Justification of noninferiority margin: methodology considerations in an exposure-response analysis
| Autor: | Kellie S. Reynolds, Yaning Wang, P Colangelo, M Cavaillé-Coll, Y Harigaya |
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| Rok vydání: | 2014 |
| Předmět: |
Research design
Adult Graft Rejection Male medicine.medical_specialty medicine.medical_treatment Liver transplantation Tacrolimus Young Adult Margin (machine learning) Medicine Humans Pharmacology (medical) Everolimus Intensive care medicine Exposure response Aged Randomized Controlled Trials as Topic Pharmacology Sirolimus Models Statistical Design stage Dose-Response Relationship Drug business.industry Data interpretation Reproducibility of Results Middle Aged Surgery Clinical trial Research Design Data Interpretation Statistical Drug Therapy Combination Female business Immunosuppressive Agents medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 97(4) |
| ISSN: | 1532-6535 |
| Popis: | The pivotal clinical trial to support the indication of liver transplantation for everolimus was based on a noninferiority trial design. The unique trial design made it impossible to estimate the noninferiority margin at the design stage. Even though the trial was conducted based on a noninferiority margin of 12% for the primary efficacy endpoint, the lack of consensus on this margin made the efficacy results difficult to interpret. A novel pharmacometric approach was applied to derive a new margin. Even though it was smaller than 12%, the new margin was large enough so that the observed efficacy results became interpretable. This novel analysis was an important contributor to the "totality of evidence" approach that led to the approval of everolimus for the new indication. This approval represents the approval of a new drug in more than 10 years for the indication of liver transplantation. |
| Databáze: | OpenAIRE |
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