Outlier-response pattern checks to improve measurement with the Montgomery-Asberg depression rating scale (MADRS)

Jonathan Rabinowitz, Alon A. Rabinowitz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Symptom manifestations in affective disorders can be subtle. Small imprecisions in measurement can lead to incorrect estimation of change. Previously, expert-derived scoring inconsistency flags were developed for MADRS. Currently, we derive empirically based outlier-pattern flags, to further detect imprecisions in ratings. NEWMEDS data repository of almost 25,000 MADRS administrations from 11 registration trials of antidepressants was used to identify outlier response patterns reflecting potentially careless responses. Coverage of these flags was compared to previously published expert derived flags. Both sets of flags were also further tested in Monte Carlo simulated data as a proxy to applying flags under conditions of known inconsistency. The outlier flags derived provide cutting points to identify: (1) under and overuse of values (e.g., Scoring “1″ on 6 or more items), (2) disproportionate use of even or odd response choices (e.g., 8 or more odd values), (3) longest consecutive use of value (e.g., more than 5 items in a row scored with same value), (4) high variability within administration (standard deviation greater than 1.8), (5) outlier responses on multiple items (i.e., multivariate outliers), and (6) outlier scoring (e.g., scoring 4,5 or 6 on item 1). Outlier response flags were raised in 26% of the MADRS administration and in 97% of the Monte Carlo data. Of administrations with no expert flag, 21.7% had an outlier flag and of administrations with at least one expert flag, 27.7% also had an outlier flag. Outlier-pattern flags appear to be a useful adjunct to expert derived flags in the quest to improve measurement in clinical trials.

Original languageEnglish
Pages (from-to)444-448
Number of pages5
JournalJournal of Affective Disorders
StatePublished - 15 Feb 2022

Bibliographical note

Publisher Copyright:
© 2021


The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking under grant agreement n 115008 of which resources are composed of European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013). Funding source was not involved in the collection, analysis, and interpretation of data; in the writing of the report; and nor in the decision to submit the paper for publication.

FundersFunder number
Seventh Framework Programme
Seventh Framework Programme


    • Consistency of measurement
    • MADRS
    • Montgomery-asberg depression rating scale
    • Remote monitoring


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