Conditional power calculations for clinical trials with historical controls

2006 ◽  
Vol 25 (17) ◽  
pp. 2922-2931 ◽  
Author(s):  
Edward L. Korn ◽  
Boris Freidlin
Keyword(s):  
Clinical Trials ◽  
Conditional Power ◽  
Power Calculations ◽  
Historical Controls

scholarly journals POWER CALCULATIONS IN CLINICAL TRIALS WITH COMPLEX CLINICAL OBJECTIVES

2015 ◽  
Vol 28 (1) ◽  
pp. 15-50 ◽  
Author(s):  
Alex Dmitrienko ◽  
Gautier Paux ◽  
Thomas Brechenmacher
Keyword(s):  
Clinical Trials ◽  
Power Calculations

scholarly journals Comparison of futility monitoring guidelines using completed phase III oncology trials

2016 ◽  
Vol 14 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Qiang Zhang ◽  
Boris Freidlin ◽  
Edward L Korn ◽  
Susan Halabi ◽  
Sumithra Mandrekar ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Alternative Hypothesis ◽  
Phase Iii ◽  
Interim Result ◽  
Type I ◽  
Conditional Power ◽  
Phase Iii Clinical Trials ◽  
The Impact ◽  
Analytical Approaches

Background: Futility (inefficacy) interim monitoring is an important component in the conduct of phase III clinical trials, especially in life-threatening diseases. Desirable futility monitoring guidelines allow timely stopping if the new therapy is harmful or if it is unlikely to demonstrate to be sufficiently effective if the trial were to continue to its final analysis. There are a number of analytical approaches that are used to construct futility monitoring boundaries. The most common approaches are based on conditional power, sequential testing of the alternative hypothesis, or sequential confidence intervals. The resulting futility boundaries vary considerably with respect to the level of evidence required for recommending stopping the study. Purpose: We evaluate the performance of commonly used methods using event histories from completed phase III clinical trials of the Radiation Therapy Oncology Group, Cancer and Leukemia Group B, and North Central Cancer Treatment Group. Methods: We considered published superiority phase III trials with survival endpoints initiated after 1990. There are 52 studies available for this analysis from different disease sites. Total sample size and maximum number of events (statistical information) for each study were calculated using protocol-specified effect size, type I and type II error rates. In addition to the common futility approaches, we considered a recently proposed linear inefficacy boundary approach with an early harm look followed by several lack-of-efficacy analyses. For each futility approach, interim test statistics were generated for three schedules with different analysis frequency, and early stopping was recommended if the interim result crossed a futility stopping boundary. For trials not demonstrating superiority, the impact of each rule is summarized as savings on sample size, study duration, and information time scales. Results: For negative studies, our results show that the futility approaches based on testing the alternative hypothesis and repeated confidence interval rules yielded less savings (compared to the other two rules). These boundaries are too conservative, especially during the first half of the study (<50% of information). The conditional power rules are too aggressive during the second half of the study (>50% of information) and may stop a trial even when there is a clinically meaningful treatment effect. The linear inefficacy boundary with three or more interim analyses provided the best results. For positive studies, we demonstrated that none of the futility rules would have stopped the trials. Conclusion: The linear inefficacy boundary futility approach is attractive from statistical, clinical, and logistical standpoints in clinical trials evaluating new anti-cancer agents.

scholarly journals Types and causes of chronic pain after laparoscopic operations

2021 ◽  
Vol 8 (11) ◽  
pp. 5588
Author(s):  
Mohammad Saqib Siddiqui ◽  
Natheer Ibrahim Albasri ◽  
Nour Abdullah Al Hemaid ◽  
Ahmed Talal Alamoodi ◽  
Shooq Abdulaziz Alghazal ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Severe Pain ◽  
Retrospective Data ◽  
Minimally Invasive Approach ◽  
Invasive Approach ◽  
Inflammatory Status ◽  
Tissue Trauma ◽  
Incidental Pain ◽  
Historical Controls

Laparoscopy has been introduced as a minimally invasive approach that has been developed to achieve the intended outcomes by open surgeries but with less frequent body injuries and complications. However, evidence indicates that the reported favourable outcomes are mainly based on retrospective data and using historical controls and only a few prospective investigations and clinical trials were published. Furthermore, studies have also demonstrated that following laparoscopy, severe pain can develop similar to or equal to the pain reported during open surgeries that develop within the earliest hours due to the significant tissue trauma introduced by laparoscopy. The present literature review discussed the different causes and types of chronic pain following laparoscopy. We also shed more light on the potential mechanisms and pathophysiology that attributes to the development of pain following laparoscopy. Many studies have indicated the development of chronic pain after 3, 6 and 12 months after hysterectomy, cholecystectomy, nephrectomy, colorectal surgeries and other abdominal surgeries. The development of postoperative main might be attributed to the tissue or nerve injury and associated inflammatory status that can also aid to the development of pain in such settings. Evidence also shows that the incidental pain following laparoscopy is similar or superior to that following open surgeries. Therefore, further interventional approaches are needed to enhance the outcomes.

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