A drug that will be used by primary care physicians should not be studied only in tertiary care settings, and vice versa

Do not use clinical designs and/or clinical endpoints for pivotal trials that you are not sure will be acceptable to regulators. Ensure that your assumptions are endorsed by regulators.

Designing clinical trials using higher scientific and/or medical standards than currently accepted can serve as a competitive advangtage when you have competitors who adhere to older standards. The regulators are likely to force them to adapt to your higer standards, even if they are nearly finished with their NDA.

If you are thinking of having a thought leader conduct a pivotal trial but are not convinced that his or her site can perform to your standards, then assign that person an easier trial to conduct that is not critical to your development plan (e.g., a mechanism of action trial). That way they will still be able to endorse your product based on personal experience but won't be in a position to cause difficulties in the product's overall development.