Understanding the choice of the experimental and control groups: Thrombectomy under general anesthesia or conscious...

The choice of control group in randomized clinical trials (RCTs) is crucial, from both an ethical and a scientific perspective. Thrombectomy can be performed under general anesthesia (GA) or conscious sedation (CS). Non-randomized studies and the first thrombectomy trials showed worse outcomes with GA, but studies were obviously confounded: more severe strokes required intubation for airway protection. Thrombectomy centers advocating the use of GA had to compare GA and CS in a randomized fashion. But which arm should be 'experimental', and which 'standard care'?

We review the design of RCTs comparing GA to CS during thrombectomy for acute stroke, paying particular attention to the trial hypothesis.

In early trial centers GA was the standard approach, with CS considered 'experimental'. Thus, most trials tested the potential superiority of CS over GA, but most trials were too small, yielding inconclusive results that were erroneously interpreted as equivalent. In principle, GA had the burden of proof and should have been considered the experimental intervention, as GA is more invasive and associated with worse outcomes. Interventions that introduce greater risk must be justified by evidence of benefit and should be tested as experimental treatments. However, in practice, centers routinely working under GA had a learning curve to use CS, and for them the experimental intervention was CS.

We need to integrate clinical trials into practice to optimize care but the best way to compare two active treatments remains a work in progress.