Strategies and Recommendations for Using a Data‐Driven and Risk‐Based Approach in the Selection of First‐in‐Human Starting Dose: An International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Assessment
| العنوان: | Strategies and Recommendations for Using a Data‐Driven and Risk‐Based Approach in the Selection of First‐in‐Human Starting Dose: An International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Assessment |
|---|---|
| المؤلفون: | Chao Han, Marque Todd, Chunze Li, Frank R. Brennan, Zheng Yang, Sherri Dudal, Wendy J. Bailey, Yingxue Chen, Nagendra V. Chemuturi, Kapil Mayawala, Lise I. Loberg, Antoine Deslandes, Clarke David O, Michael W. Leach, Mark Rogge |
| المصدر: | Clinical Pharmacology & Therapeutics. 109:1395-1416 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Drug Industry, Drug-Related Side Effects and Adverse Reactions, Maximum Tolerated Dose, media_common.quotation_subject, MEDLINE, Risk-based testing, Decision tree, Toxicology, Lower risk, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Surveys and Questionnaires, Humans, Medicine, Pharmacology (medical), Operations management, Quality (business), Selection (genetic algorithm), media_common, Pharmacology, Clinical Trials as Topic, business.industry, Risk factor (computing), Therapeutic Human Experimentation, Clinical Trials, Phase III as Topic, Pharmaceutical Preparations, Drug development, Research Design, 030220 oncology & carcinogenesis, business |
| الوصف: | Various approaches to first-in-human (FIH) starting dose selection for new molecular entities (NMEs) are designed to minimize risk to trial subjects. One approach uses the minimum anticipated biological effect level (MABEL), which is a conservative method intended to maximize subject safety and designed primarily for NMEs having high perceived safety risks. However, there is concern that the MABEL approach is being inappropriately used for lower risk molecules with negative impacts on drug development and time to patient access. In addition, ambiguity exists in how MABEL is defined and the methods used to determine it. The International Consortium for Innovation and Quality in Pharmaceutical Development convened a working group to understand current use of MABEL and its impact on FIH starting dose selection, and to make recommendations for FIH dose selection going forward. An industry-wide survey suggested the achieved or estimated maximum tolerated dose, efficacious dose, or recommended phase II dose was > 100-fold higher than the MABEL-based starting dose for approximately one third of NMEs, including trials in patients. A decision tree and key risk factor table were developed to provide a consistent, data driven-based, and risk-based approach for selecting FIH starting doses. |
| تدمد: | 1532-6535 0009-9236 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9b9ae8f92d0d96e2c0c7071ecc9d48d https://doi.org/10.1002/cpt.2009 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....e9b9ae8f92d0d96e2c0c7071ecc9d48d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15326535 00099236 |
|---|