The equivalence margin is the largest difference that is clinically acceptable between the test (or experimental) drug and the active control (or reference) drug. This paper discusses the scientific principles, along with the regulatory issues, that need to be addressed when determining the equivalence margin for the biosimilar product. The concept of assay sensitivity is introduced, and the ways to ensure assay sensitivity in the equivalence trial are emphasized. A hypothetical example is presented to show how an equivalence margin is determined. The regulatory agency should carefully assess if the equivalence margin of the biosimilar product was determined using a scientifically valid and clinically relevant approach, not subject to selection bias. This is important because the consumer risk of erroneously declaring equivalence when in fact it is not must be controlled conservatively low in the approval of any biosimilar products.
Dietary Sucrose ; Selection Bias

Reported results of HCG treatment for cryptorchism are quite variable because many factors may influence the success of the therapy. It is possible that the anatomic stratification introduces an element of selection bias into the data. 12 cases of extracanalicularly located testis were treated with HCG from December 1988 year to June 1990 year. Five of the 12 cases were cosmetically satisfactory. 3 became retractile testis which is disturbing in all that could be treated successfully but could not be satisfactory from the cosmetic point of view. Apparent hernial sac developed in 4 cases who were clinically inapparent before initiation of the hormonal therapy.
Cryptorchidism ; Male ; Selection Bias ; Testis*

BACKGROUND/AIMS: To evaluate the therapeutic outcomes of the endoscopic submucosal dissection (ESD) technique for the treatment of gastric subepithelial tumors (SETs). METHODS: A systematic literature review was conducted using the core databases. Data on the complete resection rates and the procedure-related perforation rates were extracted and analyzed. A random effects model was then applied for this meta-analysis. RESULTS: In all, 288 patients with 290 SETs were enrolled from nine studies (44 SETs originated from the submucosal layer; 246 SETs originated from the muscularis propria layer). The mean diameter of the lesions ranged from 17.99 to 38 mm. Overall, the pooled complete resection rate was estimated to be 86.2% (95% confidence interval [CI], 78.9 to 91.3). If the analysis was limited to the lesions that originated from the submucosal layer, the pooled complete resection rate was 91.4% (95% CI, 77.9 to 97). If the analysis was limited to the lesions that originated from the muscularis propria, the pooled complete resection rate was 84.4% (95% CI, 78.7 to 88.8). The pooled procedure-related gastric perforation rate was 13% (95% CI, 9.4 to 17.6). Sensitivity analyses showed consistent results. Finally, publication bias was not detected. CONCLUSIONS: ESD, including endoscopic muscularis dissection, is a technically feasible procedure for the treatment of SETs. However, selection bias is suspected from the enrolled studies. For the development of a proper indication of ESD for SETs, further studies are needed.
Gastrointestinal Stromal Tumors ; Humans ; Publication Bias ; Selection Bias

Randomized controlled trial is widely accepted as the best design for evaluating the efficacy of a new treatment because of the advantages of randomization (random allocation). Randomization eliminates accidental bias, including selection bias, and provides a base for allowing the use of probability theory. Despite its importance, randomization has not been properly understood. This article introduces the different randomization methods with examples: simple randomization; block randomization; adaptive randomization, including minimization; and response-adaptive randomization. Ethics related to randomization are also discussed. The study is helpful in understanding the basic concepts of randomization and how to use R software.
Bias (Epidemiology) ; Ethics ; Probability Theory ; Random Allocation ; Selection Bias

Random allocation is commonly used in medical researches, and has become an essential part of designing clinical trials. It produces comparable groups with regard to known or unknown prognostic factors, and prevents the selection bias which occurs due to the arbitrary assignment of subjects to groups. It also provides the background for statistical testing. Depending on the change in allocation probability, random allocation is divided into two categories: fixed allocation randomization and dynamic allocation randomization. In this paper, the author briefly introduces both the theory and practice of randomization. The definition, necessity, principal, significance, and classification of randomization are also explained. Advantages and disadvantages of each randomization technique are further discussed. Dynamic allocation randomization (Adaptive randomization), which is as yet unfamiliar with the anesthesiologist, is also introduced. Lastly, the methods and procedures for random sequence generation using Microsoft Excel is provided.
Classification ; Random Allocation* ; Research Design ; Selection Bias

Random allocation is commonly used in medical researches, and has become an essential part of designing clinical trials. It produces comparable groups with regard to known or unknown prognostic factors, and prevents the selection bias which occurs due to the arbitrary assignment of subjects to groups. It also provides the background for statistical testing. Depending on the change in allocation probability, random allocation is divided into two categories: fixed allocation randomization and dynamic allocation randomization. In this paper, the author briefly introduces both the theory and practice of randomization. The definition, necessity, principal, significance, and classification of randomization are also explained. Advantages and disadvantages of each randomization technique are further discussed. Dynamic allocation randomization (Adaptive randomization), which is as yet unfamiliar with the anesthesiologist, is also introduced. Lastly, the methods and procedures for random sequence generation using Microsoft Excel is provided.
Classification ; Random Allocation* ; Research Design ; Selection Bias

