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Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation.
Health Technol Assess. 2009 Feb; 13(11):iii, ix-xii, 1-246.HT

Abstract

OBJECTIVES

To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of influenza.

DATA SOURCES

A MEDLINE search strategy was used and searches were carried out in July 2007.

REVIEW METHODS

An independent health economic model was developed based on a review of existing cost-effectiveness models and clinical advice.The model draws together a broad spectrum of evidence relating to the costs and consequences associated with influenza and its prevention. Where direct evidence concerning the effectiveness of prophylaxis within specific model subgroups was lacking, the model uses estimates from mixed subgroups or extrapolates from other mutually exclusive subgroups.

RESULTS

Twenty-six published references relating to 22 randomised controlled trials (RCTs) were included in the clinical effectiveness review, along with one unpublished report. Eight, six and nine RCTs were included for amantadine, oseltamivir and zanamivir respectively. The study quality was variable and gaps in the evidence base limited the assessment of the clinical effectiveness of the interventions. For seasonal prophylaxis, there was limited evidence for the efficacy of amantadine in preventing symptomatic, laboratory-confirmed influenza (SLCI) in healthy adults [relative risk (RR) 0.40, 95% confidence interval (CI) 0.08-2.03]. Oseltamivir was effective in preventing SLCI, particularly when used in at-risk elderly subjects (RR 0.08, 95% CI 0.01-0.63). The preventative efficacy of zanamivir was most notable in at-risk adults and adolescents (RR 0.17, 95% CI 0.07-0.44), and healthy and at-risk elderly subjects (RR 0.20, 95% CI 0.02-1.72). For post-exposure prophylaxis, data on the use of amantadine were again limited: in adolescents an RR of 0.10 (95% CI 0.03-0.34) was reported for the prevention of SLCI. Oseltamivir was effective in households of mixed composition (RR 0.19, 95% CI 0.08-0.45). The efficacy of zanamivir in post-exposure prophylaxis within households was also reported (RR 0.21, 95% CI 0.13-0.33). Interventions appeared to be well tolerated. Limited evidence was available for the effectiveness of the interventions in preventing complications and hospitalisation and in minimising length of illness and time to return to normal activities. No clinical effectiveness data were identified for health-related quality of life or mortality outcomes. With the exception of at-risk children, the incremental cost-utility of seasonal influenza prophylaxis is expected to be in the range 38,000-428,000 pounds per QALY gained (depending on subgroup). The cost-effectiveness ratios for oseltamivir and zanamivir as post-exposure prophylaxis are expected to be below 30,000 pounds per QALY gained in healthy children, at-risk children, healthy elderly and at-risk elderly individuals. Despite favourable clinical efficacy estimates, the incorporation of recent evidence of viral resistance to amantadine led to it being dominated in every economic comparison.

CONCLUSIONS

All three interventions showed some efficacy for seasonal and post-exposure prophylaxis. However, weaknesses and gaps in the clinical evidence base are directly relevant to the interpretation of the health economic model and rendered the use of advanced statistical analyses inappropriate. These data limitations should be borne in mind in interpreting the findings of the review.

Authors+Show Affiliations

University of Sheffield, School of Health and Related Research, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

