title: Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov.
abstract: BACKGROUND
  Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance.
  
  
  OBJECTIVE
  We analyzed data from ClinicalTrials.gov to summarize activity in respiratory infection trials, identify gaps in research activity, and inform efforts to address disparities between antimicrobial resistance and development of new antibacterial drugs.
  
  
  METHODS
  We examined 69,779 interventional trials registered with ClinicalTrials.gov from 2007 to 2012, focusing on study conditions and interventions to identify respiratory infection-related trials. Programmatic identification with manual confirmation yielded 6,253 infectious disease trials, 1,377 respiratory infection trials, and 270 lower respiratory tract infection trials for analysis.
  
  
  RESULTS
  The 1,377 respiratory infection trials accounted for 2% of all trials and 22% of infectious diseases trials. Such trials (54.8%) were more likely than either nonrespiratory infectious diseases trials (48.1%) or noninfectious disease trials (42.8%) to receive industry funding. Stratification of respiratory infection trials by registration year demonstrated declining industry funding: 181 (64.9%) in 2007-2008 to 110 (46.0%) in 2011-2012. Respiratory infection trials more frequently evaluated vaccines (52.7 vs. 15.5% of nonrespiratory tract infection trials). Lower respiratory tract infection trials (excluding tuberculosis) focused primarily on bacterial pathogens (78.5%) followed by viral (12.6%), fungal (5.6%), and nontuberculous mycobacterial (3.0%) pathogens. Approximately 40% of 120 lower respiratory tract infection trials that were completed or terminated published results in the literature. On multivariable logistic regression analysis, a treatment focus was associated with decreased odds of publishing results (odds ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.02). There were also generally low numbers of studies evaluating novel antimicrobial agents (community-acquired pneumonia, 15.9%; hospital-acquired pneumonia, 16.7%; ventilator-associated pneumonia, 5.3%).
  
  
  CONCLUSIONS
  From 2007 to 2012, respiratory infection trials did not occur in numbers commensurate with global impact. The number of trials registered per year did not increase throughout the study period, partly due to declining industry support. There was a concerning reduction in prevention-oriented lower respiratory infection trials and an overall low number of such trials involving novel antimicrobials.
authors.affiliation: 1 Department of Medicine, Duke University.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ruopp
authors.affiliation: 2 Duke Clinical Research Institute, and.
authors.forename: Karen
authors.initials: K
authors.lastname: Chiswell
authors.affiliation: 1 Department of Medicine, Duke University.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Thaden
authors.affiliation: 2 Duke Clinical Research Institute, and.
authors.forename: Kunal
authors.initials: K
authors.lastname: Merchant
authors.affiliation: 1 Department of Medicine, Duke University.|3 Emergency Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Ephraim L
authors.initials: EL
authors.lastname: Tsalik
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D019468:Disease Management; D014943:Global Health; D006801:Humans; D009017:Morbidity / Q000639:trends; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000628:therapy*; D012189:Retrospective Studies
keywords: bacterial drug resistance; clinical trial; pneumonia; respiratory tract infections