Lancet recently published a great RCT in oseltamivir, using a Bayesian analysis:
Of interest, this study was open-label. The goal was to examine treatment benefit of oseltamivir in patients with flu-like illness, primary outcome was reduction in length of illness (days).
The study found several interesting effects not seen in prior studies on this topic. This includes:
- treatment benefit not limited to starting <24 hrs from symptom onset, but also seen w/ start even 48-72 hrs after onset of symptoms.
- Patients with more co-morbidities & older age had greater absolute benefit (up to 2-3 day reduction).
- Patient with and without Influenza had equal benefit from treatment
The really shocking finding was #3. How did patients that tested negative for influenza have equal benefit form a therapy specific for influenza?
- Is their some novel unknown mechanism of action?
- Is our serology testing for influenza insufficient (i.e. poor sens/spec), resulting in misclassification of influenza-status?
- As study is open label, is treatment benefit all purely from placebo effect?
A lot of interesting questions. The one of perhaps statistical interest to me is evaluating the placebo effect. In an open label trial, is their any way to assess how much of treatment benefit is due to placebo vs a “real” effect? Can we look at magnitude of benefit, relative vs absolute differences, etc to gain any insights?
Any thoughts or comments would be appreciated.