Statistical analysis plan of a randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy (SECURE trial)

Abstract

BackgroundCholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. However, persistent pain after cholecystectomy for symptomatic cholecystolithiasis is reported in up to 40% of patients. The aim of the SECURE trial is to compare the effectiveness of usual care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. The SECURE trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound-proven gallstones or sludge. Randomization was performed to either usual care (standard practice, according to the physician’s knowledge and experience, and physician’s and patient’s preference) or a restrictive standardized strategy: treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy based on fulfilment of pre-specified criteria. This article presents in detail the statistical analysis plan (SAP) of this trial and was submitted before outcomes were available to the investigators.ResultsThe primary end point of this trial is defined as the proportion of patients being pain-free at 12 months’ follow-up. Pain will be assessed with the Izbicki Pain Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, quality of life, the association between the patients’ symptoms and treatment, work performance, and cost-effectiveness.DiscussionThe data from the SECURE trial will provide evidence whether or not a restrictive strategy in patients with symptomatic cholecystolithiasis is associated with similar patient reported outcomes and a reduction in the number of cholecystectomies compared to usual care. The data from this trial will be analyzed according to this pre-specified SAP.Trial registrationThe Netherlands National Trial Register NTR4022. Registered on 5 June 2013.

Effects of Individualized Nursing Based on Zero-Defect Theory on Perioperative Patients Undergoing Laparoscopic Cholecystectomy

“…With the rapid development and progress of laparoscopic technology, the laparoscopic cholecystectomy has become the “gold standard” for surgical treatment of gallbladder diseases such as gallstones, gallbladder polyps, cholecystitis, and cholangitis given its merits of less trauma, bleeding, and postoperative complications, and superior curative effect and rapid recovery [ 11 , 12 ]. However, laparoscopic surgery is an invasive surgery, the artificial pneumoperitoneum and the stretching of the deltoid ligament and diaphragm fiber during surgery will stimulate the phrenic nerve, thus causing postoperative complications such as nausea and pain [ 13 , 14 ]. In addition, due to the lack of a comprehensive understanding of laparoscopic cholecystectomy, patients often have negative emotions such as fear, anxiety, and depression before surgery, especially anxiety.…”

Cost-effectiveness of Restrictive Strategy Versus Usual Care for Cholecystectomy in Patients With Gallstones and Abdominal Pain (SECURE-trial)

“…This is previously described in the study protocol and in the report of the primary results. [14][15][16] Volume and costs data on out-of-hospital care, outof-pocket expenses, and productivity losses were calculated based on results of patient questionnaires; the average costs per patient for available measurements were multiplied by the planned number of measurements. Costs were calculated as the product sum of the volumes of resources used and their respective unit costs.…”

“…Details of the SECURE-design, statistical analysis plan, and main results have been published previously. [14][15][16] The institutional review board of the Academic Medical Center (Amsterdam, the Netherlands) approved the study protocol. In short, patients with ultrasound proven gallstones or sludge and abdominal pain, who were referred to 1 of 24 participating surgical outpatient clinics, were eligible for inclusion.…”

Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants

“…Comparisons between groups were analyzed by χ 2 or Fisher’s exact test for categorical variables and by two-sample t tests for continuous variables. Alteration of parameters during follow-up were calculated by repeated measurement analysis with baseline data as covariate, using a generalized linear mixed models (GLMMs) and Bonferroni correction for multiple comparisons [ 28 , 29 ]. Correlations between parameters were analyzed by Spearman’s rank test.…”