ArticleIntensive care medicine2017
Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE's STAT-Net.
Article in Intensive care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Therapeutic drug monitoring and the role of pharmacokinetics/pharmacodynamics in optimizing beta-lactam antibiotic dosing for deep-seated infections: a systematic review.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Sankey diagrams can clarify 'evidence attrition': A systematic review and meta-analysis of the effectiveness of rapid diagnostic tests for antimicrobial resistance.Journal of clinical epidemiology · 2022Pooled it
- Treatment of severe hospital-acquired and ventilator-associated pneumonia: a systematic review of inclusion and judgment criteria used in randomized controlled trials.Critical care (London, England) · 2017Pooled it
- Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.Intensive care medicine · 2023Trial
- A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Cross-Linking-Assisted Infection Reduction: A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Outcomes in Fungal Keratitis.Ophthalmology · 2020Trial
- Gram-negative bacterial infection randomized controlled trials (RCTs) in the 21st century: characteristics and evolution.JAC-antimicrobial resistance · 2026Review
- Perpetual observational study of the clinical and microbiological epidemiology of ventilator-associated pneumonia in Europe.Critical care (London, England) · 2026Observational
- The Combat Against Antimicrobial Resistance: An Overview of EU Recent Health Policies and Drug Regulations Promoting the Development of New Antimicrobials.Pharmaceutical medicine · 2026Review
- Can Model-Informed Precision Dosing of Beta-Lactams in Critical Care Improve Clinical Outcomes?Chemotherapy · 2026Review
- Group-Sequential Designs With an Externally-Driven Change of Primary Endpoint.Statistics in medicine · 2025Article
- Reserve antibiotics: overcoming limitations of evidence generated from regulatory approval trials.Globalization and health · 2025Review
- Identification and validation of robust hospital-acquired pneumonia subphenotypes associated with all-cause mortality: a multi-cohort derivation and validation.Intensive care medicine · 2025Article
- Ultrasound-Mediated Antibiotic Delivery to In Vivo Biofilm Infections: A Review.Chembiochem : a European journal of chemical biology · 2024Review
- Public health case for microbiome-sparing antibiotics and new opportunities for drug development.mSphere · 2024Article
- Reporting of surrogate endpoints in randomised controlled trial reports (CONSORT-Surrogate): extension checklist with explanation and elaboration.BMJ (Clinical research ed.) · 2024Article
- Composite end points and competing risks analysis.Interdisciplinary cardiovascular and thoracic surgery · 2024Article
- Personalized Dosing of Medicines for Children: A Primer on Pediatric Pharmacometrics for Clinicians.Paediatric drugs · 2024Review
- Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.Annals of clinical microbiology and antimicrobials · 2024Article
- Effectiveness of Prolonged Antibiotic Prophylaxis in Radical Cystectomy: Preliminary Analysis of the MACS Randomized Clinical Trial.Bladder cancer (Amsterdam, Netherlands) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn 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.
methodsWe review and discuss the current practices and challenges regarding endpoints in RCTs in this field and propose novel approaches.
resultsUsual 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.
conclusionRegulatory 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.