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.

scholarly journals The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid and diabetes trials

2019 ◽  
Vol 6 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Heinz Drexel ◽  
Giuseppe M C Rosano ◽  
Basil S Lewis ◽  
Kurt Huber ◽  
Alexander Vonbank ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gold Standard ◽  
Randomized Clinical Trials ◽  
Clinical Endpoints ◽  
Cardiovascular Pharmacotherapy ◽  
Total Event

Abstract Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.

Treatment Efficacy Differences of Sorafenib for Advanced Hepatocellular Carcinoma: A Meta-Analysis of Randomized Clinical Trials

Oncology ◽  
2015 ◽  
Vol 88 (6) ◽  
pp. 345-352 ◽  
Author(s):  
Yu-Yun Shao ◽  
Wen-Yi Shau ◽  
Soa-Yu Chan ◽  
Li-Chun Lu ◽  
Chih-Hung Hsu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Treatment Efficacy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Advanced Hepatocellular Carcinoma

scholarly journals 2279. Study of Prescribing patterns and Effectiveness of Ceftolozane–tazobactam (C/T): Real-world Analysis (SPECTRA): a multi-national, multicenter observational study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S780-S781
Author(s):  
Alex Soriano ◽  
Laura Puzniak ◽  
David Paterson ◽  
Florian Thalhalmmer ◽  
Stefan Kluge ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Observational Study ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Prescribing Patterns ◽  
National Study ◽  
Multicenter Observational Study ◽  
E Coli ◽  
Source Of Infection ◽  
Hospital Acquired

Abstract Background C/T has demonstrated efficacy in randomized clinical trials to treat cIAI and cUTI and recently completed a study in ventilator-associated bacterial and ventilated hospital-acquired bacterial pneumonia. The purpose of this study was to evaluate the real-world clinical use and outcomes of C/T in a multi-national study. Methods SPECTRA is a multi-national, multicenter, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Spain and United Kingdom. Patients admitted with greater than 48 hours of C/T treatment were included. Demographics, clinical characteristics, treatment management patterns, microbiological findings and outcomes were analyzed. Results There were 155 patients from 20 participating hospitals in 6 countries. The average age was 58.0 years (±17.8) and most were male 114 (74%). The majority 130 (84%) had at least one comorbidity, with the most common being renal impairment 87 (56%), immunocompromised 62 (40%), and diabetes 52 (34%). The majority, 94 (61%), had previous hospitalizations ≥ 6 months prior to receiving C/T, of which 29 (31%) had an ICU stay and surgeries 64 (42%). Most patients 126 (82%) received antibacterials within 30 days of receiving C/T, 61 (40%) received carbapenems and 47 (31%) received aminoglycoside. The average duration of C/T was 15 (SD12) days. The source of infection was cUTI for 31 (20%), cIAI for 19 (12%) and respiratory for 43 (28%) of C/T treated patients. Most 107 (70%) had an ID consult with an average of 7 (SD 11.3) consults. The top pathogen was Pseudomonas 124 (81%) followed by E. coli 22 (14%), with 56 (37%) having a polymicrobial infection. Over half of the patients were in the ICU 84 (55%), 58 (38%) underwent at least 1 surgery, with 65 (48%) being related to the infection, 60 (39%) had sepsis and 21 (14%) had septic shock. All-cause in hospital mortality was 16%. 30-day all-cause readmission was 12% and 6% were infection related. Conclusion Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials. Disclosures All authors: No reported disclosures.

scholarly journals The essentials of a global index for cognitive function

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Joseph Mathew Antony ◽  
Ian Weaver ◽  
Matthew Rueffer ◽  
Najla Guthrie ◽  
Malkanthi Evans
Keyword(s):  
Clinical Trials ◽  
Cognitive Function ◽  
Randomized Clinical Trials ◽  
Brain Regions ◽  
Global Index ◽  
Cognitive Measures ◽  
Limited Sample ◽  
Cognitive Health ◽  
Clinical Endpoints ◽  
Independent Functioning

