Over and over from beginning to end. Observing your users as they confront the problem you're trying to solve, whether within the context of your prototype or not, will always yield useful insights and help to validate or invalidate your assumptions.
The goal of both the Lean Startup and Design Thinking processes is to create ventures, products and services that keep the user at the centre of the design and the business. By testing products with users at every stage and without interference or interruption we get as honest an insight as possible in to the experience of the problem and the solution. This reveals the greatest opportunities for meaningful interaction and the areas that ventures can disrupt existing experiences and markets.