Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance

Stephen Z. Levine*, Jonathan Rabinowitz, Rudolf Uher, Shitij Kapur

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Emerging data from on imaging and genetic studies have generated interest in "clinically significant" biomarkers to predict response and prognosis. What constitutes "clinical significance" and how a biomarker would reach that threshold are unclear. To develop a benchmark we reviewed different approaches for defining "clinical significance" applied in schizophrenia research and identified that an improvement of 15 points on the PANSS Total is considered meaningful in clinical settings. Using this benchmark and we simulated thousands of schizophrenia trials, using characteristics derived from the NEWMEDS database with over 8000 patients with schizophrenia, to the kind of imaging, genetic, and other biomarkers that could attain clinical significance. We plotted the interaction between frequency-of-occurrence, the effect size of biomarkers and their relationship to the clinical significance threshold. Results show that categorical biomarkers are likely to attain clinical significance when they occur in 20-50% of the clinical population, and can predict at least a 8-10 point PANSS scale difference. Genetic markers are likely to have clinical significance when they occur in 20-50% of the population and can predict 7-9 points on the PANSS scale. A marker with a lower frequency or lesser effect size would find it hard to meet clinical significance thresholds for schizophrenia. The assumptions and limitations of this approach are discussed. Compared with standards in the rest of medicine, biomarkers that can attain this benchmark will be cost-effective and are likely to be adopted by clinical systems.

Original languageEnglish
Pages (from-to)1578-1585
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume25
Issue number10
Early online date20 Jun 2015
DOIs
Publication statusPublished - 1 Oct 2015

Keywords

  • Biological markers
  • Biological psychiatry
  • Translational medical research
  • Treatment response

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