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The planned analysis is expected to be powered to show an association of 1.23 with >90% power.
For both of these reasons, it is advantageous to measure standard clinical outcomes in studies that have a biomarker as a primary outcome, even though the studies may not be powered to show significance on a clinical effect.
Second, the quantitative nature of the imaging biomarkers often have far less variability than the primary cognitive and functional endpoints, and thus will require smaller sample sizes to be powered to show a statistically significant effect.
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The Swedish randomized controlled trial (n = 5049) was the only trial adequately powered to show a difference in metabolic acidosis, and the Plymouth randomized controlled trial (n = 2434) was only powered to show a difference in operative delivery for fetal distress.
Due to the small number of cases of cystic PVL in our study population, our population may have been under powered to show small differences in tHcy with cystic PVL.
Although the current study was not designed and not powered to show that EPO did not increase mortality in this dosing scheme and that EPO was safe, the number of patients who died during the study period was one in the EPO group and none in the placebo group.
All patients had normal ejection fractions at baseline, however, which may partly explain the lack of a consistent beneficial effect on myocardial physiology with ramipril (it may have been difficult to demonstrate improvements in normal function), though the study may also be under-powered to show changes in these parameters.
Similarly, escitalopram was associated with a strong treatment effect in a small RCT (n=12); however, the trial was under-powered to show statistically significant superiority over placebo on the primary outcome [ 346].
This study may therefore simply have been under-powered to show any beneficial effect of TGC.
However, the study was under-powered to show small but clinically relevant differences.
It is also possible that patients did not initiate co-trimoxazole early enough to reduce HIV-associated deaths that occurred early during TB treatment, that antimicrobial resistance mitigated the benefit of co-trimoxazole, or that our study was under-powered to show a strong beneficial effect.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com