scholarly journals Streamlining Safety Data Collection in Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Trials: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team

2016 ◽  
Vol 63 (suppl 2) ◽  
pp. S39-S45 ◽  
Author(s):  
Helen Donnelly ◽  
Demissie Alemayehu ◽  
Radu Botgros ◽  
Sabrina Comic-Savic ◽  
Barry Eisenstein ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Collection ◽  
Drug Development ◽  
Bacterial Pneumonia ◽  
Safety Data ◽  
Development Project ◽  
Project Team ◽  
Antibacterial Drug ◽  
Hospital Acquired

scholarly journals Trends in hospital-acquired and ventilator-associated bacterial pneumonia trials

2020 ◽  
Author(s):  
Stephen M Bart ◽  
Daniel Rubin ◽  
Peter Kim ◽  
John J Farley ◽  
Sumathi Nambiar
Keyword(s):  
Drug Therapy ◽  
Drug Development ◽  
Bacterial Pneumonia ◽  
Asia Pacific ◽  
Multivariate Logistic Regression Model ◽  
Chronic Obstructive ◽  
Antibacterial Drug ◽  
Eastern European ◽  
The Mean ◽  
Hospital Acquired

Abstract Background New drug development for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) is critical. Challenges remain in the conduct of HABP/VABP trials, especially in the contexts of enrollment, endpoints, non-study antibacterial drug therapy, and antimicrobial resistance. Methods Four Phase 3 noninferiority trials (n=2,433 participants) submitted to the Food and Drug Administration after 2015 were analyzed for enrollment statistics, participant characteristics associated with 28-day all-cause mortality (ACM), microbiology, and receipt of non-study antibacterial drugs. All trials primarily enrolled patients with gram-negative bacterial infections. Results The mean trial length was 2.7 years and the mean recruitment rate was 0.17 participants/site/month. ACM at 28 days was 17.1% and was higher among participants diagnosed with ventilated HABP (31.9%) or VABP (19.0%) than non-ventilated HABP (9.9%). VABP participants tended to be younger, less likely to have chronic obstructive pulmonary disease, and more likely to have previously sustained an injury. Age, South American residence, diagnosis of ventilated HABP or VABP, and Acinetobacter baumannii infection were all associated with 28-day ACM in a multivariate logistic regression model. A. baumannii infection was most common in Eastern European and Asia/Pacific participants, and Eastern European isolates exhibited the highest levels of meropenem resistance. Concomitant non-study antibacterial drug therapy most commonly included beta-lactams and was initiated earliest in Western Europe. Conclusion This analysis of recent trials may assist in trial considerations for HABP/VABP development programs and promote needed antibacterial drug development for patients with serious infections.

scholarly journals P11 Neonatal and paediatric protocol development and drug safety: points to consider for risk management and safety data collection

2019 ◽  
Vol 104 (6) ◽  
pp. e21.2-e22
Author(s):  
B Aurich ◽  
V Elie ◽  
E Jacqz-Aigrain
Keyword(s):  
Risk Management ◽  
Clinical Trials ◽  
Data Collection ◽  
Drug Safety ◽  
Safety Profile ◽  
Safety Data ◽  
Age Group ◽  
Baseline Trial ◽  
Paediatric Drug ◽  
Protocol Development

BackgroundProtocol development for neonatal or paediatric clinical trials needs to take into account the age group specifics of the study population (e.g. pharmacokinetics, reference values for laboratory data and vital signs). Drug safety and risk management for neonatal/paediatric trials require an understanding of how these change throughout childhood. We were interested in reviewing and summarising the literature to identify publications which provide researchers with practical information of how the neonatal/paediatric drug safety profile informs age group specific safety data collection and risk management in the protocol.MethodsPubmed, Embase and regulatory authority (RA) websites were searched for publications up to 31/12/2018 for children (0–18 years). In addition, the bibliography of included publications was reviewed to identify additional publications.ResultsRA websites provided general and disease specific guidance on neonatal/paediatric clinical trials with sections relating to drug safety. No publication was identified describing the practicalities of how the neonatal/paediatric drug safety profile can be included throughout the various sections of a clinical trial protocol. The existing literature was summarised providing an overview of how the neonatal/paediatric drug safety profile supports the development of the various protocol sections. For example laboratory values in the exclusion criteria and safety monitoring sections need to be adjusted for age. Vital sign and psychomotor assessment should be done at least at baseline, trial completion and follow-up. Monitoring of adverse events of interest requires consideration of how these may present in neonatal/paediatric patients.ConclusionsIn order to support the protocol development with regards to neonatal/paediatric drug safety a dual competence in both paediatrics and drug safety is required. This review provides an overview of the practical aspects related to neonatal/paediatric drug safety during protocol development.Disclosure(s)Nothing to disclose

scholarly journals Cost Drivers of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase Three Clinical Trials

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Stella Stergiopoulos ◽  
Pamela Tenaerts ◽  
Kenneth Getz ◽  
Carrie Brown ◽  
Josephine Awatin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Bacterial Pneumonia ◽  
Cost Drivers ◽  
Hospital Acquired

scholarly journals Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials

2019 ◽  
Vol 69 (11) ◽  
pp. 1912-1918 ◽  
Author(s):  
Emmanuel Weiss ◽  
Jean-Ralph Zahar ◽  
Jeff Alder ◽  
Karim Asehnoune ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Trials ◽  
Treatment Efficacy ◽  
Clinical Cure ◽  
Bacterial Pneumonia ◽  
Randomized Clinical Trials ◽  
Signs And Symptoms ◽  
Antimicrobial Treatment ◽  
Clinical Endpoints ◽  
Hospital Acquired

Abstract Background Randomized clinical trials (RCTs) in hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. Methods Twenty-six international experts from intensive care, infectious diseases, and the pharmaceutical industry were polled using the Delphi method. Results The panel recommended a hierarchical composite endpoint including, by priority order, (1) survival at day 28, (2) mechanical ventilation–free days through day 28, and (3) clinical cure between study days 7 and 10 for VABP; and (1) survival (day 28) and (2) clinical cure (days 7–10) for HABP. Clinical cure was defined as the combination of resolution of signs and symptoms present at enrollment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and mechanical ventilation–free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). Conclusions We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

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