Comment from Albee Messing

My comments are limited to three topics: 1)III.C. Clinical trials and outcome measures – changes should be made to the requirement that approval/disapproval decisions hinge on a single “primary” outcome measure. With rare diseases and small populations it is much harder to repeat a trial just because the wrong choice was made regarding which outcome measure should be designated primary. Far preferable would be to allow more than one outcome measure to factor into the decisions on approval. 2)III.C. Permission for autopsies should be inserted as the default option in consent forms, so that it is an opt-out rather than opt-in choice for participants. In the current state of affairs many clinicians and pharmaceutical companies are reluctant to even raise the topic for fear of scaring people away. Yet crucial information is lost when autopsies are not permitted. For the rare disease that I work on I have found that families and individuals are receptive to the idea of autopsies when the need and value are properly explained. I once gave a presentation to a large multi-generational family of ~80 people and ran out of copies at the end. 3)III.E. The entire section on data sharing should be strengthened into requirements rather than using words such as “support”, “encourage”, and “consider”. This is particularly true with respect to natural history studies, which if as suggested become an option as historical controls instead of placebos. The FDA should convene a working group to develop a template for common data entry that could then be used to populate an open access database that is available to qualified investigators with IRB approval.