19215705

Citation

Tappenden, P, et al. "Amantadine, Oseltamivir and Zanamivir for the Prophylaxis of Influenza (including a Review of Existing Guidance No. 67): a Systematic Review and Economic Evaluation." Health Technology Assessment (Winchester, England), vol. 13, no. 11, 2009, pp. iii, ix-xii, 1-246.
Tappenden P, Jackson R, Cooper K, et al. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. Health Technol Assess. 2009;13(11):iii, ix-xii, 1-246.
Tappenden, P., Jackson, R., Cooper, K., Rees, A., Simpson, E., Read, R., & Nicholson, K. (2009). Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. Health Technology Assessment (Winchester, England), 13(11), iii, ix-xii, 1-246. https://doi.org/10.3310/hta13110
Tappenden P, et al. Amantadine, Oseltamivir and Zanamivir for the Prophylaxis of Influenza (including a Review of Existing Guidance No. 67): a Systematic Review and Economic Evaluation. Health Technol Assess. 2009;13(11):iii, ix-xii, 1-246. PubMed PMID: 19215705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. AU - Tappenden,P, AU - Jackson,R, AU - Cooper,K, AU - Rees,A, AU - Simpson,E, AU - Read,R, AU - Nicholson,K, PY - 2009/2/14/entrez PY - 2009/2/14/pubmed PY - 2009/5/15/medline SP - iii, ix-xii, 1-246 JF - Health technology assessment (Winchester, England) JO - Health Technol Assess VL - 13 IS - 11 N2 - OBJECTIVES: To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of influenza. DATA SOURCES: A MEDLINE search strategy was used and searches were carried out in July 2007. REVIEW METHODS: An independent health economic model was developed based on a review of existing cost-effectiveness models and clinical advice.The model draws together a broad spectrum of evidence relating to the costs and consequences associated with influenza and its prevention. Where direct evidence concerning the effectiveness of prophylaxis within specific model subgroups was lacking, the model uses estimates from mixed subgroups or extrapolates from other mutually exclusive subgroups. RESULTS: Twenty-six published references relating to 22 randomised controlled trials (RCTs) were included in the clinical effectiveness review, along with one unpublished report. Eight, six and nine RCTs were included for amantadine, oseltamivir and zanamivir respectively. The study quality was variable and gaps in the evidence base limited the assessment of the clinical effectiveness of the interventions. For seasonal prophylaxis, there was limited evidence for the efficacy of amantadine in preventing symptomatic, laboratory-confirmed influenza (SLCI) in healthy adults [relative risk (RR) 0.40, 95% confidence interval (CI) 0.08-2.03]. Oseltamivir was effective in preventing SLCI, particularly when used in at-risk elderly subjects (RR 0.08, 95% CI 0.01-0.63). The preventative efficacy of zanamivir was most notable in at-risk adults and adolescents (RR 0.17, 95% CI 0.07-0.44), and healthy and at-risk elderly subjects (RR 0.20, 95% CI 0.02-1.72). For post-exposure prophylaxis, data on the use of amantadine were again limited: in adolescents an RR of 0.10 (95% CI 0.03-0.34) was reported for the prevention of SLCI. Oseltamivir was effective in households of mixed composition (RR 0.19, 95% CI 0.08-0.45). The efficacy of zanamivir in post-exposure prophylaxis within households was also reported (RR 0.21, 95% CI 0.13-0.33). Interventions appeared to be well tolerated. Limited evidence was available for the effectiveness of the interventions in preventing complications and hospitalisation and in minimising length of illness and time to return to normal activities. No clinical effectiveness data were identified for health-related quality of life or mortality outcomes. With the exception of at-risk children, the incremental cost-utility of seasonal influenza prophylaxis is expected to be in the range 38,000-428,000 pounds per QALY gained (depending on subgroup). The cost-effectiveness ratios for oseltamivir and zanamivir as post-exposure prophylaxis are expected to be below 30,000 pounds per QALY gained in healthy children, at-risk children, healthy elderly and at-risk elderly individuals. Despite favourable clinical efficacy estimates, the incorporation of recent evidence of viral resistance to amantadine led to it being dominated in every economic comparison. CONCLUSIONS: All three interventions showed some efficacy for seasonal and post-exposure prophylaxis. However, weaknesses and gaps in the clinical evidence base are directly relevant to the interpretation of the health economic model and rendered the use of advanced statistical analyses inappropriate. These data limitations should be borne in mind in interpreting the findings of the review. SN - 2046-4924 UR - https://www.unboundmedicine.com/medline/citation/19215705/Amantadine_oseltamivir_and_zanamivir_for_the_prophylaxis_of_influenza__including_a_review_of_existing_guidance_no__67_:_a_systematic_review_and_economic_evaluation_ L2 - https://doi.org/10.3310/hta13110 DB - PRIME DP - Unbound Medicine ER -