The Brief Negative Symptom Scale (BNSS): A sensitive, reliable measure for clinical trials

The Brief Negative Symptom Scale (BNSS) is a new, brief measure that was developed based on the NIMH-sponsored Consensus Development Conference on Negative Symptoms criteria. The BNSS was designed to measure negative symptoms reliably and efficiently, and to be practical for use in clinical treatment trials. Key characteristics of the BNSS are that it:

• is brief, consisting of only 13-items that can be rated in a 10-15 minute interview;
• has a concise manual with a semi-structured interview guide;
• is written clearly and simply;
• covers all five of the NIMH Consensus Conference domains; and
• has good separation of the two dimensions thought to underlie negative symptoms (expressivity and anhedonia/amotivation/asociality).

Recently, Kirkpatrick and colleagues assessed sensitivity to change of the BNSS in a trial for MIN-101 a new treatment of negative symptoms, published in Schizophrenia Research. For more information on the article, please click here. The primary endpoint of the study was the PANSS Negative Symptom Factor Score, derived from the PANSS pentagonal model from Marder et al with the BNSS serving as a secondary endpoint. Using mixed-effects model for repeated measures, Kirkpatrick et al examined change in BNSS total score and in the BNSS factors of anhedonia/avolition/asociality (AAA), and expressivity (EXP).

Compared to placebo, the MIN-101 64mg group (N=83) showed a significant decrease in BNSS total score (effect size d [ES] 0.56, p<0.01) and both factor scores (AAA ES=0.48, EXP ES=0.46, p<0.02 for both). Patients in the trial had minimal depression and positive symptom scores; covarying for disorganization, positive symptoms, or anxiety/depression did not cause a meaningful change in the significance of the BNSS total or factor scores in this group. The MIN-101 32mg group (N=78) did not differ significantly from placebo (N=83) on BNSS total score (ES=0.33, p<0.09), AAA (ES=0.25, p<0.20) or EXP (ES=0.30, p<0.12) scores. These results demonstrate the BNSS is sensitive to change.

A second upcoming publication, scheduled for poster presentation at the upcoming ISCTM meeting in Washington, DC shows that a global, unified training program for raters from different countries achieved overall good-to-excellent inter-rater reliability.  Specifically, the BNSS demonstrated excellent reliability overall, with an ICC of 0.90, with some variation among individual subscales ranging from 0.97 for Anhedonia to 0.66 for Asociality. The comparatively lower reliability for the Asociality subscale suggests there is a need for additional work to improve training for domain. Further enhancements to the program are being implemented accordingly.

Taken together, these findings are part of a growing body of evidence suggesting that that the BNSS is optimal for use in global clinical trials and further confirms that the BNSS is a valid and reliable negative symptom rating scale - with excellent sensitivity to change, an essential component for drug studies. A new wave of drug targets, new behavioral interventions, new technology-oriented methods, and other techniques for improving negative symptoms will benefit greatly from the advantages that the BNSS has to offer in years to come.