title: The scrutiny of identifying community-acquired pneumonia episodes quantified bias in absolute effect estimation in a population-based pneumococcal vaccination trial.
abstract: OBJECTIVE
  To determine the accurateness of detecting community-acquired pneumonia (CAP) in the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a community-based, double-blind, randomized placebo-controlled trial in which the needed to treat (NNT) for prevention of vaccine-type pneumococcal CAP was 1,007 [95% confidence interval (CI): 613, 2,646].
  
  
  METHODS
  Study participants developing pneumonia were identified in 58 participating hospitals by research nurses (RNs) using local-adapted protocols. In addition, general practitioner (GP) records were screened for hospital referrals for suspected pneumonia. Two independent reviewers determined reasons for not identifying pneumonia episodes, and the NNT adjusted for missed episodes was estimated.
  
  
  RESULTS
  Of 2,183 hospital referrals with suspected pneumonia detected in GP records, 232 (11%) were admitted outside established screening routes and 102 (5%) were not suspected of pneumonia on admission. Of the remaining 1,849 episodes, 1,374 (63% of all episodes and 74% of identifiable episodes) were identified by RNs. Several causes of missing episodes were identified. After adjustment for missed episodes, the NNT reduced to 634 (95% CI: 386, 1,675).
  
  
  CONCLUSIONS
  With the screening procedure, 63% of suspected pneumonia episodes were identified, and the estimated NNT reduced from 1,007 to 634. Root cause analysis of unidentified episodes provides guidance for improving pneumonia detection in future trials.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands. Electronic address: c.h.vanwerkhoven@umcutrecht.nl.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: van Werkhoven
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands; Department of Respiratory Diseases, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Huijts
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands.
authors.forename: Fleur P
authors.initials: FP
authors.lastname: Paling
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands; Department of Medical Microbiology, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands.
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
mesh_terms: D000328:Adult; D015982:Bias; D017714:Community-Acquired Infections / Q000175:diagnosis / Q000517:prevention & control; D004311:Double-Blind Method; D006801:Humans; D022242:Pneumococcal Vaccines; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis* / Q000517:prevention & control*
chemical_list: D022242:Pneumococcal Vaccines
keywords: Community-acquired pneumonia; Community-based; Completeness; End point detection; Missing outcome data; Trial