neuraminidase inhibs for flu: lack of significant efficacy

BMJ just came out with 2 articles from the Cochrane group on neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) (see http://www.bmj.com/content/348/bmj.g2545.pdf%2Bhtml for oseltamivir and http://www.bmj.com/content/348/bmj.g2547 for zanamivir). these papers are updated systematic reviews, and for oseltamivir (per the editorialist) "is the culmination of a four and a half year battle for access to the raw data from industry funded trials of oseltamivir, a drug on which the world has spent billions of dollars", and reflects very different results than that presented to regulators, policy makers, the public etc by the drug makers. brief summaries:

oseltamivir: 83 RCTs on adults and kids. results:

    --treatment studies:

            --time to first alleviation of symptoms: decreased 16.7 hours (from 7 days to 6.3 days). no effect on kids with asthma, but healthy kids decreased symptoms by 29 hours

            --no diff in admissions to hospital for adult. sparse data on kids. 

            --no diff in pneumonia, bronchitis, otitis media, sinusitis or any serious complication

            --but increased nausea (number needed to harm NNTH 28) and vomiting (NNTH 22) with oseltamivir in adults and and vomiting in kids (NNTH 19). also inc QTc (NNTH 25)

    --prophylaxis trials, oseltamivir dec symptomatic flu in pts by 55% and households by 13.6%, but no effect on asymptomatic flu and no evidence of dec transmission. in prophylaxis trials, inc risk of psych adverse events (NNTH 94), with dose response curve. increased headaches (NNTH 32), renal events -- esp dec creat clearance (NNTH 150) and nausea (NNTH 25)

    --authors note: "in a primary or secondary prophylaxis indication the postulated central effect of oseltamivir is confined to suppressing symptoms, because infection, according to Roche (the manufaturer) is not prevented".

zanamirir: (see http://www.bmj.com/content/348/bmj.g2547 ). 54 RCTs in kids and adults. 

     --treatment studies:

        --zanamivir reduced time to first alleviation of sx by 0.60 days (from 6.6 to 6.0 days, 14.4 hours) in adults. not significant in kids.

        --no diff in pneumonia (investigator-reported or by CXR) in adults. also nonsignificant effect in kids

        --no diff in otitis media or sinusitis in adults and kids, small effect in bronchitis only in adults (1.8%)

     --prophylaxis studies:

        --no diff in asymptomatic flu cases in individuals or households. only 2 small studies found effect in symptomatic flu in adults by 14.8%. 

        --no signif adverse events

so, what does this all mean?  of note the WHO has oseltamivir on their list of "essential drugs". but neither of these drugs have significant effects on preventing or treating major complications of flu. the CDC also fully embraced these drugs (without having full transparent access to data) as did the am acad of pediatrics, making claims that starting these drugs early prevent serious complications. in these studies, it is unclear if using zanamivir, for example, actually reduces symptoms more than taking symptom relief meds.  the data from these studies are pretty compelling (and quite striking, since these drugs have been around for 15 years!): the benefits of these drugs are pretty minimal, the cost is high, the incidence of adverse effects (with oseltamivir) is high, and the imperative to use them comes from the lack of transparency and withholding info by big pharma.