Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE’s STAT-Net
| Autor: | David Wilson, Stéphan Juergen Harbarth, Stavros Nikolakopoulos, Emmanuel Weiss, Harriet Sommer, Marlieke E. A. de Kraker, Jean-François Timsit, Martin Wolkewitz, Esther Bettiol |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
Consensus medicine.drug_class Original Endpoint Determination Critical Illness Antibiotics Drug Resistance Critical Care and Intensive Care Medicine Risk Assessment law.invention 03 medical and health sciences 0302 clinical medicine Antibiotic resistance Randomized controlled trial law Anesthesiology medicine Clinical endpoint Journal Article Humans 030212 general & internal medicine Mortality Intensive care medicine Drug Approval Randomized Controlled Trials as Topic ddc:616 business.industry Critically ill 030208 emergency & critical care medicine Antibiotic therapy Anti-Bacterial Agents Clinical trial Drug development Severe infections Research Design Endpoints Randomized clinical trials business |
| Zdroj: | Intensive Care Medicine Intensive Care Medicine, 43(7), 1002. Springer Verlag Intensive Care Medicine, Vol. 43, No 7 (2017) pp. 1002-1012 |
| ISSN: | 1432-1238 0342-4642 |
| Popis: | Purpose: In this era of rising antimicrobial resistance, slowly refilling antibiotic development pipelines, and an aging population, we need to ensure that randomized clinical trials (RCTs) determine the added benefit of new antibiotic agents effectively and in a valid way, especially for severely ill patients. Unfortunately, universally accepted endpoints for the evaluation of new drugs in severe infections are lacking. Methods: We review and discuss the current practices and challenges regarding endpoints in RCTs in this field and propose novel approaches. Results: Usual endpoints actually recommended for drug development suffer from important flaws. Mortality requires large sample size and only partly related to the infectious process. Clinical cure rate is highly subjective in critically ill patients where symptoms may be related to other intercurrent events. Currently, composite endpoints, hierarchical nested designs, and competing risks analysis seem to be the most promising new tools for designing and analyzing clinical trials in this area, although they require further validation. Conclusion: Regulatory authorities, pharmaceutical companies, and clinicians need to agree on the most appropriate clinical endpoints for severe infections to ensure efficient approval of new, effective antibiotic agents. |
| Databáze: | OpenAIRE |
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