The increasing rate of failed trails found in mood and anxiety disorders is now being seen in Alzheimer's studies. Factors related to the administration of clinician rating scales, such as poor inter-rater reliability, poor interview quality and rater bias may be a contributing factor. Studies have found inter-rater reliability to be problematic in Alzheimer's studies, even with less subjective outcome measures. Lack of standardization of administration and scoring procedures has been identified as a major contributing factor. Remediation through better training procedures has been found to be successful, although ongoing calibration is needed to prevent rater drift. Expectancy bias and baseline score inflation is more difficult to remediate. Inflation of baseline scores increases placebo response, since lower severity has been found to be associated with higher placebo response. The use of centralized raters that are independent from study sites may help ameliorate these issues. Increased methodological research examining new approaches to these problems is warranted. The increased costs associated with this research should offset the time and expense of continuing with 'business as usual'.