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Objective: This study aimed to explore the factors affecting the bioequivalence of test and reference insulin preparations so as to provide a scientific basis for the consistency evaluation of the quality and efficacy of insulin biosimilars. Methods: A randomized, open, two-sequence, single-dose, crossover design was used in this study. Subjects were randomly divided into TR or RT groups in equal proportion. The glucose infusion rate and blood glucose were measured by a 24-h glucose clamp test to evaluate the pharmacodynamic parameters of the preparation. The plasma insulin concentration was determined by liquid chromatography-mass spectrometry (LC-MS/MS) to evaluate pharmacokinetic parameters. WinNonlin 8.1 and SPSS 23.0 were applied for PK/PD parameter calculation and statistical analysis. The structural equation model (SEM) was constructed to analyze the influencing factors of bioequivalence by using Amos 24.0. Results: A total of 177 healthy male subjects aged 18-45 years were analyzed. Subjects were assigned to the equivalent group (N = 55) and the non-equivalent group (N = 122) by bioequivalence results, according to the EMA guideline. Univariate analysis showed statistical differences in albumin, creatinine, Tmax, bioactive substance content, and adverse events between the two groups. In the structural equation model, adverse events (ß = 0.342; p < 0.001) and bioactive substance content (ß = -0.189; p = 0.007) had significant impacts on the bioequivalence of two preparations, and the bioactive substance content significantly affected adverse events (ß = 0.200; p = 0.007). Conclusion: A multivariate statistical model was used to explore the influencing factors for the bioequivalence of two preparations. According to the result of the structural equation model, we proposed that adverse events and bioactive substance content should be optimized for consistency evaluation of the quality and efficacy of insulin biosimilars. Furthermore, bioequivalence trials of insulin biosimilars should strictly obey inclusion and exclusion criteria to ensure the consistency of subjects and avoid confounding factors affecting the equivalence evaluation.
RESUMO
BACKGROUND: Human papillomavirus (HPV) infection is the most common sexually transmitted disease, and it is associated with anogenital warts and oropharyngeal and anogenital cancers. Among female malignant tumors in China, the incidence of cervical cancer ranks second, with only breast cancer being more prevalent. HPV infection and related diseases affects both women and men. HPV vaccination is an optimal prevention strategy in preventing HPV infection and related diseases. The inclusion of the HPV vaccine in the national immunization program is an effective way to increase immunization coverage, reduce the burden of HPV related diseases, and increase national life expectancy. OBJECTIVE: This study aimed to explore the factors influencing the attitudes of Chinese men toward the inclusion of the HPV vaccine in males included in the national immunization program, thus providing reference for launching the national immunization program policy. METHODS: We invited men aged 20 to 45 to participate in an online survey. The participants were requested to complete a questionnaire, including sociodemographic characteristics, sexual behavior characteristics, knowledge of HPV and the HPV vaccine, and attitudes toward the HPV vaccine. A logistic regression model was constructed to analyze the influencing factors of attitudes. RESULTS: A total of 660 males in China participated in this survey, and 80.45% supported the inclusion of HPV vaccines in national immunization programs. Participants earning CNY 100,000-200,000 (dds ratio (OR): 0.63, 95% confidence interval (CI): 0.39-1.00) or ≥200,000 (OR: 0.34, 95% CI: 0.17-0.68) were more likely to disapprove this strategy. Compared with people without a history of HPV infection, those with a history of HPV infection (OR: 1.84, 95% CI: 1.17-2.90) were more likely to approve. Men who had better knowledge of HPV were more likely to approve than men with less knowledge about HPV (OR: 1.44, 95% CI: 1.17-1.79). Compared with participants who did not know when the HPV vaccine should be given, those who knew that the ideal time of vaccination is before an individual becomes sexually active (OR: 1.75, 95% CI: 1.04-2.95) were more likely to approve. CONCLUSION: One in five men did not support the inclusion of HPV vaccines in national immunization programs, and they are likely to be from higher socioeconomic background and have poor knowledge of HPV. In order to implement comprehensive immunity, targeted actions need to be taken at national and public levels. In addition, when implementing measures, more attention needs to be paid to lower income men, men without a history of HPV infection and with poor knowledge of HPV, as well as young men.
