What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial

Pál Czobor; Barbara Sebe; Károly Acsai; Ágota Barabássy; István Laszlovszky; György Németh; Toshi A Furukawa; Stefan Leucht

doi:10.3389/fpsyt.2022.816339

What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial

Front Psychiatry. 2022 Apr 25:13:816339. doi: 10.3389/fpsyt.2022.816339. eCollection 2022.

Authors

Pál Czobor¹, Barbara Sebe², Károly Acsai², Ágota Barabássy², István Laszlovszky², György Németh², Toshi A Furukawa³, Stefan Leucht⁴

Affiliations

¹ Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
² Global Medical Division, Gedeon Richter Plc, Budapest, Hungary.
³ Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
⁴ Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.

Abstract

Introduction: Minimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence.

Methods: Data of a 26-week long, double-blind study with 454 patients [Positive and Negative Symptom Scale Negative Factor Score (PANSS-FSNS) ≥24, Positive and Negative Symptom Scale Positive Factor Score (PANSS-FSPS) ≤ 19] treated with cariprazine 4.5 mg/d or risperidone 4 mg/d were analyzed. The Clinical Global Impression-Improvement scale was used to quantify minimum improvement (CGI-I = 3) and no clinical change (CGI-I = 4) on the PANSS-FSNS, and the MCID was estimated with the following methods: as the mean PANSS-FSNS changes corresponding to the first instance of minimal improvement across all visits (MCID₁); as the difference between the PANSS-FSNS change associated with the first instance and the PANSS-FSNS changes associated with the last recorded clinically unchanged status across all visits (MCID₂); with the effect size approach (MCID₃); as the Youden Index based cut-off value between no clinical change and minimal improvement (MCID₄); as the relative likelihood of minimal improvement (MCID₅).

Results: The MCID₁ and MCID₂ resulted in, respectively, a 3.8-point (18.5%) and a 1.5-point (7.3%) decrease from baseline severity on the PANSS-FSNS. Greater values were required for the MCID at later evaluation times. The cut-off between minimum improvement and no clinical change defined by the Youden Index was a-3-point (15%) change in the PANSS-FSNS. The effect size approach indicated the 1.5-point difference between minimally improved and unchanged patients to be a medium effect (ES = 0.6).

Conclusion: Applying different methods led to different results, ranging between 7.3 and 18.5% improvement from the baseline for the MCID at its earliest occurrence in patients with predominantly negative symptoms of schizophrenia.

Keywords: MCID; cariprazine; clinical trial; minimum clinically important difference; negative symptoms; schizophrenia.