Non-inferiority versus superiority trial design for new antibiotics in an era of high antimicrobial resistance: the case for post-marketing, adaptive randomised controlled trials
| Autor: | Michel Pletschette, Virginia Di Bari, Raffaella Pisapia, Simone Lanini, Alessia Mammone, Boniface Nguhuni, Nicola Petrosillo, John P. A. Ioannidis, Gina Portella, Antonino Di Caro, Martin Langer, Stefano Merler, Francesco Vairo, Alimuddin Zumla, Giuseppe Ippolito, Sarah J. L. Edwards |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class 030106 microbiology Antibiotics Context (language use) Microbial Sensitivity Tests Drug resistance Plazomicin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antibiotic resistance Superiority Trial Drug Resistance Multiple Bacterial Drug Resistance Bacterial Product Surveillance Postmarketing medicine Humans 030212 general & internal medicine Intensive care medicine Randomized Controlled Trials as Topic business.industry Clinical study design Anti-Bacterial Agents Clinical trial Infectious Diseases chemistry business |
| Zdroj: | The Lancet Infectious Diseases. 19:e444-e451 |
| ISSN: | 1473-3099 |
| Popis: | Antimicrobial resistance is one of the most important threats to global health security. A range of Gram-negative bacteria associated with high morbidity and mortality are now resistant to almost all available antibiotics. In this context of urgency to develop novel drugs, new antibiotics for multidrug-resistant Gram-negative bacteria (namely, ceftazidime-avibactam, plazomicin, and meropenem-vaborbactam) have been approved by regulatory authorities based on non-inferiority trials that provided no direct evidence of their efficacy against multidrug-resistant bacteria such as Enterobacteriaceae spp, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia, and Acinetobacter baumannii. The use of non-inferiority and superiority trials, and selection of appropriate and optimal study designs, remains a major challenge in the development, registration, and post-marketing implementation of new antibiotics. Using an example of the development process of ceftazidime-avibactam, we propose a strategy for a new research framework based on adaptive randomised clinical trials. The operational research strategy has the aim of assessing the efficacy of new antibiotics in special groups of patients, such as those infected with multidrug-resistant bacteria, who were not included in earlier phase studies, and for whom it is important to establish an appropriate standard of care. |
| Databáze: | OpenAIRE |
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