The Clinical Global Impressions scale: errors in understanding and use

Objective: The Clinical Global Impressions Severity and Improvement scales (CGI-S and CGI-I) are widely included as efficacy data in psychopharmacology new drug application submissions. This study was conducted to determine the extent to which clinical trials investigators included information unrelated to efficacy in their CGI ratings. Method: Forty-five principal investigators provided CGI-S and CGI-I ratings of narratives of patients with major depressive disorder or generalized anxiety disorder. Investigators were blindly randomized to receive narratives that either did (experimental) or did not (control) contain indication-unrelated medical or psychiatric adverse events. Investigators then completed a survey assessing CGI-S and CGI-I rating patterns. Results: CGI-S and CGI-I ratings were significantly more severe and less improved when the narratives contained medical and psychiatric adverse events unrelated to the diseases under study (major depressive disorder and generalized anxiety disorder) than when the narratives did not (Ps < .04). In response to the survey, 46% and 56% of investigators reported that a psychiatric adverse event unrelated to the disease under study would not affect their CGI-S and CGI-I ratings, respectively. Although 87% of investigators reported that their CGI-S and CGI-I ratings Would not be affected by a medical adverse event, actual CGI-S ratings were significantly more severe when all unrelated medical adverse event was described as occurring than when it vas not (P < .03). Conclusion: Clinical trials investigators' inclusion of indication-irrelevant adverse events threatens the validity of the CGI as an efficacy measure and may contribute to failure to detect efficacy signals in psychopharmacology clinical trials. (c) 2009 Elsevier Inc. All rights reserved.