Inadequate statistical power to detect clinically significant differences in adverse event rates in randomized controlled trials

2009 ◽  
Vol 62 (6) ◽  
pp. 609-616 ◽  
Author(s):  
Ruth Tsang ◽  
Lindsey Colley ◽  
Larry D. Lynd
Keyword(s):  
Adverse Event ◽  
Randomized Controlled Trials ◽  
Statistical Power ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Clinically Significant ◽  
Event Rates ◽  
Inadequate Statistical Power

The association between placebo arm inclusion and adverse event rates in antidepressant randomized controlled trials: An examination of the Nocebo Effect

2021 ◽  
Vol 280 ◽  
pp. 140-147
Author(s):  
Christian P. Cheung ◽  
Mathura T. Thiyagarajah ◽  
Haben Y. Abraha ◽  
Celina S. Liu ◽  
Krista L. Lanctôt ◽  
...  
Keyword(s):  
Adverse Event ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Nocebo Effect ◽  
Randomized Controlled ◽  
Event Rates

Statistical Power for Analyses of Changes in Randomized Controlled Trials

2005 ◽  
Vol 84 (3) ◽  
pp. 283-287 ◽  
Author(s):  
Y.-K. Tu ◽  
A. Blance ◽  
V. Clerehugh ◽  
M.S. Gilthorpe
Keyword(s):  
Randomized Controlled Trials ◽  
Statistical Methods ◽  
Statistical Power ◽  
Change Score ◽  
Error Rates ◽  
Analysis Of Covariance ◽  
Controlled Trials ◽  
Multivariate Statistical ◽  
Randomized Controlled ◽  
Study Power

Randomized controlled trials (RCTs) are widely recommended as the most useful study design to generate reliable evidence and guidance to daily practices in medicine and dentistry. However, it is not well-known in dental research that different statistical methods of data analysis can yield substantial differences in study power. In this study, computer simulations are used to explore how using different univariate and multivariate statistical methods of analyzing change in continuous outcome variables affects study power, and the sample size required for RCTs. Results show that, in general, analysis of covariance (ANCOVA) yields greater power than other statistical methods in testing the superiority of one treatment over another, or in testing the equivalence between two treatments. Therefore, ANCOVA should be used in preference to change score or percentage change score to reduce type II error rates.

scholarly journals The adverse event profile of brivaracetam: A meta-analysis of randomized controlled trials

Seizure ◽  
2017 ◽  
Vol 45 ◽  
pp. 7-16 ◽  
Author(s):  
Li-na Zhu ◽  
Deng Chen ◽  
Tao Chen ◽  
Da Xu ◽  
Si-han Chen ◽  
...  
Keyword(s):  
Adverse Event ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Adverse Event Profile ◽  
Randomized Controlled

CLO19-052: Incidence of Ribociclib-Associated Cardiac Conduction Abnormalities in Patients With Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer: A Combined Analysis of 3 Phase III Randomized Controlled Trials

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-052
Author(s):  
Kyaw Z. Thein ◽  
Somedeb Ball ◽  
Sriman Swarup ◽  
Anita Sultan ◽  
Myo H. Zaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Event ◽  
Advanced Breast Cancer ◽  
Randomized Controlled Trials ◽  
Hormone Receptor ◽  
Advanced Breast ◽  
Phase Iii ◽  
Controlled Trials ◽  
Qtc Prolongation ◽  
Randomized Controlled

Introduction: Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, has improved survival in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER 2)-negative advanced breast cancer. Despite remarkable efficacy, potential cardiac toxicities remain a concern. We undertook a combined analysis of randomized controlled trials (RCT) to estimate the incidence of prolongation of corrected QT interval (QTcF) associated with ribociclib. Methods: We performed systematic search of Embase, MEDLINE, and meeting abstracts till September 30, 2018, to find all phase 3 RCTs comparing ribociclib with other agents or placebo in patients with advanced breast cancer and reporting QTc prolongation as adverse event. Mantel-Haenszel method was used to calculate the pooled risk ratio (RR) and absolute risk difference (RD) with 95% CI. Fixed effects model was applied. Heterogeneity was assessed using I2 statistic. Results: Three phase III studies with 2,062 participants were included. Randomization ratio was 1 to 1 in MONALEESA-2 and 7 studies and 2 to 1 in MONALEESA-3 study. I2 statistic was 0, suggesting homogeneity across studies. Prolongation of QTcF >60 msec from baseline was observed in 72 patients (61 had post-baseline QTcF >480 msec) in ribociclib arm, compared to 7 in control arm. Pooled RR for prolongation of QTcF was 7.956 (95%CI: 3.683–17.187; P<.001) and RD was 0.055 (95%CI: 0.040–0.070; P<.001). The risk of having a post-baseline QTcF >480 msec was significantly higher with ribociclib vs control (pooled RR, 4.002; 95%CI: 2.161–7.412; P<.001; and RD, 0.039; 95%CI: 0.024–0.055; P<.001). A total of 16 (1.38%) patients in the ribociclib arm had dose reduction, interruption, or discontinuation due to QTcF prolongation, as opposed to 3 (0.33%) in control arm. Pooled RR and RD were statistically significant at 4.204 (95%CI: 1.333–3.260; P=.014) and 0.012 (95%CI: 0.004–0.021; P=.006), respectively. Conclusion: Advanced breast cancer patients may have cardiac dysfunction due to prior cardiotoxic chemotherapies. In our meta-analysis, ribociclib was associated with significantly higher risk of QTc prolongation and the resultant dosing inconsistencies and discontinuation. Early detection of this potential adverse event and timely intervention are critical.

scholarly journals Statistical power considerations in genotype-based recall randomized controlled trials

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Naeimeh Atabaki-Pasdar ◽  
Mattias Ohlsson ◽  
Dmitry Shungin ◽  
Azra Kurbasic ◽  
Erik Ingelsson ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Statistical Power ◽  
Controlled Trials ◽  
Randomized Controlled

scholarly journals Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Pajaree Sriuttha ◽  
Buntitabhon Sirichanchuen ◽  
Unchalee Permsuwan
Keyword(s):  
Side Effects ◽  
Randomized Controlled Trials ◽  
Cochrane Library ◽  
Bibliographic Databases ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Clinically Significant ◽  
The Cochrane Library

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review. To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods. Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results. Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2), followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2), and etoricoxib, which ranged from 0.005 to 0.930 (×10−2). Conclusion. Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

Sign in / Sign up

Export Citation Format

Share Document