We believe that CRM is a good alternative to the standard method from both a statistical and a practical point of view but further methodological research is necessary to address the issues related to the composite nature of the endpoint.
Strengths of this study include its randomized, prospective nature as well as the comprehensive nature of the endpoint measured, which factored in measurements of in-hospital morbidity and quality of life after discharge.
The most important question was therefore whether the progressive nature of renal endpoints in patients with serum potassium ≥5.0 mmol/l is independent of other factors, and most importantly, by the prevailing renal function, as patients with low eGFR are more prone to develop high serum potassium levels.
The rationale for this choice is to minimize the chances of false negatives because of the exploratory nature of these secondary endpoint analyses.
Yet, assigning one utility to cover all endpoints seems too coarse given the very different nature of the salient endpoints.
Given the weight-dependent nature of the study endpoints, weight and weight changes were incorporated into the model as covariates.
Because of the size of the study and the nature of the treatment and endpoints we have not included an option for premature study termination due to high efficacy.
Due to the slowly progressing nature of PC, analysis of such endpoints would require at least 15 years of follow-up [ 2].
Subjects were distributed into 2 groups according to the number of intubation days: early-onset VAP (<5 days) or late-onset VAP (≥5 days).The primary endpoint was the nature of causative pathogens and their resistance profiles.
Of course, the properties needed for the action of non-cancer agents causing noncancer effects, and for the nature of background incidence of the same endpoints, could be true.
But it is important to evaluate the needed properties in view of what we have usually understood about the nature of the disease processes for noncancer endpoints.
