03]. Oseltamivir was\udeffective in preventing SLCI, particularly when used in\udat-risk elderly subjects (RR 0.08, 95% CI 0.01–0.63).\udThe preventative efficacy of zanamivir was most notable\udin at-risk adults and adolescents (RR 0.17, 95% CI 0.07–\ud0.44), and healthy and at-risk elderly subjects (RR 0.20,\ud95% CI 0.02–1.72). For post-exposure prophylaxis,\uddata on the use of amantadine were again limited: in\udadolescents an RR of 0.10 (95% CI 0.03–0.34) was\udreported for the prevention of SLCI. Oseltamivir was\udeffective in households of mixed composition (RR\ud0.19, 95% CI 0.08–0.45). The efficacy of zanamivir in\udpost-exposure prophylaxis within households was also\udreported (RR 0.21, 95% CI 0.13–0.33). Interventions\udappeared to be well tolerated. Limited evidence was\udavailable for the effectiveness of the interventions in\udpreventing complications and hospitalisation and in\udminimising length of illness and time to return to normal\udactivities. No clinical effectiveness data were identified\udfor health-related quality of life or mortality outcomes.\udWith the exception of at-risk children, the incremental\udcost–utility of seasonal influenza prophylaxis is expected\udto be in the range £38,000–£428,000 per QALY gained\ud(depending on subgroup). The cost-effectiveness\udratios for oseltamivir and zanamivir as post-exposure\udprophylaxis are expected to be below £30,000 per\udQALY gained in healthy children, at-risk children, healthy\udelderly and at-risk elderly individuals. Despite favourable\udclinical efficacy estimates, the incorporation of recent\udevidence of viral resistance to amantadine led to it being\uddominated in every economic comparison.\udConclusions: All three interventions showed some\udefficacy for seasonal and post-exposure prophylaxis.\udHowever, weaknesses and gaps in the clinical evidence\udbase are directly relevant to the interpretation of\udthe health economic model and rendered the use of\udadvanced statistical analyses inappropriate. These data\udlimitations 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