Table 3.
Comparison of clinical trials design of ultra-orphan drugs
| Anticancer drug n = 11 | Metabolic drug n = 16 | Others n = 16 | |
|---|---|---|---|
| Efficacy endpoint (Example) | |||
| True endpoint | • Overall survival (vemurafenib) | • Ventilator-free survival (alglucosidase alfa) | |
| Surrogate endpoint | • Major CyR (dasatinib) • Reduction in spleen volume (ruxolitinib) • Forced expiratory volume 1 s (sirolimus) |
• The 12-min walking distance (galsulfase) • Blood alkaline phosphatase (risedronate) • Blood phenylalanine (sapropterin) |
• Manual muscle test (freeze-dried sulfonated human normal immunoglobulin) • Haemoglobin stabilization (eculizumab) • Transcranial sonography (tetrabenazine) |
| Controls (RCT) | |||
| Placebo | 3/7 trials | 13/17 trials | 11/14 trials |
| Active controls | 3/7 trials | 1/17 trials | 1/14 trials |
| Different dosage | 1/7 trials | 3/17 trials | 2/14 trials |
| Number of patients (Min-Max) | |||
| RCT | 89–675 | 6–176 | 18–965 |
| Single-arm trial | 6–724 | 1–168 | 1-7252a |
| Statistical evidence (RCT) | |||
| Significance level | 5% | 5% | 5% |
| Power | 80–90% | 80–90% | 80–90% |
Classification of clinical trials designs of the ultra-orphan drugs for each therapeutic category. Others: drugs other than metabolic drugs, anticancer drugs
a Study on preventive administration of mefloquine and next was 168 patients of eculizumab