Progression-free survival as surrogate endpoint in advanced pancreatic cancer: meta-analysis of 30 randomized first-line trials

BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic cancer.The aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival（OS）in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine alone.DATA SOURCES： A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate Rs （Spearman＇s rank-order correlation coefficient） between PFS and post-progression survival （PPS） with OS （Rs） and between treatment effects on PFS and OS （RHR）. RESUEFS： A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS （RHR=0.78） and between the endpoint PFS and OS was high across all studies （Rs=0.75）. The slope of the re- gression line was 0.76±0.26, indicating that an agent produc- ing a 10% risk reduction for PFS will provide a 7.6%±2.6% risk reduction for OS. Correlation between PPS and OS was very strong （Rs=0.71） and accounted for more than 50% of the whole OS variability （R2=0.57）. CONCLUSION： Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.

Enlightenment and Reference of Vaccine Clinical Trial Design Based on Immunological Surrogate Endpoints in the United States

Objectives To explore the optimization method of vaccine clinical trial design based on immunological surrogate endpoint to improve the quality and efficiency of vaccine clinical research and development.Methods As to the problems in the vaccine clinical research in China,the relevant guidelines and literatures of FDA and WHO were used to analyze and summarize the methods of optimizing the design of vaccine clinical trials.Results and Conclusion The adaptive design guidelines are established to guide clinical trial design,encourage the development and application of immunological surrogate endpoints,establish qualification process for drug development tools and information disclosure procedures to improve vaccine development efficiency.

Patient-centric periodontal research:A pioneering application of patient-reported outcome measures

Conventional dentistry or periodontal research often ignores the human component in favor of clinical outcomes and biological causes.Clinical research is driven by the statistical significance of outcome parameters rather than the satisfaction level of the patient.In this context,patient-centric periodontal research(PCPR)is an approach that considers the patient´s feedback concerning their functional status,experience,clinical outcomes,and accessibility to their treatments.It is argued that data self-reported by the patient might have low reliability owing to the confounding effect of their personal belief,cultural background,and social and economic factors.However,literature has shown that the incorporation of“patient-centric outcome”components considerably enhances the validity and applicability of research findings.Variations in the results of different studies might be due to the use of different and non-standardized assessment tools.To overcome this problem,this editorial enlists various reliable tools available in the literature.In conclusion,we advocate that the focus of researchers should shift from mere periodontal research to PCPR so that the results can be effectively applied in clinical settings and the therapeutic strategy can also change from mere periodontal therapy to patient-centric periodontal therapy.

Prediction of the Outcome of Esophageal Epithelium Dysplasia by High Resolution Image Analysis

Objective: To predict the outcome of dysplasia of esophageal epithelium by means of high resolution image analysis (HRIA). Methods: Asymptomatic adults were examined for balloon cytology of the esophagus in 1983 from Heshun Commune of Linxian County. 93 severe dysplasias and 122 mild dysplasias of the esophagus were selected. By means of an Axiomat-microscope equipped with TV-camera, 100 normal nuclei of well-preserved cells in the intermediate layer of Pap-stained squamous epithelium were randomly examined. Results: Of the 93 cytologically diagnosed severe dysplasia cases, 24, 14 and 7 progressed to carcinoma in 3, 5 and 9 years, respectively. In the other 48 cases, dysplasia remained stable or regressed to normal. The other cases were used as the control. According to chromatin features, correct diagnosis of cases was achieved by HRIA in 75.0% (18/24), 85.7% (12/14) and 85.7% (6/7) of the cases examined, respectively (P<0.001). Of the 122 cytologically diagnosed mild dysplasia, 16, 13 and 12 cases progressed to carcinoma in 3, 5 and 9 years, respectively. The other 81 cases remained stable or regressed to normal. Correct diagnosis was made by HRIA in 93.8% (15/16), 76.9% (10/13) and 83.3% (10/12) of the cases examined, respective1y (P<0.001). Conclusion: Chromatin nuclear features examined by HRIA can predict the outcome of precancerous lesions and discriminate progressor from non-progressor ones. It can be used as surrogate endpoint biomarkers for the evaluation of efficiency of chemo-prevention trial.