Interesting piece on the challenges facing those trying to gain approval for new treatments for rare diseases. In rare diseases more than any other area the patients and their caregivers are ‘expert’ on the disease experience and often they themselves are critical of the clinical outcome measures being used to define success. For example the paper mentions that boys and young men with DMD say what matters to them is to be able to keep their upper body function (e.g. to put their arms on the table, retain the ability to use a keyboard or to brush their own teeth) not necessarily to see improvements in their ability to walk (which is the focused upon in trials).
The difficult choice of which outcomes to measure, the acceptance of surrogate endpoints, and the question of what represents a meaningful treatment benefit for patients have led to heated debates among regulatory agencies. Drug reviews of new orphan drugs aimed at idiopathic pulmonary fibrosis or Duchenne muscular dystrophy, for example, and the dispute over the relevance of the forced vital capacity and 6-min walk test as study endpoints to predict treatment benefit, are now turning into textbook cases