Estimating reliability and generalizability from hierarchical biomedical data

J Biopharm Stat. 2007;17(4):595-627. doi: 10.1080/10543400701329448.


It is shown how hierarchical biomedical data, such as coming from longitudinal clinical trials, meta-analyses, or a combination of both, can be used to provide evidence for quantitative strength of reliability, agreement, generalizability, and related measures that derive from association concepts. When responses are of a continuous, Gaussian type, the linear mixed model is shown to be a versatile framework. At the same time, the framework is embedded in the generalized linear mixed models, such that non-Gaussian, e.g., binary, outcomes can be studied as well. Similarities and, above all, important differences are studied. All developments are exemplified using clinical studies in schizophrenia, with focus on the endpoints Clinician's Global Impression (CGI) or Positive and Negative Syndrome Scale (PANSS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Analysis of Variance
  • Biometry / methods*
  • Clinical Trials as Topic / statistics & numerical data*
  • Double-Blind Method
  • Humans
  • Linear Models
  • Meta-Analysis as Topic
  • Models, Statistical*
  • Observer Variation
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Reproducibility of Results
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy
  • Treatment Outcome


  • Risperidone