If you are unable to take the return flight of a 2-4-1 (due to illness etc.) you are in a worse position than if you have to cancel before the outbound. You officially cannot (yet) change the return portion of a 2-4-1 and you get no refunds. In theory, you will need to buy another ticket for the return. How does insurance handle that?

I've been in that situation and BA were brilliant. Under no obligation, but just brilliant. They just said, come back to the airport when you're ready to fly and we'll do our best to sort something out. The insurance company had no idea what type of ticket (or class - which happened to be First) I was on but, after much haggling, flew me home in economy. (They paid fully flexible economy, despite me telling them that Club tickets were cheaper). Was I lucky? I think so.