title: Comparison of study designs for acute otitis media trials.
abstract: BACKGROUND
  A framework for evaluating the efficacy of antibiotics in development as well as those currently approved for acute otitis media (AOM) is needed.
  
  
  OBJECTIVE
  Review strengths and limitations of various antibiotic trial designs and their outcome measures.
  
  
  METHODS
  A review of 157 published trials involving 36,710 subjects for the treatment of AOM.
  
  
  RESULTS
  AOM trials have three designs: (1) clinical, clinical diagnosis and assessment of outcomes; (2) single tympanocentesis, microbiologic diagnosis (by middle ear fluid culture) and clinical assessment of outcomes; and (3) double tympanocentesis, microbiologic diagnosis and microbiologic outcome assessment. Identifiable strengths and limitations of each design are reviewed. Case definitions for entry of children in trials of AOM vary widely. The lack of stringent diagnostic criteria in a clinical design allows for inclusion of a significant proportion of children with a non-bacterial etiology (i.e., viral AOM or otitis media with effusion). Tympanocentesis increases diagnostic accuracy at study entry; however, the procedure is confounding because of its potentially therapeutic benefit and the procedure is not performed in a uniform manner. A second tympanocentesis allows a high sensitivity to detect microbiologic eradication, but it does not correlate with clinical outcomes in half of the cases. The timing of outcome assessment also varies widely among trials.
  
  
  CONCLUSIONS
  Improved clinical diagnosis criteria for AOM are needed to enhance specificity; emphasis on a bulging tympanic membrane has the best evidence base. Tympanocentesis within study designs has merits. At study entry it assures diagnostic accuracy but may alter outcomes and it is useful to document microbiologic outcomes but lacks specificity for clinical outcomes. For all designs, test of cure assessment 2-7 days after completion of therapy seems most appropriate.
authors.affiliation: University of Rochester, School of Medicine, Department of Microbiology/Immunology, 601 Elmwood Avenue, Box 672, Rochester, NY 14642, United States. Michael_pichichero@urmc.rochester.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
authors.forename: Janet R
authors.initials: JR
authors.lastname: Casey
mesh_terms: D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods*; D005122:Exudates and Transudates / Q000382:microbiology / Q000821:virology; D006801:Humans; D010033:Otitis Media / Q000175:diagnosis / Q000188:drug therapy*; D010043:Outcome and Process Assessment, Health Care; D019152:Paracentesis; D014432:Tympanic Membrane
chemical_list: D000900:Anti-Bacterial Agents