In praise of informed scepticism

Earlier this year, guidelines from three respected US professional societies advised doctors to give alteplase to patients with acute stroke. The recommendation was based on what the guidelines’ authors considered grade A evidence. Yet as Jeanne Lenzer reports (doi:10.1136/bmj.f3830), surveys show that many if not most emergency physicians are sceptical of the benefits and concerned about the harms of alteplase. The published evidence shows reductions in disability but not in mortality, with only two of the 12 randomised trials showing benefit and five having been terminated early because of lack of benefit, higher mortality, and significant increases in brain haemorrhage.

So how did this grade A recommendation occur? Lenzer …