Mr. Shaun Flanagan:

That is the reality. Not every country has said yes to Orkambi. There is no point going back to the discussions on the challenges around it and the evidence. The Deputy asked a general question on efficacy and cost over a timeline. It is very hard to comment on that in any scientific way because we have not done a review. In my professional opinion, over the course of my career and in particular over the past ten years, there has been a move for new medicines to come to the market at an earlier stage than they would have previously following smaller trials. Some of that may be a result of the fact that the low-hanging fruit is gone as the major clinical disease areas have been addressed. Once one gets into orphan drugs, it is harder to design trials with patients. Mr. Judge probably started a little before me, but around the time we started our careers, one would expect to have two randomised phase 3, placebo-controlled trials, namely, one big one followed by a conformity trial. It is only then one would like to see a medicine get to market. We have gone way beyond that now, however. What come before the drugs group now are single-arm trials. That means there is no comparison arm within the trial and the group is faced, like any assessment body internationally, with significant challenges. Against that, those drugs would never get to market if a phase 3 trial were expected because those are impossible to design. There are challenges that have to be weighed up around evidence. The straight answer is that the evidence is less robust than it was for medicines coming to market a decade ago. That is the nature of being into orphan diseases and smaller areas. The cost per patient has inflated significantly. The industry argues that it is because it has to harvest its research and development costs across a smaller cohort. The cost has gone up for every assessment and, it is fair to say, cost-effectiveness has worsened over the decade.