Interim analysis and data monitoring committees

CH14 INTERIM ANALYSIS AND DATA MONITORING COMMITTEES... 

The code will be broken and data will be analyzed when the 12-mo follow-up has been completed for all patients. At that time, DHA therapy will be offered to all patients who desire to receive it. Clinical and laboratory studies will be monitored by an independent data and safety monitoring committee. This committee will also perform an interim analysis when 30 patients have completed assessment and has permission to terminate the study if there are significant favorable findings or unanticipated adverse outcomes. A determination of statistical power indicates that this sample size is sufficient to detect a major effect (0.862 standard deviations). With a more modest effect of 25%, however, the statistical power diminishes to 60%. The study has been approved by the Institutional Review Board at the Johns Hopkins Medical Institutions and is supported by a research grant from the Office of Orphan Products Development at the Food and Drug Administration. Fifty-two patients are enrolled in the study at this time. The code has not yet been broken. No adverse effects attributable to the medication have been observed. 

The following parameters will be listed and analyzed both for the final analysis and for the interim safety evaluations by the independent data monitoring committee ... 

After 83 MACE events had accrued, the first interim analysis was performed and the upper bound of the confidence interval placed around the hazard ratio point estimate was 1.51. An independent statistician performed this analysis and communicated the results to the independent data monitoring committee. Having therefore discharged the 1.8 threshold, the sponsor was able to include these interim results in the NDA. To protect trial integrity and statistical validity, the researchers involved with this analysis were not involved in subsequent trial conduct, data reviews, and trial analyses and did not communicate with those still involved in the study. 

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