Clinical drug trials: practical problems of phase III.

INTRODUCTION: Phase III randomised clinical trials provide the highest level of evidence to support the superior effectiveness of a new drug or therapy. The main practical problems encountered in the initiation, design, conduct and completion of both investigator-initiated and sponsor-initiated phase III clinical drug trials will be reviewed. METHODS: A Medline search of clinical drug trials conducted in Singapore as well as journal articles highlighting important methodological considerations and practical problems encountered in phase III clinical trials was performed. RESULTS: Several phase III randomised clinical trials have been conducted in Singapore which include the investigation of interventions that include tramadol, estradiol patch and colloidal bismuth subcitrate. The main problems encountered in phase III clinical drug trials include difficulties with recruitment of subjects for the study, proper filing of case report forms, special problems in children and the elderly, adequate compensation for adverse events and the adequate archival of documents of the completion of trials. In investigator-initiated trials, careful attention should be given to identifying a suitable study question, choice of study design, sample size calculations and data analysis. In sponsor-initiated trials, a good working relationship with the sponsor is essential and publication terms should be spelt from the onset of the trial. CONCLUSIONS: Well-planned clinical trials led by a team of competent investigators are essential for the conduct of rigorous sponsor-initiated and investigator-initiated clinical trials.