Recruitment interim analysis

For practical reasons, however, the number of interims should be small in number. Undertaking interims adds cost to the trial and they also need to be very carefully managed. In particular, the results of each interim must be made available in a timely way in order for go/no-go decisions to be made in good time. Remember the trial does not stop to allow the interim to take place, recruitment and followup continues. It has been known in more than one trial for total recruitment to be complete before the results of the interim analysis become available - this is obviously a situation that you would want to avoid, the interim then becomes a... 

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 execution of an interim analysis should be a completely confidential process because unblinded data and results are potentially involved. All staff involved in the conduct of the trial should remain blind to the results of such analyses, because of the possibility that their attitudes to the trial will be modified and cause changes in the characteristics of patients to be recruited or biases in treatment comparisons. This principle may be applied to all investigator staff and to staff employed by the sponsor except for those who are directly involved in the execution of the interim analysis. Investigators should be informed only about the decision to continue or to discontinue the trial, or to implement modifications to trial procedures. 

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