Collection, synthesis, and interpretation of evidence: a proof-of-concept study in COPD

Stat Med. 2013 May 10;32(10):1621-34. doi: 10.1002/sim.5730. Epub 2013 Jan 10.


We present a clinical proof-of-concept (PoC) study in chronic obstructive pulmonary disease with the objective of assessing the bronchodilatory effect of an experimental drug as compared with an active control treatment. In such an exploratory Phase II setting, we discuss the formal inclusion of relevant historical information and tailored PoC criteria for the purpose of a more efficient use of the available evidence to support clinical decision making. We provide guidance with regard to practical and methodological aspects for assessing the relevance of the historical data, synthesizing the evidence via a meta-analytic-predictive approach, and defining transparent statistical PoC decision criteria that are aligned with the clinical context. The case study was implemented using the Bayesian approach, which offers an ideal framework for the early phases of drug development.

MeSH terms

  • Bayes Theorem
  • Biostatistics
  • Bronchodilator Agents / therapeutic use*
  • Clinical Trials, Phase II as Topic / statistics & numerical data
  • Decision Making
  • Drug Discovery / statistics & numerical data*
  • Evidence-Based Medicine
  • Forced Expiratory Volume / drug effects
  • Humans
  • Meta-Analysis as Topic
  • Models, Statistical
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology


  • Bronchodilator Agents