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Although the majority of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA, the overall number was low. Greater effort is needed to stimulate such trials.

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Background Registration of interventional trials of Food and Drug Administration–regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ClinicalTrials.gov offers an opportunity to define the clinical research landscape; here we analyze 10 years of infectious disease (ID) clinical trial research. Methods Beginning with 166 415 interventional trials registered in ClinicalTrials.gov from 2007–2017, ID trials were selected by study conditions and interventions. Relevance to ID was confirmed through manual review, resulting in 13 707 ID trials and 152 708 non-ID trials. Results ID-related trials represented 6.9%–9.9% of all trials with no significant trend over time. ID trials tended to be more focused on treatment and prevention, with a focus on testing drugs, biologics, and vaccines. ID trials tended to be large, randomized, and nonblinded with a greater degree of international enrollment. Industry was the primary funding source for 45.2% of ID trials. Compared with the global burden of disease, human immunodeficiency virus/AIDS and hepatitis C trials were overrepresented, and lower respiratory tract infection trials were underrepresented. Hepatitis C trials fluctuated, keeping with a wave of new drug development. Influenza vaccine trials peaked during the 2009 H1N1 swine influenza outbreak. Conclusions This study presents the most comprehensive characterization of ID clinical trials over the past decade. These results help define how clinical research aligns with clinical need. Temporal trends reflect changes in disease epidemiology and the impact of scientific discovery and market forces. Periodic review of ID clinical trials can help identify gaps and serve as a mechanism to realign resources.

Background Difficulty discriminating bacterial from viral infections drives antibacterial misuse. Host gene expression tests discriminate bacterial and viral etiologies, but their clinical utility has not been evaluated. Methods Host gene expression and procalcitonin levels were measured in 582 Emergency Department participants with suspected infection. We also recorded clinician diagnosis, and clinician-recommended treatment. These four diagnostic strategies were compared to clinical adjudication as the reference. To estimate the clinical impact of host gene expression, we calculated the change in overall net benefit (∆NB, the difference in net benefit comparing one diagnostic strategy to a reference) across a range of prevalence estimates while factoring in the clinical significance of false positive and negative errors. Results Gene expression correctly classified bacterial, viral, or non-infectious illness in 74.1% of subjects, similar to the other strategies. Clinical diagnosis and clinician-recommended treatment revealed a bias toward overdiagnosis of bacterial infection resulting in high sensitivity (92.6% and 94.5%, respectively), but poor specificity (67.2% and 58.8%, respectively) resulting in a 33.3% rate of inappropriate antibacterial use. Gene expression offered a more balanced sensitivity (79.0%) and specificity (80.7%), which corresponded to a statistically significant improvement in average weighted accuracy (79.9% vs. 71.5% for procalcitonin and 76.3% for clinician-recommended treatment, p<0.0001 for both). Consequently, host gene expression had greater net benefit in diagnosing bacterial infection than clinician-recommended treatment (∆NB=6.4%) and procalcitonin (∆NB=17.4%). Conclusions Host gene expression-based tests to distinguish bacterial and viral infection can facilitate appropriate treatment, improving patient outcomes and mitigating the antibacterial resistance crisis.