Expert opinions on judgment-based criteria for the assessment of antimicrobial treatment efficacy in hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are heterogenous. A convergence on approaches to evaluate antibacterial drugs is urgently needed, according to a study published in Clinical Infectious Diseases.
The heterogeneity in the endpoints of randomized clinical trials of antimicrobial drugs for HABP and VABP can cause confusion for clinicians. The current study, therefore, was designed to reach a consensus on these endpoints and to better illuminate the results in future clinical trials. To achieve this, researchers used the Delphi method to poll 26 international infectious disease, intensive care, and pharmaceutical experts.
The panel of experts recommended a composite endpoint hierarchy that includes, in order of priority: for VABP 1) survival at day 28, 2) mechanical ventilation-free-days through day 28, and 3) clinical cure between study days 7 and 10; for HABP 1) survival at day 28, and 2) clinical cure at days 7 and10.
There were disagreements regarding the optimal time-frame for endpoint assessments, and 3 Delphi rounds were needed to reach a 72% agreement on the hierarchical order of these endpoint components. The panel also reached consensus on a definition of clinical cure: the resolution of the signs and symptoms present at enrollment combined with improvement/lack of progression of radiological signs of pneumonia.
Limitations included a lack of complete consensus on the hierarchical ranking of the elements of the composite and timing for endpoint assessment, indicating a potential for subjectivity.
Study investigators concluded, “A pilot validation of our proposed [end point] by use of data from an already completed clinical trial, which was conducted with the classic [end points], should be performed first. Then, if validated, it could be considered for inclusion in future trials and, if further validated, may allow a pragmatic and homogenous assessment of antimicrobial efficacy in future HABP/VABP [randomized clinical trials].”
This study was funded by the Innovative Medicines Initiative Joint Undertaking. Several authors declare affiliations with the pharmaceutical industry. Please refer to the reference for a full list of author disclosures.
Weiss E, Zahar JR, Alder J, et al. Elaboration of consensus clinical endpoints to evaluate antimicrobial treatment efficacy in future HABP/VABP clinical trials [published online February 4, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciz093