Email updates

Keep up to date with the latest news and content from BMC Medical Research Methodology and BioMed Central.

Open Access Research article

Additive scales in degenerative disease - calculation of effect sizes and clinical judgment

Matthias W Riepe1*, David Wilkinson2, Hans Förstl3 and Andreas Brieden4

Author Affiliations

1 Department of Psychiatry and Psychotherapy II, Mental Health & Old Age Psychiatry, Ulm University, Ulm, Germany

2 Department of Old Age Psychiatry, Southampton University, Southampton, UK

3 Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany

4 Department of Wirtschafts- und Organisationswissenschaften, Universität der Bundeswehr München, Neubiberg, Germany

For all author emails, please log on.

BMC Medical Research Methodology 2011, 11:169  doi:10.1186/1471-2288-11-169

Published: 16 December 2011



The therapeutic efficacy of an intervention is often assessed in clinical trials by scales measuring multiple diverse activities that are added to produce a cumulative global score. Medical communities and health care systems subsequently use these data to calculate pooled effect sizes to compare treatments. This is done because major doubt has been cast over the clinical relevance of statistically significant findings relying on p values with the potential to report chance findings. Hence in an aim to overcome this pooling the results of clinical studies into a meta-analyses with a statistical calculus has been assumed to be a more definitive way of deciding of efficacy.


We simulate the therapeutic effects as measured with additive scales in patient cohorts with different disease severity and assess the limitations of an effect size calculation of additive scales which are proven mathematically.


We demonstrate that the major problem, which cannot be overcome by current numerical methods, is the complex nature and neurobiological foundation of clinical psychiatric endpoints in particular and additive scales in general. This is particularly relevant for endpoints used in dementia research. 'Cognition' is composed of functions such as memory, attention, orientation and many more. These individual functions decline in varied and non-linear ways. Here we demonstrate that with progressive diseases cumulative values from multidimensional scales are subject to distortion by the limitations of the additive scale. The non-linearity of the decline of function impedes the calculation of effect sizes based on cumulative values from these multidimensional scales.


Statistical analysis needs to be guided by boundaries of the biological condition. Alternatively, we suggest a different approach avoiding the error imposed by over-analysis of cumulative global scores from additive scales.

dementia; neurodegeneration; clinical studies; meta-analysis; effect sizes; Cohen's d