High heterogeneity in community-acquired pneumonia inclusion criteria: does this impact on the validity of the results of randomized controlled trials?

Abstract

Abstract Background There is no consensus on the most accurate combination of diagnostic criteria to define community acquired pneumonia (CAP). We describe inclusion criteria in randomized controlled trials (RCT) of CAP and assess their performance for the diagnosis of formally identified CAP. Methods RCTs related to CAP recorded on ClinicalTrials.gov were analysed. Due to high heterogeneity, we divided close CAP inclusion criteria into patterns (i.e. combinations of inclusion criteria). To assess their diagnostic performances, these CAP definition patterns were applied to a reference population of 319 suspected CAP patients, in whom the CAP diagnosis had been confirmed (n = 163) or excluded (n = 156) by an adjudication committee after a systematic thoracic CT-scan and a 28-day follow-up period. Results In the 47 RCTs included in the analysis, 42 different CAP inclusion criteria combinations were identified and 8 patterns created. This heterogeneity was not explained either by the trials’ methodology or by their objectives. When applied to the reference population, the performance ranges of the 8 definition patterns were 9.8–56.4% for sensitivities, 56.4 97.4% for specificities, 63.6 83.6% for positive predictive values and 50.8–66.7% for negative predictive values. None of the CAP definitions had both sensitivity and specificity superior to 65%. Depending on the CAP definition, the rate of included patients without CAP (“false positives”) ranged from 1 to 21%. Conclusions CAP diagnostic criteria within RCTs are heterogeneous, which may have far-reaching consequences on validity of RCT results.

Keywords

• Inclusion criteria
• Clinical trial
• Randomized clinical trial
• Diagnostic criteria
• Community- acquired pneumonia