SGEM#312: Oseltamivir is like Bad Medicine – for Influenza

Date: December 16th, 2020 Reference: Butler et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. The Lancet 2020 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called First10EM.com. He has a great new blog post about how we are failing to protect our healthcare workers during COVID-19. Case: A 45-year-old female presents to her primary care clinician complaining of fever, sore throat and muscle aches. She did not get a flu shot this year. You diagnose her with an influenza-like illness (ILI). She wants to know if taking an anti-viral like oseltamivir (Tamiflu) will help? Background: We covered oseltamivir six years ago in SGEM#98. This is still the longest Cochrane review (300+ pages) I have ever read (Jefferson et al 2014a). The overall bottom line was when balancing potential risks and potential benefits, the evidence does not support routine use of neuraminidase inhibitors like oseltamivir for the treatment or prevention of influenza in any individual. There has been some controversy around oseltamivir. It was approved by licensing agencies and promoted by the WHO based on unpublished trials. None of those agencies had actually looked at the unpublished data. In fact, the primary authors of key oseltamivir trials had never been given access to the data – Roche just told them what the data supposedly said. Other papers were ghost-written (Cohen 2009). The BMJ was involved in a legal battle with Roche for half a decade trying to get access to that information. When they finally got their hands on the data, the conclusions of the reviews suddenly changed. After countries had spent billions stockpiling the drug, it turned out that oseltamivir had no effect on influenza complications, was not effective in prophylaxis, and had significantly more harms than originally reported (Jefferson 2014a; Jefferson 2014b).  You can read more details about this controversy in the BMJ. The oseltamivir issue is a great example of the problems with conflicts of interest (COI) in medical research. This is something I have spoken about often. It is not an ad hominem attack on any of the authors. Our current system of medical research involves industry funding. COIs are just another data point that needs to be considered. This is because the evidence shows COIs can introduce bias into RCTs, SRMA and Clinical Practice Guidelines.  When I use the term bias I am referring to something that systematically moves us away from the “truth”. There is specific evidence of bias in the oseltamivir literature. Dunn and colleagues looked at 37 assessments done in 26 systematic reviews and then compared their conclusions to the financial conflicts of interest of the authors. Among eight assessments where the authors had conflicts, seven (88%) had favourable conclusions about neuraminidase inhibitors. However, among the 29 assessments that were made by authors without conflicts, only five (17%) were positive (Dunn et al 2014). The current best evidence shows that oseltamivir (Jefferson et al 2014a): Decreased time to first alleviation of symptoms by less than one day Does not statistically change hospital admission rate (1.7% vs 1.8%) Does increase nausea (NNH 28) and vomiting (NNH 22) Does increase neuropsychiatric events (NNH 94) Does increase headaches (NNH 32) Clinical Question: Does oseltamivir improve time to recovery in patients presenting to their primary care clinician with an influenza-like illnesses? Reference: Butler et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. The Lancet 2020. Population: Patients from 15 European countries over three influenza seasons who were one year of age and older and who presented to their primary care clin...