Statistical significance interim analysis

Timing of any interim analysis Reason for sample size Power of clinical study Level of significance Criteria for termination of study Procedure for missing and imused data Reporting procedures for deviations from statistical plan... 

In the fixed sample clinical trial approach, one analysis is performed once all of the data have been collected. The chosen nominal significance level (the Type I error rate) will have been stated in the study protocol and/or the statistical analysis plan. This value is likely to be 0.05 As we have seen, declaring a finding statistically significant is typically done at the 5% p-level. In a group sequential clinical trial, the plan is to conduct at least one interim analysis and possibly several of them. This procedure will also be discussed in the trial s study protocol and/or the statistical analysis plan. For example, suppose the plan is to perform a maximum of five analyses (the fifth would have been the only analysis conducted had the trial adopted a fixed sample approach), and it is planned to enroll 1,000 subjects in the trial. The first interim analysis would be conducted after data had been collected for the first fifth of the total sample size, i.e., after 200 subjects. If this analysis provided compelling evidence to terminate the trial, it would be terminated at that point. If compelling evidence to terminate the trial was not obtained, the trial would proceed to the point where two-fifths of the total sample size had been recruited, at which point the second interim analysis would be conducted. All of the accumulated data collected to this point, i.e., the data from all 400 subjects, would be used in this analysis. 

The FDA s statisticians expect that each clinical protocol submitted will include a description of any planned interim analyses of the data, including the anticipated monitoring procedures, the variables to be analyzed, and the statistical methods to be applied. The latter includes the choice of significance level for each interim analysis, the frequency of analysis, and a declaration of the circumstances under which the study would be terminated before the planned number of patients have been entered into the study. 

Interim efficacy analyses usually make a mess These analyses require either that the overall size of the trial has to be greater than if no interim analysis was performed, or that a smaller a must be accepted as indicating statistical significance at the end of the whole study. 

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. 

Three months after the training 346 safety attitude questionnaires were administered. At the time of writing there have been 41 returns (response rate of 12 per cent). Insufficient data are eurrently available to allow statistically valid conclusions to be drawn. Interim analysis suggests no significant change in the climates of safety or teamwork. Preliminary data are displayed in Table 19.2. 

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