NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

One of the reasons, Ex, for using external/historical/synthetic controls to supplement existing placebo controlled trials is the questionable ethics of using placebos. Hybrid trials, which include both controls, like the DCVax-l trial potentially mutually strengthen the statistical powering. Another reason to use them, is if both the placebo controlled survival (and possibly pfs) endpoints correlate with the synthetic endpoints, then future trials in other indications can be shortened by using less to possibly zero placebo controls. An ethical win.

Another reason is safety, but not the kind you are thinking of. If a trial should be stopped because the placebo arm is failing (Aka dying) but stopping the trial would preclude enough powering to demonstrate efficacy, then a hybrid trial using added synthetic control endpoints can rescue such a trial. Such a strange scenario might occur when you only have or mostly have very long time survivors in the treatment arm but none (or few) in the placebo arm.