Table 1.

Challenges associated with conducting postmarketing confirmatory trials to verify and describe the clinical benefit if PR is used as a basis for accelerated approval

Even if a trial is enrolled at the time of accelerated approval, drug availability after accelerated approval may interfere with the ability to keep patients assigned to placebo from crossing over to active treatment

Rates of relapse after achievement of treatment-induced PR are variable and have been shown to be quite high with some therapies; the use of other therapies and also, the open-label use of the new product in both treatment arms after relapse may complicate interpretation of the data and limit the ability to detect a treatment effect on renal outcomes during long-term follow-up

Missing data in subjects who are lost to follow-up or withdraw consent may also make it difficult to interpret a trial’s findings and are a particular concern in trials of very long duration