The Story of Flu Trials

Tamiflu not shown to prevent severe flu.

Consumer advice is not clear on this, so we reiterate.

The Facts:

Tamiflu, an anti-flu medication, reduces the duration of illness by about half a day on average and prevents 2­–4% of cases of symptomatic flu, but it does not prevent positive lab tests if the person has no symptoms, and it also increases the rate of nausea, vomiting, and headache. This is the evidence from a major 2014 study, whose results are mirrored pretty accurately in two of Google’s top hits for Tamiflu, consumer webpages by the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA).

Tamiflu has not been shown to reduce deaths or hospitalizations. The agencies are not trying to make it look like it did, but they are not particularly vocal about this either. True: absence of evidence is not evidence of absence; but, when multiple well conducted trials failed to prove the effect, it might be worth highlighting these findings. Otherwise, it is just logical to assume that if the drug is active against viruses, then it should reduce the risk of severe illness. At short notice, Zheln did not find much evidence people actually assume that, but at least one of the top Google results does seem to follow this logic; “Early treatment with Tamiflu can lead to milder illness, which lessens the number of hospitalizations and deaths associated with the flu,” they write. However, other top Google hits are pretty circumspect in giving account of Tamiflu’s effects. One doctor author suggested that “expectations for Tamiflu are often very high and, frankly, overhyped.” A 2022 news story revealed that health authorities of one of the regions of Canada worked to offer Tamiflu for free, with a high official saying, “It’s quite effective to prevent complications, hospitalizations.” All in all, it looks like it is worth revisiting the disheartening evidence related to Tamiflu, particularly because a newer study was published in 2023, focusing specifically on the rate of hospital treatment on Tamiflu versus placebo.

Zheln is not the first to cover that recent study: New England Journal of Medicine Journal Watch, InfectiousDisease Advisor, and MedicalXpress highlighted the findings of the study, and MedPage Today also did a great job interviewing one of the study authors. If you read all of these publications, there is not much Zheln can add, honestly.

The most important takeaway would be that when 3,000 mostly White outpatients in their 40s, with flu but relatively healthy otherwise, were treated with Tamiflu across 15 randomized trials, about the same 25 people eventually required hospital treatment as in the similar 3,000 patient group that took placebo and/or standard therapy. Additionally, the rate of nausea or vomiting was at least 13% higher and at most 2.6 times as high on Tamiflu. The quality of the trials was high enough for the researchers to be moderately certain of these findings, making the evidence somewhat less likely to change with future trials being added to the big picture. Zheln’s fifty cents would be that the piece of information enclosed in this paragraph essentially is the evidence – just some numbers with a pinch of scientific scrutiny over it. An important feature of evidence, the reader is free to interpret it the way they see fit. It’s also good to keep in mind that this stuff is as scientific as iPhones, X-rays, or antibiotics, just less visible and tangible (think astronomy).

The Evidence:

• A 2014 Cochrane systematic review found that Tamiflu (oseltamivir) reduces flu illness duration by 8–25 hours on average and prevents 2 cases in every 52­–110 cases of symptomatic influenza from happening, but not cases without symptoms. The risk of headache, nausea, and vomiting was higher on treatment. This aligns with info from some of Google’s top hits on Tamiflu, such as those from the FDA and European Medicines Agency.
• In the same study, oseltamivir has not been shown to reduce deaths or hospitalizations from flu, pooling the data from 7 randomized trials and 4,400 patients, a fact not prominent in the agencies’ statements. However, a brief overview of Google’s top hits revealed that the assumption that Tamiflu prevents serious flu, arising from the general interpretation of its antiviral properties, is not uncommon among the public.
• A 2023 systematic review included 15 randomized trials and over 6,100 patients with flu and found no difference in hospitalizations between those given Tamiflu versus those given placebo and/or standard therapy. Additionally, the rate of vomiting was 28% to 163% higher on Tamiflu, and the rate of nausea was 13% to 82% higher. The study participants were mostly White or Asian, in their 40s on average, and with few chronic illnesses.
• The quality of the trials was high enough for the researchers to claim moderate certainty of the evidence, making it somewhat less likely to change when future trials are added to the big picture.

The Research:

Notes

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Citation

Zhelnov P. The Story of Flu Trials. Zheln. 2024 Jan 18;1(1):t7e4. URI: https://zheln.com/thread/2024/01/18/1/