AbstractCognition is comprised of the faculties: perception, creativity, intuition, and ratiocination. Optimal levels of cognition are needed for independent functioning and balanced living. With an aging population that continues to grow, dietary supplements that tilt the balance towards maintenance of cognition are being marketed for vulnerable populations facing these challenges. Randomized clinical trials provide the causal inference necessary to define the efficacy of emerging nutraceuticals. Cognition testing, in particular, requires a battery of tests that encompass all brain regions involved in cognition so as to provide endpoints necessary for product validation. The lack of well controlled studies for comparison analyses, limited sample sizes, ambiguous dosages, and poor cognitive measures result in data that cannot be compared across studies to determine the efficacy of supplements claiming to enhance cognition. Clinical trials for the nutraceutical industry should consider the multifaceted nature of supplements, where clinical endpoints must be comprehensive while remaining feasible. Combining endpoints of cognition with physiological biomarkers of immunity and metabolism to arrive at a global index for cognitive health may be necessary for claim substantiation in order to fully justify and scientifically validate improvements in cognitive health. The issues and needs of a global index will be discussed here.

scholarly journals Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Camila Henriques de Aquino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Clinical Symptoms ◽  
Clinical Stage ◽  
Protein Accumulation ◽  
Clinical Endpoints ◽  
Definition Of ◽  
Biomarker Research

Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative disorders, respectively. Both are proteinopathies with inexorable courses and no approved disease-modifying therapies. A substantial effort has been made to identify interventions that could slow down the progression of AD and PD; to date, with no success. The advances in biomarker research improved the identification of individuals at risk for these disorders before symptom onset, recognizing the pre-clinical stage, in which there is abnormal protein accumulation but no clinical symptoms of the disease, and the prodromal stage, in which mild symptoms are present but the clinical diagnostic criteria for disease cannot be fulfilled. The ability to detect pre-clinical and prodromal stages of these diseases has encouraged clinical trials for disease-modification at earlier phases, seeking to slow or prevent phenoconversion into clinical disease. Clinical trials at these stages have several challenges, such as the identification of the eligible population, the appropriate choice of biomarkers, the definition of clinical endpoints, the duration of follow-up, and the statistical analysis. This article aims to discuss some of the methodological challenges in the design of trials for pre-clinical and prodromal phases of AD and PD, to critically review the recent studies, and to discuss methodological approaches to mitigate these challenges in trial design.

scholarly journals Stopping or Reporting Early for Positive Results in Randomized Clinical Trials: The National Cancer Institute Cooperative Group Experience From 1990 to 2005

2009 ◽  
Vol 27 (10) ◽  
pp. 1712-1721 ◽  
Author(s):  
Edward L. Korn ◽  
Boris Freidlin ◽  
Margaret Mooney
Keyword(s):  
Clinical Trials ◽  
Treatment Efficacy ◽  
Randomized Clinical Trials ◽  
Final Analysis ◽  
Data Monitoring ◽  
Cooperative Group ◽  
Early Stopping ◽  
The Public ◽  
Positive Results

Randomized clinical trials are designed with stopping boundaries to guide data monitoring committees with their decision making concerning ongoing trials. In particular, when extremely positive results are seen and a boundary is crossed, the data monitoring committee may recommend releasing the results earlier to the public than at the definitive final analysis time specified in the protocol. For trials that are still accruing, this also means stopping accrual. Because the information about treatment efficacy is more limited in an early analysis than in a final analysis, questions have been raised about the appropriateness of incorporating early stopping for positive results in trial designs. In particular, there are concerns that treatment effects seen early may not be real or may be overly optimistic. To examine this issue, we collected information about treatment efficacy on National Cancer Institute Cooperative Group trials that were stopped early for positive results (information both at the time the trial was stopped/released and at times of further follow-up). Twenty-seven such trials were located. For 17 of 18 of these trials with sufficient follow-up information, the treatment effect was similar or only slightly smaller at last follow-up compared with the stopping/release time. We critically evaluate reasons why one might be concerned about early stopping for positive results. We conclude that for trials with well-designed interim monitoring plans, the ability to stop early for positive results is an important component of the trial design, allowing the public to benefit as soon as possible from the study conclusions.

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