Decision-makers in the social welfare systems are facing increasing demands to reimburse pharmaceutical products that have been granted market access with little evidence of efficacy. This in turn drives the need to assess and follow up the products in real world settings. Furthermore there are limits also to the use of RCT. The question is not if, but what real world evidence can be used. Also what methods can be used to enhance that use must be explored. How do we shape an answer for the 21st century?