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Time to revision is a common and clinically relevant endpoint for studies of patients with total hip replacement. Because failures occur rarely within the first years after replacement, new surgical techniques and materials are often implemented without evidence of their effectiveness from randomized trials. Observational data may be available but this relies on the use of historical controls which has been heavily criticized. Instead the use of change-point methods has been suggested to detect changes caused by successfully implemented interventions. In the setting of a proportional hazards model we develop a semi-parametric changepoint method to detect changes in baseline hazard. The procedure is motivated by and applied to a clinical study in patients with total hip replacements, where the effect of a new cement type is of interest. Power properties of the proposed method are investigated. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

For normally distributed data, determination of the appropriate sample size requires a knowledge of the variance. Because of the uncertainty in the planning phase, two-stage procedures are attractive where the variance is reestimated from a subsample and the sample size is adjusted if necessary. From a regulatory viewpoint, preserving blindness and maintaining the ability to calculate or control the type I error rate are essential. Recently, a number of proposals have been made for sample size adjustment procedures in the t-test situation. Unfortunately, none of these methods satisfy both these requirements. We show through analytical computations that the type I error rate of the t-test is not affected if simple blind variance estimators are used for sample size recalculation. Furthermore, the results for the expected power of the procedures demonstrate that the methods are effective in ensuring the desired power even under initial misspecification of the variance. A method is discussed that can be applied in a more general setting and that assumes analysis with a permutation test. This procedure maintains the significance level for any design situation and arbitrary blind sample size recalculation strategy. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate. We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS). Patients with stage II/III rectal cancer were randomized to CRT (50.4–54 Gy) with either induction (INCT-CRT) or consolidation CT (CRT-CNCT) with fluorouracil, leucovorin, oxaliplatin (CAO/ARO/AIO-12 and OPRA) or capecitabine and oxaliplatin (OPRA) followed by mandatory total mesorectal excision (TME) (CAO/ARO/AIO-12) or selective watch-and-wait surveillance (OPRA). 311 and 324 patients were recruited from June 15, 2015 to January 31, 2018; and from April 12, 2014 to March 30, 2020 in the two trials, respectively. Pretreatment clinical and tumor characteristics included were age, sex, ECOG, cT-category, cN-category, clinical UICC stage, location from anal verge, and tumor grade. In total, 628 eligible patients were included in the pooled analysis (CAO/ARO/AIO-12, n = 304; OPRA, n = 324). Of those, 313 were randomly assigned to the INCT-CRT group, and 315 to the CRT-CNCT group. Median follow-up was 43 months (IQR, 35–49) months in the CAO/ARO/AIO-12 trial and 61,2 months (IQR, 42–68,4) in the OPRA trial. Pooled analysis of baseline clinical and tumor characteristics did not identify any subgroups of patients that would benefit by the one TNT sequence over the other with regard to DFS. To our knowledge, this is the first pooled analysis of two randomized trials after direct head-to-head comparison of both TNT sequences. Both trials reported higher rates of complete response with CRT-CNCT, and this should be considered the preferred TNT sequence if organ preservation is a priority. • Total neoadjuvant therapy (TNT) has been used for patients with rectal cancer. • The optimal sequence of chemoradiotherapy and chemotherapy is a matter of debate. • No subgroups with DFS benefit for one TNT sequence over the other were identified. • Treatment goals should guide the preferred TNT sequence. [ABSTRACT FROM AUTHOR]