Statistical methods for primary and secondary outcomes
anxiety, toxicities, hypoparathyroidism, dysphonia, CRF, paralysis
DYSPHAGIA, RECURRENCE, HYPOPARATHYROIDISM, CRF, SECONDARY, REMISSION, PND, METASTASES
Descriptive summary statistics will be provided for continuous demographic, laboratory, and clinical variables. The descriptive summary statistics will include number of patients, means and standard deviations for quantitative variables, and percentages for qualitative data.Subject demographic and baseline characteristics will be summarized by treatment group. The Student test will be used for the continuous variables (or non-parametric test if variables are not normally distributed), and the chi-square test will be used for the categorical variables.Primary outcomes s1The main endpoint will be analyzed 1 year after randomization of the last patient, once all the CRF will have been collected and the database has been cleaned. The analysis will be performed when all patients will have 1 year of follow-up, and no lost of follow-up will be tolerated.A patient will be in remission if the requirements are met at 1 year following randomization. Conversely, a patient will be considered to not be in remission if the criteria are not met at 1 year following randomization. In the absence of censored data, the proportion of patients in complete remission will be calculated as a percentage.Since the study is designed as a non-inferiority study, the primary analysis will be carried out by considering all evaluable patients (per-protocol population), as this is the most conservative approach in this context. Patient will be considered as evaluable if the treatment and the follow-up conform to the study protocol (diagnostic tests performed) and if the patient does not have detectable anti-Tg antibodies. A sensitivity analysis using the intent-to-treat (ITT) population, considering all patients in their initial group of randomization, will also be performed, to test the robustness of the results.The observed difference in patients in complete remission (∆) and its 95% unilateral confidence interval will be calculated. If the unilateral confidence interval does not include the −5% clinically relevant difference (∆L), then the TT alone strategy will be considered as non-inferior to the TT + PCND strategy.All statistical analyses will be performed using the SAS® software.Secondary outcomes s1Unstimulated thyroglobulin levels between groups will be compared between groups using a chi-square test.The rate of patients in complete remission at 3 and 5 years will be compared between groups using a chi-square test.The rate of patients in with structural incomplete response, biological incomplete response, indeterminate response, distant metastases, or further treatments at 1, 3, and 5 years will be compared between the 2 groups using a chi-square test for each type of response.For these secondary criteria we expect, based on retrospective series comparing the two surgical techniques (total thyroidectomy alone or total thyroidectomy + PND), rates of incomplete response or re-treatement in the range of the following:Difference in locoregional control = 6.9% at 10 years [Difference in rate of recurrence = 4.6% at 3 years [Difference in rate of retreatment = 8.2% at 5 years [Rate of structural recurrence = 1.4% at 8 years [The rate of patients at 1 year with persistent hypoparathyroidism requiring medication and/or with persistent vocal fold paralysis will be compared between groups using a chi-square test; subjective dysphonia (Voice Handicap Index) and subjective dysphagia (SWAL-QOL) toxicities will be compared using a Student test for each time of evaluation (or a Kruskall-Wallis non-parametric test if they are not normally distributed).Quality of life and anxiety: The investigator will inform the patient on the objective of QoL data collection. QoL data may be not exploitable in case of great number of missing questionnaires. Data will be analyzed according to the scoring manual of each questionnaire. A longitudinal analysis using a mixed model will be used to take into account of repeated QoL assessment and the initial value. If this analysis shows a significantly different effect between groups or an interaction between treatment and time, an analysis of the treatment effect on quality of life will be carried out at each time. Mean sub-scale scores will be compared using a Student test for each time of evaluation (or a Kruskall-Wallis non-parametric test if they are not normally distributed).