On Oct. 1, 1946 — exactly 65 years ago — the justices overseeing the trial rendered their verdict.
However, the lack of prospective validation of this concept in the setting of an appropriate clinical trial renders its clinical application difficult.
It can halt a trial, render a scientific question unanswered, and waste precious resources--most critically the time, effort, and health of participants.
Thus, sustained improvement of symptoms, such as pain in the placebo group with increasing duration of the trial, renders it difficult to show superiority of the active drug over placebo.
Also, the exclusion of the VELOUR trial renders the results of this meta-analysis incomplete and prone to misinterpretation, although the authors conclude that the use of aflibercept remains justified in its approved indication in patients with mCRC.
This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically.
"… methodological issues (i.e., sample attrition and exposure to the intervention in the control group) [emphasis added] of a recent randomized, controlled trial rendered its findings inconclusive (MacMillan et al., 2009)…" [ 52], p. 6. Notable in the second extraction is the statement that the control group was exposed to the intervention even though no control women were screened.
A statistician was identified in only 27% of the trials, rendering the analysis of the data questionable.
The inclusion criteria varied considerably among the trials, rendering any comparison of the primary outcomes problematic with such widely varying a priori risk factors.
This lack of accepted criteria for the success or failure of lung recruitment has precluded the conduct of reproducible clinical trials, rendering any comparison with conventional ventilation strategies difficult.
