First, this was an open-label, pre-planned crossover, non-blinded trial which may carry a certain unintended bias.
This may be because they were designed when loss to follow-up became a problem in a trial, rather than pre-planned prior to the start of the host trial.
These results, based on a post hoc, retrospective analysis of a small sample of RCC patients from a larger trial of solid tumor patients, should be further confirmed in pre-planned analyses of larger, prospective trials.
Because the focus of this study was to investigate mortality in a small defined population of captive birds, no sample size calculations were performed as might be done prior to a pre-planned observational study or randomized trial.
For ethical reasons, we conducted an interim analysis 12 months after the intervention, with a pre-planned rule to stop the trial and distribute treated nets in the control clusters if the 95% confidence interval indicated a 30% or greater reduction in the incidence rate of visceral leishmaniasis in the intervention group compared with the control group.
This outcome advantage of pemetrexed in non-squamous histology was confirmed by a retrospective unplanned subgroup analysis of a phase III trial comparing second-line pemetrexed versus docetaxel [ 10] and by a pre-planned analysis of a phase III trial of platinum-based chemotherapy in the first-line setting, followed or not by pemetrexed maintenance [ 11].
Again this trial had a pre-planned subgroup analysis showing improved survival in never smokers and patients of Asian origin[ 7 ].
While careful consideration should be given to the best method of fidelity assessment, an iterative approach allowing flexibility to adapt pre-planned methods is recommended within feasibility trials.
This pre-planned design for combination phase I trials aims to eliminate chances of falsely halting dose escalation, based on a high a priori chance of developing a DLT of one of the drugs (Hamberg et al, 2010b).
In pre-planned interim analyses of these two trials, patients treated with the lenalidomide and dexamethasone combination had a significantly longer time to disease progression compared with patients treated with dexamethasone alone.
