• The Korean Journal of Applied Statistics
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• v.25 no.4
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• pp.575-587
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• 2012

The effect of a new treatment is proven through the comparison of a new treatment with placebo; however, the number of parent non-inferiority trials tends to grow proportionally to the number of active controls. In a non-inferiority trial a new treatment is approved by proof that the new treatment is not inferior to an active control; however, both additional assumptions and historical trials are needed to show (through the comparison of the new treatment with the active control in a non-inferiority trial) that the new treatment is more efficacious than a putative placebo. The two different methods of using the historical data: frequentist principle method and meta-analytic method. This paper discusses the statistical methods and different Type I error rates obtained through the different methods employed.

• The Korean Journal of Applied Statistics
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• v.21 no.6
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• pp.947-957
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• 2008

Two-arm non-inferiority trials is often applied to parametric procedure suggested by Hauschke et al. (1999). Since this design does not allow a direct comparison of a new treatment group with placebo group, parametric procedure in a three-arm non-inferiority trial with a placebo group was suggested by Pigeot et al. (2003). But, procedures in these designs are necessary for distribution assumptions. Therefore we propose, in this paper, non parametric procedures employing Wilcoxon rank sum test in a two-arm design and linear contrast test suggested by Scheirer et al. (1976) in a three-arm design. The proposed nonparametric procedures and parametric procedures are compared by Monte Carlo simulation study.

• The Korean Journal of Applied Statistics
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• v.23 no.6
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• pp.1115-1124
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• 2010

Normal approximation methods under the null hypothesis of no difference are frequently used to test the two independent proportions in non-inferiority trials. However, these tests are not appropriate under the null hypothesis of non-zero difference. We review the likelihood score methods proposed by Miettinen and Nurminen, Farrington and Manning, and Gart and Nam and compare the performance of these tests. The simulation study shows that the likelihood score tests under the null hypothesis of non-zero difference have better performance at a Type I error and power than usual normal approximation methods.

• Archives of Plastic Surgery
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• v.47 no.3
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• pp.242-249
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• 2020

Background The Exoscope is a novel high-definition digital camera system. There is limited evidence signifying the use of exoscopic devices in microsurgery. This trial objectively assesses the effects of the use of the Exoscope as an alternative to the standard operating microscope (OM) on the performance of experts in a simulated microvascular anastomosis. Methods Modus V Exoscope and OM were used by expert microsurgeons to perform standardized tasks. Hand-motion analyzer measured the total pathlength (TP), total movements (TM), total time (TT), and quality of end-product anastomosis. A clinical margin of TT was performed to prove non-inferiority. An expert performed consecutive microvascular anastomoses to provide the exoscopic learning curve until reached plateau in TT. Results Ten micro sutures and 10 anastomoses were performed. Analysis demonstrated statistically significant differences in performing micro sutures for TP, TM, and TT. There was statistical significance in TM and TT, however, marginal non-significant difference in TP regarding microvascular anastomoses performance. The intimal suture line analysis demonstrated no statistically significant differences. Non-inferiority results based on clinical inferiority margin (Δ) of TT=10 minutes demonstrated an absolute difference of 0.07 minutes between OM and Exoscope cohorts. A 51%, 58%, and 46% improvement or reduction was achieved in TT, TM, TP, respectively, during the exoscopic microvascular anastomosis learning curve. Conclusions This study demonstrated that experts' Exoscope anastomoses appear non-inferior to the OM anastomoses. Exoscopic microvascular anastomosis was more time consuming but end-product (patency) in not clinically inferior. Experts' "warm-up" learning curve is steep but swift and may prove to reach clinical equality.

• The Korean Journal of Applied Statistics
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• v.27 no.5
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• pp.833-842
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• 2014

Non-inferiority trials indicate whether the effect of an experimental treatment is not worse than an active control. Chen et al. (2006) and Kang (2010) proposed a test method for non-inferiority trials using confidence intervals. In this paper, we suggest a new nonparametric method using a confidence interval based on Wilcoxon rank-sum test and Hodges-Lehmann estimator of active control. A Monte-Carlo simulation study compares the type I error and the power of the proposed method with previous methods.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.87.1-87.11
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• 2020

Background: A new, extended long-acting tilmicosin (TLAe) preparation was tested against intramammary ceftiofur (CEF) using a non-inferiority trial model during dry-cow therapy (DCT) in a farm with high bovine population density and deficient hygiene application. Objectives: To evaluate the possibility that TLAe administered parenterally can achieve non-inferiority status compared to CEF administered intramammary for DCT. Methods: Cows were randomly assigned to TLAe (20 mg/kg subcutaneous; n = 53) or CEF (CEF-HCl, 125 mg/quarter; n = 38 cows) treatment groups. California mastitis testing, colony-forming unit assessment (CFU/mL), and number of cases positive for Staphylococcus aureus were quantified before DCT and 7 d after calving. A complete cure was defined as no bacteria isolated; partial cure when CFU/mL ranged from 150 to 700, and cure-failure when CFU/mL was above 700. Results: TLAe and CEF had overall cure rates of 57% and 53% (p > 0.05) and S. aureus cure rates of 77.7% and 25%, respectively (p < 0.05). The pathogens detected at DCT and 7 days after calving were S. aureus (62.71% and 35.55%), Staphylococcus spp. (22.03% and 35.55%), Streptococcus uberis (10.16% and 13.33%), and Escherichia coli (5.08% and 15.55%). Non-inferiority and binary logistic regression analyses revealed a lack of difference in overall efficacies of TLAe and CEF. Apart from S. aureus, S. uberis was the predominant pathogen found in both groups. Conclusions: This study is the first successful report of parenteral DCT showing comparable efficacy as CEF, the gold-standard. The extended long-term pharmacokinetic activity of TLAe explains these results.

