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Recently we had a debate amongst our Intensivists about how to proceed with our influenza patients in ICU in light of recent controversy surrounding Tamiflu (Oseltamivir).  I’m interested in breaking down the reasons behind the controversy and seeking out others views on how they have approached the new information.

The debate was triggered by recent revelations that Roche - the drug company selling Tamiflu, and which funded the research to establish its efficacy - did not publish all of its data. In particular, the negative trials were not published and, when questioned about the missing studies, Roche was extremely slow to release them for analysis by the Cochrane review panel.  This was not illegal practice but does fly in the face of best scientific practice when establishing drug efficacy. The whole saga has raised the question about whether it should continue to be legal to withhold negative trial data.  There are several great articles discussing the whole saga (see here and here for my favourites)

The results have now been analysed (see here) and there appears to be very little benefit from Tamiflu for standard cases (a reduction in duration of symptoms from 7 to 6.5 days with no reduction in disease transmission or hospitalisation), and there are some side effects (nausea and vomiting, headache and some psychiatric symptoms).  However, in the critical care population, there is not yet enough information to know whether it has a mortality or severe morbidity benefit. Observational data from before the Roche controversy broke (see here) indicate that there may be a benefit for the critically unwell but, as with any retrospective information, there is plenty of scope for confounders and biases within that data and I am not sure what to make of the information.  It seems like the perfect opportunity for a cluster crossover trial to be ready to roll out during the next flu pandemic.

So, all in all, pretty confusing.  However, as with all medical decisions, despite shortfalls in information, we need to make practice decisions and that is where our debate arose.

Overall, my take is that Tamiflu came into prominence as result of a combination of factors.  There was a heightened awareness and fear of potential influenza pandemic catastrophe, combined with opportunistic distortion of the drug company research to strengthen the case for use.  I’m not sure whether I would have started using Tamiflu based on the current data.  It is difficult to remain objective.  I am also unsure whether my current misgivings are based on an emotional response to a breach of trust in the process which led to initial use of the drug.  This whole episode has shone a spotlight on the process of how we incorporate new treatment into practice and has certainly increased my skepticism. 

Despite that, we decided to continue to give Tamiflu to all cases of severe respiratory failure, and complete the course for those in whom the H1N1 serology is positive.  This is based on the argument that although the evidence is tenuous, there are no alternative treatments for severe influenza and it may be effective. The side effect profile appears small compared to potential increased mortality.  Also, it is relatively cheap at $4.05 per 75mg tablet.  The risks seem low and the benefits may be significant.

What do you do and have the recent revelations concerning the process affected management in your unit? What are your thoughts surrounding this controversial area? Comments below please - I am interested in your response.