It has been ten years since the FDA released rare disease guidelines for sponsors seeking FDA approval. Once a drug or biologic candidate has been identified for study, an execution strategy is needed not to only bring the candidate to regulatory approval, but to also facilitate post-approval acceptance and adoption of the new product among the physician and patient communities. All traditional clinical trial challenges are present, but rare disease studies must be designed with care with many unique aspects. This blog shares the major differences that must be strategically addressed before any study is launched.
The key points to consider include the following:
• The patient serves as their own control; this is very relevant when a placebo control is not ethical and when there is no approved active control
• Consider a Bayes design to permit penalty-free interim looks; this avoids burning Type I error so reaching significance is easier
• Choose historical controls with caution; the historical controls may involve a different population with different lab tests collected at different times
• Efficacy is multi-dimensional; FDA likes internal confirmation of efficacy
• Speed of effect and duration of benefit are critical
• Longitudinal modeling increases the chances of reaching significance by maximizing the available data
• Safety is expected; treatment-emergent events must be weighed against benefits
• Safety data can come from other populations treated with the same drug, as long as the other exposed populations had comparable co-morbidities
• Treatment-emergent adverse events must be separated from disease signs and symptoms; why double count?
• Vet the study design and results with key opinion leaders; their opinions carry weight
• Try to not make the site burdensome for the sites and the patients
• Find the sites with the cases willing and committed to participate.
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