Background: Many of the trials evaluating Tamiflu® were never published, and its manufacturer, Roche, was not willing to release the data voluntarily. After a long court battle that lasted many years, the Cochrane Collaboration was finally able to get all the unpublished data from Roche, and they performed a meta-analysis that was published in 2014. Important findings from the analysis are detailed below.

Oseltamivir for influenza in adults and children, BMJ (2014) [PubMed abstract]

• The meta-analysis included randomized, placebo-controlled trials of Tamiflu® used for the treatment, prophylaxis, and post-exposure prophylaxis of influenza
• Trials in both children and adults were evaluated as were trials involving patients with chronic illnesses (e.g. asthma, diabetes, etc.). Immunocompromised patients were excluded.
• Primary outcomes for treatment studies - symptom relief, admission to hospital, complications, and harms
• Primary outcomes for prophylaxis studies - influenza (symptomatic and asymptomatic, always with laboratory confirmation) and influenza-like illness, admission to hospital, complications, interruption of transmission (in its two components, reduction of viral spread from index cases and prevention of onset of influenza in contacts), and harms
• Of the 83 available trials, 23 trials met the inclusion criteria

• Treatment studies (adults):
• Tamiflu decreased the time to first alleviation of influenza-like illness symptoms in adults by an average of 16.76 hours (95%CI 8.42 to 25.1)
• Tamiflu increased the incidence of nausea (NNH 28) and vomiting (NNH 22)
• Tamiflu decreased the incidence of diarrhea (NNT 43)
• Tamiflu decreased the incidence of "investigator mediated unverified pneumonia" by 1% (NNT 100). When a more strict definition of pneumonia was used, there was no significant difference.
• Tamiflu had no significant effect on rates of hospital admission
• Prophylaxis studies (adults):
• Tamiflu decreased the incidence of symptomatic influenza (NNT 33)
• Tamiflu had no significant effect on the incidence of asymptomatic influenza (HR 0.78, 95%CI 0.49 to 1.24)
• Tamiflu had no significant effect on admission to hospital (HR 1.14, 95%CI 0.66 to 1.94)
• Tamiflu increased the incidence of headache (NNH 32), nausea (NNH 25), and psychiatric symptoms (NNH 94)
• Treatment studies (children):
• Tamiflu had no significant effect on the time to first alleviation of influenza-like illness symptoms in children (95%CI decrease of 33 hours to increase of 17 hours)
• Tamiflu had no significant effect on rates of hospital admission (HR 1.92, 95%CI 0.7 to 5.23)
• Tamiflu had no significant effect on the incidence of bronchitis (HR 0.65, 95%CI 0.27 to 1.55), otitis media (HR 0.8, 95%CI 0.62 to 1.02), or pneumonia (HR 1.06, 95%CI 0.62 to 1.83)
• Tamiflu increased the incidence of vomiting (NNH 19)

Summary This long-awaited meta-analysis calls into question the benefits of Tamiflu. Tamiflu appears to decrease the symptoms of flu in adults by about 17 hours at the cost of increased nausea and vomiting. Tamiflu had no obvious benefit in children. When it comes to clinically important outcomes like pneumonia and hospitalization, Tamiflu showed no proven benefit in any group.

Based on the available evidence, Tamiflu has no proven significant effect on clinically important outcomes. Widespread outpatient use is not supported. Whether Tamiflu improves outcomes in sicker, hospitalized patients is unclear.