We compared all frozen section examination of ovarian tumors during a 5 year period in our institute with permanent section diagnosis from paraffin sections. In this period, 604 ovarian tumors had frozen section examination. Final histologic diagnosis was divided into benign, low malignant potential and malignant. Sensitivity of frozen section diagnosis for malignant was 80 %, low malignant potential 73,1%, and benign 99.8%. Predictive value for malignancy was 98.5%, for low malignant potential 76.6%, and for benign disease 96.2%. Diagnostic problems occurred in huge tumors and low malignat potential mucinous tumors. Analysis of the 32 false negative(miss or under diagnosis) revealed that a sampling error was involved almostly. The cases of discrepancy between frozen section diagnosis and permanent section diagnosis, were 26/34 in mucinous tumors and 33/34 in huge size of tumors(more than 10cm). Although surgeons and pathologist are aware of the limitations of frozen section diagnosis of ovarian tumors, peroperative histologic examination can be worthwhile and prevent under or over treatment of ovarian malignancies.
Diagnosis* ; Frozen Sections* ; Mucins ; Paraffin ; Selection Bias

PURPOSE: The objective structured clinical examination (OSCE) is considered to be one of the most robust methods of clinical assessment. One of its strengths lies in its ability to minimise the effects of examiner bias due to the standardisation of items and tasks for each candidate. However, OSCE examiners' assessment scores are influenced by several factors that may jeopardise the assumed objectivity of OSCEs. To better understand this phenomenon, the current review aims to determine and describe important sources of examiner bias and the factors affecting examiners' assessments. METHODS: We performed a narrative review of the medical literature using Medline. All articles meeting the selection criteria were reviewed, with salient points extracted and synthesised into a clear and comprehensive summary of the knowledge in this area. RESULTS: OSCE examiners' assessment scores are influenced by factors belonging to 4 different domains: examination context, examinee characteristics, examinee-examiner interactions, and examiner characteristics. These domains are composed of several factors including halo, hawk/dove and OSCE contrast effects; the examiner's gender and ethnicity; training; lifetime experience in assessing; leadership and familiarity with students; station type; and site effects. CONCLUSION: Several factors may influence the presumed objectivity of examiners' assessments, and these factors need to be addressed to ensure the objectivity of OSCEs. We offer insights into directions for future research to better understand and address the phenomenon of examiner bias.
Bias (Epidemiology) ; Humans ; Leadership ; Patient Selection ; Problem Solving ; Recognition (Psychology)

PURPOSE: The purpose of this study is to enhance the quality of data by performing a methodological assessment of medical records reviews. METHODS: We reviewed the articles published in the Journal of the Korean Society of Emergency Medicine between January 2001 and December 2003 that used a retrospective medical records review as the study method. We assessed data collector's training, descriptions of inclusion/ exclusion criteria, definitions of important variables, use of standardized case record forms, monitoring the data collectors' performance, blind data collecting, inter-rater reliability/ test of inter-rater agreement, intra-rater reliability/test of intra-rater agreement, selection bias from consent, and rules regarding management of missing data. RESULTS: There were 111 articles that used retrospective medical records reviews during the study period. In 111 (100%) articles, inclusion/exclusion criteria were described, in 98 (88.3%), important variables were defined, and in 4 (3.6%), standardized case record forms were used. However no articles addressed the other items on the checklist. CONCLUSION: Study conductors should design studies to enhance the quality of data, and detailed descriptions are necessary to improve the reproducibility of the study.
Checklist ; Emergencies* ; Emergency Medicine* ; Medical Records* ; Retrospective Studies ; Selection Bias

PURPOSE: This study was a systematic review to evaluate the effects of aromatherapy on menopausal symptoms, perceived stress and depression in middle aged-women. METHODS: Eight databases were searched from their inception September 8, 2015. Two reviewers independently performed the selection of the studies, data abstraction and validations. The risk of bias was assessed using Cochrane criteria. For analysis of the data, a meta-analysis of the studies was performed. RESULTS: From the electronic databases, 73 articles were selected, and 19 removed due to duplication. After two reviewers read the abstracts of 54 studies, 34 studies were selected. Complete papers for 34 original articles were read and, 12 studies which met selection criteria were reviewed and the effects of aromatherapy on menopausal symptoms, stress and depression analyzed using meta-analysis with RevMan. In the 2 studies which included Randomized Controlled Trials testing of aromatherapy on menopausal symptoms and comparison of control and placebo groups were done. Aromatherapy massage was favorably effective in reducing the menopausal symptoms compared to the control group (n=118, MD=-6.33; 95% CI -11.51 to -1.15), and compared to the placebo group (n=117, MD=-4.14; 95% CI -7.63 to -0.64). Also aromatherapy was effective in reducing stress (n=72, SMD=-0.64; 95% CI -1.12 to -0.17) and depression (n=158, MD=-5.63; 95% CI -10.04 to -1.22). CONCLUSION: There is limited evidence suggesting that aromatherapy for middle-aged women may be effective in controlling menopausal symptoms, perceived stress and depression.
Aromatherapy* ; Bias (Epidemiology) ; Depression* ; Female ; Humans ; Massage ; Menopause ; Patient Selection