No effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza

No effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza Announcement Date: June 14, 2016

No effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza? HTA review

What did we do?

As part of our recently published HTA review we assessed the effect of oseltamivir on mortality in 2009A/H1N1 influenza patients.

(See Chapter 3, page 99 Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data. Health Technol Assess 2016; 20 (42).

To do this we did a systematic review and individual patient data meta-analysis of observational studies.  We included 2009A/H1N1 influenza patients reporting mortality outcomes and exposure to oseltamivir with at least 5% of patients untreated with influenza antivirals and five or more deaths overall.

A pre publication protocol outlining our proposed study was also registered at Prospero.

Why did we do this?

What did we find?

We found insufficient evidence from 30 observational studies to support oseltamivir having a protective effect on 2009A/H1N1 influenza patients for mortality.

 

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After taking account of time-dependent bias, potential confounding variables, and the competing risk of hospital discharge, analysis of IPD showed  oseltamivir did not reduce the risk of mortality,  HR 1.03 (95% CI 0.64 to 1.65).

Results showed no effect of age group (p=0.40) or severity of illness (p=0.38), but evidence of aneffect of log-odds of death (p=0.024) when, as odds of death increases, the treatment effect in favour ofoseltamivir increases, and log-odds of treatment (p=0.003), when, as odds of treatment increases, the treatment effect in favour of oseltamivir increases.

These effects appear to be independent as p-values in multivariable analysis are 0.031 and 0.006, respectively.

To illustrate these effects we conducted subgroup analysis by odds of treatment:
‘<5’ compared with ‘≥5’ and percentage of death: ‘<10%’ compared with ‘≥10%’ . An odds of treatment of ‘≥5’ equates to a percentage of≥83.3%. Results show treatment effect is in favour of oseltamivir and more heterogeneous in cohorts when odds of treatment were‘≥ 5’. Conversely, in cohorts for which odds were‘<5’,heterogeneity is smaller and overall effect is in favour of no treatment (Figure 18 in from Health Technol Assess 2016; 20 (42).HTA review shown ).

What were the limitations?

Although all 30 studies classified patients by treatment exposure, only two defined it: one as ‘at least one dose of oseltamivirand the other as ‘at least one day of treatment

See also  Appendix 15 (page 229)  “Illustration of time-dependent bias using individual patient data from the Canadian study”for a detailed description and example of time-dependent bias.

What does this mean?

Figures see chapter 3 page 99,  Health Technol Assess 2016; 20 (42).

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read  blog post by Mark Jones on Oseltamivir and mortality: Why does Muthuri et al (2014) conclusions differ from Heneghan et al (2016)