• Communications for Statistical Applications and Methods
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• v.31 no.6
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• pp.613-625
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• 2024

A general non-inferiority (NI) clinical trial is typically conducted using parametric testing methods with large samples. However, patient recruitment challenges often hinder rare disease trials, leading to enrollment failures. In this study, we introduce current parametric and nonparametric NI trial testing methods and propose modifications to enhance the performance of the nonparametric approach. Through a comprehensive simulation study with various sample sizes, data distributions, and sample ratios, we compare empirical levels and statistical powers as criteria for evaluating performance. Our findings indicate that the modified nonparametric methods outperformed the existing methods, particularly under conditions of small sample sizes and non-normal distributions, offering valuable insights for improving the reliability and sensitivity of NI trials in the context of rare diseases.

• 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.

• 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.

• 대한예방의학회:학술대회논문집
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• 2001.10a
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• pp.302-304
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• 2001

• 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.

• Journal of Preventive Medicine and Public Health
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• v.37 no.4
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• pp.381-389
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• 2004

Objective : To compare the efficacy between SKI306X and Diclofenac by using generalized estimating equations (GEE) methodology in the analysis of correlated bivariate binary outcome data in Osteoarthritis (OA) diseases. Methods : A randomized, double-blind, active comparator-controlled, non-inferiority clinical trial was conducted at 5 institutions in Korea with the random assignment of 248 patients aged 35 to 75 years old with OA of the knee and clinical evidence of OA. Patients were enrolled in this study if they had at least moderate pain in the affected knee joint and a score larger than 35mm as assessed by VAS (Visual Analog Scale). The main exposure variable was treatment (SKI 306X vs. Diclofenac) and other covariates were age, sex, BMI, baseline VAS, center, operation history (Yes/No), NSAIDS (Y/N), acupuncture (Y/N), herbal medicine (Y/N), past history of musculoskeletal disease (Y/N), and previous therapy related with OA (Y/N). The main study outcome was the change of VAS pain scores from baseline to the 2nd and 4th weeks after treatment. Pain scores were obtained as baseline, 2nd and 4th weeks after treatment. We applied GEE approach with empirical covariance matrix and independent(or exchangeable) working correlation matrix to evaluate the relation of several risk factors to the change of VAS pain scores with correlated binary bivariate outcomes. Results : While baseline VAS, age, and acupuncture variables had protective effects for reducing the OA pain, its treatment (Joins/Diclofenac) was not statistically significant through GEE methodology (ITT:aOR=1.37, 95% CI=(0.8200, 2.26), PP:aOR=1.47, 95% CI=(0.73, 2.95)). The goodness-of-fit statistic for GEE (6.55, p=0.68) was computed to assess the adequacy of the fitted final model. Conclusions : Both ANCOVA and GEE methods yielded non statistical significance in the evaluation of non-inferiority of the efficacy between SKI306X and Diclofenac. While VAS outcome for each visit was applied in GEE, only VAS outcome for the fourth visit was applied in ANCOVA. So the GEE methodology is more accurate for the analysis of correlated outcomes.

• Korean Journal of Clinical Pharmacy
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• v.33 no.3
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• pp.178-185
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• 2023

Objective: Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease. Both tralokinumab and dupilumab have been recommended in the European Guideline for the treatment of adult patients with severe AD. In Korea, dupilumab has been approved for patients with moderate to severe AD, and reimbursed for those with severe AD. Since there is no clinical trial directly comparing tralokinumab and dupilumab, we conducted indirect comparison to assess the clinical usefulness in patients with AD. Methods: We selected clinical trials for indirect comparison through a systematic literature review. Individual patient data were available for the tralokinumab clinical trial, and aggregated data were available for the dupilumab clinical trial. Therefore, we employed the Matching-Adjusted Indirect Comparison (MAIC) method. The treatment efficacy was assessed based on whether patients achieved a 75% reduction on the Eczema Area and Severity Index (EASI 75) after drug administration. Results: The difference in the proportion of patients achieving EASI 75 between tralokinumab and dupilumab was 4.7% (95% CI: -7.9 to 17.3). Considering the non-inferiority margin for the EASI 75 achievement rate is -10%, tralokinumab is deemed non-inferior to dupilumab as the lower bound of the CI for the difference in the EASI 75 achievement rate between tralokinumab and dupilumab was within -10%. Conclusion: We conducted a MAIC analysis comparing tralokinumab and dupilumab based on EASI 75 achievement. The findings of this study show that tralokinumab is non-inferior to dupilumab and can be implemented in Korean clinical settings with a therapeutic position comparable to dupilumab.

• International Journal of Industrial Entomology and Biomaterials
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• v.38 no.1
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• pp.14-17
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• 2019

Oral gargling solution has been used for the control of halitosis. The purpose of this study was to compare the level of hydrogen sulphide concentration between silk oral gargling solution and commercially available oral gargling solution. Total 21 volunteers were included in this study. The relative level of hydrogen sulphide concentration was calculated to the baseline level. In terms of the primary endpoint of the trial, relative level of hydrogen sulphide concentration was $50.84{\pm}33.19%$ with silk group, versus $71.07{\pm}21.83%$ with Listerine group ($P_{non-inferiority}=0.003$). In conclusion, the results of oral gargling with a silk protein for healthy individual were non-inferior to oral gargling with Listerine for hydrogen sulphide concentration reduction.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.42
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• pp.40.1-40.5
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• 2020

Background: Hyaluronic acid (HA) is well known to exert an anti-inflammatory effect during oral wound healing and is commonly applied after tooth extraction. However, no double-blind randomized controlled study comparing two hyaluronate mouthwash products has been conducted so far. The aim of this study was to comparatively analyze the efficacy of Mucobarrier^® and Aloclair^® in terms of clinical symptoms. Results: A total of 112 patients were randomly assigned to assess the degree of discomfort, pain reduction, redness, burning sensation, and swelling between two groups on the day of surgery and 7 days later in a double blind test, with a total 56 Aloclair patients and 56 Mucobarrier patients. There was no statistically significant difference in the overall discomfort, degree of pain reduction, redness, burning sensation, and swelling between the Mucobarrier and Aloclair groups. Conclusion: The local application of hyaluronic acid mouth wash after wisdom tooth extraction is beneficial in reducing overall discomfort and pain reduction, and the clinical utility of Mucobarrier^® is no different from Aloclair^®. Trial registration: Institutional Review Board of Yonsei University College of Dentistry, 2-2018-0036. Registered 10 September 2018-prospectively registered, https://eirb.yuhs.ac/