title: Mixed treatment comparison with multiple outcomes reported inconsistently across trials: evaluation of antivirals for treatment of influenza A and B.
abstract: We present a mixed treatment meta-analysis of antivirals for treatment of influenza, where some trials report summary measures on at least one of the two outcomes: time to alleviation of fever and time to alleviation of symptoms. The synthesis is further complicated by the variety of summary measures reported: mean time, median time and proportion symptom free at the end of follow-up. We compare several models using the deviance information criteria and the contribution of different evidence sources to the residual deviance to aid model selection. A Weibull model with exchangeable treatment effects that are independent for each outcome but have a common random effect mean for the two outcomes gives the best fit according to these criteria. This model allows us to summarize treatment effect on two outcomes in a single summary measure and draw conclusions as to the most effective treatment. Amantadine and Oseltamivir were the most effective treatments, with the probability of being most effective of 0.56 and 0.37, respectively. Amantadine reduces the duration of symptoms by an estimated 2.8 days, and Oseltamivir 2.6 days, compared with placebo. The models provide flexible methods for synthesis of evidence on multiple treatments in the absence of head-to-head trial data, when different summary measures are used and either different clinical outcomes are reported or where the same outcomes are reported at different or multiple time points.
authors.affiliation: Academic Unit of Primary Health Care, Department of Community Based Medicine, University of Bristol, Cotham House, Cotham Hill, Bristol BS6 6JL, U.K. nicky.welton@bristol.ac.uk
authors.forename: N J
authors.initials: NJ
authors.lastname: Welton
authors.forename: N J
authors.initials: NJ
authors.lastname: Cooper
authors.forename: A E
authors.initials: AE
authors.lastname: Ades
authors.forename: G
authors.initials: G
authors.lastname: Lu
authors.forename: A J
authors.initials: AJ
authors.lastname: Sutton
mesh_terms: D000547:Amantadine / Q000008:administration & dosage / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001499:Bayes Theorem; D002986:Clinical Trials as Topic; D003661:Decision Support Techniques; D005500:Follow-Up Studies; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D008390:Markov Chains; D015201:Meta-Analysis as Topic; D009010:Monte Carlo Method; D053139:Oseltamivir / Q000008:administration & dosage / Q000627:therapeutic use*; D013223:Statistics as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D000547:Amantadine