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: We aimed to evaluate whether cancer detection rates could vary with prostate size using a systematic sextant biopsy. MATERIALS AND METHODS: We performed a systematic sextant biopsy in 225 consecutive men from January 1997 to August 2002. Indications for biopsy included an elevated prostate specific antigen(PSA) level(more than 4.0ng/ml), or the hypoechoic lesion on TRUS. Prostate volume was calculated using the following fomula: volume=0.52 x length x width x height. We examined biopsy yield according to gland-volume intervals of 10cc. RESULTS: Adenocarcinoma was detected in 68 out of 225 patients(30.22%). The mean volume of prostate in all patients was 51.5cc. The highest biopsy rate(65.7%) was recorded among men with prostates between 20 to 29.9cc. The lowest biopsy rate (17.2%) was recorded among men with prostates larger than 80cc. Decreasing yield of sextant biopsy was strongly associated with increasing gland volume(p<0.001). The biopsy rate was significantly higher in patients with smaller prostates(<30cc) than in those with larger prostates(> or =30cc)(62.63% and 22.09%, respectively, p<0.001). Age, serum PSA, PSAD, and Gleason grade were comparable between small (<30cc) and large(> or =30cc) prostate groups. CONCLUSION: Our cancer detection rate using a systematic sextant biopsy was higher in men with prostates less than 30cc. Our results suggest that significant sampling error may occur in men with large glands, and more biopsies may be needed under these circumstances.
Adenocarcinoma ; Biopsy* ; Humans ; Male ; Prostate* ; Prostatic Neoplasms ; Selection Bias

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

STUDY DESIGN: Retrospective, controlled study OBJECTIVE: To compare one and two-caged posterior lumbar interbody fusion (PLIF) with local bone grafting for spondylolisthesis. SUMMARY OF LITERATURE REVIEW: Even though there are many reports on PLIF using cages and local bone grafting, Studies comparing one and two-caged PLIFs are rare. MATERIALS AND METHODS: Sixty-three patients who underwent pedicle screw fixated PLIF using cages and local bone grafts were followed for more than 1 year. Twenty-five patients had one cage (group I), and 38 patients had two cages (group II). Sampling error, disc height, sagittal Cobb angle, coronal Cobb angle, fusion rate, Oswestry disability index (ODI), operation time, blood loss, and neurologic complications were assessed. RESULTS: There was no sampling error between the two groups, except with regard to diagnosis: degenerative spondylolisthesis, 15 cases in group I and 9 cases in group II; spondylolytic spondylolisthesis, 10 cases in group I and 29 cases in group II (p=0.004). Fusion rates were 87.5% and 88.2% for groups I and II, respectively (p=1.000). More disc height loss occurred in group I (0.6 mm) than in group II (0.0 mm) (p=0.041). Over-3mm-disc height-losses were noted more frequently in group I (20%) than in group II (2.6%) (p=0.022). ODI improved from 28.1 to 12.3 (72.1% improvement) in group I and from 29.2 to 12.7 (79.3% improvement) in group II. There were no significant differences in operation time, amount of blood loss, or neurologic complications between the two groups. CONCLUSION: Unilateral one-caged PLIF with local bone grafting and posterior instrumentation was no different from bilateral two-caged PLIF with regard to fusion rates or radiologic or clinical results. The statistically significant differences in disc height seemed to be clinically insignificant. Disc height loss of greater than 3 mm was much more common in group I, with one-caged PLIF.
Bone Transplantation ; Humans ; Retrospective Studies ; Selection Bias ; Spondylolisthesis ; Transplants