Quality assessment of phase I dose-finding cancer trials: proposal of a checklist

Background Qualitative checklists for phase III trials have been proposed, to improve the reporting of such trials and to assess the validity of their results. Purpose Our objective was to develop such a scale for phase I cancer trials. Methods From a review of existing guidelines and checklists for phase III clinical trials, a staff team was responsible for the first selection of items and the construction of the questionnaire. The proposed quality assessment measures were rated by the survey respondents comprised of phase I research clinicians and statisticians on a 4-point Likert scale. Selected items from the quantitative analysis of the questionnaires were reviewed by an expert team who was responsible for providing the final items list. This was then applied to 103 recently published cancer phase I trials. Results Of the 48 initial items proposed by the staff team, 17 were selected from the quantitative analysis of the 99 participants' ratings. After qualitative analysis by the expert team, a 15-item checklist was derived, with 5 items related to trial objective, 5 to design, and 5 to analysis. The application to 103 recent journal articles on phase I cancer trials evaluating cytotoxic drugs showed on average the report of 10 items (range: 6-13) with 4 items reported in more than 95% of papers, while 2 were poorly reported. Limitations The response rate of participants was 20.7%. Conclusions A quality assessment checklist was developed for improved critical appraisal of the reporting of cytotoxic, dose-finding phase I oncology trials. This may be a first step toward a minimum standard of quality measures for all phase I clinical trial reports. Clinical Trials 2008; 5: 478-485. http://ctj.sagepub.com