Risk of Unmasking on Schizophrenia Double Blind Clinical Trials Using Risperidone versus Comparator As A Result of Laboratory Analysis

Abstract

Background: Randomized double blind clinical trial is the most used and accepted method of clinical research involving human subjects. Clinical researches are performed under strict regulatory regulations including Helsinki Declaration and International Conference for Harmonization Good Clinical Practice (ICH – GCP) recommendations. As per ICH GCP principles safety and well being of clinical trials patients should prevail over research objectives and their health status should be monitored throughout the trial using objective and concise indicators such as but not limited to laboratory analysis. This study aims to identify factors that might unblind risperidone treatment arms for patients enrolled in randomized double blind schizophrenia clinical trials using risperidone versus comparator, as a result of reviewing safety laboratory analysis. Methods: This study included 134 controlled schizophrenia patients who received treatment with risperidone versus antipsychotic agents with lower dopamine antagonist potency. Prolactine values were determined using imunoenzimatic and colorimetric method (ELISA) for cantitative determination of prolactine from serum or plasma. Results: 84% percent of the patients treated with risperidone showed elevated levels for prolactine above laboratory reference ranges defined as: Men ( 1.8 – 17.0 ng/ml) ; Women ( fertile 1.2 – 19.5 ng/ml, menopause 1.5 – 18.5 ng/ml) Conclusions: High elevated values of prolactin were determined for risperidone treated patients which might disclose the patient treatment arm to blinded investigator and jeopardize the research. As lab results are an essential safety factor of clinical trial those cannot be overruled and establishing Independent Data Monitoring Committee to oversee patients’ data and warn the investigator is recommended.