Clinical Question

Is oseltamivir (Tamiflu) better than usual care in shortening the duration of symptoms in patients with flulike symptoms in primary care settings?

Bottom Line

Although the authors report that compared with usual care oseltamivir shortens the duration of symptoms, the methodologic biases in this study make their conclusions suspect. (Level of Evidence = 2b)

Synopsis

The authors recruited patients from primary care settings who were at least one year of age and had flulike symptoms lasting no more than three days. The study took place during three consecutive winters. In a pragmatic open-label design, patients were assigned using a response adaptive randomization system to receive five days of oseltamivir (n = 1,629) or their primary care clinician's usual care (n = 1,637). Each patient was formally tested for influenza. Each patient or their caregiver was asked to keep a daily symptom diary for the two weeks following enrollment. The researchers adapted the diaries for children (e.g., clinginess for nonverbal children became a proxy for headache and myalgias). At the end of the study period, 91 of the patients (6%) assigned to oseltamivir dropped out or discontinued medication and 104 patients in the usual care group (7%) dropped out or discontinued treatment. The authors did not include these patients in their analysis, so it was not really an intention-to-treat analysis. At baseline, the patients in each group were comparable, including the severity and duration of their symptoms. Only 10% of the patients had received influenza vaccinations. Approximately one-half of the patients had a positive test result for influenza—close to evenly split between types A and B. At the end of the evaluation period for every age stratum, regardless of symptom severity and duration and whether or not the patient had a comorbid condition, the patients who received oseltamivir experienced faster recovery than those who received usual care. The average duration was one day less for patients taking oseltamivir. Older patients, those with comorbidities, and those with longer symptom duration at baseline tended to recover two to three days faster if they took oseltamivir.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (primary care)

Reference: Butler CC, van der Velden AW, Bongard E, et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. Lancet. 2020;395(10217):42–52.