Organization of Clinical Trials of Photosensitizer based on 5-Aminolevulinic Acid Hexyl Ester

Background: This paper deals with the statistical and methodological study conducted in order to assess the possibility of combining in one study, Phase 2 and 3 clinical trials of the Russian drug Hexasense based on 5-aminolevulinic acid hexyl ester. Methods: Hexasense drug is intended for fluorescence diagnosis of bladder cancer (the route of administration - intravesical instillation of solution). The clinical trial involved a comparative study of the effectiveness of diagnostic fluorescence depending on the exposure time of the drug solution in the bladder (1 and 2 hours). This is due to the fact that the time interval of 2 hours checked on the research Phase 1 used to cause inconvenience to patients. Results: After selecting the optimal diagnostic mode (a task of Phase 2) it is necessary to evaluate the effectiveness of the selected mode as compared to standard white-light cystoscopy (a task of Phase 3). Comparison of the effectiveness of two diagnostic fluorescence diagnostic modes with different exposure time of solution of 1 and 2 hours has been planned. At the second stage, the selected fluorescence diagnosis mode will be compared with the results of a standard white-light cystoscopy obtained in the same group of patients. A difference of 10% will be taken for significant differences in values of sensitivity and specificity. The statistical analysis showed that the required number of patients at a significance level of 2.5%, power of 80%, and for minimum difference in proportions of 10% subject to the correction of 10% for the dropout and unassessed patients would be 134 people (two groups of 67 patients). In this case, the same sample of patients allows comparing reliably the effectiveness of two diagnoses with the correction for multiplicity of comparison. Application: This will help to minimize the number of patients involved in the study and not reduce the accuracy of the results at the same time. The Ministry of Health of the Russian Federation authorized the clinical trial of the drug Hexasense with Phases 2 and 3 combined.