Biomarkers Predicting Treatment Outcome in Depression: What is Clinically Significant?

Abstract

Aim: To extend to biomarker studies the consensus clinical significance criterion of a three-point difference in Hamilton Rating Scale for Depression. Materials & methods: We simulated datasets modeled on large clinical trials. Results: In a typical clinical trial comparing active treatment and placebo, a difference of three Hamilton Rating Scale for Depression (HRSD) points at the end of treatment corresponds to 6.3% of variance in outcome explained. To achieve a similar explanatory power, genotypes with minor allele frequencies of 5, 10, 20, 30 and 50% need to attain a per allele difference of 4.7, 3.6, 2.8, 2.4 and 2.2 HRSD points, respectively. A normally distributed continuous biomarker will need an effect size of 1.5 HRSD points per standard deviation. A number needed to assess of three suggests that with this effect size, a biomarker will significantly improve the prediction of outcome in one out of every three patients assessed. Conclusion: This report provides guidance on assessing clinical significance of biomarkers predictive of outcome in depression treatment.

KEYWORDS::

• antidepressant medication
• biomarkers
• clinical significance
• major depressive disorder
• number needed to assess

Acknowledgements

The authors thank M Gray, who has provided technical support with creating an online calculator that accompanies this article.

Financial & competing interests disclosure

The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking (IMI-JU) under grant agreement No. 115008, of which, resources are composed of EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the EU‘s Seventh Framework Program (FP7/2007-2013). RH Perlis is supported by the National Institute of Mental Health MH086026. R Uher consults for the WHO. RH Perlis has received consulting fees from Proteus Biomedical, Concordant Rater Systems and RIDventures and research funding from National Institute of Mental Health. None of these organizations have direct interest in the content of this publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking (IMI-JU) under grant agreement No. 115008, of which, resources are composed of EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the EU‘s Seventh Framework Program (FP7/2007-2013). RH Perlis is supported by the National Institute of Mental Health MH086026. R Uher consults for the WHO. RH Perlis has received consulting fees from Proteus Biomedical, Concordant Rater Systems and RIDventures and research funding from National Institute of Mental Health. None of these organizations have direct interest in the content of this publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.