• Clinical Endoscopy
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• v.56 no.5
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• pp.594-603
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• 2023

Background/Aims: The necessity for pharyngeal anesthesia during upper gastrointestinal endoscopy is controversial. This study aimed to compare the observation ability with and without pharyngeal anesthesia under midazolam sedation. Methods: This prospective, single-blinded, randomized study included 500 patients who underwent transoral upper gastrointestinal endoscopy under intravenous midazolam sedation. Patients were randomly allocated to pharyngeal anesthesia: PA+ or PA- groups (250 patients/group). The endoscopists obtained 10 images of the oropharynx and hypopharynx. The primary outcome was the non-inferiority of the PA- group in terms of the pharyngeal observation success rate. Results: The pharyngeal observation success rates in the pharyngeal anesthesia with and without (PA+ and PA-) groups were 84.0% and 72.0%, respectively. The PA- group was inferior (p=0.707, non-inferiority) to the PA+ group in terms of observable parts (8.33 vs. 8.86, p=0.006), time (67.2 vs. 58.2 seconds, p=0.001), and pain (1.21±2.37 vs. 0.68±1.78, p=0.004, 0-10 point visual analog scale). Suitable quality images of the posterior wall of the oropharynx, vocal fold, and pyriform sinus were inferior in the PA- group. Subgroup analysis showed a higher sedation level (Ramsay score ≥5) with almost no differences in the pharyngeal observation success rate between the groups. Conclusions: Non-pharyngeal anesthesia showed no non-inferiority in pharyngeal observation ability. Pharyngeal anesthesia may improve pharyngeal observation ability in the hypopharynx and reduce pain. However, deeper anesthesia may reduce this difference.

• Journal of the Korean Data and Information Science Society
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• v.24 no.6
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• pp.1349-1357
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• 2013

In clinical research, sample size determination is one of the most important things. There are parametric method using t-test and non-parametric method suggested by Kim and Kim (2007) based on Wilcoxon's rank sum test for determining sample size in non-inferiority trials. In this paper, we propose sample size calculation method based on placements method suggested by Orban and Wolfe (1982) and using the power calculated by Kim (1994) in non-inferiority trials. We also compare proposed sample size with that using Kim and Kim (2007)'s formula and that of t-test for parametric methods. As the result, sample size calculated by proposed method based on placements is the smallest. Therefore, proposed method based on placements is better than parametric methods in case that it's hard to assume specific distribution function for population and also more efficient in terms of time and cost than method based on Wilcoxon's rank sum test.

• The Korean journal of internal medicine
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• v.39 no.2
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• pp.238-247
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• 2024

Background/Aims: Small rectal neuroendocrine tumors (NETs) can be treated with modified endoscopic mucosal resection (EMR). However, an optimal EMR method remains to be established. We aimed to assess the non-inferiority of Tip-in EMR versus precut EMR (EMR-P) for treating rectal NETs. Methods: This prospective, multicenter, randomized controlled trial enrolled patients with rectal NETs of < 10 mm in diameter. The patients were randomly assigned to EMR-P and Tip-in EMR groups in a 1:1 ratio. Primary outcome was margin-negative (R0) resection rate between the two methods, with a noninferiority margin of 10%. Results: Seventy-five NETs in 73 patients, including 64 eligible lesions (32 lesions in each, EMR-P and Tip-in EMR groups), were evaluated. In a modified intention-to-treat analysis, R0 resection rates of the EMR-P and Tip-in EMR groups were 96.9% and 90.6%, respectively, which did not demonstrate non-inferiority (risk difference, -6.3 [95% confidence interval: -18.0 to 5.5]). Resection time in the EMR-P group was longer than that in the Tip-in EMR group (p < 0.001). One case of intraprocedural bleeding was reported in each group. Conclusions: We did not demonstrate the non-inferiority of Tip-in EMR compared to EMR-P for treating small rectal NETs. However, the R0 resection rates for both techniques were high enough for clinical application.

• The Korean Journal of Applied Statistics
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• v.22 no.4
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• pp.793-804
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• 2009

The hypotheses of difference, ratio and odds ratio between two proportions are used for the non-inferiority trial. The approximate unconditional test suggested by Kang and Chen (2000) based on difference and ratio have the potential problem against the failure rate. When the sample size is small, the type I errors of the asymptotic test using the normal approximation suggested by Chen et al. (2000) tends to exceed the nominal level. Therefore, we propose the approximate unconditional test based on odds ratio and compare the test with the asymptotic test. And we compare the three hypotheses used in the approximate unconditional tests of two proportions with respect to the type I errors and power.