ABSTRACT
This article discusses issues that are essential to ensuring the reliability of the conclusions of oncology clinical trials. Though quality control is important at every stage of a well-run clinical trial, the authors focus on the quality of the data as evidenced by the results and conclusions of the study. Good quality control principles and practices are discussed for study planning, design, conduct, analysis, and interpretation.
Subject(s)
Clinical Trials as Topic/standards , Neoplasms/therapy , Clinical Trials as Topic/methods , Data Collection , Drug Approval , Drug Industry , Drug Utilization , Forms and Records Control , Government Agencies , Humans , Neoplasms/drug therapy , Neoplasms/mortality , Patient Selection , Quality Control , Reproducibility of Results , Research Design , Safety , Time Factors , Treatment Outcome , United States , United States Food and Drug AdministrationABSTRACT
STUDY OBJECTIVES: To evaluate the safety, tolerability, and pharmacokinetics of increasing dose levels of oral dolasetron mesylate, a new 5-HT3 antagonist. DESIGN: Double-blind, placebo-controlled, dose-ranging phase I study. SETTING: A clinical research center. PATIENTS: Forty healthy male volunteers. INTERVENTIONS: Eight subjects at each dose level were randomized in a ratio of 3:1 to receive either dolasetron mesylate 25, 50, 100, 150, or 200 mg in a single oral dose on days 1 and 9, and twice/day on days 2-8, or placebo for 9 days. MEASUREMENTS AND MAIN RESULTS: Dolasetron was well tolerated at all dose levels. The adverse event rates for dolasetron- and placebo-treated subjects who experienced at least one adverse event were 80% and 50%, respectively. Most frequently reported by subjects receiving dolasetron were headache, constipation, flatulence, and lightheadedness. They generally were mild, and none was severe. No dose-response relationship was apparent for any adverse event. There were no clinically significant changes in mean laboratory values or vital signs. Asymptomatic treatment-related electrocardiographic changes were consistent with the drug's electrophysiologic properties. These changes have been well characterized and have thus far been clinically unimportant. Pharmacokinetics of the reduced metabolite were dose independent, and multiple-dose exposure of this metabolite can be predicted from its single-dose values. CONCLUSION: Oral dolasetron mesylate was well tolerated when administered in doses up to 200 mg/day for 9 days in healthy volunteers.
