Statistical methods for primary and secondary outcomes {20a}
REGRESSION, PRESSURE SORE, PRESSURE SORES
The analysis will be performed according to the intention-to-treat (ITT) principle. Descriptive statistics will be calculated to summarize patient characteristics collected at study entry according to the randomization group. Categorical variables will be reported as absolute frequencies and percentages. Continuous variables will be represented as mean and standard deviation or median first and third quartiles if not normally distributed according to the Shapiro–Wilk test.The raw risk of pressure sore will be calculated at each time point as the ratio between the number of subjects who developed a pressure sore at a given time point divided by the number of subjects undergoing NIV at that time point. Patients having a planned break at the time point considered, but not weaned off NIV, will be considered as patients undergoing NIV.Mixed effect logistic regression models will be used to estimate the risk of pressure sores and the difference between interfaces, including a random intercept to account for clustering of the subjects within the center and repeated measures within patients. The response variable will be the presence/absence of pressure sores, whereas the independent variables will be the treatment, time (12, 24, 36, 48, 60, 72, 84, 96 h), and their interaction. The marginal predicted probabilities estimated by the model will provide the incidence of pressure sores at different times as well as overall. The inclusion of time as a covariate will allow to test the presence of a time trend in the incidence of pressure sores and to investigate the variation of time trends according to treatment group.If the descriptive statistics will detect unbalanced characteristics between randomization groups (e.g., indication for NIV), the corresponding variables will be added as covariates in the logistic regression model.Regarding the number of pressure sores, different mixed effect Poisson regression models will be applied: one for each time point to estimate the average number of pressure sores at each time point and a model in which only the highest number of pressure sores will be considered for each patient. Time will be included as offset to evaluate the average number of pressure sores per day.The grade and location of pressure sores will be summarized using descriptive statistics at each time point.The analyses will be also performed according to the modified intention-to-treat approach (mITT) excluding subjects with a NIV duration shorter than 12 h to ensure patients in the rotational group performed at least one rotation of the interface.Regarding the economic evaluation, the incremental cost-effectiveness ratio (ICER) will be calculated considering two outcomes: (i) the proportion of pressure sores and (ii) the patient comfort. ICER, which is the ratio between the difference of each outcome in the two groups (i.e., difference in the proportion of pressure sores or comfort score) and the difference in the average cost for each treatment will allow to evaluate the incremental costs needed to reduce of 1 point the outcomes thanks to interface rotation. The confidence intervals of the ICER will be calculated using the non-parametric bootstrap method. Specifically, the 2.5