As stated in the review (1), our aim was to summarize the available data on influenza antivirals in an objective way, and not to provide our own clinical recommendations. Instead, we complemented our results with treatment recommendations from professional societies and international public health institutes.
The primary question addressed by the clinical trials for drug approval was whether disease duration is shortened by neuraminidase inhibitors (NIs). For this purpose, the patient groups were kept as homogeneous as possible—as is commonly done, also in other drug registration studies. Thus, particularly vulnerable patients, such as pregnant women or immunosuppressed or seriously ill patients, were excluded. This leads to the concern of missing data from randomized controlled trials (RCTs) for some relevant patient populations, such as hospitalized patients, as also highlighted in the correspondences.
In the absence of active control therapies, RCTs should have been placebo-controlled, which would have been difficult to justify on ethical grounds after approval of the NIs. In addition, the acuity of influenza disease (time window), the varying severity of influenza seasons, and regional differences in influenza activity (pre-selection of study centers) can render the implementation of RCTs difficult, particularly for clinically relevant patient populations. The latter two factors are especially unpredictable.
It should be kept in mind that the RCTs were performed during seasonal influenza waves leading to generally mild disease. Hence, for these studies, it might not have been possible to show efficacy with regard to more clinically relevant endpoints, such as reduction of influenza-related complications. Observational studies cannot replace the evidence from RCTs (the methodological problems of observational studies are also discussed in the article).
However, since data from RCTs are lacking, the results of some very large observational studies should not be overlooked. In conclusion, we would also welcome better data on influenza antivirals, especially for the known risk groups.
On behalf of the authors:
Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany
Conflict of interest statement
The authors of all contributions declare that no conflict of interest exists.
|1.||Lehnert R, Pletz M, Reuss A, Schaberg T: Antiviral medications in seasonal and pandemic influenza—a systematic review. Dtsch Arztebl Int 2016; 113: 799–807 VOLLTEXT|