FLO-ELA
’ initiation failure
EVENT
As described earlier, FLO-ELA is an open-label trial comparing two methods of fluid delivery (cardiac output monitor vs clinician judgement) in participants undergoing emergency laparotomy. The primary outcome measure is the number of days that participants are alive and out of hospital within 90 days of randomisation. The intercurrent event of interest is the cancellation of surgery, which precludes treatment from being initiated (as fluid delivery is only relevant once participants begin surgery). This is an example of a ‘cause-specific’ initiation failure, as some participants who do undergo surgery may also not initiate treatment for other reasons. We note that ideally randomisation would be done at the point surgery was due to begin, to minimise the number of cancellations; however, in practice, this is not always feasible due to the time required to prepare the intervention combined with the emergency setting.In this trial, the mITT estimator is appropriate. First, the intercurrent event can be easily identified and measured in both treatment groups, and second, the decision on whether to cancel surgery or not will almost certainly not be affected by the allocated treatment arm. This is because in most cases, the relevant decision-makers (surgeons) will be unaware of trial group allocation until surgery starts (i.e. at the point the decision is made). Furthermore, the decision not to proceed with surgery has large health implications for the patient and is only undertaken in response to a major change in the patient’s clinical condition since surgery was initially planned, and it is implausible that such a fundamental change in patient care would be undertaken on the basis of the planned method of fluid delivery.