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Table 3 Comparison of clinical trials design of ultra-orphan drugs

From: Points to consider: efficacy and safety evaluations in the clinical development 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%

  1. Classification of clinical trials designs of the ultra-orphan drugs for each therapeutic category. Others: drugs other than metabolic drugs, anticancer drugs
  2. a Study on preventive administration of mefloquine and next was 168 patients of eculizumab